She wanted to know one thing, and nobody had been able to tell her. Would this ever have hurt her?

There is no test that answers that. She was choosing between a lumpectomy, a mastectomy, radiation, five years of endocrine therapy, and some combination of those, for a finding that might have sat in her breast quietly for the rest of her life. She had no insurance and was paying out pocket to find answers to questions no one can answer with certainty. Including paying out of pocket for a repeat MRI that would at least tell her if her self-prescribed protocol was working.

Ductal carcinoma in situ is breast cancer, but it is noninvasive. The abnormal cells sit inside the duct and have not grown through the wall. Whether they ever will is the whole question, and for any one woman nobody can answer it. Estimates of how often untreated DCIS turns invasive run from roughly one in ten to one in two, usually over ten to twenty years, and the range is that wide because we almost never leave it alone long enough to find out. High grade, comedo necrosis, a larger lesion, younger age and close margins all push the risk up, which is why hers was taken seriously.

Treatment changes those odds in a specific way. Adding radiation after lumpectomy cuts the chance of an invasive recurrence roughly in half. It does not improve overall survival.

Screening gave her a diagnosis she cannot give back, a decision with permanent consequences, and no way to know whether the DCIS would ever have become invasive, or negatively impact her. Nobody prepares people for questions like this, but at the same time, it is not a rare place to end up.

The Screening Paradox

When you pool the randomized screening trials and ask whether the screened group died less often of the cancer being screened for, the answer is often yes. When you ask whether the screened group lived longer overall, the answer is not really.

Both can be true at once, let’s talk about how this is possible.

The first is arithmetic. Any one cancer kills a small fraction of people. Colorectal cancer accounts for roughly two of every hundred deaths in this country. Prevent a quarter of those and you have prevented half a death per hundred people. Set that half against the other ninety-eight deaths from everything else and it disappears into the noise. The modeling on this suggests a breast screening trial would need something like three hundred thousand women in each arm, followed for twenty years or more, before a difference in total mortality could be seen at all. No trial has ever been built at that size, so the missing signal is partly a missing telescope.

The second is that screening causes some deaths and does not get charged for them. When a colonoscopy perforates a bowel, or radiation for a cancer that was never going to spread injures a heart, that person does not die of colon cancer or breast cancer. They die of something else. The cancer-specific number stays clean and the total does not. There is a name for it, slippery linkage, and it only ever makes screening look better.

The third is that people saved from one cancer stay mortal. Preventing a colon cancer death at seventy is a real gain to the person it happens to, and it is not the same thing as adding years to a life.

But screening is sold to patients as a way to live longer, and for most of these tests we have never shown that it does. It moves your odds on one disease. It moves your total odds less than the marketing implies.

The Cancers We Were Better Off Not Finding

Overdiagnosis means finding a cancer that was never going to cause symptoms or shorten a life. The person gets treated anyway. Nothing is gained.

In breast screening it is about one in seven of the cancers found. The number rises with age, because the older you are, the more likely something else reaches you before the cancer would have. Between 70 and 74 it is closer to one in three. Between 75 and 84, nearly half.

In prostate screening, roughly six of every ten cancers PSA finds are overdiagnosed. Of the men who go on to surgery, 85% still had erectile dysfunction six years later in the largest randomized trial. After radiation it was about 70%. Incontinence was worse after surgery. That is changing, because active surveillance is now the preferred management for low-risk disease, and fewer men go straight to treatment than a decade ago.

Thyroid is the extreme. A model published this year estimates that between 72% and 94% of the papillary thyroid cancers diagnosed in this country since 1991 were overdiagnosed. That is somewhere between 550,000 and 730,000 people who were told they had cancer and treated for it. The death rate from thyroid cancer did not move.

But Not Looking Has a Cost Too

Around the same time last spring, I picked up a patient about the same age whose colon had never been examined once. She reached me after an emergency admission for a colon cancer that had already perforated, weeks in a hospital bed, and a scan that read the abscesses in her liver as metastases before anyone sorted it out.

Colorectal screening is one of the places where the evidence is strongest, because the test removes precursors rather than finding early cancers. She fell through anyway, the way people fall through when they have no consistent primary care, or when the prep requires a day off work and a driver, or when a previous medical experience made the exam unthinkable.

So I hold two facts at once. And the duality isn’t easy to hold, justify or explain. We find things that would never have hurt anyone, and we miss people entirely, and both failures come from a system built around averages.

The New Hot Take: Look for Everything at Once

Most commonly in this space we talk about Galleri, a blood test that looks for signals from more than fifty cancers at once. It costs $949, almost no insurance covers it, and it is not FDA approved. Its application is under review, and an FDA advisory committee votes on it on September 23.

Its largest trial read out this year. More than 142,000 people in England, aged 50 to 77. The goal was to reduce the number of cancers diagnosed at stage three or four, meaning catch them earlier, while treatment can still cure. It did not meet that goal.

Stage three and four combined did not move. Stage four alone did. Measured against the people who got usual care, those who also got the blood test had 22% fewer stage four diagnoses in the second year of screening and 26% fewer in the third. They were also about a quarter less likely to have their cancer found during an emergency, which is the worst way to find out you have cancer and the way my perforated-colon patient found out. There is no mortality data yet and there will not be for years.

I think the endpoint worked against the test. It lumped twelve cancers together, including colon and lung, where existing screening already catches disease earlier. The cancers with nothing else looking for them, pancreatic and ovarian among them, got averaged in with the ones already covered, so the places where this test adds the most disappeared into the places where it adds the least.

About half the positive results turned out to be cancer, which is far better than most people assume. For the other half, the test says a cancer signal was found and nothing is ever confirmed. What follows is months of scans and blood draws, sometimes a biopsy, and it usually runs longer than it does for the people who do have cancer. Maybe the lesion is too small to find. Maybe there is nothing there and no obvious place to stop looking. Sometimes the search ends without an answer. Nobody tells you that you are fine. They tell you to keep watching. Decide who is going to walk you through that before you order the test, not after.

Whole-body MRI is the weaker version of the same idea. Pooling the studies in asymptomatic people, the confirmed cancer detection rate is somewhere around 1.5%. Incidental findings are common, and in earlier reviews roughly a third of people scanned had something critical or indeterminate turn up. There is no long-term outcome data at all.

These tests are getting cheaper, and some can be ordered without a doctor. The woman I opened with had ordered a consumer lab panel herself and brought me the results to read. The test is no longer the expensive step. Deciding what to do with what it finds is.

Before You Go Looking

I believe finding cancer early can be better. I have watched it be better. What I do not believe is that finding it early is automatically better, and the difference between those two sentences is a roadmap.

A test result is only worth having if somebody knows what to do with it. Before you order any of these tests, and I do order some of them, I would settle five things first.

Who reads the result. If a blood test says there is a cancer signal and points at your pancreas, who orders the imaging, who interprets it, and who calls you back. If the answer is nobody in particular, do not run the test yet.

What you will do with an ambiguous answer. Most of what these tests turn up is not a cancer and not nothing. Decide in advance whether you are a person who can watch something, or whether you will need it removed, because that is the actual choice you are buying.

Who pays for the cascade. The test is the cheap part. The scans, the biopsies, the repeat imaging in three months, and the specialist visits are not, and most of them are not covered when the trigger was a screening test nobody’s insurer recognizes.

Whether the finding would change anything. For pancreatic cancer, finding it earlier plausibly changes the whole story. For a small thyroid nodule, finding it earlier mostly changes how long you live knowing about it.

Whether you would change how you live. The plan after a positive result, alongside whatever workup follows, is not a mystery. Minimal to no alcohol. Whole foods that keep your blood sugar flat, your body nutrient dense and your gut microbes happy. Daily movement, strength work twice a week, regular sweating, protected sleep, and stress handled rather than absorbed. Decide before you order the test whether you would actually do any of it. If the answer is yes, the harder question is why you are waiting for a blood test to give you permission. If the answer is no, the test is buying you information you have already decided not to act on.

Those five questions are the difference between early action and an expensive way to become a patient.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington and Oregon residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

It usually comes at the end of the visit, hand already on the doorknob. We have spent fifty minutes on her cancer. Then she asks the question that has been waiting underneath the rest: does any of this matter for her kids?

What she is really asking is whether she has already done something wrong. I have watched women carry that question through an entire course of treatment without ever saying it out loud.

Here is where I land. Most of what parents are afraid of is not there. The few things that are there are almost embarrassingly cheap to address. And the intervention most likely to move the needle is not something you can buy, which is probably why nobody is selling it to you.

Childhood cancer is rare, and much of its biology begins early. In most childhood ALL and some AML, the first leukemic genetic event can be traced back to cord blood or a neonatal blood spot. The clock started before anyone knew there was a clock.

But prenatal is not predetermined.

Screen the cord blood of healthy newborns and you will find that first genetic change already sitting there in 1 to 5% of them, depending on the test used. Childhood ALL affects about 1 in 2,000 children. Of the babies born carrying the change, only about 1 in 500 will ever develop leukemia.

Almost everything that decides the difference happens after birth.

Is food giving my child cancer?

There is no food I can point to and tell you it causes childhood cancer. Not one. What exists is a set of signals, three of which come up often enough that I take them seriously.

Cured meat has the mechanism you would invent if you were trying to convince someone. Nitrite plus amines in the stomach forms N-nitroso compounds, the most potent nervous system carcinogens known in animal models. A meta-analysis put maternal cured meat consumption at 68% higher risk of childhood brain tumors, and prenatal vitamins blunted the association, exactly what you would predict if vitamin C were interrupting nitrosation. It is also the only one of the three not confined to pregnancy. A 2025 meta-analysis put children’s own processed meat intake at 72% higher odds of acute leukemia, and their vegetable intake at 39% lower.

Coffee has the larger literature and gets almost none of the attention. Pooling eight studies and 2,552 cases, the international consortium found more than two cups a day at 27% higher odds of ALL, with a dose response.

Alcohol is the third. Across 39 case-control studies and more than 16,000 cases, maternal drinking in pregnancy tracked with childhood AML, from 64% higher odds at moderate intake to more than double at high. Nothing for ALL, which is the far more common disease.

The pattern nobody mentions

Every time researchers stopped asking mothers to remember and started measuring instead, the signal shrank or vanished.

Pesticides.

Pooled across 12 case-control studies, household pesticide use during pregnancy carried about 40% higher odds of childhood ALL, and a 2021 meta-analysis of 55 studies put maternal exposure at nearly double. The risk concentrated on indoor insecticides and on pregnancy rather than later childhood. Then investigators measured 20 actual insecticides in household carpet dust and found nothing.

Glyphosate, the same. IARC calls it a probable human carcinogen on occupational evidence: farm applicators, high cumulative exposure, adult lymphoma. Even that is contested, and the largest prospective cohort of 54,000 applicatorsfound no association. The childhood question has been asked exactly once with measurement. Researchers tested house dust in the homes of 181 leukemia cases, found glyphosate in 99% of them, and found no relationship to concentration.

Cured meat, the same. A 2023 review of 181 studies found the association in the case-control data and not in the cohorts, where mothers are asked before anyone knows which child will get sick.

Coffee, the same. A Danish cohort of 141,000 pregnancies found nothing.

Why?

• A mother whose child has leukemia remembers her pregnancy differently than a mother whose child is well. That is not dishonesty. It is what memory does after catastrophe.

• The technical name is differential exposure misclassification. If both groups misremember equally, a study only misses real effects. If one group misremembers more, a study can invent an effect that was never there. And parents do misremember. When researchers checked interviews against medical records six years after birth, parents recalled fewer than half the infections and medications their charts had documented. In a study of childhood ALL, the gap between case and control parents only showed up where parents had already heard that exposure blamed.

To be clear, I don’t think the above makes these exposures safe. A 2025 study dosing rats from prenatal life at the European acceptable daily intake found dose-related tumors including early leukemias. But when an umbrella review graded the entire environmental literature for childhood ALL, exactly two exposures were rated convincing: ionizing radiation in early childhood, and pesticide exposure around conception. No food made that tier. A 2025 overview of thirteen systematic reviews put it plainly: the certainty is too low to establish a clear association between any nutritional factor and childhood ALL.

We have spent decades interrogating what mothers ate, and we still do not know.

What if the exposure is the protective part?

Greaves’ model proposes that common B-cell precursor ALL takes two steps. The lesion in utero, then a second event when an ordinary childhood infection meets an immune system that was never trained, because the early microbial exposure never came. Children with leukemia show delayed gut microbiome maturation.

If that holds, the most common cancer of childhood is partly a disease of insufficient exposure. Not too much of something. Too little.

The evidence is mixed. In the UK childhood cancer study, formal day care in the first year carried about half the odds of ALL against population controls and about 30% lower against a stricter comparison group, with a dose response either way. Then the same Danish registry that produced the breastfeeding finding followed 1.1 million children and found no protection from childcare whatsoever. It remains a hypothesis and not a settled one.

This holds a lot of similarity to the peanut story from the first piece, where a decade of telling parents to withhold allergens was causing the allergy it was meant to prevent. The protective instinct, remove the challenge, produced the harm. I have watched that pattern hold in allergy, in the microbiome, and in exercise physiology. I would not bet against it here.

Can food change my child’s genes?

Probably not in the same way we all think.

People conceived during the Dutch Hunger Winter still had less methylation of the IGF2 gene six decades later than their own unexposed siblings, and later work showed those differences statistically mediated the famine’s effect on adult BMI and triglycerides. Early nutrition does leave durable molecular marks in humans.

But, let’s keep it in proportion. The exposure was starvation, not a mediocre diet. The effect was largest around conception. The differences are a few percentage points, and there is a serious argument that part of the signature reflects which embryos survived rather than which genes were reprogrammed. None of it tells us what an ordinary diet does.

It does reach one generation further. A small follow-up found higher adult BMI among the children of men exposed to famine in utero. Intriguing, and not proof of transgenerational inheritance: the father’s germ-cell precursors were physically present during that exposure. The grandchild was already in the room.

What about soy?

Almost every version of this question comes from a family with breast cancer in it, and the fear runs precisely backward from the data.

Asian American women who ate the most soy as children have about 60% less breast cancer as adults than those who ate the least, and childhood is the window where the association is strongest. That number rests on mothers of 99 cases recalling their daughters’ diets, so hold the size of it loosely. But nothing in humans shows soy foods harm girls, and the signal is reasonably consistent across Asian and Asian American populations. A Taiwanese study of children’s own diets found bean curd running the same protective direction.

One of many meals in Japan showcasing the incredible variety of fermented soy, from miso and natto to tofu and beyond.

Tofu, edamame, and miso are food. Soy protein isolate in a bar is a formulation. It frustrates me that one conversation covers both.

What cancer risk are we not talking about?

Everything above concerns childhood cancer, which is rare. The larger lever points at adult cancer decades out, through body fat. Childhood BMI predicts adult obesity-related cancer across 46 cohorts. But the UK Biobank result is the one I repeat to parents: risk was determined mostly by adult BMI. Childhood sets the trajectory. It does not seal it.

Which means the mother at the door is worrying about the wrong window.

What about red meat and sugar?

The right window is longer and quieter. It opens in childhood too, but nothing in it announces itself for decades, which is why I almost never get these questions from a parent. I get them from the woman sitting in front of me, after her own diagnosis.

Meat

has recently written on eating for cancer prevention, and I agree with most of it. The studies on red meat and cancer risk are sloppy, food frequency questionnaires are a weak instrument, and the whole dietary pattern matters far more than any single food in it. I would go further than she does on processing. Nitrites, preservatives and oxidized fats are almost certainly doing damage, and a hot dog and a grass-fed steak should never have been counted as the same exposure in the first place.

Where I would push a little is the idea that the risk lives entirely in the processing. Five mechanisms get proposed. Three are about what is done to the meat: nitrites from curing, polycyclic aromatic hydrocarbons from smoking, heterocyclic amines from high-heat cooking. She is right about all three. The other two are in the meat itself. Heme iron catalyzes N-nitroso formation and lipid peroxidation in the gut, and Neu5Gc, a sugar humans cannot make, incorporates into our own tissue and provokes an inflammatory response. Neither cares how the animal was raised.

Fed to ileostomy patients, unprocessed red meat raised gut N-nitroso compounds roughly fourfold, and in the Black Women’s Health Study unprocessed red meat carried 33% higher colorectal cancer risk per 100 g a day while processed meat carried none.

The Maasai comparison I would hold loosely too. Kenyan cancer registries cover less than 20% of the population and African cancer registration carries a well documented urban bias, so Maasai cancers are largely uncounted rather than absent. Cancer is also mostly a disease of old age, so a population that dies younger will look protected whether it is or not. None of which makes a steak dangerous. Pooled across cohorts, unprocessed red meat raises the risk of these cancers by roughly 10 to 25%. Smoking multiplies lung cancer risk roughly twentyfold. And those cohorts did not record how the animal was raised, so what they measured is the beef supply as it actually is, which is overwhelmingly conventional. That gap is real, and it is why the heme evidence carries the weight here, because heme is the one thing that does not depend on the question nobody asked. Grass-fed does not remove it. If anything it adds a little, since grass-finished beef runs consistently higher in iron than grain-finished.

Sugar

In NutriNet-Santé, 101,279 adults followed prospectively, top-quartile sugar intake carried 51% higher breast cancer risk, and it held after adjusting for weight gain. But most studies of total sugar find nothing. The signal sits in added sugars and sugary drinks, which is what you would expect if the pathway runs through insulin rather than through the molecule. Same argument as children’s processed fruit snacks. The type of sugar and delivery matters!!

The two sections of Connealy's piece I would put in front of any cancer patient are the ones on sugar and on starving cancer. She takes apart the idea that cutting carbohydrates starves a tumor, and she is right. Restrict glucose and the body manufactures its own from muscle, while the tumor shifts to fatty acids and glutamine. That is a different question from the one above, and the two get lumped together constantly. Sugar intake over decades tracking with getting cancer is not the same claim as glucose restriction treating one.

Which brings it back to children. The Nurses’ Health Study II followed 44,231 women who had reconstructed their high school diets. Those who ate the most red meat as adolescents had 43% higher premenopausal breast cancer risk. Breast tissue between puberty and a first pregnancy is undifferentiated and dividing fast, which is exactly when a carcinogen does the most damage. Same vulnerable window as the leukemia story, different tissue.

One more thing, missing from nearly every version of this conversation …including mine is alcohol. In a diet-wide analysis of 542,778 women, alcohol had the strongest positive association with cancers of the 97 dietary factors examined, and calcium the strongest protective one. Before we argue about whether to eat grass-fed meat or not, we should spend the worry where the evidence is.

So where is the effort actually worth it?

The data are mixed. I think we should act anyway. My threshold is simple: if an intervention is cheap, reversible, independently good for you, and lands in a window that closes, I am willing to act on weaker evidence. If it is expensive, permanent, or displaces something better, I want much more.

Cured meat in pregnancy clears that bar easily. Nine months, no cost, no nutritional loss, coherent mechanism. Same for keeping coffee to a cup or two, which has better established pregnancy reasons anyway. Same for minimizing indoor insecticides and unnecessary outdoor pesticides. The signal is imperfect but persistent, and other than inconvenience, there is little downside to reaching for alternatives first.

Alcohol and sugary drinks clear that bar faster than anything else on this list. Alcohol is a known carcinogen with the strongest signal of the 97 dietary factors examined, and sugary drinks are the delivery system behind most of the sugar association. Neither has a nutritional argument to defend. If you were going to change one thing this week, it should be one of those, not the beef.

Fruit and vegetables clear the bar for the opposite reason. Maternal fruit intake of two or more daily servings is associated with 29% lower odds of childhood ALL, and pooled data put vegetables, legumes, and fish in the same direction. Maybe some of that is confounding. I still lose nothing by acting on it. That asymmetry is why I spend far more clinic time on what to add than what to remove.

A typical farmers market haul: seasonal vegetables, minimally processed whole grains, and as much fresh variety as we can carry home.

Adolescence deserves the same attention as pregnancy and almost never gets it. The advice itself is no different from any other age, which is the unglamorous part. Vegetables, fiber, soy, not much processed meat. What changes is the timing. Breast tissue between puberty and a first pregnancy is proliferating and undifferentiated, so the same diet does more work at fourteen than it will at thirty. It is also when the first drinks happen and when sugary drink intake peaks, and those are the two things I would actually intervene on.

Breastfeeding has some of the strongest prospective evidence on the list. In a Danish cohort of 309,000 children, exclusive breastfeeding for three months or more was associated with a 38% lower risk of B-cell precursor ALL. That is a relative reduction in an already rare disease, and breastfeeding is neither possible nor the right choice for every family. It is a signal, not a mandate.

Organic is where I am less consistent. I buy it for the highest-residue produce. Organic diets consistently reduce measured pesticide exposure; what has never been shown is that this translates into less childhood cancer. The wellness industry routinely collapses those two statements into one. I will not. I simply choose the lower-exposure option when it is practical.

For children I limit processed meat, and I do not make red meat a daily staple either, because the heme signal does not disappear with better sourcing. Neither is a food to fear. Both are foods I would rather see three times a week than seven. But population-level risk is not individual causation. Nothing in these data can tell a parent that something they fed their child caused their leukemia. That distinction matters enormously when you are looking backward for something to blame.

So yes, the effort matters. Just not all of it, and not equally. Most weight on pregnancy, because that window is short, cheap, and closes. Real weight on adolescence, because it is the one nobody is watching. And the most weight of all on the twenty years after that: sleep, movement, a plant-rich diet, and enough exposure to the world to build a competent immune system. Those are the habits that shape a metabolic trajectory long after childhood cancer risk has become vanishingly small.

Next: the chemical environment, what the evidence actually supports, and where I think the fear is miscalibrated, including plastics, pesticides, and EMFs.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington and Oregon residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

This series is about raising healthy children in an environment that was not designed for the task. This isn’t about your child becoming a purity project. My argument and the framing underneath all four parts is borrowed from toxicology and exercise physiology: hormesis. Biological systems do not thrive at zero stress. They thrive on the right dose of the right stress, with recovery in between. Unfortunately, the stress the modern world hands a child is the wrong kind.

I am using hormesis somewhat broadly here - not to argue that allergens, vegetables, microbes and exercise act through one pathway, but because they share a developmental principle: appropriate exposure can build capacity that avoidance cannot.

A child’s metabolism, immune system, and nervous system are all built by challenge. The modern environment fails children in both directions at once. It removes the stressors that build them, the microbes, the boredom, the bitter vegetables, the temperature swings, and replaces them with stressors that do not, the engineered food, the endocrine disruptors, the light at 9pm.

We’ll talk about food first, because it is the largest input by volume and the one with the best evidence. But rest assured, next articles will cover environmental exposures, sleep and nervous system regulation, and immunity.

The category is the problem, not the ingredient

Roughly 2/3rds of the calories American children eat are ultraprocessed. Not “processed,” which includes frozen vegetables and canned beans. Ultraprocessed: industrial formulations engineered from refined starches, extracted oils, protein isolates, and additive systems designed to make the product soft, palatable, and shelf stable.

The evidence against the category has firmed up considerably. In children followed over time, higher ultraprocessed intake tracks with greater fat mass, waist circumference, and overweight risk. The ALSPAC birth cohort found the children eating the most ultraprocessed food gaining more BMI and fat mass every year from childhood into early adulthood, and a recent meta-analysis in adolescents put the excess odds of overweight at over 60%.

The inflammation story in children is a bit messier. Some studies find higher IL-8, leptin, and CRP in the heaviest consumers. One Brazilian cohort found its highest cytokine levels in the children eating a moderate amount rather than in the children eating the most. A 2026 systematic review that pulled this literature together split the difference. It found the metabolic outcomes reasonably consistent and the inflammatory markers not, and concluded that pediatric data is still too limited to establish causality.

My attempt to explain some of the inconsistency, and why these limitations push results toward finding nothing.

1. Standard inflammatory markers in healthy children run low, often at the bottom of what the test can measure, which leaves little room to detect a difference between one group and another.

2. A single CRP is also moved by a cold from two weeks ago, by puberty, by body fat, so a diet signal has to be larger than all of that to surface. Diet is measured roughly, usually with one 24 hour recall, which captures a Tuesday rather than a childhood and misclassifies who the heavy consumers actually are.

3. Adiposity is probably a strong mediator, which means studies adjusting for BMI are adjusting against part of what they are trying to detect.

I believe the inflammation is real and largely downstream of fat mass accumulating over years, which would put childhood at the start of the process and adulthood at the point where we typically meet it in clinic.

The mechanism is rather straightforward and it is not any single ingredient. A good example of this is the Hall’s inpatient trial at NIH where adults who were randomized to an ultraprocessed diet ate about 500 calories a day more than the same people on a whole food diet matched for presented calories, sugar, fat, and fiber. They were not weaker willed on ultraprocessed weeks. The food was doing something, through energy density, soft texture, speed of eating, and a disrupted food matrix that outruns satiety signaling.

