Chris Masterjohn, PhD

VO2max has not been measured or predicted in any of the studies popularly claimed to tie it to longevity.

One set of papers from Finland that nobody cites showed that measuring VO2 offers ZERO utility to predict longevity relative to performance on a cycling task. In fact, using VO2 was slightly worse at predicting longevity compared to cycling performance.

Worse, none of the papers that built the equations predicting VO2max from treadmill performance used by the American College of Sports Medicine even measured VO2max.

They measured VO2peak and claimed it was VO2max even though in none of the papers did VO2 plateau, which is needed to measure VO2max.

Michael Pollack, who pioneered the aerobic craze of the 70s and 80s to the point that his obituary proclaimed “aerobics is dead” when he died of a stroke at age 61, was involved in the largest study demonstrating the utility of the equations in 1984, and the paper makes the wild justification for not seeking a plateau of VO2 that Robert Bruce, “the father of the treadmill exercise stress test,” did not look for a plateau when he first made the equations in 1973.

The ACSM blindly propagates these equations even though their own methodological discussion says that if you don’t observe a VO2 plateau you didn’t measure VO2max!

Koutlianos 2013 shows that when you *do* observe a plateau, the treadmill performance only has 7% utility to predict VO2max!

Koutlianos measured it in athletes.

It’s almost impossible to measure VO2max in the general population because they give up before the VO2 plateau.

For example in the Finnish paper by JA Laukkansen, they tried to look for a plateau on a progressively increasing cycling test in 1294 men.

735 stopped because of fatigue, 207 stopped because of exhaustion, 155 stopped because of breathlessness, 50 stopped because of pain in the legs, joints, or back, and 86 stopped because of cardiorespiratory symptoms or abnormalities.

No one stopped because they hit VO2max.

In short, the papers show FITNESS is strongly predictive of longevity but hyperfocusing on VO2max is completely outside the evidence base.

1 day ago | [YT] | 32

Chris Masterjohn, PhD

Is VO₂ Max Really a Longevity Metric?

What the research actually shows about oxygen uptake, treadmill performance, and lifespan.

A popular claim in the longevity space is that VO2max, a metric taken from exercise science, is strongly associated with increased lifespan and represents a major measurement you should make as a key performance indicator for your longevity strategy.

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.

This Is Article Free For One Week

This article will be reserved for Masterpass members (learn more about the Masterpass here) beginning 11AM Eastern on December 19, 2025.

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 Bad Data Generate Stronger Correlations?
* Other Mortality Data
* So What Do We Do With This?

Click through to read the article while it’s still free!

chrismasterjohnphd.substack.com/p/should-you-optim…

2 days ago | [YT] | 32

Chris Masterjohn, PhD

Carsick?

The prevailing theory of why the vestibular system promotes nausea during motion sickness is that for most of our history a discordance between sensory inputs was a sign we had ingested neurotoxins.

In the model of nausea I presented in the last post, this is a form of dysregulation we all share.

However, if you get much more easily motion sick than the average person you are hypersensitive.

If you are *only* hypersensitive to motion, you should consider whether the motion in your life is too “regular.”

Your exercise should include training quick changes in momentum and direction, spinning, and irregular paths of motion.

Some ideas for this would be dance involving a lot of turning (e.g. standard ballroom, especially Viennese Waltz; Hustle), spinning squat jumps (you could start with 90 degrees and work your way up), sports that involve tricks that spin; and the momentum shift drills used in various sports.

Simply playing a sport that involves you having to shift momentum or move in reaction to the unpredictable behavior of your opponent will involve a lot of this.

If you don’t have a car, get one and go for rides. I started getting motion sick when I lived in NYC and only took trains because they always go in the straightest path possible so I got detrained from the more varied motions of a car.

But if it correlates to hypersensitivity to nausea across the board the chances are higher it’s idiosyncratic mitochondrial dysfunction.

Notably most neurotoxins are
mitochondrial toxins and most mitochondrial toxins are neurotoxins, and mitochondrial dysfunction most commonly causes neurological dysfunction due to the massively outsized energy requirements of the nervous system, so these are all intimately connected.

You could also have specific abormalities in the vestibular system that are well beyond the scope of this post. However, these could be, for example, a heterozygous mutation in the vestibular system synergizing with a deficit in mitochondrial function, neither of which are severe enough to receive any kind of medical diagnosis but both of which combine to bias your mitochondrial dysfunction toward manifesting as motion sickness.

