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VO2max is the maximum rate at which you are able to take up oxygen from your lungs and transfer it out of your blood to the tissues that need it.

You can test your VO2max at an exercise science lab for some $75-250 a pop, or you can get a device like a VO2Master for just under $8000, and then you can predict your lifespan or optimize your workout for VO2max to lengthen your life.

There’s just one problem: none of the studies used to make this claim have measured VO2max. In fact, they don’t even claim to have predicted VO2max.

This is educational in nature and not medical or dietetic advice. See terms for additional and more complete disclaimers.

In This Article

• The Short Answer

• What The Studies Actually Measured

• How Do These Tests Relate to VO2max?

• What the Mortality Papers Actually Show

• Do These Papers Even Claim to Measure or Predict VO2max?

• Why Does It Matter?

• Why Does Bad Data Generate Stronger Correlations?

• Other Mortality Data

• So What Do We Do With This?

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Masterpass members can download this article to print it out and read it in natural lighting as recommended in What Everyone Should Be Doing For Their Health here:

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The Depression Protocol has been updated on page 12 to include four suggestions for people who experience negative side effects from increasing their protein to the suggested target.

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This article explains the scientific rationale behind it.

Principally, it is based on hundreds of randomized controlled trials of psychotherapy, exercise, and 44 different nutritional supplements.

This body of literature has twelve times as many trials and five times as many participants as the placebo-controlled SSRI trial literature, and the effect sizes are larger, in most cases the risk of publication bias is no larger, and the nature of these strategies allows many of them to be safely combined for better results, whereas doing so with drugs just increases the risk of serious side effects.

It also refers to trial literature for other non-drug approaches such as repetitive transcranial stimulation and electroconvulsive therapy, though not everything makes the cut.

This article is reserved for Masterpass members.

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Signs you need to pay attention to your glycine status to fix a health problem include any of the following: anxiety, poor sleep (lack of deep sleep, waking up in the middle of the night, trouble falling asleep or long sleep latency), poor memory, excessive startle response, increased muscle tension and discomfort, poor muscle tone leading to poor posture, poor joint alignment, poor joint health, poor skin quality, excessive aging of the skin, osteopenia or osteoporosis, slow wound healing, intolerance to methylated B vitamins, intolerance to glycine supplements, blood sugar problems, brain fog, lack of alertness, unusually persistent hiccups or episodes of temporary breathing cessation (during the day or as sleep apnea), attention deficit, hyperactivity, schizophrenia, weakness, jerks, or seizures.

One or more of these are sufficient to suspect the relevance of glycine. Some are common, others are rare and extreme. No one will have all of them.

Animal experiments show glycine extends lifespan, so if you are healthy and simply looking to optimize for longevity, this alone should be a reason to optimize your glycine status.

Glycine supplementation is very safe according to existing studies. However, many people anecdotally report adverse effects from glycine supplements such as insomnia, overstimulation, or headaches.

Even if you do not notice any adverse effect from a glycine supplement, it could be generating oxalate, which is a mitochondrial toxin and probably nullifies the benefits of glycine toward lifespan. Oxalate could crystallize in the kidney, joints, or brain, contributing to long-term loss of function in those organs over time.

Hypothetically, excess glycine could also generate methylglyoxal, which could aggravate oxidative stress, accelerate aging, and cause diabetes.

Most glycine is synthesized from carbohydrate using an input of nitrogen from the amino acid glutamate and an assortment of vitamin and mineral cofactors. Thus, it is important to consume enough protein and carbohydrate to maintain endogenous glycine synthesis, and it is probably much safer to default to promoting robust endogenous synthesis than to jump straight into taking glycine supplements.

The ability to tolerate glycine supplements depends on robust nutritional support for two primary ways to convert glycine to carbon dioxide instead of oxalate, ensuring also that excessive glycine does not accumulate, which could lead to an awkward mix of excess neurological excitation and inhibition and general neurotoxicity.

This Article Accompanies The Glycine Protocol

The Glycine Protocol is my 7-Page quick guide to optimizing glycine status that guides you step-by-step through all the reasons your glycine levels or glycine tolerance could need improvement.