That finding has since been replicated. The UK UPDATE trial tested the obvious objection - whether an ultraprocessed diet that meets nutrition guidelines is fine. Fifty-five adults ate both diets (one ultraprocessed and one minimally processed, both compliant with national dietary guidance) for eight weeks each. Both met UK guidelines, but participants lost twice as much weight on the minimally processed one. Meeting the nutrient targets did not cancel out the processing.

Then a follow-up trial changed nothing but texture. Both diets were ultraprocessed. One was built from foods that took more chewing and more time to get through, and people ate about 370 calories a day less on it. That is most of the way to Hall’s 500 calories just from texture alone! One of the biggest costs of ultraprocessed food is simply that it is soft and fast.

Back to pediatric data, which at this point is mostly observational. Cross-sectional studies in children are frequently null; it is the cohorts with years of follow-up that show the signal, which suggests the damage is cumulative rather than immediate. I don’t think you need any formal training in medicine to understand that about food. NOVA sorts food by how it was made, not by how good it is for you. Whole grain bread with an emulsifier counts as ultraprocessed. So does soda. The line is soft enough that when researchers reclassified the ambiguous items, the national estimate moved by 6 percentage points. So I hold the category firmly and the single foods loosely. A diet that is mostly ultraprocessed is a problem. One food that lands in the category usually is not.

What this means practically is that the label reading I do is mostly a shortcut for one question: is this food or is this a formulation. Baby food pouches, including the organic ones, read as formulation. Fruit and vegetable purée as filler, the fiber matrix destroyed, sucked through a spout at the exact age a child should be chewing. Soft and fast, by design.

The same test catches most of the children's aisle. Fruit snacks made with real fruit are juice concentrate and starch with the fiber engineered out. Yogurt tubes are a sugar delivery system with stabilizers. Veggie straws are potato starch tinted with vegetable powder. Kids' protein bars are protein isolate and syrup. Toddler milks are skim milk powder, oils, and added sugar sold as an upgrade over the whole milk they replace. None of it is poison, and one of these in a lunchbox is not a crisis. And, for all you label readers, the back of the package tells you what was added to the product, it is also important to ask what was done to the ingredients.

Build the palate, don’t just feed it

The conversation about children’s food is dominated by what to remove. I am a big believer in adding and crowding out.

Fiber is the chronic shortfall that matters most, and not just nutritionally or for GI health. Fiber feeds the microbial community that trains the immune system and produces the short chain fatty acids that regulate inflammation, and American children get roughly half of what they should, around 13 grams a day against targets in the mid 20s and up. In one adolescent cohort, two participants out of 754 met the fiber recommendation. Read that again. Lower fiber intake in adolescents tracks with higher fasting insulin, HOMA-IR, and blood pressure, so this is not a “are you pooping consistently” issue, it is a metabolic one. The fix is not supplements or shakes, it is soaked-from-dry beans, berries, vegetables, intact grains, presented at every meal, and from a young age.

Bitterness deserves its own paragraph, as one of my favorite food groups and the best example of nutritional hormesis. The polyphenols and glucosinolates in vegetables are not vitamins. Many of them work as mild toxins, and the body responds by upregulating its own antioxidant and detoxification machinery through pathways like Nrf2. Sulforaphane, the compound chewing releases from broccoli, is the stimulus. The response is your own cells turning on glutathione synthesis and the phase II detoxification enzymes, and that output keeps running for days after the meal. You are not eating an antioxidant. You are building one.

This is the same logic as exercise, and not only by analogy. Exercise activates Nrf2 too, and in older adults exercise plus sulforaphane activates it more than either alone. It fails the same way too: in Ristow’s trial, high-dose vitamin C and E blocked both the insulin sensitivity gains from training and the rise in the body’s own antioxidant enzymes. Blocking the stress blocks the adaptation. That said, the human trial evidence for specific phytochemicals is thinner than the mechanism deserves.

Learning to eat bitter food is a training problem, not a nutrition problem. Flavor learning starts in utero, continues through breast milk, and heightens through the first two years. I share this one for the comical factor, in Mennella’s randomized carrot juice experiment, mothers who drank carrot juice in the third trimester or while nursing had babies who later ate carrot flavored cereal with visibly less aversion than controls. Comedy aside, amniotic fluid and breast milk carry the flavors of the maternal diet, and your fetus is the food critic in training.

Food neophobia arrives on schedule too: it climbs steeply from around 18 months, stays high through the preschool years, and is developmentally normal. Acceptance of a new food takes 8 to 10 exposures, and the acceptance you build generalizes to similar foods within the same category, another reason vegetables are worth the repetitions. Most parents stop offering after three to five tries and conclude the child dislikes it. The infant window is also the easy one, babies under a year accept new foods after remarkably few exposures, so the cheapest time to build the palate is before the year mark and before the neophobia arrives.

My son eats from our plates, at home and in restaurants. He gets the spicy food, the fermented things, the dishes I know he will reject again and again, until one day he doesn’t. My job is repeated exposure without pressure. His job is deciding whether to eat.

The kids’ menu - beige, fried, and sweet, served at precisely the age when food preferences are taking shape - is the food environment working against our children. It is a construct of modern food culture that makes my blood boil. We are feeding the population with some of the highest nutritional needs some of the least nutritious food.

The case against avoidance

For years, official guidance told parents to delay allergenic foods. The LEAP trial - thankfully - ended that. It showed that high risk infants who ate peanut early and regularly had 81% less peanut allergy than infants who avoided it. The follow-up work gets even better! In LEAP-On, a year of deliberate avoidance after age five did not undo the protection. In LEAP-Trio, the same children at age 12 still carried a 75% reduction in peanut allergy, eating peanut or not as they pleased in the intervening years. The tolerance was built once, early, and it held. Avoidance has a cost. Sometimes that cost is the disease it was meant to prevent.

I keep coming back to LEAP because it is the best documented case of a larger pattern, and it is the pattern this whole series is about. The developing system needed the exposure. The protective instinct, remove the challenge, produced the harm.

What does organic actually buy you?

We buy mostly organic. But, what does it actually get us? Intervention studies show an organic diet drops children’s urinary pesticide metabolites quickly and substantially. In Lu’s studies, malathion and chlorpyrifos metabolites fell to undetectable within days of the switch and returned when the conventional diet did. Two caveats though.

• In children from agricultural communities, the reductions are partial, closer to 40 or 50%, because their exposure is not only dietary.

• And a few small trials have found shifts in oxidative stress biomarkers on organic diets, which is interesting and not the same thing as a health outcome.

What no study has yet shown is that the reduction in exposure improves a measured clinical outcome in those children. That trial has not been done and would be hard to do. The observational literature does not settle it either. Organic consumers are wealthier, leaner, and eat more plants, and the studies split accordingly: one large French cohort found 25% less cancer, a UK cohort of 623,000 women found no reduction, and a 2025 meta-analysis pooling them found no association at all. So organic buys a documented reduction in exposure with a plausible but unproven benefit, at real cost. I pay it, prioritizing the produce that carries the highest residues. EWG publishes the “dirty dozen” list annually.

That said, I will always tell anyone on a budget that conventional produce beats eating fewer vegetables, every time, and that the ultraprocessed question matters far more than the organic one.

So what are you to do?

Feed the family one meal from whole ingredients and let the child eat it. Count additions, protein, fiber, and plants, before subtractions. Make food that takes chewing, because soft and fast is most of what ultraprocessing costs you. Offer the bitter thing fifteen times without commentary. Introduce allergens early and keep them in rotation. Spend organic dollars on the highest residue produce or do not spend them at all, but do not let that decision distract from the one that matters, which is whether the food is food.

If you are pregnant or nursing, eat the foods you want your child to eat, because they are already tasting them. That window is cheap, it is short, and it does not come back.

Then hold all of it loosely. Childhood sets a trajectory, not a verdict. What I am actually asking for is not a clean, perfectly fed child. It is a child who got handed enough of the right stress, early enough, to build something that holds.

Next: A Companion Guide on Food and Cancer landing in your mailboxes early next week. A discussion on whether anything in your child’s lunchbox causes childhood leukemia, what the epigenetics data really shows, + meat and soy.

Then Part 2: the chemical environment, what the evidence actually supports, and where I think the fear is miscalibrated, including plastics, pesticides, and EMFs.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington and Oregon states residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

This is arithmetic.

Give an inert pill to 100,000 people with advanced cancer. Depending on which symptom you ask about, somewhere between 6,000 and 27,000 of them will report feeling better. One or two will have a documented tumor regression with no treatment at all, and if the cancer in question is kidney cancer, closer to a thousand will. If 1 in 100 of the people who felt better writes about it, you have a couple of hundred stories, complete with dates, doses, and photographs, for a substance that did not affect the tumor, at all.

Those figures come from the placebo arms of 82 randomized cancer trials and a database of 21,000 drug development programs.. All linked as we go.

My goal in writing this, isn’t to suggest that people are foolish to be moved by the story. I want the story to be true, too. And, wanting it to be true is the most honest human response to being told you have a terminal disease, or that there is not much left to try. Learning from other people’s experience is how our species figured out nearly everything. Someone ate the root, the fever broke, the village remembered. That instinct is beautiful, and rooted deeply. Through, I think, cancer might be the one place it reliably betrays all of us, for reasons that have nothing to do with how carefully you are thinking.

My goal isn’t to take hope away. It's to make sure hope is informed. Hope doesn't harm people. Misinformation, misrepresentation, and an incomplete understanding of the evidence can.

Placebo does not shrink tumors, and that is exactly the problem

A 2022 analysis in eClinicalMedicine pooled the placebo arms of 45 phase 3 trials in advanced solid tumors, covering 5,684 patients. The objective response rate on placebo was 1%, with a confidence interval running from 0 to 2. Complete response was 0%. Sugar pills do not dissolve tumors.

Now let’s take a look at what placebo pills did do. Chvetzoff and Tannock reviewed 37 placebo-controlled cancer trials and found that among individual patients on placebo, 0 to 21% reported reduced pain or cut their analgesic use, 8 to 27% had appetite improvement, 7 to 17% gained weight, and 6 to 14% improved in performance status.

Their own conclusion is worth quoting, because it cuts against the lazy version of this argument: substantial improvements in symptoms and quality of life are unlikely to be due to placebo. What they mean is that those improvements are probably not caused by the pill. Pain and appetite fluctuate on their own, symptom scores drift back toward average after people enroll at their worst, and being asked attentively how you feel changes how you answer. For our purposes the cause is beside the point. A meaningful fraction of people taking something inert will report feeling better, and that report is the raw material of every testimonial you have ever read. Because testimonials are not written by tumors. They are written by a person describing how they feel, and feeling somewhat better is the one thing placebo does produce.

Spontaneous regression is real, and happens in some cancers more than others

Cancers sometimes regress with no treatment at all. Everson and Cole collected 176 documented cases and estimated the rate across all cancers at roughly 1 in 60,000 to 1 in 100,000. That estimate is from 1964 and is almost certainly low, since it depends on cases being noticed, confirmed, and published.

It also hides enormous variation. For example, in clear cell renal cell carcinoma the figure is closer to 1%, particularly after the primary tumor is removed. Melanoma and B cell malignancies also regress more often than average, which is unsurprising, since these are the tumors the immune system is most capable of recognizing.

These regressions happen on their own, on no treatment, on nobody's protocol. What matters is who happens to be taking something when one occurs, because whatever they were taking gets the credit. Give a sugar pill to 100,000 people with mixed cancers and one or two of them will have a documented regression. Give it to 100,000 people with kidney cancer and the number is closer to 1,000. I imagine, every one of those people will write about it in some way, because a thing like that demands to be written about.

You cannot tell that world apart from a world where the drug works by reading the stories. The stories look identical from the inside, and no amount of reading more stories resolves the issue.

Dishes and mice are not small people

Dare I say, that most every protocol circulating online rests on preclinical data, meaning based on cells in a dish or tumors in mice. Those experiments are usually real, but very few of them survive the complexities of a live human body.

Turns out, killing an isolated cancer cell outside its environment is easy.

A drug that kills cancer cells in a dish has to kill them at a concentration a human body can actually reach. Let’s take, ivermectin, for example. In culture, ivermectin kills cancer cells when the fluid around them holds about 3µM of drug. A person taking a standard dose peaks at roughly 1/60th of that in their blood. Push to the very high doses the protocols call for and you might get to 1/10th. Then subtract further, because ~93% of circulating ivermectin is stuck to blood proteins and unavailable to act on anything. The free drug actually reaching a tumor cell is more than a hundred times below what the dish experiment required for killing.

Mouse studies are better, but not by a lot. The tumor is usually a single cell line, genetically uniform, implanted under the skin of a mouse bred to have no immune system, and treated when it is a few days old and a few millimeters wide. A human cancer has evolved inside a living immune system for years, is genetically heterogeneous from one region to the next, and sits in tissue with its own blood supply and stroma. Doses are given in milligrams per kilogram, and a mouse dose does not convert one for one into a human dose. Do the conversion properly and the protocols circulating online usually land well below the dose that worked in the mouse. Additionally, the endpoint is usually tumor volume over a few weeks and where survival is reported, it is a mouse surviving a few extra weeks.

Mak, Evaniew, and Ghert put the rate of successful translation from animal models to human cancer trials at under 8%. Begley and Ellis, at Amgen, tried to reproduce 53 landmark preclinical cancer papers and were able to confirm 6. The Reproducibility Project: Cancer Biology spent eight years repeating 50 preclinical experiments from 23 high-profile papers, and where replication succeeded at all, the effect sizes came in 85% smaller than the original data suggested.

So when a post tells you a drug “kills cancer cells” and links a paper, the paper is usually real... and the gap between that paper and a person is real too.

The people who are no longer with us, are no longer posting

I don’t mean to sound crass. But testimonials have a trajectory. Survivors write. The ones who took the identical protocol and progressed drift offline, and their families do not come back six months later to post the correction.

Then add the “attribution problem.” Most people start an off-label drug alongside a new line of standard treatment, or while on immunotherapy, which can produce responses months after the starting of it. The response gets credited to the thing they chose rather than the thing they were given. The drug you sought out, paid for, and swallowed on a schedule feels like something you did. The infusion you sat through feels like bad weather.

A possible example of this and, a story known by many is this. In 2019 an average Joe with metastatic small cell lung cancer took veterinary fenbendazole, had a dramatic response, and wrote about it. He was also on an experimental immunotherapy at the time. His blog reached millions of people, and the immunotherapy part mostly did not travel with the story.

Why certainty should make you pause

Of every cancer drug that enters phase 1 testing, 3.4% eventually reach approval. Oncology is the worst performing field in medicine (though it’s marginally getting better). Everything outside oncology runs at about 21%.

Even after a cancer drug has survived phase 1 and phase 2 and entered a large randomized phase 3, it reaches approval only 35.5% of the time. Every one of these drugs had a plausible mechanism, real money behind it, a trial designed by statisticians, and a control group to compare against. Each was tested in the cancer its developers believed was most likely to respond. 2 out of 3 still fail at the last step. The median oncology program spends ~13 years in the clinic to find that out.

There is a name for part of what is happening: regression to the mean. A phase 2 result that looks spectacular tends to be followed by a phase 3 result closer to nothing, because extreme results are extreme partly by luck, and, alas, luck does not repeat. The stories that reach you are selected the same way. They are the tail of a distribution, and tails regress.

So when someone hands you an exact protocol for an off-label drug, mandatory additional off-label therapeutics, mandatory pulsing strategy with precise dosing strategy - a confident claim about what happens in stage 4 disease for all cancer types - they are claiming a level of certainty that no one has. Cancer is not one disease. It is thousands, behaving differently in different bodies, evolving continuously under treatment and without. Certainty in that setting means someone has stopped looking, or has something to sell.

The clinicians I trust most say “I think,” “we do not know yet,” and “let’s watch this closely and change course if we need to.” That is what expertise sounds like in this field.

There is no one protocol that works for all cancers.

But I object!

There is an elephant in the room with a real argument.

Nobody is going to fund a phase 3 trial of an off-patent animal dewormer. There is no patent, no return, and no sponsor. Demanding a randomized trial for a drug that will never receive funding for one can function as a permanent no, and that is a legitimate grievance.

It is also largely true. It explains why the evidence is missing, but t does not fill the gap. A drug without a comparison group has neither taken the test, not failed a lower bar.

You might notice that by my own numbers, cancer drugs fail 96.6% of the time. Why should the bar be higher for something cheap and widely available? It isn’t higher. The difference is that we know those drugs failed, because somebody measured. A paid newsletter with a mandatory dosing schedule is not a solution to the funding problem. If anything it relieves the pressure to solve it, because it lets everyone feel the question has already been answered.

Same arithmetic, different bottle

Ivermectin, fenbendazole, high-dose vitamin C, mistletoe, low-dose naltrexone, metformin, ketogenic protocols, hyperthermia, ozone… I could go on. They are not equivalent, some integrative/alternative cancer therapies have more to show for their name. Metformin, mistletoe, high-dose vitamin C, and hyperthermia have been studied in humans, some in randomized trials, with results ranging from encouraging to not. Fenbendazole, ozone, and low-dose naltrexone have almost no human oncology data at all. Ivermectin has a phase 1/2 trial hopefully being read out this year.

I use the ones with human data in my practice. I use others in cancer patients for treatment on conditions other than cancer. I advise on risk stratification for the therapies that don't have a lot of data behind them.

What integrative oncology shares is a thick bias layer because most of these things you are actively choosing, paying for, and believing in. The test is not whether something is conventional vs. off-label vs. investigational. Plenty of standard care started as somebody’s odd idea. The test is whether anyone has ever compared people who took “it” to people who did not.

The cost is not only money

The usual defense is that these drugs are cheap and mostly safe, so there isn’t a downfall. Let’s look at what has actually been published about humans taking fenbendazole.

Six case reports of drug-induced liver injury. A woman with lung cancer on pembrolizumab. A woman with colon cancer on nivolumab. A man with cirrhosis and liver cancer. A patient on immunotherapy whose cholestatic markers rose tenfold. A woman who took it for a year for a precancerous skin lesion. A man with prostate cancer taking fenbendazole and ivermectin together, whose ALT reached 1764. All resolved after stopping.

Notice what these cases share. Many were on immunotherapy, and the liver injury looked exactly like immune-related hepatitis, which is treated with high-dose steroids and stopping immunotherapy. So the risk is not only an overloaded liver. It is also losing the treatment that might have been working.

What the positive reports actually say

There are two of them (that I could find), describing four patients.

A 2020 report describes an 83-year-old man with stage IV diffuse large B-cell lymphoma who declined chemotherapy, took fenbendazole, and had improving lymphadenopathy over twelve months. He also developed peripheral neuropathy and had to cut the dose, which is what tubulin poisons do. And, from our earlier discussion, B cell lymphomas are among the tumors more likely to regress on their own.

A 2021 series describes three patients with genitourinary cancers. The first received three doses of nivolumab and a course of steroids the same month he started fenbendazole, and his own authors write that he may well have responded to nivolumab alone. The second had prior pembrolizumab and chemotherapy, and took fenbendazole alongside vitamin E, curcumin, and CBD oil. The third received six cycles of standard combination chemotherapy with fenbendazole running concurrently.

A third case series was published in 2025 and retracted.

That is the complete human record for tumor response. Four patients. Three of them receiving standard cancer treatment at the same time.

What to do with the next story you find

Read it. Save it. Evaluate 3 factors:

What else was on board? Very few take an off-label drug alone. If this person was also on chemotherapy, immunotherapy, radiation, a clinical trial, or 7 other off-label therapies, it’s likely that several things changed at once and only one of them is being credited.

Who is missing? You cannot count them, and that is the problem. Everyone who took this and got worse stopped posting.

Compared to whom? Someone has to have looked at people who took it alongside people who did not. Without that comparison there is no way to know what would have happened anyway.

If the answer to the third is no, what you have is a hypothesis. That is a real thing to have. Hypotheses are where every treatment I use started, and some of them are worth exploring. It is just not evidence yet.

Bring the protocol to your provider anyway. I would rather read it with you and tell you honestly what it is built on than have you run it alone.

I have seen off-label therapies work:

And I have seen them not:

There is a middle ground between a story and a phase 3 trial, and it is where most of my work happens. If we decide something is worth trying, we agree in advance on what we are watching, how long we are giving it, and what would make us stop. Markers, imaging intervals, liver enzymes, counts, symptoms, whatever is relevant to you and the drug. That is a structured trial of one. It will not tell the world anything, but it will tell you something, which is more than a protocol run on faith can offer.

Either way, you were right to look. Hope and evidence are not opponents. I would rather help you hold both than watch you pick one.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

And, here’s a complete list of hormones on it: none.

Not testosterone, the one thing men's health has become synonymous with. Not SHBG, not estradiol, not anything upstream of either. The recommended panel covers blood pressure, cholesterol in some men, glucose in some men, and a handful of cancers and infections. That is the whole picture of male physiology as the guidelines see it.

More providers are correcting for this, though not by much. One hormone. Total testosterone, drawn whenever, which tells you almost nothing without SHBG and free testosterone beside it, and compares the result to a range that already treats decline as normal. PSA becomes the entire cancer conversation despite being at its weakest as a single value. Everything else is a metabolic panel and a lipid screen. Zero hormones by guideline, one by habit, and neither one assesses the whole person.

The result is a man in his fifties with rising visceral fat, flattening libido, poor recovery from workouts he used to handle easily, and a stack of results that read as unremarkable or borderline or “fine for his age.” Fine for his age is a comparison to a population that is itself getting sicker.

Part 1 covered labs I order in women. Most of that panel applies to men without modification, so I am not going to rewrite it here. What follows is what changes in men, what the numbers should be, and the tests that get skipped almost universally.

The core panel, with male thresholds

Fasting insulin. Same test, same reasoning, different urgency. Men store fat viscerally rather than subcutaneously, which means the same body weight carries more metabolic cost. A man with a normal BMI and a thickening waist can be profoundly hyperinsulinemic. I would like fasting insulin to be below 5. and typically order it with fasting glucose so we can calculate HOMA-IR. I’ve linked it, so you can check it out for yourself if you’ve had your fasting insulin drawn.

ApoB and NMR LipoProfile. Men develop coronary disease roughly a decade earlier than women. ApoB is the number that matters, not LDL-C. Under 80 mg/dL for primary prevention, under 60 for anyone with established disease, strong family history, or elevated Lp(a). The LP-IR score on the NMR gives you a second read on insulin resistance from the lipid side.

Lipoprotein(a). Get familiar with your risk ideally in your forties or earlier. Roughly one in five people carry an elevated level, and it is the single most common inherited driver of premature myocardial infarction in men who otherwise look low risk. And foundational in deciding whether we worry about your high cholesterol or not.

hsCRP. Above 1.0 mg/L gets my attention. Visceral fat is an active endocrine organ secreting inflammatory cytokines, and in men that fat is disproportionately visceral.

Ferritin with iron studies and transferrin saturation. This one shifts meaningfully in men. Without monthly menstrual iron loss, iron accumulates across a lifetime with no physiologic offload. Hereditary hemochromatosis is genetically equal between sexes but clinically expresses far more in men, and it presents as fatigue, joint pain, low testosterone, and elevated liver enzymes long before anyone thinks to check iron. Labs flag ferritin at 300 or 400. I start paying attention above 200, and transferrin saturation above 45% warrants HFE testing.

Homocysteine. Under 9. Cheap, actionable, and one of the better midlife predictors of cognitive decline.

Full thyroid panel. TSH, free T4, free T3, reverse T3, TPO and thyroglobulin antibodies. Thyroid disease is less common in men, which is exactly why it is missed for longer when it happens.

25-OH vitamin D. 60 to 80 ng/mL. Adiposity sequesters vitamin D, so heavier men need higher doses to reach the same serum level.

Plus the whole 9 yards

Total and free testosterone, LC/MS, morning draw

A random, Total testosterone alone tells you little. Free testosterone is what reaches the receptor and what correlates with symptoms, and the two diverge widely because of a Sex Hormone Binding Globulin (SHBG), which climbs steadily with age. A 60-year-old can have a total testosterone of 500 ng/dL and a free testosterone in the bottom decile, because SHBG has bound most of it.

Do the draw between 8 and 10 AM. Testosterone follows a diurnal rhythm and an afternoon draw can read 20 to 25% lower than your AM reading. Day-to-day variability is significant enough that a single low result should be confirmed on a second morning before anyone starts treatment. Specify that you want LC/MS draw, because this methodology provides high specificity, high sensitivity at low hormone ranges, and freedom from the chemical cross-reactivity that can occur with traditional immunoassays.

The conventional cutoff for hypogonadism is a total testosterone below 300 ng/dL. I treat symptomtomatically alongside numbers. This is “off label use” and is not FDA approved.

SHBG

Low SHBG in a man predicts type 2 diabetes and metabolic syndrome more strongly than low testosterone does, even after adjusting for testosterone. It is one of the more useful single markers on this list. High insulin suppresses SHBG. Falling SHBG in a man with a growing waist is metabolic dysfunction announcing itself two ways at once.