Of the two, maximizing your mitochondrial energy production will almost always be more actionable and it will feed forward into many other benefits to all other aspects of your health.

Train everything.

Think of mitochondria first.

Use a food-first pharma-last approach to optimize your mitochondrial function.

5 days ago | [YT] | 48

Chris Masterjohn, PhD

You know what the best cure for nausea is?

Throwing up.

The entire purpose of nausea is to expel the stuff in your gut because your gut cannot handle it. The way you listen to your body when you are nauseated is you let it throw up.

That's why you may often feel better after throwing up.

Often the problem is *real* and you *need* to throw up.

Examples:

1) Food poisoning
2) Alcohol poisoning
3) Intestinal obstruction

Disclaimer: this is not medical advice.

In each of these cases, you have either toxins that need to be purged out, or you have food that will create metabolic stress and associated toxins if it is not purged out.

It is possible that binders like activated charcoal or bentonite clay or something similar could provide relief by binding the toxic substances, in which case this could provide a similar relief as vomiting that is less unpleasant, but this won't always work. When it does, it isn't interfering with the goal of purging toxins.

It is also possible for the nausea system to be dysregulated or hypersensitive.

In a dysregulated system, your main priority should be to fix the dysregulation. Anti-nausea meds can mask the problem but their nausea suppression shouldn't make it worse.

In a system that is hypersensitive, you have a similar issue as the examples of toxicity: the toxic load may not be high, but it may be harmful due to your sensitivity to it. So nausea suppression would be harmful.

Nevertheless in an acute situation you *may* weigh relieving pain and suffering as a higher priority than fixing the underlying problem, and this may call for anti-nausea meds.

In such a case, it would be better to use bismuth, which combats nausea by binding hydrogen sulfide, instead of anti-serotonergics. This is because anti-serotonergics carry the risk of impairing mitochondrial function by inhibiting mitochondrial membrane serotonin receptors.

Here are some specific examples of dysregulation and hypersensitivity.

Dysregulation

Examples of dysregulation would be poor clearance of hydrogen sulfide, or the transient nausea of early SSRI treatment.

For dysregulated hydrogen sulfide clearance, my "Sulfur Protocol" (see my web site menu>protocols>sulfur) can resolve it.

SSRIs cause nausea and vomiting through increasing synaptic serotonin in the gut, but this is usually transient and self-resolving (probably because gut serotonin is lowered by the whole-body drive to pour your serotonin into your urine).

While gut serotonin can be increased in response to metabolic stress, this is NOT dysregulation. This is *supposed* to happen, as serotonin helps mitochondria adapt to handle that stress.

Gut serotonin could be degraded poorly due to deficiencies of riboflavin (vitamin B2) and niacin (vitamin B3), and this would be an example of dysregulation resolvable by correcting nutritional deficiencies.

In general the gut is supposed to be quite rich in serotonin and it is actually supposed to be absorbed into the general circulation and stored in platelets, so I doubt this impaired degradation is a frequent problem.

Using anti-nausea meds to fix dysregulation is just masking the problem.

Hypersensitivity

If the system is too sensitive this is essentially mitochondrial dysfunction that should be studied and resolved.

For example, in "Nausea and Vomiting of Pregnancy Is Mitochondrial Dysfunction" I explained why pregnancy itself is essentially a form of *relative* mitochondrial dysfunction -- NOT meaning a disease state but instead meaning an imbalance that taps into the body's mitochondrial dysfunction signaling to try to restore balance -- and that when it is much worse than usual it is driven by idiosyncratic *absolute* mitochondrial dysfunction.

In the case of pregnancy, hydrogen sulfide and GDF15 work together to signal mitochondrial dysfunction to the center of the brain stem that regulates the gag reflex, nausea, vomiting, and appetite suppression.

The placenta makes soluble leptin receptors to create a temporary state of leptin resistance by serving as decoys for leptin molecules, and this increases appetite.

The H2S and GDF15 signaling results in increased sensitivity to specific foods and food components to drive food aversions while purposeful transient leptin resistance abolishes their appetite suppression.

This ensures that the unborn baby, who is more sensitive to mitochondrial toxins than the mother, is protected, but also well nourished.