Get the Glycine Protocol here:

Click Here to Get the Glycine Protocol

This article is reserved for Masterpass members. You can learn more about the Masterpass here. You can subscribe to the Masterpass here.

In This Article

• Download the article as a printable PDF.

• Glycine: So Simple, So Important

• What We Can Learn From Human Trials

• What We Can Learn From Disorders of Glycine Synthesis, Clearance, and Receptor Function

• The Relation of Glycine to Serine, Glucose, and Its Derivatives

• How the Conversion of Glucose to Glycine is Regulated

• The Importance of Total Protein

• How We Break Down Excess Glycine

• How We Dispose Of Extra One-Carbon Units

• Balancing Methionine and Glycine

• The Possible Conversion of Glycine to Methylglyoxal

This is educational in nature and not medical or dietetic advice. Any products linked herein may be affiliate links. See terms for additional and more complete disclaimers.

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Crohn’s disease is one of two disorders grouped together as inflammatory bowel disease (IBD), the other being ulcerative colitis. Ulcerative colitis exclusively impacts the colon, whereas Crohn’s can impact any part of the gastrointestinal tract from mouth to anus, though the ileum and proximal colon (that is, the last section of the small intestine and first section of the large intestine) are the most often affected. In ulcerative colitis, inflammation is limited to the mucosa, the mucus-rich superficial layer of the inside of the gut. In Crohn’s, by contrast, the inflammation is considered “transmural,” meaning that it can be found in every layer of the gut tissue, but it is also characterized by “skip areas” where diseased sections of the gut are interspersed by normal healthy sections.

The transmural nature of Crohn’s leads to laying down of scar tissue and the consequent narrowing of sections of the gut, known as strictures, which do not usually occur in ulcerative colitis. Recent research suggests that strictures are driven in part by adipose tissue surrounding the diseased intestinal tissue, possibly as a means of preventing bacterial translocation that could lead to abscesses or sepsis, which causes the space inside the intestine, known as the lumen, to become narrowed. This process is called “creeping fat.”

This diagram summarizes some of the basic abnormalities found in the gut tissue in association with Crohn’s:

The microbiome is altered in a negative fashion associated with low microbial diversity, low butyrate production, and low presence of its receptor GRP 43; bacteria become abundant that adhere to and/or degrade the protective layer of mucus, form biofilms, and move through the intestinal cells to the deep layers of the gut; there is loss of tight junctions (TJ) that form the gut barrier and consequent increases in intestinal permeability; there are decreased antimicrobial peptides known as defensins; and there are decreased regulatory T cells (Tregs) that keep inflammation in check and a proliferation of Th17 cells, a form of helper T cell associated with autoimmune conditions.

The causation of IBD is usually stated as involving an interaction between genetic susceptibility, the microbiome, and the immune system. It is probably better stated as an interaction between genetic susceptibility and diet with a completely unappreciated but very likely involvement of joint misalignments putting pressure on the gut, where the interaction between the microbiome and the immune system play intermediate roles in translating these factors into the manifestation of the disease.

In This Article:

• Overview: Epidemiology of Crohn’s, Pharmacological Treatment, Surgical Treatment

• The Role of the Gut Microbiota

• Dietary Management of Crohn’s

• The Role of Unabsorbed Iron in Hurting the Microbiome

• Genetic Risk Factors for Crohn’s

• The Contribution of Mitochondrial Dysfunction

• What Is the Ultimate Cause of Crohn’s?

This Article Accompanies The Crohn’s Protocol

How to Heal From Crohn’s Disease is my four-page quick guide that serves as a complete strategy to induce and maintain remission from Crohn's disease using diet and supplements.