Labs report a range somewhere around 10 to 57 nmol/L in men, which is wide enough to be nearly useless. Ideally I am looking for SHBG to be between 30 to 50 nmol/L. Below 20 is a metabolic red flag regardless of how the rest of the panel looks. Above 60 is why a man with a reasonable total testosterone value feels like he has none. Read it alongside free testosterone and fasting insulin, because SHBG earns its keep as a triangulation point rather than a standalone number.

When SHBG is low

I think of low SHBG as a liver finding. SHBG is made in the liver, and a liver busy making fat makes less of it. Fructose drives that fat production harder than glucose does, which is why it lowers SHBG faster. A low SHBG in a man with central adiposity means hepatic fat until proven otherwise. I check ALT, AST, GGT, and ferritin alongside it, then go further when those move: ultrasound, elastography by FibroScan or FibroTouch, or an Enhanced Liver Fibrosis score. Also, Rule out hypothyroidism, and review any exogenous androgens or glucocorticoids, both of which suppress SHBG on their own.

The intervention here is healing the liver and the insulin, rather than the hormone. Cut fructose specifically rather than carbohydrate generally, cut out alcohol, build muscle, and treat the insulin resistance directly. Berberine and metformin both have a place depending on the patient.

Best part? SHBG climbs as hepatic fat falls. That makes it an inexpensive way to track whether your liver is actually responding, months before imaging would show you anything.

When SHBG is high.

Typically high SHBG is a bioavailability problem. Total testosterone reads adequate, free testosterone is low normal, but you feel like shit. This is the single most common missed diagnosis I see in men over sixty.

High SHGB is a bane of my existence.

I cannot overstate the importance of looking for the cause before reaching for a supplement or another intervention. SHBG rises with age, with hyperthyroidism, with liver disease, with chronic caloric restriction and inadequate protein, with endurance overtraining, with celiac disease, with anticonvulsants such as phenytoin and carbamazepine, and with estrogen containing medication or exposures. To name a few.

Beyond that, the evidence thins out... but here’s what we do know:

• Boron at 10 mg daily lowered SHBG roughly 9% within six hours and raised free testosterone about 28% at one week, in a small short study.

• Magnesium appears to reduce testosterone binding to SHBG, though that work is in vitro.

• Zinc can often have an inverse relationship with SHBG. Men with highest dietary intake of zinc (above 25 mg daily), had about 22% lower SHBG. Reasonable to add 15 to 30 mg daily.

• Nettle root can be used

The practical point matters more than any of the supplements. If SHBG stays high and free testosterone stays low with symptoms, testosterone therapy gets dosed against free testosterone rather than total. Men with high SHBG frequently need higher or more frequent Testosterone dosing to reach the same free level, and dosing to a normal total testosterone leaves them exactly where they started.

Estradiol

Turns out, men need estradiol, just like women need testosterone. It drives bone mineral density in men more directly than testosterone does, and it governs libido, joint comfort, lipid handling, and cognition. Below roughly 15 pg/mL, men develop joint stiffness, bone loss, and worsening lipids.

This is where I see the most iatrogenic harm in men’s health. Anastrozole gets prescribed reflexively alongside testosterone to men whose estradiol was never actually high, and they end up with aching joints, no libido, and accelerating bone loss while being told their hormones are optimized. Use the sensitive LC/MS assay, because standard immunoassay is unreliable at male concentrations. I aim for 20 to 40 pg/mL in men on therapy.

LH and FSH

LH and FSH determine whether the problem is testicular or central, and that distinction can change the entire landscape. High LH and FSH with low testosterone means primary testicular failure. Low or inappropriately normal LH and FSH with low testosterone means the signal from the pituitary is the problem, which requires investigation rather than a prescription. Obesity, opioids, chronic stress, sleep apnea, and pituitary pathology all produce that pattern, and treatment at the source.

Prolactin

Order prolactin in anyone with low testosterone and low or normal LH. Elevated prolactin in that setting means prolactinoma until imaging says otherwise. It is uncommon, and can be missed for years. Treatment is straightforward once identified.

IGF-1

IGF-1 a proxy for growth hormone axis function. It is produced mainly in the liver under growth hormone signaling. It promotes cell survival, inhibits apoptosis, and mediates exercise-induced neurogenesis in the hippocampus. Protein intake is the main dietary lever on circulating levels in humans, and protein restriction lowers it. That same anti-apoptotic signaling is why high IGF-1 tracks with cancer risk, which is what makes it a marker worth reading in both directions.

• Low IGF-1 goes along with sarcopenia (muscle loss), poor recovery, central adiposity, and declining bone density.

• High IGF-1 is a different conversation. Men in the highest category of circulating IGF-1 carry roughly 38% higher prostate cancer risk than men in the lowest. Every growth hormone secretagogues (examples are Sermorelin, Ipamorelin, and Ibutamoren (MK-677)) sold in a longevity clinic work by raising IGF-1. If you were to start any of these peptides, I want the baseline number, and in a man with a prostate cancer history I want a real discussion before he does.

DHEA-S

DHEA is marker of adrenal reserve. Measure the sulfated form rather than DHEA itself, because it has a long half-life and stays steady across the day, while DHEA swings hour to hour and gives you a random number and no-one knows what it actually means.

DHEA-S peaks in the mid-twenties and falls roughly 2 to 3% a year after that. Alas. Labs report age-stratified ranges, which means the decline is built into the reference range and a 60-year-old can be flagged normal at a level that would have been alarming at 30. I aim for roughly 300 to 450 mcg/dL in men, which is the range of a healthy man in his late 20ties and 30ties. I do not chase the top of the range, because there is no evidence that a higher is better however there is real evidence that pushing androgen precursors has negative implications.

When DHEA-S is low.

Sorry to use a cop out answer here, but normal aging decline does account for a lot of the decline. Beyond that, the causes worth ruling out are exogenous glucocorticoids, which suppress ACTH and take DHEA-S down with it. These medications include oral, inhaled, and topical steroids. Opioids can do the same thing. So do chronic caloric restriction, overtraining, untreated sleep apnea, chronic kidney disease, insulin resistance, and any significant illness or surgery.

A low DHEA-S with fatigue, low blood pressure, salt craving, or hyponatremia is a reason to evaluate for adrenal insufficiency rather than to reach for a supplement. Morning cortisol and ACTH first, cosyntropin stimulation if the picture warrants it. Then rule out “adrenal fatigue” with a salivary cortisol curve.

You might have heard of “Pregnenolone Steal” an argument that chronic stress diverts pregnenolone away from DHEA toward cortisol. I am skeptical of that model, because adrenal steroid production is compartmentalized by zone and enzyme rather than drawing on one shared pool. Chronic stress does track with low DHEA-S. The mechanism is probably not the one commonly described.

In naturopathic medicine, removing the obstacles to cure is always Step 1. So, if able, taper the unnecessary steroids with whoever prescribed them, address the opioids, treat the apnea, eat enough, and fix the insulin resistance. Next, reasonable to start with 25 to 50mg of DHEA daily and recheck DHEA-S along with total and free testosterone, estradiol, and PSA at eight to twelve weeks. Through years of practice, I have found that OTC DHEA is not equivalent to compounded form and sustained release micronized capsule is best.

DHEA is a precursor to both androgens and estrogens, and men aromatize it. It is important to watch the downstream numbers.

When DHEA-S is high.

Look at your supplements first! DHEA usually turns up under another name or buried in a blend: prasterone, dehydroepiandrosterone, pregnenolone, androstenedione, adrenal glandulars, adrenal cortex extract, and most products sold as testosterone boosters, adrenal support, cortisol support, libido formulas, or anti-aging stacks.It is far and away the most common cause, and most elevations resolve on a recheck four weeks after stopping.

If it stays high, the differential is worth taking seriously. Non-classic congenital adrenal hyperplasia is the one people miss, so check 17-hydroxyprogesterone. ACTH-dependent Cushing syndrome raises DHEA-S, while adrenal Cushing typically lowers it, which makes DHEA-S a useful discriminator when cortisol is the question.

A markedly elevated DHEA-S, particularly above 700 mcg/dL or climbing on serial draws, warrants adrenal imaging. Adrenal tumors, including carcinoma, secrete DHEA-S, and this is one of the few times a single lab value should move directly to a CT. Milder elevations in a man with insulin resistance and high stress load usually track back to those, and treating them can be a slow process, because it took decades to get here.

Hematocrit and CBC

If you are on testosterone therapy of any kind, your provider will get this tested and track it. Red cell mass rises with testosterone, and erythrocytosis is the most common adverse effect. Above 50% warrants investigation. Above 54%, hold therapy until it normalizes, then restart at a lower dose. Therapeutic phlebotomy works, and if you are phlebotomizing repeatedly, recheck ferritin, because you will drive it into depletion.

One thing I would like to point out — since the question comes up in nearly every consult — is the erythrocytosis and cardiovascular risk question. The TRAVERSE trial randomized over 5,000 hypogonadal men with cardiovascular disease or high cardiovascular risk to testosterone gel or placebo. Testosterone was noninferior to placebo for major adverse cardiac events, with no increase in prostate cancer incidence. The FDA removed the boxed warning language about cardiovascular risk from testosterone labeling in February 2025.

PSA as a starting point

A single PSA value in isolation is a weak test. Used well, it is a strong one.

Get a baseline in your forties. Baseline PSA measured between 40 and 50 is one of the strongest available predictors of lifetime prostate cancer mortality. A man with a PSA under 1.0 at 45 has a very different thirty-year trajectory than a man at 1.5, and neither number triggers anything on a standard report.

Track velocity. The rate of change carries more information than any single value. This requires that someone is actually looking at the trend, which requires that the values are in one place.

Free PSA percentage. In the 4 to 10 ng/mL range, a free PSA at or below 25% shifts probability toward cancer, while above 25% points toward benign prostatic hyperplasia. This is cheap and very useful test!

PSA density. PSA divided by prostate volume from MRI or ultrasound. PSA density above 0.15 is meaningful, in a bad way, and it is the single best tool for distinguishing a large benign prostate from a concerning one.

Pre-biopsy markers. The Prostate Health Index, 4Kscore, SelectMDx, and ExoDx all reduce unnecessary biopsies in the gray zone. As does a multiparametric MRI, arguably more accurate that anything else. So if the response to your PSA is "get a biopsy" with no imaging and no secondary marker, ask why.

If you are on androgen deprivation therapy

If you are on androgen deprivation therapy ADT is designed to make you hypogonadal on purpose, and everything that comes with that arrives simultaneously and with speed. By year one, you would have lost muscle, accumulated both subcutaneous and visceral fat, be measurably more insulin resistant, and lose bone at the lumbar spine at rates far exceeding normal aging. Cardiovascular risk rises alongside all else.

There’s a general consensus for monitoring all of this, but to no one’s surprise population-level data published in 2025 found that adherence to those recommendations is poor, with large proportions of men on ADT never receiving baseline lipid, glycemic, or bone density assessment at all. You, by virtue of reading this, are here to help close the gap.

Here’s a list for every man on ADT:

• Fasting insulin, fasting glucose, and hA1c at baseline and every 6 mo. Insulin resistance on ADT develops fast and precedes any change in hA1c.

• Full lipid panel with ApoB at baseline and annually.

• DEXA at baseline and every one to two years, with FRAX scoring. Bone loss on ADT starts immediately.

• 25-OH vitamin D, calcium, and consideration of a bone turnover marker such as CTX

• Estradiol. ADT collapses it alongside testosterone, and that collapse drives the hot flashes and much of the bone loss.

• Obviously, CBC.

• Serum testosterone by LC.MS to confirm castrate level. A meaningful subset of men on LHRH agonists never reach adequate suppression, and breakthrough testosterone predicts worse oncologic outcomes. Roughly 7% of men fail to stay under 50. Against the 20 target, 41% fail. Standard immunoassay cannot measure that low anyways. If nobody is measuring it, nobody knows, and men absorb every side effect of ADT for less suppression

• hsCRP, because the inflammatory environment matters for both cardiovascular and oncologic trajectories

And highest impact interventions get breezed over: resistance exercise and optimal lean protein consumption. Every man starting ADT should leave that appointment with a strength training and a meal plan.

Muscle is your largest site of glucose disposal, so building it lowers fasting insulin, pulls fat out of the liver, and raises SHBG from the liver side. Loading bone is also the only non-pharmacologic intervention that reliably holds bone density, which matters most in exactly the men who lose it fastest, those on ADT and those post-gonadectomy. Two to three sessions weekly, progressive load, compound movements.

Inadequate protein raises SHBG, lowers IGF-1, and costs lean mass, and men who train hard while eating the way they did at twenty-five hit all three at once. I want 1.2 to 1.6 g/kg of body weight daily, toward the higher end on ADT or in survivorship, spread across meals at roughly 30 to 40 g each rather than loaded into dinner.

A few more!

• GGT. The earliest marker of hepatic fat and oxidative stress, an independent predictor of diabetes and cardiovascular events, and an honest reflection of alcohol intake.

• ALT. Labs flag it around 50. In men, anything sustained above 30 deserves a look at hepatic fat.

• Uric acid. An independent metabolic and cardiovascular risk marker that rises years before a first gout flare and tracks tightly with insulin resistance and fructose intake.

• Omega-3 index. Below 4% carries meaningfully elevated cardiac mortality risk.

• Cystatin C. Catches early kidney decline before creatinine-based eGFR moves. Particularly relevant in muscular men, in whom creatinine overestimates dysfunction.

• AM cortisol. Chronic stress physiology drives visceral fat, suppresses the gonadal axis, and erodes bone.

• Sleep apnea screening. Not a lab, but an important screening tool. Untreated apnea suppresses testosterone, raises hematocrit, worsens insulin resistance, and drives hypertension. Treating it moves more numbers on this list than any supplement will.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

But in a surprising number of well-run randomized trials, doing more did not help people live any longer. Sometimes it only added harm. These are trials have quietly reshaped how some oncologists think, and most of us have never heard of. The pattern touches on multiple kinds of treatments, so let’s get into it.

Surgery

Start with the most intuitive one, cutting the cancer out.

For most of the twentieth century, surgeons believed breast cancer spread outward in an orderly march, so more radical surgery should mean more cures. In the NSABP B-04 trial, women were randomized to radical mastectomy (which removes the breast along with the underlying chest wall muscles and all the axillary nodes) or to a total mastectomy (which leaves the muscles intact and skips the routine node dissection), and the survival curves were identical.

The twenty-five-year results, published in 2002, showed the same thing. The conclusion was that breast cancer is often systemic from early on. Cells have frequently already left the breast by the time we find the tumor, so how aggressively you attack the local site does not change the outcome. If B-04 dismantled the radical mastectomy, the B-06 trial then proved that lumpectomy was a safe option.

The same lesson came for the axilla. For decades, a positive sentinel node meant a full axillary dissection, which carries a real risk of lifelong lymphedema. Published in 2017, the ACOSOG Z0011 trial randomized women with one or two positive sentinel nodes to full dissection or none. At ten years, overall survival was the same!! 86 versus 84 %. Removing the extra nodes bought arm swelling, not time. And many women with limited nodal disease keep their axilla today.

Next came the metastatic kidney cancer discovery. In the 2018 CARMENA trial, removing the primary tumor in patients whose cancer had already spread did not extend survival over drug therapy alone.

And, in melanoma, the 2017 MSLT-II trial found that removing all remaining lymph nodes after a positive sentinel node did not improve survival. It produced more lymphedema, not more life.

Chemotherapy

For decades, node-negative, hormone-positive breast cancer meant chemotherapy for almost everyone, because we didn’t know who benefited, so everyone got the “just in case” chemo. Genomic testing changed that. In the 2018 TAILORx trial, women were assigned chemo or no chemo based on a 21-gene recurrence score. For the large midrange group, adding chemotherapy did not improve survival. The 2016 MINDACT trial reached a parallel conclusion using a different genomic signature. today that means that a great many women were given chemotherapy, with all its toxicity and all its ugliness, that never changed their odds of living longer.

The deeper point is that adjuvant chemotherapy, chemo given after surgery to lower recurrence, is measured in relative risk reduction, which can sound impressive while the absolute benefit is small. A 1/3rd drop in recurrence sounds like a lot, but for a low-risk patient, say 5 to 15 %, it can mean a single percentage point of actual survival gain, sometimes less. For higher-risk disease the absolute benefit is real and larger. Who (you?) decides if that’s worth it?

Probably, the most dramatic example here is from the 1990s. Tens of thousands of women with breast cancer received high-dose chemotherapy with an autologous bone marrow or stem cell transplant, an ordeal that killed a meaningful fraction of them outright. The theory was that more chemo, pushed to the edge of what the body could survive, would wipe out more cancer. Not so. High-dose therapy did not improve survival over standard chemotherapy. Median survival was 24 months versus 26.

I recently read a lovely piece by , that names the mechanism underneath a lot of this. A tumor is not one uniform mass. It is billions of genetically different cells under constant selection. When we hit it with a drug, we are not teaching it to resist. We are clearing the field for the rare cells that were already resistant, then letting them repopulate. Push the same pressure harder and longer and you often make it worse, because you are running an evolution experiment and evolution is very good at those. Read full article below -

Ken's Substack

The Four Ways Cancer Survives the Cure

Here is the fact that should unsettle every oncologist and patient: a cancer is often resistant to a drug before the patient ever takes the first dose. The resistance was already sitting there, in one cell out of billions, waiting. (Even a tumor the size of a thumb nail has 1 billion cells). It turns out there are only four …

Read more

2 months ago · 23 likes · 2 comments · Cancer Ecology by Ken Pienta

Genetic testing that can spare you harm

There is a different kind of “more” worth questioning. Some people carry inherited enzyme variants that make standard chemo doses toxic, sometimes fatally so. A cheap blood or cheek swab test before treatment can identify them, yet preemptive testing is still rarely done.

• One example is DPYD. This gene makes the enzyme that clears fluoropyrimidine chemotherapy, the 5-FU and capecitabine backbone used in colorectal, breast, and many gastrointestinal cancers. People with a DPYD variant break the drug down slowly, so a standard dose behaves like an overdose and can cause severe, occasionally lethal toxicity. Testing first lets us reduce the dose to a safe level. Europe now recommends DPYD testing before fluoropyrimidines. The United States has been slower, per usual, and only far and few clinics are testing this on the regular.

• Others include UGT1A1 testing before irinotecan (most often used in colorectal and pancreatic cancer); mutation in UGT1A1flags people at risk for severe diarrhea and neutropenia.

• TPMT and NUDT15 testing before thiopurines like 6-mercaptopurine and thioguanine, used in leukemia, can explain up to half of serious toxicities and is standard of practice.

• G6PD testing before rasburicase and high dose vitamin C IVs prevents dangerous hemolysis.

• CYP2D6 status affects how well tamoxifen is activated, though the clinical data there is somewhat mixed

• CYP2D6 also drives ondansetron and opioid metabolism, so poor and ultrarapid metabolizers get unpredictable antiemetic and pain control.

• CYP2C19 affects voriconazole antifungal dosing, which comes up constantly in neutropenic patients.

• One panel can cover all of these. CPIC-guided pharmacogenomic panels run DPYD, UGT1A1, TPMT, NUDT15, CYP2D6, and often G6PD off a single sample.

• CPIC publishes the dosing guidelines for every one of these and is the best reference I have found.

Getting pharmacogenomic testing is not about doing more. It is about not being harmed by a dose that was never right for your biology.

Testing the tumor, not just you

There is a second kind of genomic testing, and it looks at the cancer rather than your inherited genes. Sequencing the tumor, either from a tissue biopsy or from a liquid biopsy that picks up circulating tumor DNA in a simple blood draw, can find specific alterations that predict whether a targeted drug will actually work. It cuts both ways. A match can open a treatment built for your biology. No match can spare you a drug that was never going to help. Liquid biopsy is easy to repeat over time and can flag resistance as it emerges, though a tissue sample is still more sensitive for the first full profile. Before starting any targeted therapy, ask whether your tumor has been profiled.

Drugs approved without proof you will live longer

Ahhh, a topic quite possibly the most mind boggling of them all. Many cancer drugs are approved by regulators on surrogate endpoints, meaning the tumor shrank or growth was delayed on a scan, not proof that patients lived longer or better. Progression-free survival and response rate are easier and faster to measure than survival, so that is what many approvals are based on.

The problem is that a shrinking tumor does not reliably translate into a longer (or happier) life. When researchers followed cancer drugs approved on these surrogates through their confirmatory trials, only about one in five went on to actually demonstrate that patients lived longer.

Bevacizumab (most commonly used to treat colorectal cancer, lung cancer, and ovarian cancer) was granted a metastatic breast cancer indication on delayed progression, then the indication revoked in 2011 when the survival benefit failed to materialize and the toxicity was real. The drug looked good on a scan but not so much in real life.

In 2021 the FDA ran an industry-wide review of these “conditional” approvals, and many of them were retracted.

• Atezolizumab lost both its metastatic bladder cancer and its PD-L1-positive triple-negative breast cancer indications when the confirmatory trials failed to show a survival gain.

• Durvalumab was pulled in bladder cancer for the same reason.

• Nivolumab was withdrawn in third-line small-cell lung cancer and in previously treated liver cancer.

• Pembrolizumab in third-line stomach cancer.

• Melphalan flufenamide, arguably most alarming, was approved in multiple myeloma in early 2021 on progression-free survival, its confirmatory trial showed patients on the drug actually died sooner, 19.7 months versus 25.0. The drug was off the market within months.

This does not mean these drugs don’t help. Some control symptoms, delay progression, and make a meaningful difference in quality and duration of life. Several of these same molecules are lifesaving in other cancers. It means the label “approved” does not automatically mean “helps you live longer,” and it is fair to ask which one you are getting.

Treatment at the very end of life

The hardest example is chemotherapy in the last weeks of life. It is often given in the hope of buying time. Does it?

In a 2015 study of patients with advanced cancer and good performance status, chemotherapy near the end did not extend survival, and it worsened quality of life in the final weeks.

Radiation shows the same pattern. For painful bone metastases, multiple randomized trials found that a single dose of radiation relieves pain as well as ten, yet the longer course is still routinely given.

Meanwhile, a few trials suggest that adding palliative care early, alongside treatment rather than only at the end, improves quality of life and in some cases survival. Patients who got it felt better, chose less aggressive care near death, and sometimes lived longer.

What about screening and treating slow cancers

One more version of “more” deserves a mention, because it starts before treatment. Some cancers grow so slowly that finding and treating them changes nothing except how much harm you absorb. The ProtecT trial followed 1,643men with localized prostate cancer randomized to active monitoring, surgery, or radiation. At fifteen years, prostate cancer survival was about 97 percent in every group. Surgery and radiation cut the risk of the cancer spreading, but that did not translate into living longer, and both carried real costs to urinary and sexual function. For many low-risk prostate cancers, watchful monitoring is now the standard, not a compromise.

The same logic increasingly applies elsewhere. Small, low-risk thyroid cancers are now often watched rather than removed. In chronic lymphocytic leukemia, watch and wait has been standard for decades, since treating early adds toxicity without extending life. Low-tumor-burden follicular lymphoma follows the same rule, with immediate treatment showing no survival gain over monitoring. Small kidney tumors under about four centimeters are increasingly followed with serial imaging rather than surgery, especially in older patients. Smoldering myeloma and MGUS are watched rather than treated, because most never progress. And some cases of DCIS in the breast are now being tested against active monitoring (trials like LORIS and COMET).

I believe this is where integrative care, diet and lifestyle can make the biggest impact. When the standard is to monitor rather than cut or irradiate, that is a window for real meaningful change and the best chance we get to alter the terrain the cancer sits in. Indolent tumors are shaped by their environment, and much of that environment is modifiable. Metabolic function, insulin resistance and glucose control, chronic inflammation, immune surveillance, and hormone balance all influence whether a slow cancer stays slow.

What you can do

• Before any major treatment, ask the direct question: does this improve my survival, my symptoms, or neither, based on trial data for my exact cancer and stage. All three can be valid reasons to treat. They are not the same reason.

• For early breast cancer, ask whether a lumpectomy or a smaller axillary surgery is an option before agreeing to a bigger operation. Removing more tissue has not meant more life.

• For hormone-positive, node-negative breast cancer, ask whether Oncotype or MammaPrint can tell you if chemotherapy would actually help before you agree to it.

• For any adjuvant chemo, ask for the absolute benefit, not the relative one. A one-third drop in recurrence can still mean a single percentage point of survival. Then decide whether that is worth it to you.

• Before fluoropyrimidines, irinotecan, thiopurines, rasburicase, or high-dose IV vitamin C, ask whether you have been tested for the relevant enzyme variant: DPYD, UGT1A1, TPMT, NUDT15, or G6PD. One CPIC-guided panel covers them.

• Before any targeted therapy, ask whether your tumor has been profiled, by tissue or liquid biopsy, to confirm the drug matches your biology or if there’s a better match available

• For any new or expensive drug, ask whether it has been shown to help people live longer, or only to shrink the tumor or delay progression on a scan.

• If you are facing advanced disease, ask about early palliative care alongside treatment, not only at the end.

