Chris Masterjohn

Your cells are aging faster than you think. After age 18, mitochondrial density declines by 1% every year—one of the clearest biological markers of aging. By 70, you’ve lost more than half your cellular energy capacity. Here’s what most people miss: this decline isn’t inevitable. 🧵👇

@MicroBerto @AndrewDBaird1 I must have misunderstood you. The post you were replying to was almost entirely about vitamin A, so I thought you were relating it to that.

@ChrisMasterjohn @AndrewDBaird1 First off, where did I even relate my egg situation to vitamin A here? Second, I would never sabotage my health like that All I asked for was a better egg testing strategy from Andrew's opinion. What a really weird slide-in, Chris.

Garrett Smith has made so many mistakes on Vitamin A toxicity it's laughable to suggest he's making meaningful content. Perhaps you don't recognise your issues in these points. Then one day you do your own research and find out he got it wrong. 1. He thinks you detox Vitamin A by lowering Vitamin A to near zero. No, that's not the way you treat hypervitaminosis A. 2. For the last 7.5 years until recently he thought very small amounts of retinol in eggs and dairy were toxic. This made a mockery out of Vitamin A toxicity and now he's reversed his position saying 1,000 IUs of Vitamin A is still low. He's lost all credibility: Vitamin A supplements 25,000 IUs per day for 4 years reversed then 250 IUs toxic even in eggs for 7 years and now they are low and okay. 3. His stance on eggs being toxic deprived people of one of the most nutritious foods that benefits liver health. 4. His toxic bile theory without mentioning how helpful phosphatidylcholine proves what a lightweight he is. 5. He claims to be doing a detox but then ignores the importance of methylation for detox. 6. For years he ignored the advice that B vitamins are necessary co-factors in enzyme reactions. 7. His myopic thinking about Vitamin A toxicity and soft tissue calcification led him to overlook the importance of calcium intake. 8. Vitamin A is essential for intestinal barrier integrity and his whole very low vitamin A sabotaged any hope of reducing endotoxemia for some people. 9. Interpreting every twinge and bowel movement as being about Vitamin A toxicity and bile leaks stopped people thinking more clearly and identifying what was really going on. Low calcium, salicylate sensitivity, leaky gut, sulfite toxicity, oxalate dumping and glutamate sensitivity being some possibilities. 10. Interpreting Vitamin A as a poison from the beginning leads you to draw many wrong conclusions regarding serum retinol. Ruling out deficiencies means you never realise retinol not converting to retinoic acid is causing some problems. And there can be a few reasons for that including the leaky gut caused by the very low Vitamin A. 11. This was a new subject to him and his inability to take on board suggestions and experienced points of view in a timely fashion was a dreadful mistake that many have suffered because of. Folinic acid and nicotinic acid being mentioned years after he was told about them. 12. Experimenters who did badly were ignored and neglected whilst he moved on to the next great thing. Those experimenters actually provide useful and potential correcting information that the vitamin A is indeed essential. Particularly, those who don't convert beta carotene to retinol well. People needing calcium. Those with choline deficiency and not eating much meat.

Bro this is so utterly non-specific it’s a joke. A great experiment would be to see if a single capsule of vitamin A induces another 2.5 years of egg intolerance. If it did I would start to take this observation seriously. But this is so non-specific it could be that you grew out of an egg allergy or that you through completely other means improved your intestinal fat absorption or any other number of explanations unrelated to vitamin A.

Aggressive post! Ok so let's say at the beginning of my journey, eating any number of eggs causes a nearly immediate d-bomb in the toilet. But at 2.5 years in, 1-2 eggs does not. Somewhere in between these points, I clearly 'resolved' the problem. How would you have phased it back in? Like test an egg once a month?

I read Genereaux up to the point where he started mocking the concept of “gene expressions” wholesale and saying essentially that transcriptional regulation is “insults to DNA” and realized that he was throwing out the entire edifice of molecular biology as we know it and that’s quite a tall order. Haven’t seen much in that field to justify that level of baby being thrown out with the bath water.

@IT_Guru74 @___iaini You’d rather take phenobarbital?