Using anti-nausea meds for hypersensitivity is like fixing your car by taking a hammer to smash the warning light in your dashboard.

If you have increased sensitivity to mitochondrial toxins, gut hypoxia, or metabolic stress in the gut, nausea is the warning signal that protects you from eating what will stress that system that you cannot handle.

Conclusion

If you are nauseated, it is best to allow your body to throw up.

If you can bind up whatever may be triggering the nausea with charcoal or clay, this is an alternative way to achieve the same freedom from toxicity.

If you need to prioritize relief from pain and suffering, bismuth is preferable to anti-serotonergics, but anti-serotonergics might be necessary.

If your system is dysregulated this is *probably* due to hydrogen sulfide problems and my Sulfur Protocol can help.

If your system is hypersensitive this is *probably* due to idiosyncratic mitochondrial dysfunction and mito.me can help.

6 days ago | [YT] | 75

Chris Masterjohn, PhD

2 weeks ago | [YT] | 162

Chris Masterjohn, PhD

Statins Are Mitochondrial Toxins

And CoQ10 isn't enough to fix this.

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

Blood cholesterol levels, along with LDL particle count, ApoB concentration, LDL particle size, LDL pattern, and the ratio of cholesterol between LDL and HDL are all governed centrally by the LDL receptor.

Genetic mutations in LDLR cause familial hypercholesterolemia by lowering LDL receptor expression. One in a million people are born with homozygous mutations, and this can cause heart attacks as young as 18 months old. One in 300 people are born with heterozygous mutations, which shifts heart disease forward from a phenomenon that primarily kills between the age of 60 to 80 to one that primarily kills between the ages of 35 and 60.

The LDL receptor is the main way you bring cholesterol from outside the cell to inside the cell. While the liver only makes about 16% of the body's cholesterol, it is overwhelmingly responsible for controlling the concentration of cholesterol in the blood by taking it up using the LDL receptor. That cholesterol can then be put to productive use, especially for the synthesis of bile acids to support digestion.

However, there are two primary governors of LDL receptor production:

Thyroid hormone governs it by signaling abundance. This causes the liver to take up more cholesterol than it needs to meet its basic needs, and this is what drives bile acid production to support digestion.

Cholesterol deficiency within the liver cell governs it by signaling scarcity. The liver takes up cholesterol from the blood not to put it to productive use but simply to replenish its own stores.

Statins work by inducing a cholesterol deficiency in the liver. The liver responds to this by taking up more from the blood to bring its stores back up to normal.

In his 1976 book, Solved: The Riddle of Heart Attacks, Broda Barnes reviewed the history of using thyroid hormone to control both cholesterol levels and heart disease risk. It worked extremely well, but it was discontinued due to what Barnes describes as irresponsible dosing that had killed a few people.

It is important to understand here that you do not need to be “hypothyroid” for thyroid hormone to lower your cholesterol. It will work at any dose. Practitioners using it did not realize they were playing with fire by using a hormone to signal a degree of abundance that was not present in the body. Thus, some of them let the dosing get out of hand because it had nothing necessarily to do with correcting a thyroid deficiency.

Nevertheless, their approach was the same as using statins because both thyroid hormone and statins increase the LDL receptor.

On the other hand, it was the opposite, because thyroid signals abundance while statins signal scarcity.

What everyone involved fails to fundamentally understand is that your LDL receptor does not work in a vacuum. It is powered by mitochondrial ATP production.

If your mitochondria are not working well, your LDL receptor simply will not work.

Doctors who use a pharma-first approach have little respect for nature and doctors who use a statin-first, mitochondria-never approach do so because they do not understand the most basic elements of cellular biology.

As covered in What Everyone Should Be Doing For Their Health, everyone must use a food-first, pharma-last approach, which means everyone needs their doctor to follow the same approach. Do your research until you find a good one.

Click through to read my article on how mitochondrial function optimizes your thyroid hormone and LDL receptor activity, how statins act as mitochondrial toxins beyond a simple impairment in CoQ10 synthesis, and what to do about it:

chrismasterjohnphd.substack.com/p/statins-are-mito…

3 weeks ago | [YT] | 96

Chris Masterjohn, PhD

How to Taper Off SSRIs

About 29 million American adults, adolescents, and children are on selective serotonin reuptake inhibitors (SSRIs). In many countries globally some 5-10% of the population are on SSRIs. These have become the first-line treatment for depression.