• For painful bone metastases, ask whether a single dose of palliative radiation will do.

• For a slow-growing, low-risk cancer in active monitoring get an integrative provider on board and use that window for metabolic, inflammatory, immune, and hormonal work.

• Get a second opinion for any non-emergent cancer treatments

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

Michael Retsky and Patrice Forget argued the uncomfortable explanation. The early peak is not just cancer being cancer. Part of it may be created by the surgery itself.

https://doi.org/10.3332/ecancer.2020.1050

This is not an argument against surgery. Surgery removes the tumor. It works, and for most patients it should not be skipped. It is important to recognize, however, that local tumor control does not always translate into improved overall survival. In select settings, such as metastatic kidney cancer in the CARMENA trial, removing the primary tumor did not improve survival compared with systemic therapy alone. For most localized solid tumors, however, surgery remains the cornerstone of curative treatment. I will come back to that in a future post. The point here is different. The act of cutting sets off a physiological storm that, for a brief window, tilts the body in favor of any cancer cells left behind. Not because surgeons do anything wrong. Because this is what a body does when you wound it. And that window is one we can actually do something about.

A while back, I wrote that cancer is as much a disease of the tissue environment as of the cell, that the terrain a tumor sits in can push it toward growth or hold it in check, linked below for your viewing.

The perioperative window is that idea compressed. Surgery briefly turns the terrain tumor-permissive. Unlike chronic stress or inflammation, this shift has a start date on the calendar, which is exactly what makes it something we can act on.

What actually happens when you cut

The moment surgery begins, the body floods with catecholamines and prostaglandins. Adrenaline, noradrenaline, and the inflammatory signaling that drives wound healing. These are the same molecules that let you survive an injury. They also happen to be growth signals for cancer.

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1796434/full

Three things follow:

• Surgical stress suppresses natural killer cell function, the exact immune cells whose job is to find and destroy circulating tumor cells, and that suppression lands right when it matters most.

• The inflammatory surge, IL-6, CRP, and the rest, feeds any residual disease and can wake micrometastases out of dormancy.

• Catecholamines acting on beta-adrenergic receptors push tumor cells toward an invasive, mobile state and stimulate the new blood vessels a growing metastasis needs.

We can even watch part of this happen in real time now. Circulating tumor cell counts measurably spike during and immediately after an operation. Removing the tumor physically sheds cells into the bloodstream. So you have a window of maybe two weeks where the immune system is down, the inflammatory signaling is up, more tumor cells are in circulation, and whatever escaped is getting a growth signal. That is the biology behind the early relapse wave.

The elegant part

If catecholamines and prostaglandins are the problem, we already have cheap, decades-old, well-understood drugs that block both. Propranolol, a beta-blocker, and a COX-2 inhibitor to blunt the prostaglandin arm.

In a randomized phase II trial in 2017, thirty-eight women with early-stage breast cancer received eleven days of perioperative propranolol plus etodolac (NSAID), starting five days before surgery. The drugs were well tolerated, with side effects no different from placebo. Then they looked at the excised tumors and the blood.

The treated tumors showed reduced epithelial-to-mesenchymal transition, the shift that lets a cell become mobile and invasive. The prometastatic and proinflammatory transcription factors driving spread were turned down. Ki-67, a marker of proliferation, dropped. The surgical spike in IL-6 and CRP was blunted. The immune profile shifted in a favorable direction. In eleven days, with two generic drugs, they changed the molecular behavior of the tumor and the host in exactly the direction you would want.

This is biomarker data, not survival data, but it is human data, it is randomized, and the mechanism underneath it is not controversial.

And it is not only breast cancer. The same perioperative propranolol and etodolac approach was tested in colorectal surgery, and at eight years the treated patients had fewer recurrences, two of fifteen versus nine of eighteen. Tiny numbers, but a hard endpoint from a randomized design. Angiosarcoma, a vascular tumor driven through the same beta-adrenergic signaling, sometimes regresses on propranolol outright. Retrospective data in breast and melanoma link beta-blocker use around diagnosis to lower recurrence, and there are roughly twenty active trials across tumor types.

Other levers in the same window

Once you see the window, other cheap tools line up on the same pathways.

Aspirin strips the platelet cloak that shields circulating tumor cells from immune attack, on top of blocking prostaglandins. The signal is strongest in PIK3CA-mutated colorectal cancer, and the Add-Aspirin trial, running since 2015, is testing it across tumor types. Cimetidine, an old H2 blocker, lowers E-selectin on blood vessel walls so shed tumor cells lose the docking sites they use to exit circulation and seed. Omega-3 fatty acids feed the resolvin pathway, the body’s active off-switch for the same IL-6 and prostaglandin surge. None of these replaces treatment. Each aims at the same residual-disease biology the window exposes.

What we do and do not know

We do not yet have a large randomized trial proving that perioperative beta-blockade lowers recurrence or extends survival. The strong human evidence is at the level of biomarkers and mechanism. The clinical outcome signals we do have come from weaker designs. A 2018 prospective cohort out of Florence by Vincenzo De Giorgi gave off-label propranolol to patients with thicker melanomas and reported roughly an eighty percent reduction in recurrence risk. That number is striking, and it is also a cohort study where patients chose whether to take the drug, which invites bias.

The good news is we may finally be getting a way to measure this per patient. Tumor-informed circulating tumor DNA tests can now detect molecular residual disease after surgery, below the resolution of any scan, and a positive result is one of the strongest predictors of relapse we have. That gives us a real endpoint for whether anything done in the window actually clears residual disease, instead of waiting years to find out. A bit more on that from the archives below.

Why you have never heard of this

No company owns propranolol or generic anti-inflammatories. There is no financial engine to run the large trials or market the idea. The surgical window is short and nobody’s specialty fully owns it, so it falls between the surgeon, the oncologist, and the anesthesiologist and gets picked up by none of them. This is not a conspiracy. It is what happens to a good idea with no sponsor.

I believe the perioperative window is one of the most underused opportunities in oncology. Low cost, low risk, biologically sound, and begging to be used.

What you can actually do

This is not a DIY therapy. Propranolol has real contraindications, including asthma, certain heart conditions, and low heart rate or blood pressure, and it has to be dosed and supervised by a physician. So the move here is a conversation, not a prescription you get on the internet.

If you have a cancer surgery coming up, here is where I would push.

• Ask the specific question: “Would you be open to prescribing perioperative propranolol with a COX-2 inhibitor like celecoxib or etodolac, on the eleven-day schedule from the 2017 Ben-Eliyahu trial, starting five days before surgery?” Bring the trial printed, and stay open to their answer.

• Expect to be told no, and know why. The likely answer is “there is no large survival trial,” which is true. Decide in advance whether an eleven-day course of two generic drugs, with a placebo-level side effect profile and solid mechanism, is worth it to you without that trial.

• Talk about your anesthesia plan. Ask about an opioid-sparing plan and regional or neuraxial anesthesia where the surgery allows. Opioids and the surgical stress response both suppress natural killer cells, the exact defense you want intact that week. The recurrence data here is mixed, but it is worth the conversation.

• Get molecular residual disease tracking, by name. Ask for a tumor-informed ctDNA test such as Signatera, drawn a few weeks after surgery and then serially every three months. A positive result is one of the strongest relapse predictors we have, and it turns “wait and scan” into something you can actually track.

• Do not stop the right drugs. If you already take a beta-blocker, aspirin, or metformin, tell your surgical team and do not stop them around surgery without guidance. Each one touches the same catecholamine, platelet, and metabolic pathways this window runs on.

• Take matters into your own hands. In the two weeks around surgery, protect sleep, keep blood sugar stable, get fresh air and cut stress inputs where you can. These feed the same catecholamine and inflammatory surge as the incision. It is free, it is safe, and almost no one tells you it matters.

• Assume you are the only one connecting the dots. The surgeon, oncologist, and anesthesiologist each own a piece of this window and none of them own the whole thing. Bring me or your integrative physician into the planning before the date is set, not after. This window is measured in days, and it does not reopen.

  Thanks for reading Integrative Oncology Insights. I keep these articles free because everyone deserves access to clear, practical answers, including specific strategies, products, and recommendations. If something here was useful, share it with someone who would benefit.

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  Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

  She provides medical care for Washington residents and offers global health coaching.

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  To schedule a free 15-minute consult, visit drkseniamalarkey.com

She had already completed a comprehensive set of labs. Her fasting glucose was 99 mg/dL, hemoglobin A1c was 5.5%, her cholesterol was mildly elevated, her hormones were consistent with the postmenopausal range, and her thyroid function was normal. Her previous providers had reviewed the results and found nothing that explained what she was experiencing. The conclusion she kept hearing was, “It’s just normal aging.”

A fasting glucose of 99 is normal. A TSH trending upward for two years is normal. Testosterone essentially undetectable on active therapy is, technically, normal. None of those findings triggered any follow-up. This is not a failure of clinical judgment. It is a failure of the questions being asked.

Most routine laboratory panels are designed to detect disease once it is already present. They are not designed to identify the subtle physiologic changes that precede it by years. The tests below ask different questions. They look for the early shifts in metabolic and hormonal health that standard screening often misses.

1. Fasting insulin

Glucose is a lagging indicator. By the time fasting glucose climbs out of range, insulin resistance has typically been building for years. Sometimes a decade. Fasting insulin catches it early, often before HbA1c moves, before glucose tips, before any of the metabolic downstream effects become visible on a standard panel.

The conventional reference range goes up to around 25 uIU/mL. I want it below 7, ideally below 5. Anything above that, in the context of abdominal weight gain that is resistant to diet and exercise, tells me we are dealing with hyperinsulinemia driving fat storage, not a willpower problem.

Insulin resistance is upstream of type 2 diabetes, cardiovascular disease, certain cancers, and cognitive decline. It is also one of the most modifiable things on this list. If you take nothing else from this piece, request this test.

2. ApoB + NMR LipoProfile

Standard LDL is a cholesterol concentration. It does not tell you how many atherogenic particles are in circulation or what they look like. ApoB counts the particles. The NMR LipoProfile shows their size and metabolic behavior. Together, they give you a cardiovascular risk picture that a standard lipid panel simply cannot.

Two people with identical LDL-C can have very different particle counts and very different risk profiles. Small, dense LDL particles are significantly more atherogenic than large, buoyant ones, and someone with borderline LDL but predominantly small particles is in a different situation than their cholesterol number suggests. The NMR also generates an LP-IR score, a validated insulin resistance measure derived from lipoprotein concentrations, which means you can sometimes detect metabolic dysfunction through the lipid picture before fasting insulin is even ordered.

For anyone with abdominal adiposity, a family history of early cardiovascular disease, or a metabolic syndrome picture, these are the labs that add real resolution. My patient’s triglycerides had improved significantly over three years with diet and lifestyle modifications, surprisingly LP-IR score worsened showing significant insulin resistance.

WHy? Improving triglycerides tells you the diet is working. A worsening LP-IR tells you the underlying metabolic dysfunction is not resolved and may be progressing despite all your dietary efforts. They are not contradictory findings; they are measuring different layers of the same problem.

3. Lipoprotein(a) — Lp(a)

Lp(a) is one of the strongest independent predictors of early cardiovascular disease and aortic stenosis, and about 20% of the population carries significantly elevated levels. Genetics account for roughly 70 to 90% of an individual’s baseline, which is why it is largely non-modifiable with lifestyle but that does not make the information useless.

If Lp(a) is high, it reframes the cardiovascular risk conversation entirely: how aggressively to manage every other modifiable factor, when pharmaceutical intervention becomes appropriate, and how closely to monitor. If it is normal, you can largely set it aside. One draw establishes your baseline and changes the clinical picture for years.

That said, Lp(a) is not perfectly fixed across a lifetime. It behaves as an acute phase reactant and can rise temporarily during illness or infection. Estrogen tends to lower it, which means levels can shift around menopause or with hormone therapy. Certain conditions move it in both directions i.e. nephrotic syndrome and hypothyroidism raise it, liver disease and hyperthyroidism lower it. PCSK9 inhibitors and high-dose niacin can also modestly reduce it. For most people a single baseline is sufficient; I recheck in patients going through significant hormonal transitions or new diagnoses that could affect the reading.

4. High-sensitivity C-reactive protein (hsCRP)

Chronic low-grade inflammation does not announce itself. There is no pain, no obvious sign, no moment where something clearly feels wrong. It just quietly drives atherosclerosis, degrades insulin sensitivity, accelerates tissue aging, and creates the environment cancer requires to establish itself.

hsCRP is one of the best tools available to measure inflammation. Anything above 1.0 mg/L warrants attention. Above 3.0, the cardiovascular risk data is significant and consistent. The key is trending it over time and reading it in context because elevated hsCRP in a postmenopausal woman with abdominal adiposity, joint pain, and poor sleep tells a very different story than an elevated reading in someone who just ran a marathon.

Visceral fat is not passive. It is an endocrine organ that actively secretes inflammatory cytokines. In my patient’s case, I expected hsCRP to be elevated. The weight gain was not just weight, it was a source of ongoing inflammatory signaling. If you want to quantify visceral fat directly, a DEXA scan is the most practical clinical option; it separates visceral from subcutaneous adipose tissue and gives you lean mass and bone density in the same scan.

5. Ferritin

Both directions matter here, and that is what makes ferritin easy to overlook.

Low ferritin causes fatigue, hair loss, cold intolerance, and cognitive fog that gets attributed to everything else like stress, perimenopause, poor sleep. It is frequently not caught because hemoglobin remains normal long after stores are depleted. Ferritin can be critically low while blood counts continue to remain within normal range… for now.

Elevated ferritin is a different problem. Even within the conventional “normal” range, a ferritin trending upward is an independent predictor of insulin resistance, non-alcoholic fatty liver disease, and metabolic syndrome. I start paying close attention above 100 in women.

Before treating an elevated ferritin, rule out secondary causes. Ferritin is an acute phase reactant, so inflammation alone can drive it up. Also consider hemochromatosis (check transferrin saturation and HFE testing when indicated), liver disease, alcohol use, and, less commonly, malignancy.

6. SHBG — Sex Hormone Binding Globulin

SHBG is a proxy for insulin sensitivity that almost nobody orders. Low SHBG, independent of any other marker, predicts type 2 diabetes and cardiovascular events with enough consistency that some researchers have proposed it as a metabolic disease biomarker on its own.

Beyond metabolic risk, SHBG determines how much free hormone is bioavailable. When I am managing someone on testosterone, or evaluating a hormonal picture, SHBG tells me whether the hormone being produced or prescribed is actually getting to the tissues. A total testosterone that looks adequate can mask near-zero free testosterone when SHBG is high.

When SHBG is low alongside elevated insulin, abdominal adiposity, and androgen symptoms (fatigue, hair loss, low libido, difficulty building muscle) you are looking at a woman whose metabolic dysfunction and hormonal insufficiency are feeding each other. High insulin suppresses SHBG. Low SHBG leaves fewer androgens available. Low androgens worsen body composition and insulin sensitivity. The cycle is self-reinforcing, and none of the individual markers alone closes the case. Hormone optimization without metabolic intervention will underperform. Metabolic intervention without addressing androgens will leave significant symptoms on the table. Both have to move together.

7. Homocysteine

Homocysteine is an amino acid that accumulates when methylation is impaired, typically from inadequate B12, folate, or B6. Elevated levels are an independent predictor of cardiovascular disease, stroke, and dementia. The dementia data specifically is worth taking seriously: elevated homocysteine in midlife predicts cognitive decline a decade or more out.

It is also one of the more actionable markers on this list. In most cases, elevated homocysteine responds well to targeted B-vitamin support, particularly methylated forms in patients with MTHFR variants. Testing homocysteine without at least considering methylation status misses part of the picture.

This is a cheap test. The intervention, when needed, is cheap. The downstream consequences of missing it are not.

8. Free testosterone

In every woman. Every time.

Testosterone is not a male hormone that women happen to have a little of. It is central to muscle synthesis, metabolic rate, bone density, cognitive sharpness, libido, mood, and the ability to respond to exercise. When it is low — truly low, not just normalized against an age-adjusted reference range calibrated for decline — the effect on body composition is profound and almost entirely resistant to lifestyle intervention.

It’s important to look at free and total testosterone, not just total. Free testosterone reflects what the cells can actually use, and it is the number that correlates with symptoms. Specify LC/MS (liquid chromatography-mass spectrometry) methodology; immunoassay-based testosterone testing in women is notoriously inaccurate at low concentrations and will routinely underestimate or misreport levels.

My patient had been on testosterone gel for over nine months. Her total testosterone came back essentially undetectable, less than 3 ng/dL. Part of the problem was the delivery method: gels have notoriously variable transdermal absorption, and some patients simply do not absorb them reliably regardless of dose. She had been symptomatic the entire time and told nothing was wrong. I switched her to a compounded cream, which tends to achieve more consistent absorption.

9. Full thyroid panel: TSH, fT4, fT3, reverse T3, thyroid antibodies

TSH alone is not a thyroid assessment. It is a pituitary output signal, the brain’s commentary on thyroid function, not a direct measure of it. It does not tell you how much active thyroid hormone is reaching the cells.

The full picture requires free T4 (circulating hormone), free T3 (the biologically active form), and reverse T3 (the inactive form that competes with free T3 at the receptor). Someone can have a normal TSH and a flagged fT3-to-reverse T3 ratio that explains years of fatigue, cold intolerance, constipation, and weight resistance.

I add thyroid antibodies (TPO and thyroglobulin) routinely, including in patients who had negative antibodies years ago. Autoimmunity can develop at any point in life, and a clean result from five years ago does not tell you what is happening now. Hashimoto's often smolders for years before TSH moves, with antibodies rising long before the pituitary registers a problem. Early identification changes the clinical conversation: it shifts the framing from "your thyroid is borderline" to "you have an autoimmune condition we can monitor and address," which opens different treatment options and a different conversation about triggers. My patient's TSH had been trending upward over two years with no downstream labs ever ordered.

10. 25-OH Vitamin D

More than 40% of American adults are deficient. The number is higher in women, higher in postmenopausal women, and higher still in anyone carrying excess adiposity, because vitamin D is fat-soluble and gets sequestered in adipose tissue, away from the circulation where it can function.

The conventional cutoff for deficiency is below 20 ng/mL. Insufficiency is pegged at 20 to 30. I rarely consider anything below 50 acceptable for anyone with joint pain, autoimmune history, cardiovascular risk, or a history of cancer. The data on vitamin D and colorectal cancer, breast cancer, and all-cause mortality is among the most consistent in nutritional medicine.

A few more worth knowing about

I can’t help myself!

• Uric acid is an independent cardiovascular and metabolic risk marker that most people only associate with gout. Elevated levels are present years before a first flare and track closely with insulin resistance

• The omega-3 index measures EPA and DHA concentration in red blood cell membranes; below 4% is associated with meaningfully elevated cardiac mortality risk

• AM cortisol gives a baseline read on HPA axis function; chronic stress physiology drives visceral adiposity, immune suppression, and bone loss in ways that show up elsewhere in the panel

• Cystatin C is a more sensitive marker of early kidney function decline than creatinine, catching glomerular changes before standard eGFR moves

• Lastly, for anyone with a significant stress or surgical history, DHEA-S reflects adrenal reserve and is one of the earlier hormonal markers to drop as the system ages or becomes chronically taxed.

My patient came in with five years of unexplained weight gain, a stack of normal results, and the working diagnosis of aging. She left with a hormone regimen that actually made sense for her - testosterone switched from gel to compounded cream, an estradiol patch, progesterone. Specific diet and lifestyle adjustments: stop intermittent fasting, start lifting heavy. Not because those are the right answers for everyone, but because her labs told us they were the right answers for her. She had a clear plan for improving insulin sensitivity with measurable milestones, and a DEXA order so we could stop guessing about body composition and bone health.

She had not been failing. She had been working without a map.

If any part of her story sounds familiar, bring this list to your next appointment:

1. fasting insulin

2. ApoB + NMR LipoProfile with LP-IR score

3. lipoprotein(a)

4. hsCRP

5. ferritin with iron and TIBC

6. SHBG

7. homocysteine

8. free and total testosterone LC/MS

9. full thyroid panel (TSH + free T4 + free T3 + reverse T3 + TPO antibodies + thyroglobulin antibodies)

10. 25-OH vitamin D

    Bonus: uric acid, omega-3 index, AM cortisol, cystatin C, DHEA-S.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

In Germany, Austria, and Switzerland, Viscum album is one of the most commonly prescribed supportive therapies in all of oncology. 60 to 70 % of cancer patients in German-speaking countries receive it at some point during treatment. It is not prescribed by naturopaths. It is prescribed by medical oncologists, administered in hospital oncology departments, and in some cases partially covered by insurance. It has been studied in hundreds of clinical trials over five decades.

In the US, it decorates doorframes in December.

What it is

Mistletoe is a semi-parasitic plant that grows on the branches of host trees. The host tree matters because it shapes the phytochemical profile of the extract. Mistletoe grown on oak, pine, apple, elm, and other trees produces preparations with meaningfully different lectin concentrations. The main commercial preparations used in oncology are Iscador, Helixor, and Abnoba Viscum, each derived from specific host trees and harvested at specific seasons. They are not interchangeable, and the clinical literature does not always distinguish between them carefully enough, which is part of why the evidence looks messier than it probably is.

The two primary active compounds are mistletoe lectins and viscotoxins. The lectins are the more studied of the two. They bind to receptors on immune cells, particularly dendritic cells and macrophages, stimulating IL-12 production and activating natural killer cells. NK cell counts have been shown to increase by up to 35 percent above baseline with regular use. We care because NK cells are your immune system's standing patrol: they kill cancer cells on contact without needing prior exposure, specifically targeting cells that have lost the "I belong here" surface signal that healthy tissue displays. We also care because during chemotherapy your immune system is often the first casualty and being proactive can pay off in the long run.

The clinical evidence

Quality of life is where the data is most consistent. A systematic review and meta-analysis found a significant, medium-sized effect across quality of life outcomes in cancer patients receiving mistletoe alongside conventional treatment. 50 percent of the subdomains examined, including pain, fatigue, and nausea, showed statistically significant improvement.

Survival data is more contested. A 2013 randomized trial in pancreatic cancer reported a survival benefit in the mistletoe arm. The MISTRAL trial, a 290-patient, double-blind, placebo-controlled RCT published in 2024, did not. No survival benefit, no quality of life difference. That is a significant finding and it is dishonest to bury it.

Several systematic reviews show trends toward improved survival across cancer types, and others do not. All that to say for now, the quality of life signal remains more consistent than the survival signal… and that we are in need of more randomized control data.

The most important recent development in the United States is the phase I trial published in Cancer Research Communications from the Johns Hopkins Kimmel Cancer Center. It was the first American trial of intravenous mistletoe extract in patients with advanced solid tumors. Twenty-one heavily pretreated patients with colorectal, ovarian, pancreatic, and other cancers were enrolled. The therapy was safe. Stable disease was seen in five patients. Tumors decreased in three patients. Quality of life improved. Phase II planning is underway.

In the UK, the MAB study confirmed feasibility of conducting a placebo-controlled mistletoe trial within the NHS, a foundation for a larger efficacy trial that does not yet exist.

Types of administration

• Subcutaneous injection is the most common delivery method and the one with the longest clinical record. Patients inject three times weekly, typically into the abdomen or outer thigh, using small insulin-gauge needles. A local skin reaction at the injection site, mild redness and mild warmth, is expected and is actually considered a sign of immune activation rather than a problem to suppress. Dosing is titrated gradually, starting low and increasing based on response.

• Intravenous administration was granted FDA authorization for clinical trials in 2023 and is what the Hopkins trial used. IV delivery allows for higher doses, bypasses the subcutaneous immune priming step, and appears to produce a different and more potent immune activation profile. It is administered in a clinical setting, it can be administered every day for 1-2 weeks, weekly or biweekly.

• Intratumoral injection is used in some European protocols, particularly for accessible tumors. The direct injection of mistletoe extract into the tumor mass is intended to stimulate local immune activation. This approach is less studied than systemic delivery but has been used in practice, especially in anthroposophic medicine settings.

• Oral preparations exist but are far less common in oncology and have significantly lower bioavailability of the active lectins. The raw plant, particularly the berries, is toxic. Oral medicinal preparations use standardized leaf and stem extracts but are not the primary route for oncology use.

What to expect: side effects, labs, and imaging

For subcutaneous use, the most common experience is a local reaction at the injection site: redness, warmth, itchiness, mild induration. All of which is expected and desired.

Systemic effects are generally mild: low-grade fatigue, occasional flu-like symptoms, and transient fever, particularly as the dose is titrated up. These reflect immune activation, not toxicity.

Intravenous administration has a different and more pronounced side effect profile. In the Hopkins phase I trial, treatment-related adverse events occurred in 62% of patients. The most common were fatigue (29%), nausea (10%), and chills (10%). Grade 3 or higher adverse events occurred in about 15% of patients. Fever is both expected and, at higher IV doses, intentional. Many European protocols use IV mistletoe specifically to induce therapeutic fever, this is how I use mistletoe IV in practice. Allergic reactions are possible, particularly at higher doses, which is why IV administration requires clinical supervision and slow titration.