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• obesity

• diabetes

• fatigue

• any psychiatric or neurological problem, difficulty sleeping, muscle tension, or excessive startling

• any issues with allergies or histamine

• nausea and vomiting, including but not limited to pregnancy

• “hangriness” that is not verifiably due to low blood sugar and resolved by stabilizing blood sugar

• diarrhea, excessive gastrointestinal transit time

• heart palpitations, twitches and spasms, chronic pain, tremors

• high estrogen, low testosterone, any problems that appear as high estrogen or low testosterone but are not accompanied by the expected changes in those hormones

• petechiae, purpura, cancer, anything resembling hypoxia such as blue hands and feet upon standing

• any sulfur-related odors such as rotten eggs or matches

• any form of intolerance to any dietary or supplemental component that contains sulfur anywhere in its structure, like thiamin or lipoic acid

• or any intolerance to any of the following: fasting, fasting-mimicking diets, ketogenic diets, any kind of catabolic state, B6, calcium, riboflavin, or CoQ10.

This article explains the science behind the Sulfur Protocol. The Sulfur Protocol is what to use if you want practical tips to solve the problems listed above. You can get the Sulfur Protocol here:

Click Here to Get the Sulfur Protocol

If you want the science, keep reading.

The Three Problematic Sulfur Compounds

The three sulfur compounds we care most about are hydrogen sulfide (H2S), sulfite, and S-sulfocysteine.

H2S is an essential “gasotransmitter” that contributes to vasodilation, which can lower blood pressure and cause erections but also cause headaches. It is central to the hypoxia response, which prevents anemia and raises sex hormone production, but also drives cancer into a more aggressive phenotype and causes abnormal blood vessel growths. It promotes fat storage, which for a given caloric balance prevents diabetes but can make it hard to lose weight. At high concentrations, H2S becomes unambiguously harmful: it displaces oxygen on hemoglobin, and it displaces oxygen in complex IV of the respiratory chain. This constitutes poisoning, and, at its extreme, it can be lethal.

Sulfite is formed from H2S on the way to producing either sulfate or S-sulfocysteine. Sulfite appears to have no necessary role except by way of being an intermediate. It depletes B vitamins. It acts as a triple mitochondrial toxin by inhibiting two enzymes in mitochondrial energy metabolism and making mitochondria lose control over what substances take in. It depletes NADPH, which causes oxidative stress, messes with neurotransmitters, destroys sex hormone synthesis and is generally catabolic.

S-sulfocysteine is likely a normal excitatory neurotransmitter, acting as a sidekick to glutamate the way glycine and another sulfur compound, taurine, act as a sidekick to the main inhibitory neurotransmitter GABA. However, this also means it can contribute to anxiety, chronic pain, sensory overstimulation, muscle tension, sleep disruption, heart palpitations, and neurodegeneration.

Exploring the evidence for the different effects of these compounds requires an understanding of the different enzymes involved in their metabolism. We therefore consider the biochemical pathways first, and address the effects of dysregulation in “Exploring the Effects of Sulfur Metabolism Dysregulation” toward the end.

In This Article

• How These Sulfur Compounds Are Produced

  • Endogenous Sulfur Catabolism

    • Regulation and Cofactors for Endogenous Synthesis and Clearance

    • The Main Strategies for Shutting Down Sulfur Catabolism

    • Nutritional Strategies for Enabling Safe Sulfur Catabolism

  • H2S Production in the Gut

    • Why This One Specific Fruit May Help

    • Sulfur Amino Acid Restriction: A Last Resort

    • Sulfur-Rich Vegetables and Sulfur-Inclusive Supplements

• Exploring the Effects of Sulfur Metabolism Dysregulation

  • Nausea, Vomiting, Abnormal Blood Vessel Growth, Hypoxia, CoQ10, and H2S

  • Pregnancy and the Menstrual Cycle: Nausea, Vomiting, and More

  • H2S, Vasodilation, Flushing, Headache, and Diarrhea

  • Sulfite and Allergies

  • Sulfite and Testosterone

  • S-Sulfocysteine, Overstimulation, Palpitations, Pain, and Psychiatric Illness

  • Sulfite and Mitochondrial Dysfunction

  • H2S, Obesity, and Diabetes

• Special Concerns About Molybdenum Cofactor Synthesis

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This means oxalate could be sapping your energy and causing your blood sugar problems.