SSRIs can cause sexual dysfunction and emotional blunting in up to half of people, an unclear incidence of sleep disruption, and a rare risk of suicidality, self-harm, and new-onset psychosis.

Getting off SSRIs can cause discontinuation syndrome in 20-50% of people. It is more common, more severe, and lasts longer when people have been SSRIs for years instead of weeks or months. Many of the discontinuation symptoms represent new-onset dysfunction that cannot be explained by the withdrawal of an effective treatment for the pre-existing depression, such as headache, derealization, depersonalization, cramps, gait abnormalities, and “brain zaps.”

Tapering for many people needs to be extremely slow and it should always be hyperbolic rather than linear, meaning your dose reductions get smaller and smaller as you go on.

Click through to read about the best approach to tapering:

chrismasterjohnphd.substack.com/p/how-to-taper-of-…

1 month ago (edited) | [YT] | 29

Chris Masterjohn, PhD

Masterjohn's Weekly Five is a new newsletter where I give you my health insight, food/supplement experiment, coolest paper, worst scientific malpractice, and best mitochondrial story for the week.

Edition 1 covers an underappreciated way the pharmaceutical industry is completely at odds with nature, whether lima beans are friend or foe to the mitochondria, a paper on rare bottlenecks causing common problems, a case of hiding the control group, and a story about bonk-free marathoning fueled by chocolate.

Enjoy!

chrismasterjohnphd.substack.com/p/masterjohns-week…

chrismasterjohnphd.substack.com
Masterjohn's Weekly Five

1 month ago | [YT] | 24

Chris Masterjohn, PhD

Resolve Your Inflammation With This One Highly Unique Form of Lactoferrin

One of the most promising natural resolvers of inflammation is a milk-derived protein known as lactoferrin.

As we will see momentarily, however, not all lactoferrin is created equal.

Click through to read on about the amazing power of the right form of lactoferrin:

chrismasterjohnphd.substack.com/p/resolve-your-inf…

1 month ago | [YT] | 20

Chris Masterjohn, PhD

The Problem With St. John's Wort

Is this herbal medicine an alternative to treating depression with drugs, or just a drug in another form?

Saint John’s Wort has a large body of literature supporting its use for depression, but it is relegated to a position of last resort in the Depression Protocol because it is really an herbal version of an SSRI rather than an alternative.

A meta-analysis of 27 trials including 3,808 patients supports St. John’s Wort as a monotherapy having nearly identical efficacy to SSRIs when used for four to twelve weeks, but with a 41% lower rate of dropping out due to side effects.

A meta-analysis focused on clinical recommendations concluded that “St John’s wort flowers at doses of 600mg to 1800mg (3:1–7:1 extract depending on product) per day standardised to a dose of approximately 0.2–0.3% hypericin and/or 5–6% hyperforin (once to three times per day depending on extract) is recommended for monotherapy in mild to moderate depression.”

However, St. John’s Wort makes little sense as a substitute for SSRIs when it essentially is an example of the closely related drug class of SNRIs. Pharmacological investigations suggest that it is a modest inhibitor of monoamine oxidase and a powerful inhibitor of the reuptake of serotonin, norepinephrine, and dopamine. It may also activate the sigma-1 receptor, a powerful mitochondrial effect exhibited to varying degrees by the different SSRIs. By blocking the cellular uptake of serotonin, we would expect it to have all the same effects on mitochondrial function as SSRIs broadly have.

Indeed, this herb might have a similar withdrawal syndrome as SSRIs do. One case was reported where a 58-year-old postmenopausal woman used 1800 milligrams three times a day for 32 days. She started developing photosensitivity, so stopped using it. Within 24 hours, she developed nausea, anorexia, dry retching, dizziness, dry mouth, thirst, cold chills, and extreme fatigue. These problems peaked on day 3, started getting better on day eight, and led to nine pounds of weight loss.

In a telephone survey of 43 individuals who used St. John’s Wort, thirteen developed withdrawal symptoms when they tried stopping. Nine had to restart it to make them go away, one had them resolve in a week, two in two to three weeks, and one was still suffering from them at the time of the survey.