On labs, mistletoe produces real and measurable changes. NK cell counts rise, sometimes substantially, and lymphocyte counts shift as immune activation takes hold. CRP and other inflammatory markers can transiently increase. This is not a sign of infection or disease progression, it is the immune system responding. Tumor markers including CEA and CA-125 can transiently rise for the same reason: immune-mediated tumor cell disruption releases antigens into circulation. If your oncologist sees a bump in tumor markers shortly after starting mistletoe and does not know you are on it, that is a problem. They need to know.

For imaging, this matters more than most patients realize. Mistletoe stimulates immune activation in lymph nodes, and that activation shows up on FDG-PET as increased uptake. This increase in the uptake that can be misread as nodal involvement or disease progression. There is a published case report of exactly this happening in a lymphoma patient whose PET/CT was nearly misinterpreted as treatment failure because of active mistletoe use. Mistletoe should be held for a minimum of three days before any PET/CT or CT imaging.

Choosing the right preparation

Not all preparations are interchangeable, and selection is based on tumor type and patient constitution together.

For anyone looking for more guidance on selecting the appropriate mistletoe preparation for a specific cancer type, feel free to send me a message. I’m happy to help you and your provider navigate the options and determine what may be the best fit for your situation.

Synergistic agents

The most compelling combination data involves checkpoint inhibitors. A registry analysis of 300 patients with advanced non-small cell lung cancer found that adding Viscum album to PD-1 and PD-L1 inhibitor therapy doubled median overall survival from 6.8 to 13.8 months. A follow-up analysis in 405 patients showed three-year survival rates of 34.3% in the combination group versus 17.2% in the checkpoint inhibitor only group. These are registry studies, not randomized trials.

An active clinical trial in Switzerland, NCT06408688, is evaluating the safety and immune modulation of Iscador in patients on checkpoint inhibitors. The mechanistic rationale is strong: mistletoe promotes dendritic cell maturation and induces immunogenic cell death, both of which amplify the downstream immune response that checkpoint inhibitors are trying to unleash.

High-dose intravenous vitamin C is a pairing I use clinically and that has emerging case-level evidence. A published case report in integrative oncology described prolonged survival in advanced myxofibrosarcoma with the combination of high-dose IV vitamin C and Viscum album. The theoretical basis is additive: vitamin C drives reactive oxygen species-mediated cytotoxicity in cancer cells while mistletoe contributes immunogenic cell death and NK activation. These mechanisms do not overlap, which makes them worth combining rather than competing.

Chemotherapy combinations have been looked at in glioblastoma. Mistletoe-based drugs worked synergistically with radio-chemotherapy in glioblastoma cell lines and in a mouse model. The cytotoxic effects were additive, and mistletoe appeared to sensitize tumor cells to radiation and temozolomide. This is preclinical data.

Within the mistletoe extracts themselves, there is evidence of synergy between the aqueous lectin-containing fraction and the hydrophobic triterpene fraction. Combining them produces greater apoptosis in cancer cells than either fraction alone. This is why preparations that preserve the whole plant complexity may outperform standardized single-compound isolates. I find this to be true with most, if not all, plant compounds.

In European anthroposophic oncology practice, Helleborus niger is the classic complement to mistletoe. It supports lymphatic drainage and excretion pathways and is typically given in the evening when mistletoe is the morning injection, or on alternating days. The two are considered to work on different axes. The formal trial evidence for the combination is limited, but the clinical tradition is long and the biological logic makes sense to me.

What this actually is

Most of my patients are not looking for a miracle. They are looking for something real they can do alongside their treatment. Mistletoe has earned that role in European oncology for fifty years: a genuine mechanism, a long safety record, and quality of life data that consistently shows up even when the survival numbers are contested. It will not cure cancer. But it may help patients stay stronger through treatment, keep their immune system more functional, and in the right context work synergistically with the therapies already doing the heavy lifting. And, it might be one of the cheapest adjunctive cancer treatments out there.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

Most people think of glyphosate as a weed killer. It is also a registered antibiotic. Monsanto received a patent for its antimicrobial properties in 2010. The shikimate pathway it targets exists in plants, but also in the microbes living in your gut. Every time you eat a residue of it, you are running a low-grade antibiotic course against your own microbiome. That would matter less if your gut microbiome were just a digestive footnote. It is not.

The Gut-Brain-Immune-And-Everything-Else Axis

Researchers Ted Dinan and John Cryan coined the term psychobiotic to describe specific microorganisms that, when consumed in adequate amounts, produce a measurable benefit to mental health. Certain gut bacteria synthesize GABA and serotonin precursors, communicate with the brain via the vagus nerve, produce short-chain fatty acids that cross the blood-brain barrier, and directly modulate immune tone. Disrupting that microbial ecosystem does not just affect digestion. It affects mood, cognition, anxiety, and stress response. The gut-brain axis is bidirectional, and it is exquisitely sensitive to what lives in the colon.

Glyphosate is not selective. It targets the shikimate pathway across all microbial species that use it, which includes many of the Lactobacillus and Bifidobacterium species that produce these neuroactive compounds. One study found that glyphosate damages more than half of the beneficial microbes in the human gut. Glyphosate-resistant bacteria that survive tend to be inflammatory strains. So the net effect of chronic low-level glyphosate exposure is a gut that skews toward dysbiosis, elevated systemic inflammation, and a progressively compromised gut-brain axis. A 2022 Canadian study found that glyphosate-resistant microbes may affect neurodevelopment, and that this altered microbial composition can be passed to subsequent generations.

The longevity space is saturated with wearables, peptides, NAD+ IVs, GLP-1s, rapamycin, CGMs, hyperbaric chambers, and cold plunges. But one of the cleaner signals keeps pointing back to something much simpler: prebiotics and probiotics, and specifically to Bifidobacterium. It is one of the organisms most consistently associated with healthy aging. Centenarian gut microbiome studies from Japan and Italy repeatedly show higher Bifidobacterium abundance compared to average elderly populations. It produces acetate, supports gut barrier integrity, synthesizes B vitamins, and keeps intestinal pH low enough to limit pathogen colonization. It also declines predictably with age under normal circumstances. Add chronic low-level glyphosate exposure to that trajectory and you accelerate a process that was already working against you. The gut-brain axis gets most of the press, but Bifidobacterium and its microbial neighbors are communicating with every major organ system: the liver through tryptophan and lipid metabolism, the heart through LDL modulation and cardiometabolic signaling, the kidney through oxidative stress pathways, and bone through osteoclast regulation and calcium signaling. Disrupting this ecology is not a localized problem.

Image from The role of Bifidobacterium in longevity and the future of probiotics https://doi.org/10.1007/s10068-024-01631-y

The Microbiome-Cancer Connection

The International Agency for Research on Cancer classified glyphosate as a probable human carcinogen in 2015. The strongest epidemiological signal has been for non-Hodgkin lymphoma, particularly diffuse large B-cell lymphoma, where pooled analyses of agricultural cohorts showed a meta-hazard ratio of approximately 1.36 (meaning people with occupational glyphosate exposure had a 36 percent higher rate of developing diffuse large B-cell lymphoma compared to unexposed people, pooled across multiple studies).

Image from Comprehensive assessment of pesticide use patterns and increased cancer risk https://doi.org/10.3389/fcacs.2024.1368086

More recent meta-analyses continue to show elevated risk in occupationally exposed populations, though the data from the Agricultural Health Study have been less consistent, which keeps this debate alive. A 2025 hypothesis paper in Environmental Sciences Europe raises another angle entirely: glyphosate may persist in bone, creating extended exposure to hematopoietic tissue that could explain some of the lymphoma signal.

The carcinogenicity question is important, but it is not the only reason oncologists should care about this. The deeper story is what a damaged microbiome does to cancer outcomes.

We now have substantial evidence that gut microbial diversity determines, in part, how well a patient responds to immune checkpoint inhibition. Patients with higher abundance of Akkermansia muciniphila and Ruminococcus species, and higher circulating short-chain fatty acids, show longer progression-free and overall survival on checkpoint inhibitors, particularly in melanoma and non-small-cell lung cancer. Butyrate, a fermentation byproduct, modulates PD-1 expression on CD8+ T cells, reducing exhaustion. Fecal microbiota transplant trials in checkpoint-refractory melanoma have achieved objective response rates of 20 to 40 percent in patients who had failed prior immunotherapy. That is really significant!

If you are eating a diet high in conventionally grown oats, lentils, chickpeas, and beans, you may be getting significant glyphosate exposure through desiccation. This is the practice of spraying Roundup on crops just before harvest to dry them uniformly for the combine. These crops absorb the herbicide. You cannot wash it off. The glyphosate lands in a gut that needs to be in optimal condition to run your immune system, and specifically to mount a cancer-fighting immune response.

It Starts in the Soil

The food is less nutritious than it used to be, independent of pesticide exposure. Industrial agricultural practices have depleted soil microbiomes and stripped mineral content from farmland. Magnesium levels in vegetables and wheat have declined by roughly 25 percent over the past several decades. Trace minerals including zinc, manganese, and copper have also fallen in measurable quantities. An estimated 50 percent of the population now has inadequate magnesium levels. Magnesium is required for over hundreds of enzymatic reactions, including DNA repair.

The soil microbiome and the gut microbiome are connected through the food we eat. Healthy soil produces microbe-rich, nutrient-dense food. Depleted soil, managed with synthetic inputs and herbicides that kill soil organisms, produces food that feeds neither you nor the microbes that protect you. Glyphosate degrades soil microbial communities directly. It compounds a problem that was already worsening.

What Can You Do

Testing

If you want to know your actual exposure level, urine testing is the standard method. The gold standard is LC-MS/MS (liquid chromatography-tandem mass spectrometry), which has 98 to 99 percent sensitivity and specificity and measures both glyphosate and its primary metabolite AMPA. Mosaic Diagnostics and US BioTek both offer urine-based testing that can be ordered through a clinician or functional medicine practitioner. ELISA-based tests are cheaper and more widely available but are prone to false positives and false negatives, I would not make clinical decisions based on an ELISA result alone. Collect a first-morning urine sample for the most concentrated reading, and be aware that a single negative result does not rule out chronic low-level exposure. Glyphosate's urinary half-life is roughly 5 to 12 hours in the rapid elimination phase, with over 90 percent cleared within 48 hours of exposure. Test within a day or two of a high-exposure meal and you may catch it; test a week later and you likely will not.

Detox protocol

There is no proven glyphosate detox protocol with high-quality human data behind it. What we have is mechanistic reasoning and a small amount of supportive evidence, which I think is enough to act on given the exposure burden, the known downstream risks and the interventions being low risk.

1. The first and most effective intervention is reducing exposure. Buy organic for oats, legumes, and grains whenever possible. These are the crops most likely to have been desiccated with glyphosate. For water filtration, reverse osmosis is the most effective option, removing up to 99% of glyphosate. High-quality coconut shell activated carbon can reach similar levels, but basic pitcher and fridge filters remove less than 20% and are not reliable for this purpose. An RO system with NSF/ANSI 58 certification combined with a carbon stage is the strongest home option.

2. Glycine supplementation: glyphosate is a structural analog of glycine and substitutes for it in proteins, causing misfolding. Flooding the system with glycine may competitively reduce that substitution and support renal clearance. The typical recommendation is 2 to 4 grams twice daily for a few weeks, then a lower (1 to 2 grams) maintenance dose.

3. Aspergillus oryzae, the fungus used in miso, sake, and soy sauce, has demonstrated capacity to biodegrade glyphosate. This is one of many reasons to increase fermented foods in the diet. Fermentation also degrades glyphosate in other contexts, and fermented foods introduce organisms that may help restore microbial diversity.

4. Fiber and ferments are foundational. Short-chain fatty acid producing organisms are the ones most vulnerable to antibiotic disruption and most critical to immune function and gut-brain signaling.

5. Activated charcoal is worth adding for patients with significant ongoing exposure. It adsorbs glyphosate in the gut before it can be absorbed — take it away from medications and food, or it will bind those too.

One System, Not Five

Glyphosate is engineered into 90 percent of conventional soy, corn, sugar beet, and canola in the US. It also reaches oats, wheat, lentils, chickpeas, dried beans, peas, and almonds through pre-harvest desiccation. Farmers spray it on these crops shortly before harvest to dry them uniformly, and it absorbs into the grain. The result is detectable glyphosate in nearly every American body tested. That exposure is chronic and low-grade, layered on top of soil depletion, ultra-processed food, and decades of routine antibiotic use, all of which push the microbiome in the same direction.

The organisms being depleted are the same ones modulating your neurochemistry, running your immune response, protecting your liver and kidneys, signaling your cardiovascular system, and tracking with healthy longevity in centenarian populations. Losing Bifidobacterium is not a minor digestive inconvenience. It is losing a key node in a network that reaches every major organ, and a major “longevity biohack.”

I believe the microbiome is one of the most underutilized levers in integrative oncology. The immunotherapy data alone (better survival outcomes, meaningful FMT responses in refractory disease) should make gut health a clinical priority for every cancer patient. Glyphosate is the thread connecting the soil depletion story, the mental health story, and the cancer story. The soil, the food, the gut, the brain, the immune system all run on the same underlying biology. Treating them in isolation is part of how we got here.

Actionable takeaways

• Prioritize organic for oats, lentils, chickpeas, and beans These crops most often undergo glyphosate application

• Upgrade your water filtration to reverse osmosis; an NSF/ANSI 58-certified RO system with a carbon stage removes up to 99% of glyphosate

• Build a high-fiber, ferment-forward diet to protect and restore SCFA-producing organisms

• Take a Bifidobacterium-containing foods or probiotic. It is one of the clearest longevity signals in the microbiome literature and one of the first casualties of antibiotic disruption

• Consider glycine supplementation (2–4g twice daily for a few weeks) if your exposure has been high. It competes with glyphosate at the protein substitution level

• Eat miso, real fermented tofu, real soy sauce, and other Aspergillus-fermented foods regularly. The fungus degrades glyphosate and the ferment restores diversity

• Use activated charcoal short-term if exposure is significant; take it away from medications and food

• Consider urine glyphosate testing (LC-MS/MS via Mosaic Diagnostics or US BioTek) if you eat a conventional diet or live near agricultural land; test within 48 hours of a typical high-exposure meal for the most accurate read

• If you are an oncology patient heading toward immunotherapy, request a baseline gut microbiome assessment and address dysbiosis before treatment starts

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

The first plan was carboplatin and pemetrexed, the standard chemotherapy backbone for her cancer. It worked for about six weeks before her disease progressed into her lung, liver, and bones.

What changed everything was the molecular profile. Her tumor came back positive for a HER2 exon 20 insertion mutation, found on a Tempus panel ordered up front because we insisted. That one result opened doors standard chemotherapy never would have. She qualified for Enhertu, a HER2-directed antibody-drug conjugate. When that progressed, she qualified for a clinical trial of zongertinib, a HER2-selective targeted therapy that has since received FDA approval. Each treatment bought her time. Time to enjoy one more summer, to sit at the table with her family, to know her grandchildren a little longer.

Julie passed away last year.

We built this patio in memory of Julie, a place for gathering, deep conversation, and the kind of ordinary magic she loved most.

Standard chemotherapy gave her six weeks. The targeted therapies opened by that one molecular test gave her sixteen more months. Every time a new patient sits down with metastatic disease, I think about her.

Most oncology appointments are structured to deliver a plan, not to interrogate whether the plan is the right one. When your oncologist walks in, they already have something in mind for you. That is not a criticism. It is how the system runs. But harder questions make better medicine, and you are allowed to ask them.

A written question list is the single highest-leverage thing you can bring into that room. Amid some of the most overwhelming moments of anyone's life, a list keeps you on track. Here my list:

On the diagnosis

• Help me understand cancer. I know this sounds like an odd question. You know what cancer is... But do you really understand what that means?

  Before making decisions about treatment, ask your oncologist to explain how your cancer forms, grows, spreads, interacts with the immune system, and sustains itself. Understanding the biology of your disease makes every conversation that follows easier to navigate and every treatment decision easier to understand.

• What is the exact name of my cancer, including subtype and any mutations found so far?

• Has my tumor been sent for comprehensive genomic profiling? If not, can it be ordered now, not later? And can it be repeated at progression, since tumors change?

• Given my cancer type and history, should I also have germline testing? Some mutations that look somatic are actually hereditary. This matters for your family and sometimes for your treatment options.

• What is my stage, and what does that actually mean for treatment and prognosis?

On the treatment

• What is the goal here: cure, prolonged remission, or symptom control? Be direct with me.

• Why this regimen for someone with my exact molecular profile? Is this guideline-based or is there a better fit?

• Are there targeted therapies, immunotherapies, or clinical trials that match my mutation status? Have you checked TrialSpark or the NCI’s trial matching tools, or do you have someone who does that?

• What are my alternatives, including doing less than you are recommending? Different drugs, lower doses, less frequent dosing?

• Has my case been reviewed by a tumor board, and if not, is that something we can do?

On side effects and preparation

• Which side effects are most likely, and which should make me call the same day?

• Between now and when treatment starts, what can I do to improve tolerability and response? Are there any prehabilitation strategies you recommend?

• What does the evidence say about diet, exercise, and sleep during this regimen? I want specifics, not general wellness advice. If a provider tells you lifestyle modifications will not make a difference in cancer, find a different provider.

On integrative care

• Are you open to adjunctive, integrative care? Ask this question directly. The answer tells you a lot.

• Do you have an integrative oncology team, or someone you trust to refer me to?

• Here is my supplement list. Which would you pause, which are fine, and which do you not have an opinion on? Are the interactions you are concerned about theoretical or established in the literature?

• Have you seen any data on metabolic interventions in my cancer type?

• Are there any off-label drugs that have shown promise in my type of cancer?

• What integrative oncology centers do you know and would consider for a parallel consult?

On monitoring and the long view

• How will we know if this is working, and how soon? Will you use imaging alone, or is ctDNA monitoring or liquid biopsy an option for earlier signal?

• If this regimen stops working, what is the next line? Is there a plan B and plan C already, or do we figure that out when we get there?

• When should I seek a second opinion, and where would you send someone you love?

• If the goal is cure, when do we start planning for life after treatment?

Bring this on paper. Hand a copy to whoever is in the room with you, because two memories beat one in a long appointment. Ask the awkward, uncomfortable questions out loud: about goals, about alternatives, about what happens if this does not work. If you run out of time, ask for a follow-up to finish the list. Do not apologize for needing it.

Julie’s story is not unusual anymore. Targeted therapies are expanding across lung, breast, colorectal, gastric, melanoma, prostate, and a growing list of other cancers. The molecular landscape is also shifting. Germline mutations, rare fusions, resistance mechanisms found on liquid biopsy are now informing second and third-line decisions in ways they were not five years ago. No two cancers are the same. The only way to access what fits your tumor is to know what is driving it, and the only way to know that is to ask for the test. Early, and again at progression.

Germline findings also let us tailor integrative interventions, from nutraceuticals and IV therapies to off-label drugs with mechanistic rationale for your specific mutation profile. The molecular data that unlocks your systemic treatment can inform your integrative plan too.

Despite how some medical professionals act, this is not a dictatorship. You are not a passive recipient of a plan someone else made for you. The best oncology care is built on collaboration and trust, and that only works if both people in the room are actually talking. Your questions are not an inconvenience. They are how good medicine gets better.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

This is the most misunderstood topic in my field. Antioxidants carry a reputation as something close to universally good, the more the better. The real story is that they are dose-dependent and context-dependent, and there are settings where loading up on them is the wrong move.

Your cells produce reactive oxygen species as a normal part of being alive, and antioxidants keep those in check. Cancer cells, though, often run hot with oxidative stress already, and that is something we can use. Radiation and many chemotherapy drugs kill cancer cells partly by driving reactive oxygen species past what the cell can survive. Flood the body with high-dose antioxidants during that window and you may be handing the tumor exactly the buffer it needs to make it through.

The laboratory work points the same direction. In animal models, antioxidants like NAC and vitamin E have accelerated the progression and spread of lung cancer and melanoma. That is animal data, and I hold it loosely until we see the same thing in people. But it lines up with the mechanism, and that combination is enough to make me careful. An analysis from the SWOG S0221 chemotherapy trial found that breast cancer patients who used antioxidant supplements during treatment tended to have worse outcomes. That study shows association, not causation. Still, when the trials, the biology, and the treatment data all tell a similar story, we listen.

There is a deeper version of this story that almost nobody is telling patients, and I think it matters. Your body runs its own internal antioxidant defense system through a transcription factor called NRF2. NRF2 senses oxidative stress and switches on a fleet of protective genes, and several of the food compounds I love, sulforaphane from broccoli sprouts, curcumin, EGCG from green tea, work largely through it. Activating NRF2 in healthy cells is part of why those foods earn their reputation in prevention.

Here is the twist. Once a tumor exists, it can hijack the same system. A subset of lung cancers carry KEAP1 mutations that lock NRF2 permanently on, and those tumors are notoriously harder to treat with chemotherapy and radiation because the cancer cell is already running its antioxidant defenses at full tilt. The pathway we cheer on for prevention is the pathway some established cancers use to survive treatment.

I do not read this as a reason to stop eating broccoli. I read it as a reason to stop pretending prevention biology and treatment biology are the same biology. Pumping in heroic doses of concentrated NRF2 activators during chemo or radiation deserves attention and pause.

Here is the distinction that resolves most of the confusion. The antioxidants in vegetables, fruit, herbs, and tea are consistently tied to lower cancer risk. The failures and the warning signs come from isolated compounds at pharmacologic doses in a capsule.

Food delivers these molecules in physiologic amounts, packaged with cofactors, in a form your body has spent a very long time learning to handle. A supplement delivers a single compound at a dose you would never reach by eating. Same molecule, completely different signal to the body. When I tell a patient to eat widely and in color, I mean it. When I see the megadose capsules, that is a different conversation.

People always ask about high-dose IV vitamin C here, and it deserves a quick answer. At the concentrations reached through an IV, vitamin C stops behaving like an antioxidant and acts as a pro-oxidant, which is the opposite mechanism. Different route, different dose, different biology.

Bottom line:

• Skip the megadose vitamin C, E, and beta-carotene taken just in case. Just in case is not a reason, and in this case it may be a risk.

• During radiation and chemotherapies that work through oxidative stress, I pause high-dose isolated antioxidant supplements and want food-based antioxidants in their place.

• For prevention, I do not recommend high-dose single-antioxidant supplements. Topical antioxidants are fine. The goal is plenty of antioxidants from food.

• In survivorship, specific antioxidants, at specific times, for specific reasons, do have a role, particularly to address treatment-related reactive oxygen species and ongoing inflammation.

These choices belong with your oncology team and a clinician who knows your full picture. If you are in or near cancer treatment and you have a supplement drawer, bring it to your next appointment. Every bottle. Including the gummies. Most of those are worthless anyway.

Sometimes too much of a good thing can be harmful.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

I am all for healthspan. That is the entire point of preventive medicine. But a meaningful portion of what is being sold as anti-aging is, at best, untested in humans, and at worst, biologically aligned with the very pathways that drive dysfunction.

In my previous post I laid out where I would start if I wanted to lower my cancer risk in my 30s, 40s, and 50s. This is the companion piece. What I would steer away from, even if a podcast host promises it adds five years to my life.

When I sort through the current longevity menu, I find two patterns. Some interventions deliver a real short-term benefit and quietly extract a long-term cost that is not on the label. Some interventions deliver a feeling that is not actually supported by human data while still carrying real risk.

A note before we get into it. I prescribe peptides. I use NAD precursors in specific cases. I order biological age testing when it is appropriate. My critique is about how these tools are being prescribed. To the wrong patients, by clinics with insufficient patient education and no monitoring, on evidence that does not yet exist. I am pro-evidence in humans, pro-monitoring, pro-asking the questions, pro-informed consent on experimental therapies and pro doing the unsexy, hard things.

Real benefit, real long-term cost

This is the most interesting category, because the short-term win is genuinely there. The trade-off is what gets quiet in the marketing.

TRT prescribed casually

In men with documented hypogonadism, testosterone replacement reliably improves libido, body composition, and mood. The TRAVERSE trial confirmed cardiovascular safety in that population. The clinical use case is real.

The longevity clinic version is not the same medicine. A symptom checklist, a single morning testosterone level, no SHBG, no estradiol, no PSA, no hematocrit, no fertility conversation, and a script. Patients walk out with prescriptions for a therapy whose long-term costs include testicular atrophy, suppressed fertility that is often not reversible after years on therapy, polycythemia that requires monitoring or dose adjustment, with the pulmonary embolism signal seen in TRAVERSE, sleep apnea worsening, and dependency.

The reality is that I have sat across from many men in their 30s and 40s who were not properly counseled about fertility before starting TRT and are now struggling to conceive with their partners.