Oxalate is also a powerful inhibitor of D-lactate dehydrogenase. D-lactate is a normal intermediate in human energy metabolism but if it increases in circulation it is neurotoxic and an impairment in its clearance could raise methylglyoxal levels, which would contribute to diabetes and cardiovascular disease.

Oxalate levels in autistics are tripled, suggesting oxalate may contribute to the neurological dysfunction of autism.

As covered below, oxalate crystals have been found in human brains, offering an explanation for neurological effects that go beyond metabolic disturbances.

Oxalate also inhibits the delivery of iron to cells. It has been suggested that oxalate rises high enough to cause anemia in autism.

Oxalate also causes kidney stones. Oxalate kidney stones can probably be largely prevented by maintaining urine pH at 6.5 or slightly higher, providing oxalate levels stay within the normal range.

Sally Norton collected anecdotal reports of oxalate sensitivity in her book Toxic Superfoods. They include trouble swallowing, acid reflux, and other types of gastrointestinal distress; fatigue, weakness, brain fog, trouble with bodyweight, slow healing; rashes, migraines, hot flashes, cold intolerance, arrhythmias, respiratory problems, light sensitivity, clumsiness, spasms, stiffness, joint problems, or bleeding gums; watery, itchy, or dry eyes; ringing or buzzing in the ears; genital and pelvic discomfort including pressure, soreness, itching, redness, blistering, or stinging; incontinence, and cloudy, sediment-filled, or powdery urine.

You may come across high oxalate levels on a Genova ION + 40 if you are using the Comprehensive Nutritional Screening.

I recently covered how seed oils might be behind your oxalate problem, and how biotin, folate, and B12 might help in oxalate detoxification, in these articles:

• Are Seed Oils Behind Your Oxalate Problem?

• Can Biotin Help Detoxify Oxalate?

• Can B12 and Folate Help Detoxify Oxalate?

In this article we talk about whether carbs could be causing your oxalate problem and whether sugar and sugar alcohols could making an independent contribution.

Glucose can be converted to oxalate. Fructose and sugar alcohols have peculiarities in their metabolism that may strongly influence the degree to which they are converted into oxalate. Yet, carb restriction could under some circumstances enhance the synthesis of oxalate. So, some people may find their oxalate goes up from eating carbs, while others may find it goes up when they restrict carbs.

In this article we look at how to know if carbs, sugar, or sugar alcohols are behind your oxalate problem and what to do about it.

This is educational in nature and not medical or dietetic advice. See terms for additional and more complete disclaimers.

In This Article

• The Short Answer

• Affluent Diets and Xylitol Infusions

• The Biochemistry of Carbs and Oxalate

• Experimental Evidence That Carbs Generate Oxalate

• Reconciling the Evidence

• Oxalate Metabolism MUST Be Dynamic

• Conclusions: Conversion of Carbs to Oxalate Depends on Context

• Energy Status as a Regulator of the Oxalate Shunt From Glycolysis

• Could a Low-Carbohydrate Diet Raise Oxalate?

• The Bottom Line

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Dr. Mark Hyman lists it as the best way to clean up old mitochondria and create new ones, central to fixing the feeling of having no energy. Hyman has endorsed Mitopure, the major brand behind the product, as “a real scientific breakthrough. It’s the first product to unlock a precise dose of purified urolithin A.”

Dr. Rhonda Patrick lists it as a central way to address age-related mitochondrial decline.

The Swiss company Amazentis makes Mitopure. They developed it in conjunction with the Swiss Federal Institute of Technology de Lausanne, protected it with 56 patents, and launched a long-term research program on it. “At our core,” they write, describing the purpose of their research program, “we stand against pseudoscience.”

A 2016 paper in Nature Medicine by Amazentis authors launched the mechanistic claims that urolithin A lengthens lifespan in worms and leads to increased endurance and strength in rodents by stimulating mitophagy. Mitophagy is the clearance of bad mitochondria to make way for new, freshly made mitochondria.

Ever since this paper was published, nearly every other paper and review that studies urolithin A cites it as foundational evidence that stimulating mitophagy is its central mechanism of action.