Twenty of them reported side effects, four reporting photosensitivity, eight gastrointestinal upset, ten sleeping difficulties, two fatigue, seven anxiety and restlessness, and one reported sexual dysfunction. Among five who were using it in conjunction with other serotonin-modulating medications, two developed serotonin syndrome.

39 of them used the herb alongside aged meats and cheeses or over-the-counter cough and cold medications, with two of them acutely developing flushing and pounding headaches from the combination. One blacked out after combining it with alcohol.

St. John’s Wort traditionally had many uses, and in some areas it was used against the melancholy of winter, probably an early name for seasonal affective disorder.

The rationale was that it flowered on the summer solstice at the time of the feast of St. John the Baptist. Since winter caused depression from lack of sunlight, this yellow flower captured sunlight from the summer solstice that could be administered during winter.

Brain serotonin levels are primarily determined by exposure to light. This lines up well with serotonin’s primary role being to support mitochondrial function during hypoxia because when we rise from sleep we are instantaneously experiencing “relative hypoxia” until our mitochondrial function can rise to adapt to the higher metabolic demand of wakefulness.

If St. John’s Wort indeed activates the sigma-1 receptor, it would be expected to increase brain serotonin and thereby act similarly to sunlight.

The fact that one of its principal adverse effects is photosensitivity also lines up with this: by providing too much biochemical similarity to sunlight, one overdoses on the sunlight.

These collectively support the traditional concept that the flower captured sunlight as it bloomed on the summer solstice and then delivered it during winter to those who consumed it.

The photosensitivity of St. John’s Wort can include sun-induced pain, paresthesia, and rashes.

SSRIs can cause various forms of photosensitivity as well, including hyperpigmentation, epilepsy, and skin rashes.

Since photosensitivity is shared across these substances, it probably results from their main mechanisms of action regarding serotonin synthesis and transport.

This might be due to driving tryptophan into the synthesis of serotonin and away from the synthesis of NAD+. Sunlight exposure causes DNA damage, which requires the irreversible loss of NAD+ to repair, thereby synergizing to aggravate NAD+ deficiency in the tissues most exposed to sunlight, such as the skin and the eyes. This principle underlies the photosensitivity of classical pellagra expressed as the “dermatitis” of the “three D’s” (or four, if you include “death”).

Alternatively, elevated catabolism of serotonin to 5-hydroxyindoleacetic acid (5-HIAA) could cause photosensitivity because this compound becomes cytotoxic when exposed to light.

If we put the St. John’s wort data into historical perspective, it seems that traditional flower concoctions probably had lower doses, and use for the melancholy of winter limited the duration of use to twelve weeks.

This is in gross contrast to the modern diagnostic framework that identifies people as depressed instead of identifying “melancholy” as something that occurs due to “temporary deficiency of sunlight,” that demanded a temporary fix. The modern treatment framework then puts people on SSRIs for years, which has no basis whatsoever in the randomized controlled trial literature and is tied to horrific imprisonment of people with the threat of severe and protracted withdrawal.

While randomized controlled trials should indeed be used as the gold standard for inferring causation between a strategy and its outcome, they should not provide the boundaries of safe use in most cases except to potentially restrict them beyond the traditional use of an herb.

While the pharmaceutical-medical industrial complex claims to follow randomized controlled trials to make treatment decisions, this is mostly fake. For example, SSRIs are mostly studied up to twelve weeks but SSRIs are on average prescribed for five years.

Ironically, the medieval European use of St. John’s Wort better conformed to the boundaries of modern randomized controlled trials without even knowing about them, since its use lasted for one season rather than being used indefinitely for years.

Since St. John’s Wort has equivalent efficacy and superior tolerability to SSRIs, it is better to use St. John’s Wort than SSRIs.

However, since it does work in much the same way and it does pose a similar risk of withdrawal-induced mitochondrial dysfunction, it should be used toward the lower end of the effective dose range and for no longer than twelve weeks. It should be used only if still needed after addressing nutritional deficiencies, idiosyncratic mitochondrial dysfunction, and the low-hanging fruit of depression prevention such as boosting protein intake up to the range that powerfully protects against depression.

This is exactly how I have positioned it in the Depression Protocol.

Read the article with live links and references by clicking through here:

chrismasterjohnphd.substack.com/p/the-problem-with…

2 months ago | [YT] | 35