Most men presenting with fatigue, low libido, and brain fog have a metabolic, sleep, or stress problem first. Yes, TRT will mask those problems for a while. But the original problem keeps progressing in the background. Sleep apnea continues to damage cardiovascular and metabolic health. Insulin resistance keeps advancing. TRT will improve some of these markers, the patient feels better, and stops asking why he felt bad in the first place. Five years later, the underlying disease has compounded and the TRT can no longer paper over it. Many men end up needing more testosterone.

GLP-1s as longevity drugs

The short-term win here is unambiguous and well-documented. Semaglutide and tirzepatide produce real weight loss, real glucose control, real lipid improvements, and real cardiovascular benefit in the populations they were trialed in. SELECT, STEP, and SURMOUNT are not small studies. The data is the data.

The longevity application is a different question. Microdoses prescribed off-label in metabolically healthy adults have not been studied for long-term safety in that population. The safety profile we know is in patients who needed the drug.

The bigger trade-off is body composition. GLP-1 weight loss is not all fat. Significant lean mass loss is well documented in the trials and visible in clinic. In a 45-year-old who is not actively resistance training and eating high protein, the loss of muscle mass over months to years is the opposite of what longevity should be doing. Sarcopenia is one of the most underappreciated predictors of poor outcomes in cancer treatment, surgical recovery, and falls in your 70s. Losing muscle in your 40s for cosmetic reasons is borrowing from your eighth decade.

If a patient has obesity, prediabetes, or metabolic syndrome that has not responded to first-line lifestyle work, GLP-1s are reasonable medicine. If they are looking lean and want to look leaner, my answer is no.

High-dose protein and the leucine arms race

Adequate protein in older adults is essential. The short-term effects on muscle protein synthesis and body composition are well-established. I am not pulling protein out of anyone’s diet.

The longevity world often treats protein optimization as if more is always better. Chronically very high protein intake, particularly from animal sources rich in branched-chain amino acids, sustains mTOR activation. mTOR is part of how we build and preserve muscle. It is also part of how cells proliferate when we do not want them to. The cleanest longevity epidemiology, including Adventist cohorts and other Blue Zone-style populations, tends to support moderate protein intake with a stronger plant emphasis for lower cancer risk and overall mortality.

The other long-term cost is opportunity. People prioritizing protein bars, shakes, and meat-heavy meals are often displacing the thing most consistently associated with better long-term outcomes: fiber. Fiber is not just about bowel regularity. It shapes the microbiome, improves insulin sensitivity, lowers LDL cholesterol, supports estrogen metabolism, increases short-chain fatty acid production, and is consistently associated with lower cardiovascular disease, colorectal cancer, and all-cause mortality risk. Most Americans are profoundly under-consuming it.

The irony is that many people chasing “optimal” longevity macros are eating less than 20 grams of fiber daily while meticulously tracking leucine thresholds. Meanwhile, some of the strongest nutrition longevity data we have repeatedly points back toward minimally processed plant foods, legumes, vegetables, intact grains, nuts, seeds, and overall dietary diversity.

The clinical version. Get enough protein to build and maintain muscle, generally around 1.2 to 1.6 g/kg of ideal body weight for most adults, often higher for older adults, cancer patients, and those actively training. Get it from whole, lean sources: fish, eggs, poultry, legumes, fermented soy foods, dairy if tolerated, and moderate amounts of less-processed red meat. Build meals around plants first, not around protein products. Aim for fiber intake that actually reaches physiologic relevance, often 30 to 50+ grams daily from real food.

Whole foods carry micronutrients, polyphenols, fermentation substrates, and satiety signaling that isolated protein strips out. Powders, bars, and isolates have a role for genuine logistical gaps, not as the dietary foundation. Periodize. Cycle higher and lower intake days. Train enough to justify the extra protein.

GH secretagogue peptides

Tesamorelin is FDA-approved for HIV-associated visceral adiposity and produces measurable reductions in visceral adipose tissue. The short-term effect on a defined endpoint is real. Sermorelin, ipamorelin, and CJC-1295 also raise IGF-1 measurably, and many patients report improved sleep and recovery in the early months.

The long-term cost is the IGF-1 story. The IGF-1 axis is one of the most well-characterized proliferative signals in human biology. Acromegaly, where GH and IGF-1 are chronically elevated, is associated with higher rates of colorectal cancer, cardiovascular disease, and connective tissue overgrowth. We do not have human data on what years of supraphysiologic GH stimulation does in people who started with normal levels.

There is also the dependency issue. Patients who stay on these compounds for a year or two often struggle when they try to stop. The hypothalamic-pituitary feedback loop adapts, endogenous signaling downregulates, and many end up feeling worse coming off than they did before they started.

I prescribe peptides selectively, for short and clearly defined clinical situations. I do not view them as casual longevity add-ons. Longevity is not about shortcuts. It is about respecting biology over decades. The recovery, body composition, and performance gains patients feel today may come with physiologic consequences we cannot yet fully see, especially when these pathways are chronically manipulated in healthy individuals without a real discussion of tradeoffs.

The short-term claim itself does not hold up

This is the category the longevity industry would rather you not look at too closely. The marketing implies a robust short-term effect. The human data does not.

NAD IV infusions and most NAD precursors

NMN and NR raise blood NAD. That much is well-established. Whether the biomarker change translates to functional or subjective benefit in healthy adults is far less clear. The trials are small, short, and inconsistent. Some show modest insulin sensitivity improvements. Some show nothing.

NAD IV infusions, the version sold at $400 to $600 a session, have no controlled efficacy data despite the marketing. The “feel sharper” claim is anecdotal. I have experimented on myself. Did I feel different? Maybe. Which could entirely be chalked up to the placebo plus the saline volume itself.

There is also a mechanistic problem worth naming. NAD does not readily cross cell membranes. IV NAD is broken down to nicotinamide and other precursors before cellular uptake, which means the biological endpoint of an IV may not be meaningfully different from oral NR, despite the price and the theater.

The biology gives one more reason for caution. NAMPT, the rate-limiting enzyme in the NAD salvage pathway, is upregulated in many cancers and supports tumor metabolism. Active oncology research is targeting NAMPT inhibition as anti-cancer therapy, which sits in tension with chronically loading the system in someone who may have undiagnosed disease. This remains controversial and far from settled. Many integrative providers routinely use IV NAD and NAD precursors in cancer patients and report doing so without apparent harm. We do not yet have strong long-term human outcome data to confidently define the risk-benefit profile in oncology.

BPC-157 and TB-500

These get bundled into peptide stacks for “recovery” and “gut healing.” There are essentially no controlled human trials for either. The animal data shows angiogenic effects, which is a property tumors require to grow. The subjective improvements patients report are anecdotal in a population already paying thousands for the protocol, which is the definition of a setting where placebo effects dominate.

What to focus on instead. For tissue recovery, the practical tools are not exotic. Sleep is the biggest lever. Adequate protein at meals supports remodeling. Collagen peptides 15 g with vitamin C taken 30 to 60 minutes before targeted tendon or ligament work improves tissue collagen synthesis (Shaw, Baar lab). Creatine has decades of human safety and efficacy data, with emerging signals for connective tissue and brain. Omega-3s, curcumin, and tart cherry have modest data for post-exercise soreness and inflammation. Sauna has cardiovascular and recovery data that BPC-157 does not.

For gut work, start by removing what injures it. NSAIDs, alcohol, ultra-processed food, sleep deprivation, and unmanaged stress drive most of what people are trying to heal with peptides. From there:

• Zinc carnosine 75 mg twice daily for mucosal repair, particularly NSAID-induced damage

• L-glutamine 5 g once or twice daily for enterocyte support

• DGL (deglycyrrhizinated licorice) for upper GI mucosal protection

• Slippery elm or marshmallow root for mucilaginous coating

• Saccharomyces boulardii during and after antibiotics

• Strain-specific probiotics matched to the indication, not generic blends

• Polyphenol-rich foods (berries, green tea, olive oil) for microbial diversity

The boring version is more likely to actually work than a peptide stack.

I have absolutely met patients who have tried everything, done the work consistently, and still feel stuck with no meaningful movement despite addressing the fundamentals. In select cases like that, I think it is reasonable to consider peptides thoughtfully and cautiously as a tool, not a shortcut.

At-home senolytic protocols

Fisetin and the dasatinib-plus-quercetin combination are still primarily supported by animal data and a handful of short-term human trials in narrow populations. The doses promoted on podcasts and social media are not the doses used in the human work that does exist.

Reported benefits like less inflammation, better recovery, and less joint stiffness are subjective and uncontrolled. People may genuinely feel something. That is not the same as established clinical benefit.

The strongest caution applies to dasatinib. It is a prescription tyrosine kinase inhibitor used in oncology, with known risks including pleural effusions, cytopenias, immunosuppression, and cardiac toxicity. Casual self-directed use in longevity protocols deserves more caution than it currently gets.

There is also a tendency to frame senescent cells as universally harmful. They contribute to aging and chronic disease, and they also play roles in wound healing and tissue repair. Clearing them indiscriminately may not be biologically neutral.

Off-label rapamycin for healthy aging

Most patients feel nothing in particular on rapamycin, which is the honest read. The short-term subjective benefit is essentially absent. The case for it rests entirely on extrapolation from animal lifespan data.

The long-term human safety in healthy adults is also essentially absent. We know rapamycin’s profile in transplant patients and in tuberous sclerosis. Possible side effects include glucose dysregulation, lipid elevation, mucositis, impaired wound healing, and infection susceptibility. Lower intermittent dosing for longevity may have a different profile, but in practice I have seen even low-dose rapamycin worsen blood glucose and lipid profiles.

What to focus on instead. The pathways rapamycin is meant to modulate, mTOR inhibition and autophagy induction, are also accessible through inputs with far better human evidence.

Caloric restriction has the strongest data. The CALERIE trial of 25 percent caloric restriction over two years showed improved metabolic flexibility, lower inflammatory markers, and slowed biological aging on the DunedinPACE clock. Fasting-mimicking diet protocols (Longo) lower IGF-1 and glucose markers in human trials. Time-restricted eating with a 10 to 12 hour window produces modest mTOR cycling and autophagy activation with metabolic benefit. Start the eating window earlier rather than later. Eat breakfast like a king, lunch like a prince, and dinner like a pauper.

Exercise activates AMPK and induces autophagy directly. Endurance training drives the AMPK side. Resistance training builds the metabolic and physical reserve that rapamycin cannot. Both have human outcome data that rapamycin does not.

Sleep! Autophagy is heavily circadian. Disrupted sleep blunts the same housekeeping rapamycin is supposed to upregulate.

Dietary spermidine, found in wheat germ, aged cheese, mushrooms, legumes, and whole grains, is associated with reduced all-cause mortality in observational cohorts (Kiechl 2018). Polyphenols like EGCG, curcumin, and resveratrol activate AMPK and SIRT1 pathways with varying levels of human data.

What actually compounds in your favor

The pattern across all of the above is that the interventions sold hardest in the longevity space are often the ones with the weakest data. The interventions that compound in your favor have a different shape. They do not feel dramatic in the first week or even month. They quietly accrue benefit over years.

Sleep on a consistent schedule. Resistance training to build and maintain muscle. Aerobic capacity that protects mitochondria and immune surveillance. Adequate but not excessive protein from whole foods. Fiber from diverse plants, north of 30 grams a day. Metabolic health with fasting insulin under 6 and ApoB optimized. Vitamin D in range. Reduced alcohol. Reduced exposure to endocrine disruptors. Functional labs to find deficiencies and over-accumulation, then fix them. Periodic prolonged fasts of 24 to 72 hours, one to four times a year if appropriate for you. Strong relationships. Time outdoors. Sunlight in the morning. Stress regulation that you actually practice rather than buy.

Let the body do the housekeeping it already knows how to do.

Boring? Yes. That is the point.

How I think about it

When a patient brings me a longevity protocol, I ask the same questions. What else are you doing as far as diet and lifestyle modifications? Are you aware of the long-term effects of the protocol you are on? What will it look like to come off it?

If you want to add something investigational on top of a strong foundation, I am not opposed, as long as you are doing it with full information, real monitoring, and honest acknowledgment that you are running a single-patient trial on yourself. What I see going wrong is people skipping the foundation and stacking new molecules on top of bad sleep, alcohol, and unmanaged stress.

I hate to sound like a broken record, but healing is practice. Not something you buy in a bottle.

The point of all of this is to live a life that is well-lived for as long as it is well-lived. Love. Connection. Community. Time in nature. Mistakes and imperfections along the way. That part has not changed since the last post and it is not going to.

I am keeping an open mind on every one of these molecules and protocols as the human data comes in. Several will probably earn a place. Several will not. I am not in a rush to find out which is which on my own body, or on yours.

Most of what is being sold to you in this space is wearing grandma’s bonnet. The teeth are still teeth. Ask the question early enough to matter.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

Most of oncology is built around what goes in: the drug, the surgery, the radiation. I spend an equal amount of time on what comes out.

Elimination is a rate-limiting step in cancer biology. It shapes inflammation, hormone signaling, microbial balance, and treatment tolerance. It matters in prevention, during active treatment, and in survivorship.

Bile flow and the estrogen loop

Bile is the primary exit route for fat-soluble toxins, conjugated estrogen metabolites, and the byproducts of hepatic phase I and phase II detoxification. When the liver conjugates a compound, the plan is for it to ride bile into the intestine and leave the body in stool. If bile is sluggish, from low dietary fat, sedentary lifestyle, poor gallbladder motility, or prior cholecystectomy, those conjugated compounds sit in the gut longer than they should.

This is where the microbiome enters the equation. Dysbiotic bacteria express beta-glucuronidase, an enzyme that cleaves the conjugate and liberates the parent compound, including estrogen metabolites. That estrogen re-enters circulation through enterohepatic recirculation. In symptom management and hormone-sensitive cancers, this is a clinically meaningful place to intervene. In prevention, constipation, high-glucuronidase gut flora, and stagnant bile may be modifiable risk factors for breast and endometrial cancers.

I tell patients this plainly. If you are not pooping at least once per day, you are recycling what your liver is trying to get rid of.

Gut barrier integrity and systemic inflammation

The microbiome gets a lot of attention, but if the gut barrier is not intact, even a “healthy” microbiome cannot function the way it should. Tight junction proteins are what keep the intestinal lumen separate from systemic circulation. When those junctions are disrupted, by chemotherapy, radiation, NSAIDs, PPIs, alcohol, or chronic dysbiosis, lipopolysaccharide from gram-negative bacteria translocates into the bloodstream. LPS activates TLR4 and drives NF-kB, one of the most potent inflammatory signaling cascades in the body.

Image from Bhat et al., Frontiers in Physiology, 2019

In active treatment, this is what underlies chemo-induced mucositis and poor treatment tolerance. In prevention and survivorship, it is subtler and more insidious. A compromised barrier can exist without GI symptoms or a slew of other systemic symptoms, at first glance unrelated to GI system. Or the patient might feel fine, but their baseline inflammatory tone is elevated, cytokine signaling is dysregulated, and the tumor microenvironment is primed for progression. Chronic LPS exposure is associated with hepatocellular carcinoma, colorectal cancer, and immune exhaustion that matters in any oncology context.

I believe barrier support belongs in standard supportive care during cytotoxic therapy, and in risk modification for anyone else.

The oral-gut-immune axis

This is the part the field has caught up on in the last five years. The bacteria in your mouth show up inside your tumors. Fusobacterium nucleatum, a periodontal pathogen, has been identified inside colorectal, pancreatic, and esophageal tumors, where it is not a passive contaminant. It actively promotes tumor progression and chemoresistance.

Fig. 1: The role of Fusobacterium within the tumor microenvironment from: Fusobacterium in the microbiome: from health to disease across the oral–gut axis and beyond

Porphyromonas gingivalis is associated with elevated pancreatic cancer risk. The clinical separation of dentistry and oncology is no longer an option.

In the gut, microbiome diversity and specific commensal species predict whether a patient responds to checkpoint inhibitor immunotherapy. Akkermansia muciniphila and Faecalibacterium prausnitzii are two of the best-studied. Routy et al. in Science showed that patients whose microbiomes were disrupted by broad-spectrum antibiotics before starting a checkpoint inhibitor had significantly worse outcomes. Fecal microbiota transplant trials are now underway to convert non-responders into responders. The microbiome is a treatment variable, not a wellness add-on.

For prevention, the implication is the same. A diverse, short-chain-fatty-acid-producing microbiome is associated with lower risk across multiple cancer types. Diet shapes it, stress shapes it, antibiotics disrupt it, and most people do very little to actively maintain it.

A word on antibacterial mouthwash

For the love of your health, stop using antibacterial mouthwash unless you have a specific clinical reason. Chlorhexidine, cetylpyridinium chloride, and high-alcohol formulations wipe out the oral microbiome indiscriminately, including the nitrate-reducing bacteria on the tongue that are essential for nitric oxide production. Disruption of that pathway raises blood pressure within days of regular use and has emerging links to glucose dysregulation and cardiovascular risk. These rinses also leave a scorched-earth oral environment that pathogens recolonize faster than commensals, which means the long-term effect is often more dysbiosis, not less. Post-surgical use, active periodontal treatment, and specific circumstances in immunocompromised patients are reasonable indications for short-term use. Daily cosmetic use for fresh breath does more harm than good.

Mold and biofilms

Two additional layers the standard workup misses. Biofilms are structured bacterial and fungal communities that adhere to mucosal surfaces, produce a protective polysaccharide matrix, and resist both the immune system and antimicrobial treatment. In the oral cavity they drive periodontal disease. In the gut they house the dysbiotic species that keep recurring after you treat them. Fusobacterium forms biofilms inside colorectal tumors, which is part of why it is so difficult to clear. If a patient has been treated for SIBO or dysbiosis three times and it keeps returning, you are dealing with biofilm.

Mold is the other blind spot. Environmental mold exposure and mycotoxin load drive chronic immune activation, disrupt the gut barrier, and feed intestinal fungal overgrowth. Aflatoxin is a class 1 carcinogen with direct hepatocarcinogenic activity. Ochratoxin A is associated with renal and urothelial malignancies. In patients with unexplained inflammation, treatment-resistant dysbiosis, or a history of water-damaged building exposure, a urinary mycotoxin panel and a careful environmental history belong in the workup.

Fasting and the fed-fasted cycle

One of the simplest tools is fasting. It is also one of the oldest. Hippocrates advocated it. Every major religious tradition has built a fast into its calendar, from Ramadan to Lent to Yom Kippur to the Hindu Ekadashi cycle. Ayurveda has prescribed it as langhana for thousands of years. Fasting is a conserved biological rhythm.

The body cleans in the fasted state. The migrating motor complex sweeps debris and bacteria out of the small intestine every 90 to 120 minutes between meals, which is a primary defense against SIBO and small bowel dysbiosis. Autophagy, the cellular recycling system, ramps up during prolonged fasts and is part of how the body clears damaged proteins, organelles, and malignant cells. Constant grazing shuts both of these off.

For prevention, a 12 to 14 hour overnight fast is associated with reduced breast cancer recurrence in the Marinac et al. data. During active treatment, Valter Longo's fasting-mimicking diet carries the strongest evidence base, with data suggesting it can protect healthy cells during chemotherapy and improve treatment response. Work with a clinician who can tailor it to your plan. Prolonged fasting carries real risk in patients with active weight loss, sarcopenia, or nutritional compromise. The clinical picture matters.

Daily intermittent fasting suits some people poorly, particularly those with already dysregulated endocrine systems. A longer fast (either water or vegetable broth) of 24 to 72 hours every couple of months often works better, and for otherwise healthy individuals it is one of the most effective tools for primary prevention. It keeps the house clean and the trash going out on schedule.

My nutrient dense broth for the next few days

How to assess it all

If you want to know whether these pathways are functioning, test them. A comprehensive stool panel with beta-glucuronidase, calprotectin, short-chain fatty acid production, and microbial diversity gives a functional read on the gut. Zonulin and LPS antibodies, while imperfect, can support a barrier assessment. A urinary mycotoxin panel is worth adding in anyone with unexplained inflammation, chronic dysbiosis, or known mold exposure. An oral microbiome panel is worth considering in patients with a GI or pancreatic cancer workup, chronic periodontal disease, or a strong family history. Cost varies. Individual tests like zonulin or an oral panel run $150 to $300. A full stool panel runs $300 to $500 cash pay, though private insurances and even Medicare will cover the pathogen PCR portion of GI-MAP when clinically indicated.

Targeted support

For bile flow: dietary fat at each meal, bitters before eating, taurine, and ox bile when motility is sluggish or the gallbladder has been removed. Build meals around bitter greens like arugula, dandelion, radicchio, and endive. Beets and artichokes directly support bile production. Lemon water or apple cider vinegar before meals primes gastric and bile acid release. Extra-virgin olive oil stimulates CCK and gallbladder contraction. Castor oil packs and adequate hydration are underused. Address constipation aggressively. Daily transit is non-negotiable.

For beta-glucuronidase and estrogen recirculation: calcium-D-glucarate, cruciferous vegetables or concentrated DIM, insoluble fiber to bind and move conjugated estrogens out, and treating the underlying dysbiosis at the source. Eat cruciferous vegetables daily, including broccoli, cauliflower, Brussels sprouts, cabbage, kale, bok choy, and arugula. Ground flaxseed, two to three tablespoons daily, provides lignans that bind circulating estrogen and shift metabolism toward safer estrogen fractions. Pomegranate, green tea, and shiitake or white button mushrooms offer aromatase inhibition. Adequate protein and choline from eggs, liver, and legumes fuel the methylation pathways that clear estrogen metabolites.

For barrier repair during or after cytotoxic therapy: L-glutamine, zinc carnosine, and deglycyrrhizinated licorice. Bone broth, wild salmon and other omega-3 rich fish, and collagen peptides. Cooked and stewed vegetables sit more easily on inflamed mucosa than raw. Ginger and turmeric support inflammatory resolution. Fermented foods once tolerance is established. Aloe inner leaf where tolerated. Removing the ongoing insult, whether NSAIDs, alcohol, chronic PPI use, or industrial seed oils, matters more than any supplement.

For microbiome diversity: fiber variety first, ideally 30 different plants per week. Fermented foods daily. Targeted prebiotics like partially hydrolyzed guar gum, resistant starch, or larch arabinogalactan. Specific probiotic strains when there is a clinical reason, including Bifidobacterium longum, Lactobacillus rhamnosus GG, and Saccharomyces boulardii for antibiotic-associated dysbiosis. Akkermansia muciniphila is now available as a direct-feed strain and worth considering in metabolic and immunotherapy contexts, but best outcomes are achieved through feeding your own Akkermansia through prebiotics:

• Polyphenols: pomegranate, green tea, cranberry, dark chocolate

• Inulin/FOS: garlic, onions, leeks, chicory root

• Resistant starch: green bananas, cooled potatoes or rice, legumes

• PHGG (supplement)

For biofilm disruption, often the reason microbiome interventions finally hold: bismuth, NAC, lactoferrin, EDTA, proteolytic enzymes like serrapeptase, nattokinase, and lumbrokinase, and botanicals such as berberine, oregano oil, and garlic. Pharmaceutical options include rifaximin and tinidazole for gut and SIBO-associated biofilm, nitazoxanide for broader spectrum coverage including protozoal involvement, and sub-antimicrobial dose doxycycline for periodontal biofilm.

The interventions shift based on testing, treatment phase, and what the patient is actively managing. A patient on active chemo has different priorities than someone in year three of survivorship.

What this means clinically

For clinicians, this means asking about bowel frequency and stool character at every oncology intake, screening for periodontal disease in any GI, pancreatic, or esophageal workup, and treating bile flow and constipation as first-line interventions in hormone-sensitive cancers. Barrier support belongs in the supportive care plan during and after cytotoxic therapy. A urinary mycotoxin panel belongs in the workup of any patient with unexplained inflammation, treatment-resistant dysbiosis, or a history of water-damaged building exposure. If a patient has been treated for SIBO or dysbiosis three times and it keeps returning, biofilm is the next layer. Be thoughtful about PPIs and broad-spectrum antibiotics around immunotherapy initiation whenever the clinical picture allows.

For patients, focus on building healthier habits over time. Aim for a daily bowel movement. When transit slows, the body reabsorbs what it was trying to eliminate. Oral health is systemic health, so reconsider the antibacterial mouthwash if you are using it daily. Build meals around fiber variety, working toward 30 different plants per week. Cruciferous vegetables belong on the plate most days. Fermented foods can come in once your gut is ready for them, and ground flaxseed offers gentle support for estrogen clearance. Bitter greens, beets, and olive oil help bile move. Reducing NSAIDs, alcohol, chronic PPIs, and industrial seed oils gives a compromised gut lining the space to heal. If you are on immunotherapy, anything that disrupts your gut flora without a strong clinical reason is worth a conversation with your oncology team.

Elimination is part of treatment. The barrier is part of treatment. The microbiome is part of treatment. In prevention, they are the protection.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

He was 14 months out from a glioblastoma diagnosis.

He went to the party.