Amazentis-affiliated papers love to call urolithin A a “first.” It is a “first in class” natural plant-based stimulator of mitophagy. In 2019, they published the “first-in-human” randomized, double-blind, placebo-controlled trial with urolithin A.

According to Amazentis-affiliated randomized controlled trials, four weeks of 500-1000 milligrams per day of urolithin A has a similar impact on mitochondrial health as ten weeks of aerobic exercise or twelve weeks of high-intensity interval training.

Better yet, these trials show that 1000 milligrams per day of urolithin A for four months will make you 12% stronger and increase your VO2 max by 14% without even exercising!

Most urolithin A papers take the mitophagy claims at face value without probing deeper into what urolithin A is doing at a mechanistic level. Close examination of the foundational 2016 paper suggests it is stimulating more fundamental pathways shared by other polyphenols, and these include inhibition of complex I of the mitochondrial respiratory chain.

That puts urolithin A into the class of “Good-For-You Toxins” that I described in my Hormesis Lesson, where a little bit of something bad for our cells can provide the stimulus we need to improve our cellular defenses.

It also raises important questions about how much is too much over what period of time, whether it needs to be cycled, and whether it is equally good for everyone or could be hurting some people who are bad candidates for it.

There are some indications from the trials that headaches and gastrointestinal problems are fairly common side effects, indicating not everyone’s metabolism is being optimized.

Further, Mitopure costs $100-125 per month. Is this doing something special over and above what a good diet does for you that is worth that kind of money?

Finally, while Amazentis stands against pseudoscience at its core, the claim that you can increase strength and VO2 max without exercising deserves some closer scrutiny before we throw $125 per month at it.

In this article, we examine the findings of the randomized controlled trials, put urolithin A into its appropriate context as a plant polyphenol, and form a working model of its mechanism of action that can help us properly interpret the trials. From this, we form conclusions about who should be taking urolithin A and why, and how to know if it might be right for you.

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This is educational in nature and not medical or dietetic advice. See terms for additional and more complete disclaimers.

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The lack of documentation in the literature for a supplement so extremely well studied indicates that the side effects are idiosyncratic. This means that they are not predictable dose-response effects but are instead driven more by the person’s unique response.

In the comments of Your Cells Are Starving for Creatine, people mentioned elevated creatinine, insomnia, cramps, and constipation. On X, they mentioned water retention, and hair loss. On Instagram, they mentioned irritation and anger, lightheadedness during lifting, bloating, aggravation of restless leg syndrome, irritation of asthma, and bloody noses. On Facebook, they mentioned anxiety. Others have mentioned to me headaches. We also cover heart palpitations, twitching, and fast or slow heartbeat.

In this article, we use biochemical reasoning to ascertain the likely causes and solutions to creatine side effects so that individuals can better help themselves by trying things predicted to work.

There is also a podcast version here:

Listen to the Podcast

This is educational in nature and not medical or dietetic advice. See terms for additional and more complete disclaimers.

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Good news.

Version 3 of Testing Nutritional Status: The Ultimate Cheat Sheet is now out. This and all future updates are available exclusively to you as members.

Here are the main updates:

• The screening in the Cheat Sheet has been streamlined for simplicity and compatibility with the Comprehensive Nutritional Screening that is on our web…

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To make matters worse, they may even have a moderate predisposition to iron overload due to the presence of one of the common HFE gene polymorphisms, seeming to clinch the case that they need to use my Iron Overload Protocol, when in fact iron depletion strategies could make things considerably worse.

If that person suffers from fatigue, which can be a manifestation of both iron deficiency and iron excess, then it may be all the harder to come to the right conclusion.

Or take low dopamine as an example. Dopamine synthesis requires iron, and myelin synthesis requires iron, but iron overload causes brain damage. This has been most studied in the contexts of iron deficiency causing restless leg syndrome from low dopamine and wrecking childhood IQ from poor myelin synthesis, and in the context of iron overload being a risk factor for Parkinson’s. But at the end of the day, any kind of neurological, psychiatric, or cognitive problem could easily be a manifestation of iron that is too low or too high.

And since it is fairly easy to deplete the blood of iron rather quickly, but could take months to deplete other tissues with low turnover, it could take months to see the negative effects of iron loss, making the puzzle even more confusing to solve.

Fortunately, solving iron issues becomes much easier if we understand the nuances of iron metabolism. Therefore, this article traces the metabolism of iron from the moment you eat it through its distribution to tissues and incorporation into iron-dependent enzymes, with an aim of gaining practical insights into how to interpret lab data and make high-quality decisions to fix problems with iron metabolism.

In This Article

• Key Insights

• How Much Iron We Have, How Much We Lose, How Much We Need (and The Secret 1.8 Rule for Vegetarians Hidden in the RDA Documents)

• Redox States of Iron Are Central to Its Metabolism (and how to remember the perpetually confusing "ic" and "ous" of iron names)

• The True Complexity is Staggering

• How We Absorb Dietary Iron

• The Absorption of Non-Heme Iron

• The Absorption of Heme Iron

• How to Wreck Your Iron Absorption

• Iron Inside the Intestinal Cell

• Circulation in Transferrin (and surprising roles of oxalate)

• Import of Iron Into the Mitochondrion

• Storage of Iron in Ferritin (and why impaired release may throw a monkey wrench in your interpretation of lab work)

• The Liver and Beyond

• Cellular Regulation of Iron Metabolism

• Systemic Regulation of Iron Metabolism (and the surprising potential value of succinate and fumarate)

• Implications for Hyperbaric Oxygen Therapy (it is unfortunately less paradoxical than its advocates argue)

• Serum Vs Cellular Ferritin

• A Specific Example of Where the Divergence Could Matter

• Is There a Role for the Soluble Transferrin Receptor?

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Vitamin B6 is an essential nutrient required to prevent blood glucose from dropping too low, to allow your muscles to burn glycogen during exercise, to prevent anemia, to clear histamine, to keep oxalate levels low, and to provide smooth, shiny, beautiful skin.

Without enough B6 your mood can crash, your handling of stress can deteriorate, your anxiety can rise, your sleep can tank, your joints can hurt, and you’ll start getting sick more often.

Estrogen raises your need for B6, so anything that correlates with your menstrual cycle or your use of HRT as a woman, or your body fat gain as a man, could be related to B6.

Inflammation raises your need for B6, so getting sick or being chronically inflamed can launch a vicious cycle of needing more.

As I covered in The Three Nutrients You Need More of On a High-Protein Diet, most people don’t get enough, and people eating high-protein diets almost universally don’t get enough.

If you have sulfur dysregulation issues, moreover, this could send your B6 requirement into megadose territory, especially if you eat a lot of protein.

Before you go reaching for that bottle of B6, however, know this: B6 supplements can cause neuropathy.

The neuropathy often starts in the toes, usually affects the feet, hands, and lower legs the most, and when it gets bad it can prevent you from being able to walk. More commonly, it manifests as a sense of tingling, numbness, burning, crawling, stinging, itching, metal scraping, or biting ants along the skin, but can be widely variable, cause bone problems, and affect the genitals, leading to the loss of libido. It can make it more difficult to run, lift, or climb stairs; to type, play piano, grip a steering wheel, or otherwise use the hands for things more complex than holding objects; and it can lead to twitching, fidgeting, or sensations of other types of movement running underneath the skin.

If you stop B6 at the first sign of symptoms, it typically gets worse for 2-3 weeks then goes away.

If you stop the B6 months or years into the symptoms, it typically is gone within six months after stopping if you were taking less than 500 milligrams a day, or it can take three years to fully resolve if you were taking a gram or more per day.

Now here’s the big problem.

Classically, B6-induced neuropathy is considered a “toxicity” from “megavitaminosis” or “hypervitaminosis” even though there is literally no remotely settled science on how the accumulation of B6 could drive neuropathy, and even though experimental induction of B6 neuropathy in humans doesn’t resemble a phenomenon driven by bioaccumulation of a toxin at all.

This misunderstanding of B6-induced neuropathy has led to the erroneous belief that there is a predictable dose-response relationship, where doses under the National Academy of Medicine’s tolerable upper intake level and found on supplement shelves are “safe” — they aren’t — and where doses above those levels are predictably harmful — they aren’t.