GBM is not a diagnosis I soften. It is IDH-wildtype, WHO grade 4, and it carries a median overall survival of roughly 14 to 16 months on the Stupp protocol — temozolomide plus radiation, then adjuvant TMZ. Roughly one in three patients are gone within a year. The ones who do better almost always have one thing in common: MGMT promoter methylation. When that gene is methylated, the tumor can’t repair the DNA damage temozolomide inflicts. The drug actually works.

Fred’s MGMT was hypermethylated at over 80%. That matters. It is not a guarantee, but it is the single most favorable prognostic marker in newly diagnosed GBM, and it changes how aggressively I approach the integrative protocol. There is more to work with.

He came to me a few weeks after a near-total resection of a large left frontal mass. The tumor sat directly at Broca’s area. He had expressive aphasia. He could understand everything, but the words wouldn’t come out right. He was a health and fitness teacher. Words were his work.

He had just started chemoradiation. I had about six weeks to get a protocol in place before the real work of adjuvant chemotherapy began.

What we built, and why

The integrative protocol in GBM has to do several things at once: sensitize the tumor to chemotherapy, support the immune system, reduce cerebral edema without relying entirely on dexamethasone, and maintain whatever neurological function is still intact. These are not independent goals. The biology connects them.

Curcumin was the first layer. The preclinical evidence in GBM is more substantial than most people realize. Curcumin sensitizes GBM cells to temozolomide by generating reactive oxygen species and simultaneously suppressing phosphorylated AKT and mTOR, two pathways GBM uses to evade cell death. In U87-MG cell lines and xenograft models, the combination outperformed TMZ alone. I started Fred at 1200 mg twice daily with meals and held it there through the radiation phase.

Trametes versicolor (turkey tail) at 1500 mg twice daily, away from food. The goal here is NK cell activation and white blood cell support during chemotherapy. TMZ is myelosuppressive. Turkey tail’s polysaccharopeptide fraction has immunomodulatory properties that have been studied in breast cancer patients during treatment, and the in vitro data on NK cell potentiation is solid. In the context of GBM, where the tumor actively suppresses local immunity, this is not a small consideration.

1:1 THC:CBD at 50 mg twice daily. I want to be precise about the intent here. This was not about antitumor effects — the data in humans is not there yet for that framing. The goal was quality of life, specifically his aphasia. Cannabinoids are neuroprotective and anti-inflammatory in the CNS. There is also a signal worth paying attention to: a GW Pharmaceuticals phase 2 study showed an 83% one-year survival rate in the 1:1 THC:CBD plus TMZ group versus 53% in the TMZ-only control, with median survival of 662 days versus 369. That data needs replication in a larger trial before I lead with it, but it informed the decision to include it. The dose was reasonable, titrated slowly, and unlikely to cause harm. I made that framing explicit to Fred and his wife.

Boswellia extract was the intervention I was most confident would affect his outcomes positively. His neuro-oncologist at Swedish had given his the same recommendation. Boswellic acids reduce cerebral edema (there is a longitudinal pilot study in GBM patients specifically showing this) and the mechanism is COX and 5-LOX inhibition at the tumor margin. It is important that your Boswellia supplement contains AKBA (3-O-acetyl-11-keto-β-boswellic acid) as it is the most potent anti-inflammatory compound found in Boswellia serrata. I started him at 1200 mg daily and titrated to 3800 mg as tolerated. Several months in, imaging showed improvement in cerebral edema. He was tolerating ~3g twice daily without issue. This matters because every milligram of dexamethasone he doesn’t need is a win. Steroids cause weight gain, dysglycemia, immune suppression, and bone loss, and getting a GBM patient off them is almost always the right direction.

Ketogenic diet and 14-hour intermittent fasting for metabolic pressure on the tumor. GBM is highly glycolytic. Restricting glucose while elevating ketones exploits the Warburg effect and is the most evidence-informed dietary intervention we have in gliomas. The systematic review by Sargaço et al. supports its safety and feasibility. I referred him to oncology-specialized dietitians for support because this transition during active treatment requires guidance.

What actually happened

Nothing went smoothly. It never does with GBM.

His aphasia improved completely after surgery, then came back two weeks later. We navigated steroid tapers repeatedly; every time we got him below 2 mg dexamethasone, his speech worsened. A few months into adjuvant chemotherapy, imaging showed significant cystic expansion at the resection site. His neurosurgeon placed an Ommaya reservoir. Shortly after, he was diagnosed with a pulmonary embolism and started anticoagulation. The same month, he got COVID-19. We added nattokinase, liposomal lactoferrin, and L-arginine plus vitamin C for the post-COVID syndrome.

He went to Italy for three weeks and had a wonderful time sans his medical team.

When he came back, we added two more interventions. Low dose naltrexone at 4.5 mg four nights per week for immune modulation, endorphin upregulation, and its antiproliferative effects, which have been documented since the 1980s. He tolerated it well. His aphasia improved and his right motor function improved on it. I believe LDN belongs in most integrative oncology protocols for its safety profile alone. The risk-benefit here is not complicated.

All in all, Fred was doing relatively well. He and his wife were still taking short trips and spending time together. At one visit, they were both quieter than usual. His wife finally said they had a question neither of them wanted to say out loud. Since the start of treatment, they had not been able to be intimate. Fred was experiencing erectile dysfunction.

Tadalafil is an intervention that isn’t often discussed in GBM care but I think it belongs in the conversation. Male GBM patients on chronic dexamethasone are at high risk for steroid-induced hypogonadism and erectile dysfunction. This is rarely addressed, even though it directly affects quality of life and relationship functioning during an already devastating illness. Tadalafil (a PDE5 inhibitor) addresses this while offering a mechanistic bonus: preclinical data shows PDE5 inhibitors reduce myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment. MDSCs are one of GBM's primary tools for evading immune destruction, they suppress T-cell and NK-cell activity locally. By reducing MDSC burden, tadalafil may help the immune system regain ground. The evidence here is early and mostly preclinical, but the drug while closely monitored is safe, the QoL rationale is clear, and the potential anti-tumor immune benefit makes it a reasonable addition in male GBM patients on steroids. I discuss it with every eligible patient.

After some tinkering with the dose, Fred was able to achieve and maintain an erection. His life went on.

Valganciclovir came last. The Stragliotto data out of Sweden is hard to ignore: in newly diagnosed GBM patients receiving valganciclovir as an add-on, median OS was 24.1 months versus 13.3 months in controls. The 2-year survival rate was 49.8% versus 17.3%. The proposed mechanism involves cytomegalovirus, which is found in GBM tissue in a high percentage of tumors and is thought to drive tumor-promoting inflammation. Though his tumor was not tested for CMV, his serum titers were suggestive for CMV reactivation. The data needs a prospective randomized trial to be definitive, but it is safe, it has a plausible mechanism, and the survival signal is large enough that I discuss it with every GBM patient.

By the one-year mark, Fred was on 1.5 mg of dexamethasone, down from 10 mg at his worst. He was having what his wife described as “really good weeks.” He was answering in short sentences on our telehealth visits. But recent imaging was suggestive of progression at the posterior rim, and the central portion of the lesion appeared non-viable on PET. His neuro-oncologist was following closely.

One year after diagnosis, he had his retirement party.

What I want clinicians and patients to take from this

GBM is MGMT-stratified medicine whether we acknowledge it or not. If your patient is newly diagnosed, the first question is: what is the methylation status, and what is the percentage? That shapes the whole protocol.

The integrative approach in GBM is not about replacing Stupp, it is about making Stupp work better, protecting neurological function, getting patients off steroids faster, and giving the immune system something to work with. Every intervention in Fred’s protocol has a rationale and a reference. None of it is universally reproducible, and not all of it has RCT-level evidence in humans. I say that clearly to every patient.

Something else happens when a diagnosis carries a prognosis this heavy. Providers get focused on the protocol, the next scan, the next decision point, and the rest of the person quietly disappears from the conversation. No one asked Fred about sex. No one asked his wife. Two people in a long marriage navigating something unsurvivable, and that part of their life had simply stopped. It took them months to bring it up, and only because there was enough trust in the room to ask. The retirement party, the trip to Italy, the quiet question about intimacy, these are not detours from the clinical work. They are the clinical work. When we stop seeing the person behind the diagnosis, we lose the most important information: what they are still living for, and what they need to keep living well.

What I believe, based on years of working in this space: the integrative layer matters. Whether it is curative or contributory or simply supportive, I cannot tell you from a single case. What I can tell you is that Fred made it to his retirement party, he felt as well as he could have during it. He also felt the uttermost love and support and devastation that happens when you are in his position.

Fred lived with GBM for two and a half years. Not long before he died, he was reminiscing and told me he was disappointed I had missed his retirement party, and that he expected me at his second — his memorial service. He passed at home surrounded by his family.

I went to the party.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

Over the past three decades, cancer incidence in people under 50 has risen by 79%. Adults born around 1990 now have roughly double the risk of colon cancer and four times the risk of rectal cancer compared with those born around 1950. Colorectal cancer is now the leading cause of cancer death in adults under 50. Among women under 50, cancer incidence is 82% higher than in men, up from 51% in 2002.

We don’t have a single, clean explanation for why this is happening, but there are hints…

I’ve stopped thinking about cancer prevention as something that starts at 50. It starts with at conception, and even before that with your biological parent. Certainly by the time we are in our 30s, there’s lot’s that can be done. The exposures you accumulate, your metabolic patterns, your inflammatory tone, your circadian rhythm — these are not neutral. They are writing a long term script.

The good news is that much of it is modifiable.

This is what I focus on with my patients, and what I try to practice myself.

Before we get into that, a reminder: the goal is not perfection. The goal is a life that is well-lived. Love. Connection. Community. Time in nature. With all the mistakes and imperfections along the way.

One of my favorite spots, Lake Ann Trail in Mount Baker Snoqualmie National Forest

Get your metabolic house in order first.

Insulin resistance is one of the most underappreciated cancer risk factors we have. When insulin and IGF-1 are chronically elevated, they activate the PI3K/Akt/mTOR signaling pathway, a core driver of cell proliferation and tumor growth. The epidemiological associations between metabolic syndrome and breast, endometrial, ovarian, colorectal, and prostate cancers are well-established, and Metformin, which works largely by activating AMPK and suppressing mTOR, has earned serious attention in oncology prevention trials on the strength of its anti-cancer signal in observational data. To be clear, I would never reach for a medication before adjusting diet, lifestyle and layering targeted herbs/nutraceuticals.

One of the most important numbers to know in your 30s is your fasting insulin. If it's above 6 µIU/mL, that's worth addressing. The tools are straightforward: reduce refined carbohydrate and ultra-processed food load, eat real food with real protein and high fiber, build muscle, and move your body 30min after eating.

If you are doing all of that and your numbers still are not moving, it is time to look upstream. Genetics, nutrient deficiencies, PCOS and other hormonal imbalances, and gut dysbiosis are common drivers that get missed.

Additional support worth considering at that point includes:

• Apple cider vinegar (ACV) 1–2 tbsp before meals
  Slows gastric emptying and reduces postprandial glucose excursions. Simple, effective

• Digestive bitters (gentian, dandelion, artichoke blends) 10–20 drops or 1–2 mL before meals
  Stimulate cephalic phase digestion, support bile flow, and can modestly improve postprandial glucose handling through improved digestive signaling.

• Berberine 500 mg 2–3x daily with meals
  Improves insulin sensitivity through AMPK activation and reduced hepatic glucose output. One of the most studied nutraceuticals in this category.

• Chromium (picolinate or polynicotinate) 200–400 mcg daily
  Enhances insulin receptor signaling and can modestly improve glucose control, particularly in deficiency states.

• Gymnema sylvestre 200–400 mg daily (standardized extract)
  Reduces intestinal glucose absorption and may support pancreatic beta cell function.

• Bitter melon (Momordica charantia) 5–6 oz juice or extract BID
  Insulin-mimetic effects with evidence for lowering fasting glucose and improving glucose uptake.

• Targeted probiotics (strain-specific, not generic blends)
  Focus on strains with metabolic data such as Lactobacillus reuteri, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium lactis, Bifidobacterium longum, and Akkermansia muciniphila. Gut-mediated insulin sensitivity is often overlooked.

• Psyllium husk 5–10 g before meals
  One of the most reliable tools for blunting postprandial glucose and improving insulin response. Start low and slow not to worsen GI symptoms.

• Myo-inositol 2–4 g daily
  Especially effective in insulin resistance with ovarian involvement, but broader metabolic benefits apply.

It takes some humility to question whether you actually know which foods work for your metabolism. I didn’t! Foods labeled “healthy” can spike blood sugar dramatically. Instant oatmeal, granola, smoothies, crackers, noodles, yogurts — intuition fails here regularly. I am a big fan of a month-long trial with a continuous glucose monitor (CGM). One month of data will show you more about your personal metabolic response to food, stress, and sleep than years of general nutrition advice. CGM data also captures something most people don’t expect: stress and poor sleep raise glucose independently of anything you eat.

Seeing that pattern on a graph changes behavior in a way that knowing it intellectually does not. That brings us to the next topic:

Treat sleep like the oncology intervention it is.

The International Agency for Research on Cancer classified shift work involving circadian disruption as a probable human carcinogen, this applies well beyond people working nights. Chronic late nights, variable wake times, and light exposure after dark suppress melatonin, which has anti-proliferative, antioxidant, and immunomodulatory properties beyond regulating sleep. Its suppression raises estrogen bioavailability (relevant in breast and other hormone-sensitive cancers) and reduces natural killer cell activity (immune system defense that fights cancer and virally infected cells).

A 2025 systematic review confirmed associations between circadian disruption and breast, prostate, and colorectal cancer risk. I would protect sleep timing as aggressively as I protect anything else. Consistent wake time, dim light after 9pm, and a cool dark room are the intervention.

Move in a way that mobilizes your immune system.

Exercise reduces tumor incidence by 60% in preclinical models, and the mechanism is increasingly understood. Aerobic exercise drives catecholamine-mediated redistribution of natural killer cells into circulation, enhancing immune surveillance. It also reduces systemic inflammation, lowers insulin, and improves body composition, all independently relevant to cancer risk. did a fabulous deep-dive on how movement lowers chronic inflammation, and it is worth reading alongside this.

There is also a ventilation component that is often overlooked. During sustained aerobic exercise, your respiratory rate and tidal volume increase, supporting more efficient gas exchange and clearance of volatile compounds through the lungs. This is not detox in the oversimplified sense, but it is a meaningful part of how the body handles metabolic byproducts and environmental exposures.

At a minimum, I would aim for 150 minutes per week of moderate-to-vigorous aerobic activity, with strength training twice weekly to preserve muscle mass and insulin sensitivity.

If you are otherwise healthy, you should be sweating when you are working out. Exercise is not supposed to feel easy. Adaptation requires a signal strong enough for your body to respond.

Reconsider your relationship with alcohol entirely.

There is no safe amount of alcohol for cancer. The IARC rates alcoholic beverages as a Group 1 carcinogen, the same category as tobacco. Acetaldehyde, the primary metabolite of ethanol, is directly genotoxic. Even one drink per day increases breast cancer risk meaningfully in women. About 5 to 6% of cancer cases in US adults are attributable to alcohol.

I am not going to tell you never to drink. What I will say is that alcohol should be a conscious choice with an understood tradeoff. If you drink regularly and want to lower your risk, reducing intake matters. The IARC Handbook (2024) reinforces that risk decreases with reduction, not just complete cessation, particularly for oral and esophageal cancers. The dose-response curve works both directions.

Some practical ways to approach this:
• Replace some drinks with non-alcoholic options. A well-made NA cocktail with bitters can still support digestion and the ritual of drinking.
• If you do drink, have it earlier in the evening. Alcohol close to bedtime disrupts sleep architecture and recovery.
• Something like Anti-Alcohol Complex (Life Extension) or methylene blue likely has modest benefit in supporting alcohol metabolism and reducing some of the downstream oxidative stress.
• If cravings or patterns feel hard to shift, it is worth discussing with your provider. Tools like low-dose naltrexone (LDN) may be appropriate in some cases.

Address your toxic load, especially the estrogenic ones.

PFAS, BPA, and phthalates are in water supplies, food packaging, cookware, personal care products, and receipts. They are found in nearly every human body tested. The Endocrine Society’s evidence review is unambiguous: these chemicals disrupt hormonal signaling, alter puberty timing, and are associated with breast, kidney, testicular, prostate, and thyroid cancers, as well as non-Hodgkin’s lymphoma.

There is also a reproductive biology piece worth naming.

• Women today are getting their first period earlier and having children later than previous generations. That means more uninterrupted menstrual cycles and more lifetime estrogen exposure, a direct amplifier of risk for hormone-sensitive cancers. EDCs compound this by adding synthetic estrogenic signals on top of an already higher baseline. The two trends together are more concerning than either alone.

• In men, the picture is different but equally concerning. Sperm counts have dropped by more than 50% globally since the 1970s, and phthalates and BPA are directly implicated in that decline through androgen disruption. Lower testosterone and impaired reproductive function are markers of broader hormonal dysregulation, and that same dysregulation carries cancer risk. The reproductive system is a sensitive readout of toxic load, and the signals coming from both sexes right now are worth paying attention to.

Trying to eliminate everything leads to anxiety and not much else. I would be strategic. Filter your drinking water with a reverse osmosis system, which removes PFAS and reduces microplastic load (but make sure you are adding your minerals back). Cook with stainless steel or cast iron and stop storing or heating food in plastic. Clothing is an underappreciated exposure. Most people wear synthetic fabrics for 16 or more hours a day, and microplastics shed from textiles are both absorbed through skin and inhaled. Natural fibers are worth prioritizing, especially for what you sleep in. For personal care, default to unscented everything. Fragrance is a catch-all term that can legally conceal dozens of hormone-disrupting compounds. None of these swaps is dramatic in isolation. The cumulative reduction in daily burden is where it adds up. I wrote a separate post on where to start and what to replace with here.

Build your gut microbiome deliberately.

Every 10 grams of daily dietary fiber reduces colorectal cancer risk by approximately 10%, based on dose-response meta-analyses covering more than 100 prospective studies. The mechanism runs through short-chain fatty acids, particularly butyrate, which act as HDAC (Histone Deacetylase) inhibitors, modulating gene expression in colonic epithelial cells in a way that promotes apoptosis of abnormal cells and reduces proliferation.

I would prioritize 30 or more grams of fiber daily from diverse plant sources. Eat the rainbow, eat seasonally. Diversity matters as much as quantity because different fibers feed different bacterial populations, and microbial diversity is independently associated with reduced cancer risk. The data are strongest for colorectal cancer but extend to breast as well.

My favorite summer meal: one-pan dinners.

Take your stress seriously.

Chronic stress dysregulates the HPA (hypothalamic-pituitary-adrenal) axis, drives sustained cortisol elevation, and impairs immune surveillance through multiple pathways: suppressed NK cell activity, altered T-cell function, and a pro-inflammatory cytokine profile that supports tumor microenvironment development. Stress hormones directly promote tumor progression in preclinical models, including through effects on the p53 tumor suppressor pathway. Chronic physiological stress creates conditions that favor cancer initiation and progression through documented biological pathways.

What most people miss is that stress physiology has three distinct phases, and the right intervention depends entirely on which one you are in. Test your cortisol rhythm with a 4-point salivary cortisol (Labcorp Cortisol, Salivary, 4 Specimens, test code: 004051 or Quest Diagnostics Cortisol, LC/MS/MS, Saliva, 4 Samples, test code: 19806) or a DUTCH test. Do not guess.

Phase 1: Acute / High Cortisol Cortisol is elevated, rhythm is intact but amplified. Symptoms: anxiety, wired-but-tired, difficulty falling asleep.

• Nervines to calm the nervous system: Scutellaria, Passiflora, Valerian, Humulus lupulus, Piper methysticum

• B-complex vitamins and vitamin C

• Melatonin

• Magnesium glycinate

• Exercise, meditation, deliberate rest and recreation

• Reduce caffeine

Phase 2: Chronic Dysregulation The rhythm has flattened or inverted. DHEA begins to drop. Symptoms: fatigue, brain fog, poor recovery, mood instability, early signs of metabolic and connective tissue breakdown.

• Phosphatidylserine 400mg to blunt dysregulated cortisol output

• L-ornithine 400mg/day for sleep quality and recovery

• DHEA as cortisol antagonist, dose guided by testing

• Hypericum perforatum and tyrosine if depression is part of the picture

• Chromium for glucose regulation

• Ascorbates, zinc, glucosamine sulfate for connective tissue support

• Calcium, magnesium for bone protection

• Omega-3 fatty acids for lipid metabolism and inflammation

• Strict sleep and light timing to begin restoring circadian rhythm

• Stabilize blood sugar throughout the day

Phase 3: Depletion Cortisol is globally low, DHEA is suppressed, and the system has downregulated output. Contributing factors often include history of steroid use, chronic systemic disease, nutritional deficiencies, inherited conditions such as pyroluria or pernicious anemia, and functional hypoglycemia.

This is the pattern I see in most patients by their 40s and 50s.

Symptoms: profound fatigue, salt cravings, poor immune resilience, hypoglycemia. Rest comes before everything else. Pushing through with stimulants or Phase 1 adaptogens makes this worse.

• Botanicals: Glycyrrhiza, Eleutherococcus, Rhodiola, Withania, Astragalus, Crataegus, Rosmarinus, Dioscorea, Schizandra

• Nutrients: pantothenic acid, vitamin C, vitamin B12

• Sodium chloride to support adrenal output

• Anabolic amino acids: arginine, ornithine, lysine

• Adrenal glandular support

• Graduated moderate exercise, not intense training

• Hypoglycemic diet, reduce antigenic load

The foundation across all three phases remains the same: consistent sleep, regular exercise, and structured downregulation. Pick one practice and do it every day.

Check and optimize your vitamin D.

Vitamin D is a hormone with roles in immune regulation, inflammation, and cell signaling, all directly relevant to cancer biology.

The VITAL trial (≈26,000 participants) did not show a reduction in overall cancer incidence with 2,000 IU daily (which is too low of a dose, in my option). But secondary analyses showed a 17% reduction in advanced cancers, and 38% in those with normal BMI. Across meta-analyses, vitamin D has not lowered incidence, but it has shown a modest reduction in cancer mortality, especially with daily dosing.

Observational data is consistent: low vitamin D levels are associated with higher colorectal cancer risk and worse outcomes across multiple cancers.

I do not view vitamin D as a stand-alone prevention strategy, but as a foundational terrain variable. Deficiency is common, especially in the Pacific Northwest. I routinely measure and optimize, targeting 25(OH)D ~40–60 ng/mL. For most adults, 5,000 IU daily is a practical and safe range. And, goes without saying, I prioritize vitamin D from sunlight over supplementation.

The honest version of this list.

40% of cancer cases and nearly half of cancer deaths in US adults are attributable to modifiable risk factors. For someone who has never smoked, maintains a healthy weight, exercises regularly, limits alcohol, uses sun protection, and is vaccinated against HPV and hepatitis B, lifetime cancer risk drops from roughly 40% to approximately 20-25%. The remaining risk is driven by genetics, aging, and random DNA replication errors that no lifestyle intervention fully eliminates. Going from 40% to 20-25% is a meaningful reduction in probability, achieved without a prescription.

I do not believe any of these interventions requires perfection. I believe the compounding effect of several modest changes, sustained over time, is where the protection actually lives. Start with the ones that feel most tractable, build the habits, and let them compound.

That is what I would do.

Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.

She provides medical care for Washington residents and offers global health coaching.

To schedule a free 15-minute consult, visit drkseniamalarkey.com

These are my saved hikes. The ones I keep coming back to. Don’t let the difficulty levels deter you, and remember it’s ok not to finish an hike, it’ll be memorable and beautiful regardless.

Easy / Moderate — When You Need Beauty Without the Suffering

Spirit Falls - Gorge (0.6 mi, 380 ft gain) on the Little White Salmon River near Cook is less a hike and more a steep scramble to one of the most dramatic waterfalls in the Gorge. Short, rugged, and refreshing at the end.

Artist Ridge – Huntoon Point (1.2 mi, 200 ft gain) is the one I recommend when someone says they want to get outside but isn’t sure where to start. Mount Baker Area, absurdly scenic, minimal effort. Go July through September before the road closes or in the wonder for an ultimate snowshoe/backcountry wonderland. Bonus, dog friendly!

Fremont Lookout (5.6 mi, 1,200 ft gain) at Mount Rainier is a steady, rewarding climb to a fire lookout with one of the best views of the mountain. Mid-July to October is your window.

Skyline Trail Loop (5.5 mi, 1,450 ft gain) at Paradise is wildflower season at its finest — late July and August are peak bloom.

Blue Lake (4.4 mi, 1,050 ft gain) in the North Cascades is a perfect half-day. Brilliant turquoise water, golden larches in late September. One of those hikes that makes you feel like you stumbled into a painting.

Summit Lake near Carbon River (6.1 mi, 1,300 ft gain) is a quieter gem with mountain views and far fewer crowds than the more popular Rainier corridors. August through September the trail is covered with wild blueberries and huckleberries.