Even if you take the erroneous dose-response beliefs seriously, you still are in a quagmire of conflicting ideas: sulfur dysregulation could lead you to require neuropathic doses; doses used to treat PMS, nausea and vomiting of pregnancy, high oxalate levels, and some forms of seizures are neuropathic; and doses used to treat some forms of drug-induced neuropathy are themselves neuropathic.

But once you leave this erroneous belief behind you can look at the broad base of evidence suggesting people can develop neuropathy on doses less than 20 milligrams per day, very close to the typical requirement, which I estimate at 5-6 milligrams per day.

In fact, there are numerous Facebook groups dedicated to people who believe they are suffering from B6-induced neuropathy, and within them there are people who claim to have developed neuropathy from as little as 2 milligrams of supplemental B6!

While there is some evidence that within each person, the dose determines the neuropathy, the variation between each person’s threshold is vastly more important, making any predictions about the safety or tolerability of a given dose virtually meaningless on an individual level.

(Even though the average response makes such predictions somewhat useful on a population level).

I did my own experiment in self-induced B6 neuropathy, and I showed that neuropathy can be induced at the same dose that provides normal physiological benefits of B6. In contrast to what I had believed for over a decade, I showed that it can be induced rather easily with P5P, and is not the specific province of pyridoxine hydrochloride, used in cheaper supplements. I consider my conclusions extremely valuable for shedding light on what causes it, and on how to get rid of it.

Once we leave behind the traditional idea of “toxicity” and think about B6 neuropathy as an imbalance created within a complex web of biochemical pathways, the light bulb will go off in our heads allowing us to understand it with the clarity needed prevent it and resolve it.

And that is what we will do in this article.

This is educational in nature and not medical or dietetic advice. See terms for additional and more complete disclaimers.

In This Article:

• The Short Answer

• This Is How B6 Neuropathy Manifests

• Why the Upper Limit Is Misleading

• A Broader View of How the Neuropathy Manifests

• What We Learned From the Scientists Who Induced B6 Neuropathy in Themselves

• Why Megadoses Aren’t Needed

• What Causes B6 Neuropathy? Lessons From Animal Experiments

• What Causes Neuropathy In General?

• The Role of Energetic Failure

• Why Your Individual Idiosyncrasy Matters

• Lessons From My Own Self-Experiment in B6-Induced Neuropathy

• The Bottom Line: What to Do

This Article Is Reserved for Masterpass Members

You can sign up for the Masterpass here. You can learn more about the Masterpass here.

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Acne is a horrible problem to have. It can wreck your self-esteem, give you anxiety, and make you depressed.

It may seem cosmetic on the …

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One of the arguments in favor of protein for longevity is that the people in the highest 50% of lean mass live longer than the people in the lower half.

Further, we know beyond the shadow of a doubt that the obesity crisis is a major driver of the most common health problems, and protein plays an important role in weight loss. Protein is the most satiating macronutrient, up to around 15% of calories, which would be 1.3 grams per kilogram bodyweight for a 70-kilogram (154-pound) male maintaining stable weight on a 2418-Calorie diet.

More importantly, when you lose “weight” you lose not only fat, but lean mass. And lean mass does not just mean muscle. It means internal organs and bones, too. Protein helps preserve lean mass during weight loss. In meta-analysis, the amount of protein needed to preserve lean mass during weight loss is consistently higher than the RDA of 0.8 grams per kilogram, with 1.3 grams per kilogram being favored. This has been shown to specifically preserve bone mass as well.

One stunning finding from a short-term study showed that if you double this to 2.4 grams per kilogram bodyweight, you can cut calories by 40% and gain lean mass while simultaneously losing fat mass.

Yet these high levels of protein will stress your requirements for two vitamins and a mineral. Without them, you could find your anxiety levels rising, break out in acne or eczema, feel on edge all the time, or start to have poorer and shorter sleep.

If these things are happening, you definitely are becoming less healthy, and that’s definitely not going to make you live longer.

Indeed, since these nutrients are needed for healthy energy metabolism, it probably isn’t going to help you avoid diabetes either, even if you’re losing weight.

In this article, we cover just how much of these extra nutrients you need, and how to get them.

This article is reserved for Masterpass members. You can learn more about the Masterpass here.

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Lab testing for molybdenum status is unsatisfactory. LabCorp and Quest both treat molybdenum tests as if they are designed for the sole purpose of ruling out toxicity.

Even Quest’s ridiculously labeled “Micronutrient, Molybdenum, Blood” reports a healthy or deficient molybdenum level simply as less than the cutoff for toxicity.

HDRI offers a whole blood molybdenum test, but I have found them very difficult to work with, being hit by months of delays.

Here I report a simple DIY home test for molybdenum status that requires no more than $10-50 worth of equipment, a molybdenum supplement, and 2-4 days of data collection. I have tested this on myself and believe that it works, although my validation should be considered anecdotal.

This article is reserved for Masterpass members. You can learn more about the Masterpass here.

You will always be able to find this article conveniently placed under lab tests in the menu.

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I have short chain acyl coa dehydrogenase deficiency and have been using riboflavin with success. Eventually I plateaued and was still left with terrible symptoms that come and go throughout the day like head pressure, anxiety, rumination and muscle twitching. A practitioner suggested upping my dose of riboflavin to over 800mg which lowered my ethylmalonic acid levels before they went all the way back up to baseline, along with raising pyruvate in urine above normal for the first time ever. Even after stopping the high dose and going back to 100mg riboflavin my urine smells like sulphur sometimes. Is it possible such a high dose of riboflavin interfered with thiamine status? I also have borderline low copper levels.

I am not a doctor, this is not medical advice, Rae is not my patient, but there’s some basic biochemistry that we can dig into to answer Rae’s question.

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Thiamin deficiency in its classical form, beriberi, causes latent mitochondrial dysfunction that becomes apparent upon eating carbohydrate or going out into sunlight, with a rapid pulse, low blood pressure, a much easier than normal activation of the fight-or-flight response, low stomach acidity, loss of sensation and sometimes paralysis in the extremities, poor eyesight, irregular eye movements, and dizziness. So supporting your mitochondria, your nervous system, and your eyesight requires getting enough thiamin.

In fact, some people with genetic impairments in thiamin metabolism or thiamin-dependent enzymes may need as much as 500-2000 milligrams a day, which is vastly higher than both the adult RDA of 1.1 milligrams as well as the higher amount I set in my custom nutrient targets.

On the other hand, while thiamine has no reliably reproducible toxicity syndrome, anecdotally I can say after months of experimentation that almost any degree of thiamin supplementation above my custom target adversely shortens my sleep, and that I know a number of people who have had thiamin worsen their peripheral neuropathy, or debilitating mitochondrial dysfunction.

Dr. Derrick Lonsdale writes in the book he authored with Chandler Marrs, Thiamine Deficiency Disease, Dysautonomia, and High-Calorie Malnutrition that every case he saw of a “paradoxical” reaction to thiamin was self-resolving, with benefit arising after the initial hump of difficulty. My experience from a different and broader context suggests that there are many people who get adverse reactions that do not end until thiamin supplementation is stopped rather than these self-resolving paradoxical reactions.

Excessive thiamine supplementation would not be expected to directly interfere with the absorption of other nutrients, but it could puts stress on four metabolic pathways that either creates an imbalance with other nutrients or worsens a genetic impairment, and it probably generates sulfite within the human body. Sulfite is toxic, accelerates glutamate excitation of and damage to nerves, can degranulate mast cells and cause pseudo-allergies, and the process of generating and detoxifying sulfite puts stress on the requirements for coenzyme Q10, glutathione, molybdenum, and copper. It could also worsen mitochondrial dysfunction by backing up the mitochondrial respiratory chain and inhibiting short-chain fatty acid metabolism.

Thus, it is critical to have a strategy to know when to supplement thiamin, when to continue through difficulty, when to stop and give up, and when to put your focus elsewhere. That is exactly what you will learn in this article.

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