Moderate/Hard — The Ones That Earn It

Snow Lake in Snoqualmie Pass (7.2 mi, 1,800 ft gain) is probably the most accessible hard-ish hike on this list. Busy for good reason. August is ideal for wild blueberry picking

Lake Valhalla (7.0 mi, 1,500 ft gain) near Stevens Pass is stunning in early fall — fewer people, cooler temperatures, the kind of quiet that genuinely resets your nervous system.

Dog Mountain (5.9 mi, 2,800 ft gain) in the Columbia River Gorge is a different kind of hard — relentlessly steep from the start, with almost no flat sections. The payoff is summit meadows covered in balsamroot in spring and wide views of the Gorge and Mount Hood. Peak bloom runs mid-April through mid-June; a permit is required during that window. One of the best wildflower hikes in the Pacific Northwest.

Kendall Katwalk (12 mi, 2,600 ft gain) deserves its reputation. The narrow ridge section is one of the most dramatic trail features in the state. Late July through September.

Ingalls Pass and Lake Ingalls (9.0 mi, 2,600 ft gain) in the Alpine Lakes Wilderness is one of the better hikes in the Teanaway and shares a trailhead corridor with Esmeralda. The pass gives you a wide open view of the Stuart Range before you drop into the lake basin. That lake — turquoise, set hard against the rock — is the payoff. No dogs past the Esmeralda junction, but lot’s of mountain goats!

Lake Ann at Mount Baker (8.2 mi, 2,150 ft gain) is one I keep returning to. The glacier views are extraordinary and the trail is manageable for most fit hikers.

Cutthroat Pass (10.0 mi, 2,000 ft gain) via the PCT from Rainy Pass on Hwy 20 is one of the better larch hikes in the state and significantly less crowded than the obvious alternatives. Late September is the window. The elevation and open ridgeline deliver views that are hard to argue with.

Hard — The Full Commitment

Mount Ellinor (6.2 mi, 3,344 ft gain) on the eastern Olympic Peninsula is steep, relentless, and worth every foot. From the lower trailhead you earn the full experience — Hood Canal, Lake Cushman, and the jagged Olympic peaks laid out below you at the summit. Upper trailhead shortens it to 3.3 miles if your knees have opinions. One of the best summit hikes on the Peninsula.

Yellow Aster Butte (7.5 mi, 2,550 ft gain) in the Mount Baker Area hits different in late September when the heather turns crimson. One of the best fall hikes in the state.

Blanca Lake (8.0 mi, 3,400 ft gain) is tough on the way up and completely worth it. That emerald glacial lake doesn’t look real.

Hidden Lake Lookout (8.0 mi, 3,300 ft gain) along Hwy 20 is one I recommend to anyone who asks for a single “best hike” in the North Cascades. Mid-July through September, check road conditions first.

Big Heart Lake (13.9 mi, 4,137 ft gain) via West Fork Foss Lakes Trail near Skykomish is one of the better hard-day or overnight options in the Alpine Lakes Wilderness. The trail passes through Trout and Copper Lakes on the way up before the final push to Big Heart. Bring a permit; Alpine Lakes Wilderness self-issue required.

Sourdough Mountain (10.4 mi, 4,870 ft gain) is genuinely hard and genuinely one of the most rewarding days I can imagine spending outside. This one asks something of you.

Jade Lake and Pea Soup Lake (20+ mi, 4,000+ ft gain) in the Alpine Lakes Wilderness deserve their own category. The trail to Marmot Lake is maintained; past that you're navigating unmaintained path, scree fields, and snow that lingers well into summer. Jade Lake is breathtaking. And, yes, the water really is that color.

Pea Soup Lake — accessed through Dip Top Gap — extends the route to roughly 22.7 miles and 5,590 feet total gain. Best treated as a two-to-three day backpacking trip, with Jade Lake as base camp the first night. My cat might have been the first cat to reach Pea Soup, who is to say!

These are the places I go when I need to remember why I do this work. Not to optimize anything. Just to be somewhere that asks nothing of me except to pay attention.

If you’ve done any of these, I’d love to hear which ones. Drop a comment : ) I’m always looking for friends on the trails and hidden gems.

The skin is the body’s largest organ. Transdermal drug delivery works precisely because the skin absorbs compounds, and it does not selectively absorb only things we intend. What sits against it for sixteen hours a day matters. This is especially true before, during, and after cancer treatment, when metabolic and hormonal pathways are already under stress.

The problem with synthetic fabrics

Most clothing is polyester, nylon, acrylic, or spandex, often blended. The fibers themselves are one issue. The finishing chemicals applied during manufacturing are another.

Fabrics are routinely treated with:

• Formaldehyde-releasing resins for wrinkle resistance

• PFAS for water and stain repellency

• Azo dyes that can release carcinogenic aromatic amines

• Phthalates as softeners and plasticizers

• Flame retardants, particularly in children’s clothing and sleepwear

• Nonylphenol ethoxylates, weak estrogen mimics left over from textile processing

For anyone navigating a hormone-driven cancer, including ER-positive breast, endometrial, or prostate cancer, reducing exogenous compounds that interact with estrogen or androgen pathways is a reasonable clinical goal. Fabric is part of that conversation.

There is also the microplastic issue. Synthetic fabrics shed microplastics with every wash and every wear. These are now measurable in human blood, placenta, and breast milk. We do not yet have a clean dose-response story, but I am not waiting for one.

Where to start

Prioritize what touches your skin the longest and most directly:

• Underwear and bras

• Sleepwear (eight hours of uninterrupted skin contact in a warm environment that increases absorption)

• Workout clothing, which is almost universally polyester or nylon, often with added “antimicrobial” chemical treatments

• Bras, chest-area and underwear and garments (chest and pelvic areas are the largest area of lymph drainage)

Brands worth knowing

For underwear and everyday basics: Pact and Mate the Label are GOTS-certified organic cotton at an accessible price point. TomboyX, Odd Body, and Skin Worldwide cover inclusive sizing in cleaner materials. Jungmaven and Groceries Apparel make organic cotton and hemp basics. Le Bon Shoppe for softer knits and loungewear. DONNI layers in beautifully here too, with soft cotton and silk pieces that wear like a second skin.

For sleepwear: Lunya makes washable silk, which is best for temperature regulation and makes going to bed feel like luxury every night.

For sleepwear and bedding: tbco is my favorite for fun-pattern-cottons that invite layering and personal styling. Sønderhaus is another worth knowing, Scandinavian linen loungewear and bedding that reads calm and considered.

For activewear: Woolly Clothing and Organic Basics both have natural fiber options. Icebreaker and Smartwool make merino wool activewear that works well for yoga, walking, and lower-intensity training.

For yoga and studio wear specifically, Indigo Luna, HARA the Label, Studio K, Bodypeace Bamboo, bai active, and Pinky and Kamal are all doing natural and low-tox fabrics well. Reprise Activewear and OLESSA round this category out.

A note on activewear: Bamboo clothing is often marketed as “natural,” but most bamboo fabrics (viscose or rayon) are heavily processed with chemical solvents. By the time they reach your skin, they are far removed from the original plant. Tencel (lyocell) is a reasonable middle ground. It is semi-synthetic, but made in a closed-loop process with significantly less chemical exposure than conventional rayon. If you can, choose less processed fibers like cotton, wool, hemp or linen. They carry a lower chemical burden and tend to be more breathable.

For elevated staples: Assembly Label, Nude Lucy, aere, and Posse are worth exploring for linen and quality cotton. ARCAA Movement, Rowie the Label, and Maurie and Eve lean into quality cottons with a clean aesthetic. La Relaxed, Wear Kent, and SKFK round out this category. Quince remains one of the most accessible options for linen, organic cotton, and cashmere without the luxury price tag. On the opposite side, babaà is worth the hype, they make hand-knit cotton and wool sweaters out of Spain that last for years and get better with wear, but are expensive! Which brings me to my next topic.

The case for buying second-hand

Buying a used linen blazer or silk blouse is a better choice than buying new natural fiber, because it removes demand for new production entirely and significantly reduces your exposure to finishing chemicals, which break down with repeated washing over time. It also cuts textile waste and microplastic pollution in a way that buying new, even from the best brands, does not.

For online resale with a sustainability focus: Noihsaf Bazaar curates higher-quality natural fiber pieces and is worth bookmarking. Depop skews younger but has strong vintage linen and wool finds if you search by material. ThredUp is the highest volume option and has a filter for fiber content. The Real Real is useful for silk, cashmere, and wool at the higher end. Vestiaire Collective for European natural fiber brands that do not always make it to US resale markets.

If you are in Seattle, I shop Hoste, Ere, Editor Consign, Creature Consign, Friend Museum, and Bon Voyage Vintage specifically for natural-fiber finds. The quality of what comes through consignment in this city is genuinely good.

Certifications worth knowing

OEKO-TEX Standard 100 means the finished fabric has been tested for a list of harmful substances. GOTS certification covers the full organic supply chain. Both are searchable on brand websites and worth verifying before you buy.

Avoid labels that read “wrinkle-free,” “stain-resistant,” “water-repellent,” or “antimicrobial.” These almost always signal chemical treatments.

The bottom line

You do not have to replace your entire wardrobe… but going forward you should start investing in natural fiber clothing. Start with sleepwear, then underwear, then workout clothing. Build from there at whatever pace makes sense. The goal is not perfection. It is a lower total exposure burden over time, and these are some of the easiest swaps to make.

There is a moment I see in almost every patient on long-term hormonal therapy. They sit down. Scans are stable. The intensity has eased. I ask how they are really doing.

Joint pain waking them at three in the morning. Sleep that has not been right in months. Sex that has quietly disappeared. A body that feels unfamiliar in ways they do not have words for. And no one on their care team has offered them anything except a refill.

This is what finishing active treatment actually looks like for a lot of people. It is less like stepping back onto solid ground and more like kite surfing. The initial pull of the wind gets you moving, sometimes fast, sometimes forcefully. From the outside, it can look controlled, even smooth. But underneath, you are constantly adjusting. Balancing. Reading conditions that shift without warning. And no one hands you a manual for how to do that part well.

Video of my husband enjoying everything that PNW has to offer, including year-round cold plunges to support immune function, vagal tone, and overall vitality.

Aromatase inhibitors. Tamoxifen. ADT. Long-term targeted therapy. Maintenance immunotherapy. These medications extend survival and reduce recurrence risk. They also reshape nearly every system in the body. The downstream effects deserve the same clinical attention as the treatment that came before them.

That is what this post is about.

Part One: Endocrine Therapy

The long game with aromatase inhibitors and tamoxifen

The evidence for aromatase inhibitors and tamoxifen in hormone receptor–positive breast cancer is strong. They meaningfully reduce recurrence risk. What is becoming more nuanced is the question of duration and who truly benefits.

The field is actively re-examining how long therapy should be continued. The ABCSG-16/SALSA trial found no advantage to five years of extended anastrozole over two years, with higher fracture risk in the longer arm. Similarly, the IDEAL trial showed no superiority of five years of extended letrozole compared to two and a half years. These trials challenge the assumption that longer is always better and open the door to more individualized decisions based on risk profile, tolerability, and patient goals.

I discuss this with patients not to discourage endocrine therapy, but to ensure duration decisions are guided by current evidence rather than inertia. I explore this in more detail in a previous article here.

What I actively manage during endocrine therapy

Bone health. Aromatase inhibitors accelerate bone loss, and tamoxifen in premenopausal women can reduce bone density as well. I get a baseline DEXA scan at the start of AI therapy and recheck at two years. Vitamin D should be optimized to 70 to 100 ng/mL, not just flagged as sufficient at 20. Calcium from food first, supplemented to 1000 to 1200 mg daily if dietary intake is low, more is not better. Weight-bearing and resistance exercise are part of the bone protection plan. If a patient crosses into the osteopenia territory, I want to start support right away.

Strontium citrate supports bone health through a dual mechanism that most supplements cannot claim: it both stimulates osteoblast activity and inhibits osteoclast-mediated resorption, acting on both sides of the remodeling cycle simultaneously. The important caveat is that strontium incorporates into bone mineral and artificially inflates DEXA readings, so apparent gains in bone density overestimate true structural improvement. This is not a reason to avoid it. It is a reason to interpret the DEXA correctly, which means applying a strontium correction factor and tracking trends with that in mind rather than reading the numbers at face value. My favorite product is this Bone Builder Pack.

Metabolic health. Tamoxifen carries specific risk of fatty liver, elevated triglycerides, and insulin resistance that is undermonitored in most practices. Insulin resistance develops well before fasting glucose or HbA1c begin to shift, which is why I check fasting insulin at baseline and every six to twelve months rather than waiting for the standard markers to flag a problem. A full lipid panel rounds out the picture. A Mediterranean-forward diet combined with consistent resistance training can offset many of these effects. For liver health specifically, I assess for fibrosis using FibroScan or FibroTouch in patients with ongoing tamoxifen use, particularly when liver enzymes are trending or fatty liver is suspected. Both use transient elastography to measure liver stiffness non-invasively. FibroScan is more widely available; FibroTouch is an alternative worth asking about if FibroScan is not accessible in your area. For hepatic support I regularly use Thorne SAT (Silymarin, Artichoke, and Turmeric) and Heron Botanicals Liver Support as part of a broader liver protection strategy. When insulin resistance is already present, a metformin conversation with the prescribing oncologist is worth initiating, given accumulating evidence for both metabolic protection and potential cancer-related benefit.

Joint pain. Aromatase inhibitor-related arthralgia is the most common reason patients stop endocrine therapy early, and it is undermanaged. Consistent exercise, specifically aerobic movement combined with strength training, has some of the strongest evidence for reducing AI-related joint pain and should be the first recommendation, not the last. I check omega-3 status and typically recommend two to three grams of EPA plus DHA daily, optimize vitamin D and magnesium, and assess inflammatory markers. Acupuncture has RCT support for this specific indication. When joint pain remains unmanageable, switching between non-steroidal and steroidal AI agents is sometimes effective.

Sleep and mood. Hot flashes and night sweats are a primary driver of mood dysregulation, cognitive fog, and relationship strain on endocrine therapy. I treat them as a clinical target, not a complaint to tolerate. Cognitive behavioral therapy for insomnia (CBT-I) is the gold standard for sleep and should come before sedative hypnotics. For hot flashes, venlafaxine, escitalopram, and gabapentin all have evidence as nonhormonal options and are underused. Melatonin and magnesium glycinate are low-risk starting points I use routinely. For an in-depth conversation about restoring sleep, read my earlier article.

Sexual health. Vaginal dryness, painful intercourse, loss of libido, and changes in body image are common on endocrine therapy and almost universally underaddressed. I raise it with every patient because most will not raise it themselves. Local vaginal estrogen has minimal systemic absorption and a growing evidence base supporting safety even in ER+ breast cancer, though it always warrants a direct conversation with your oncologist. Non-hormonal options like vaginal hyaluronic acid and Replens are useful adjuncts, but let's be honest about what they do: they add moisture and lubrication. They do not address the underlying tissue changes driving the problem. Pelvic floor physical therapy works at a deeper level and is significantly underutilized. Ospemifene is a non-estrogen oral option for painful intercourse that acts at the tissue level and is worth raising if other approaches are not enough.

Two areas that almost never come up

’s recent deep dive into tamoxifen’s systemic effects covers territory worth flagging. The bone story is more paradoxical than most patients realize: tamoxifen is bone protective in postmenopausal women but causes meaningful bone loss in premenopausal women, an effect made significantly worse by adding ovarian suppression. Two monitoring areas get almost no airtime in standard oncology visits. Eye health: retinopathy occurs in up to 12% of patients on standard dosing beyond two years, which calls for a baseline ophthalmologic exam and OCT screening every six months after year two. Oral health: tamoxifen accelerates periodontal disease and alveolar bone resorption in ways most patients are never warned about. Tell your dentist what you are on. It matters.

Periodontal disease is highly influenced by the oral and gut microbiome, which is often disrupted during cancer treatment and endocrine therapy. Shifts toward a more inflammatory microbial profile can accelerate gum disease, bone loss, and systemic inflammation. From a naturopathic perspective, this is modifiable. I focus on mechanical care first: twice-daily brushing, flossing, water flossers, tongue scraping, oil pulling, and regular cleanings. I often use tools such as Simply O3 Pure Organic Ozonated Olive Oil, Simply O3 Ozone Pulling Solution, and Biocidin toothpaste as part of a broader oral care strategy. Then I layer in microbiome and tissue support: oral probiotics containing Lactobacillus reuteri, Lactobacillus brevis, Lactobacillus salivarius NK02 or/and Streptococcus salivarius, xylitol to reduce pathogenic biofilms, and antimicrobial botanicals when appropriate. Nutritionally, vitamin C, vitamin D, vitamin K2, magnesium, zinc, CoQ10, omega-3s, collagen support, and a polyphenol-rich, low-sugar diet all help support connective tissue integrity, microbial balance, and healthier periodontal outcomes over time.

Part Two: ADT

The metabolic cost of androgen deprivation therapy

Androgen deprivation therapy extends survival and also fundamentally alters the hormonal environment in nearly every organ system. I see metabolic syndrome develop quickly in men on ADT: rising fasting glucose, insulin resistance, central weight gain, lipid shifts. Bone density drops. Cardiovascular risk increases. Cognitive function changes in ways many men never connect back to treatment.

This warrants proactive management from the start, not reactive intervention after damage has accumulated. Structured resistance training has the strongest evidence base for counteracting these effects and should be in place by the first month of therapy. I pair that with metabolic monitoring every three to six months, a baseline DEXA followed by annual rechecks, vitamin D optimization, and cardiovascular risk assessment in collaboration with primary care or cardiology when indicated.

The psychological dimension deserves direct attention. Identity, sexuality, mood, and self-perception all shift during ADT, often in ways men are not warned about. Silence around it makes it harder to manage, not easier.

The estradiol piece most people miss

Most of ADT side effects are not from testosterone suppression itself but from the loss of estradiol that follows. Men produce estradiol by converting testosterone, and when testosterone is suppressed to castrate levels, estradiol disappears with it. Estradiol is the primary regulator of bone turnover in men and a key player in thermoregulation and metabolic signaling. Hot flashes, brain fog, bone loss, fatigue: these are largely estradiol-deprivation symptoms. ADT creates a dual hormone deprivation state, and recognizing this reframes these effects as predictable endocrine consequences rather than vague, unavoidable side effects. The evidence is strongest for vasomotor symptoms and skeletal health, with more mixed data for cognition and mood.

I really enjoyed ’s piece in , which interviews Dr. Paul Schellhammer (former AUA president and prostate cancer patient himself), makes the case for transdermal estradiol as an alternative ADT strategy. High-dose transdermal estradiol can suppress testosterone to castrate levels while simultaneously restoring the estradiol that standard LHRH agents eliminate. The UK PATCH trial demonstrated comparable testosterone suppression, markedly fewer hot flashes, preserved bone density, and more favorable metabolic parameters, at the cost of higher rates of gynecomastia. The historical cardiovascular concern with estrogen turned out to be delivery-route specific, not estrogen specific, and long-term outcomes appear comparable. Transdermal estradiol remains outside standard guidelines and is not FDA-approved for prostate cancer, which continues to limit adoption more than the underlying biology does. For men struggling with ADT side effects, it is worth raising with their oncologist.

Managing inflammation on ADT

Inflammation drives many ADT-related changes and is often under-monitored. I track hs-CRP, fasting insulin, HbA1c, and triglyceride-to-HDL ratio as a baseline cardiometabolic picture, adding d-dimer, fibrinogen, ferritin, and LDH when I need a broader view. When I need deeper resolution, cytokine panels including IL-6, TNF-alpha, and IL-1beta help characterize the pattern of immune activation. The foundation remains lifestyle: resistance training with aerobic movement, a Mediterranean-forward high-fiber diet with adequate protein, sleep optimization, and minimizing alcohol and ultra-processed foods. I most often supplement with omega-3s, curcumin, EGCG, magnesium, vitamin D, and targeted polyphenols. Quercetin, PEA, and boswellia are in regular rotation, individually or in combination formulas. Some of my most commonly used products are Xymogen Cytokine Balance, Cymbiotika Inflammatory Health, or Vital Nutrients BCQ.

In selected cases I discuss off-label options with the oncology team: metformin for insulin resistance, statins when lipid-driven inflammation is present, and low-dose naltrexone for immunomodulation. The goal is not perfection. It is to keep inflammatory signaling as low as possible while patients remain on therapy.

A note on adherence

The adherence data for endocrine therapy are sobering. Many patients stop early because side effects become intolerable. I do not see this as a compliance failure. I see it as a signal that the downstream effects of these medications are not being managed adequately.

A medication can only help if someone can stay on it. My role is to make that possible. And when it is not, I want to be the person helping patients have an informed conversation with their oncologist about dose adjustment, switching agents, or reconsidering duration based on their specific biology, risk profile, and goals.

What should be in place

If you are on an aromatase inhibitor or tamoxifen:

• Baseline DEXA before starting, recheck at two years. If osteopenia is found, start bone support, supplements first if no improvement in 6 mo (yes, a good quality supplement can work that quickly!) pivot to the bisphosphonate or denosumab conversation before density declines further.

• Vitamin D optimized to at least 70 ng/mL. Being told you are “normal” at 30 is not the same as being optimized.

• Fasting insulin, HbA1c, and full lipid panel at baseline and every six to twelve months. Fasting insulin catches insulin resistance years before glucose or HbA1c shift.

• Liver enzymes at baseline and every six to twelve months on tamoxifen. If they trend up, ask about FibroScan or FibroTouch.

• On tamoxifen: baseline eye exam with OCT, then OCT every six months after year two.

• A structured exercise plan from day one that includes resistance training. This is not optional.

• A management plan for joint pain, hot flashes, and sleep disruption if any are affecting your daily life. These are treatable. Ask if you have not been offered anything.

• A direct conversation about sexual health. If your provider has not raised it, you might need a new provider?

• Tell your dentist you are on tamoxifen.

If you are on ADT:

• Baseline DEXA, fasting insulin, HbA1c, lipid panel, CMP, testosterone, and estradiol before starting.

• Structured resistance training in place by month one.

• Metabolic monitoring every three to six months including inflammatory markers.

• Annual DEXA recheck. If bone density is declining, address it before a fracture.

• Vitamin D optimized to at least 70 ng/mL.

• Cardiovascular risk actively co-managed with primary care, cardiology or integrative provider.

• Hot flashes, sexual health, and mood addressed directly. These are hormonal consequences, not incidental complaints.

• If side effects are significantly affecting quality of life, ask your oncologist about transdermal estradiol or an alternative ADT strategy (decreased dosing, pulsed dosing etc.)

• Psychological support on the table from the start, not offered only when things fall apart.

This new terrain may be unfamiliar, but you do not have to navigate it alone.

Part 1 of this series covers the acute transition when active treatment ends. Part 3 addresses the long tail of uncertainty with modern immunotherapy and targeted therapies.

I am intentionally keeping these articles free for the first two weeks because everyone deserves access to clear, practical answers, including specific strategies, products, and recommendations. If you found this helpful, consider sharing it during this window with someone who might benefit.

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Educational content only. Not medical advice. For individualized care, visit drkseniamalarkey.com

Iodine helps regulate estrogen signaling. It downregulates estrogen receptors, supports healthier estrogen metabolism, and stabilizes estrogen-sensitive tissue. That is why it repeatedly appears in the clinical literature around fibrocystic breasts, breast cysts, breast dysplasia and hyperplasia, ovarian cysts, heavy periods, ovulation pain, endometriosis, fibroids, PMDD, and symptoms of perimenopause..

A 2024 review also found iodine supports metabolic health — reducing inflammation, improving insulin sensitivity, and modulating the microbiome.

Image from PMID: 38567251

Before you try it, one non-negotiable: test thyroid antibodies first.

If anti-TPO or anti-thyroglobulin antibodies are positive, stay at or below 300 mcg. Especially avoid potassium iodide, which is more likely to trigger or worsen Hashimoto’s. Stop if thyroid function changes.

If antibodies are negative, 1,000–3,000 mcg of molecular iodine (I₂) is a reasonable starting point. Molecular iodine is significantly gentler on the thyroid than potassium iodide. Pairing with selenium adds further thyroid protection. Higher-dose iodine is not appropriate during pregnancy or breastfeeding.

Topical application. For breast pain and fibrocystic changes specifically, painting Lugol’s iodine solution directly on breast tissue is a traditional naturopathic approach. Breast tissue concentrates iodine, and transdermal application delivers it locally while reducing systemic thyroid exposure. Avoid the nipple and areola.

Food sources: seafood (cod, shrimp, and tuna are particularly high), egg yolks, dairy from pasture-raised cows, iodized salt, navy beans, potatoes with skin, cranberries, prunes, and seaweed — though kelp also contains bromine, which competes with iodine uptake.

If this was useful, share it with a woman in your life who's been told her breast pain or cysts are "just hormonal." There's often more to the story.

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