@ChrisMasterjohn @___iaini I get your point, but I’d appreciate a clarification than benzodiazepines being “safer” was misguided. youtu.be/NzddTvqFzF4?si…

Prolonged water fasting also treated seizures effectively long before this, but you’ll die if you do it forever, so the Mayo Clinic invented the ketogenic diet in 1929 as a way to achieve the same effect while keeping someone well fed. The keto diet works by raising GABA levels in the brain but doesn’t *force* synaptic GABA effects like the drugs do, so it didn’t make people as zombified as phenobarbital, a barbiturate, the then-leading treatment for seizures. Mayo invented the keto diet as an alternative to phenobarbital. In the 1970s barbiturates were largely replaced with benzodiazepines, which have a lower side effect profile, have a lower risk of fatal overdose, and are less zombifying. Big Pharma got the keto diet reclassified as for “refractory epilepsy” meaning it is the last resort when all the drugs fail, but that is not why it was invented. Keto diets likely have broad efficacy where fasting and GABAergic drugs have efficacy. They have downsides and limitations and not everyone is a good candidate for them but they are profoundly under-utilized in psychiatry.

*1921, not 1929.

@CarnalDancer Yes, sorry, you are right. First proposed 1921, major papers 1924-1933.

@ChrisMasterjohn Great post, but didn't the Mayo Clinic invent the diet in 1921?

@sugarxaxaxa That's horrible. What were the gradually experienced positive results that made her keep increasing?

@ChrisMasterjohn My mom gradually increased fiber per prevailing medical advice for gut issues and wound up with an impaction she almost died from and ended with a section of her small intestine removed. I have least problems on 0 fiber

Being ideologically pro-fiber is tremendously incompetent nutritional advice. Fiber is utterly catastrophic for someone with a Crohn's-related intestinal obstruction and can put them in the emergency room. Clinical guidelines are restrict fiber to less than 5 grams per day. Fiber is NOT a good solution for constipation in IBS-C. This meta-analysis claimed in the abstract that there was "no evidence that fibre was effective in the relief of abdominal pain in irritable bowel syndrome" but the data shows that insoluble fiber made abdominal pain 22% worse and soluble fiber made abdominal pain 33% worse. The only good advice about fiber is to self-experiment with different types and amounts of fiber from different whole foods, focusing on the food itself, to see which gets you closest to 1-2 bowel movements per day of well formed poop that comes out easily without straining. Any other advice about fiber is catastrophically stupid and likely to hurt someone.

A short treatise on the self-experimenter, the highest form of scientist.

Ok we are closer to agreement than it first appeared. N=1 experiments that are not randomized are equivalent to case reports, especially if documented to a similar degree. N=1 randomized experiments are the highest tier evidence for the individual in whom they are done provided that the time course is feasible and relevant to the outcome of interest. N=1 randomized experiments cannot be used for population-level guidelines because they don't apply outside the individual. However, since all information from any source is imperfect, and since many areas of interest have enormous gaps in knowledge, it is very valuable to use findings from N=1 experiments as potentially relevant to other individuals especially when those individuals are similar in genetics, history, and constitution in the variables thought to be relevant to inter-individual differences. Randomized self-experiments are practical on short time scales, especially when effects are acute over the course of hours. They are reasonably practical for time horizons of one day or several days. They are entirely feasible for time horizons that take weeks or longer but are difficult enough at those timescales that one would have to be extremely motivated to do it, either because the stakes seemed high or because one is a scientist in the classical sort, which is now almost absent from science. The classical scientist, the most genuine of all scientists, loved to experiment out of curiosity and loved to experiment on himself. There are many such scientists in history but they are a rare breed. Barry Marshall most famously with ulcers, Carl Wilhelm Scheele most notoriously for smelling and tasting every chemical he could, William Brown who working with George Burr tried to give himself an EFA deficiency. A R Berger 1, H H Schaumburg, C Schroeder, S Apfel, and R Reynolds taught us a lot about vitamin B6 toxicity by purposefully inducing it in themselves in self-experiments that lasted YEARS. They published their report in 1992. So the answer to your question is that no it is not practical but it is the sign of a genuine scientist of the highest breed.

Maybe not? Let me explain: 1. You’re talking about n-of-1 trials, not n = 1 anecdotal evidence. Thats not the dispute. 2. N-of-1 as “better” tier of evidence is theoretical; I can understand the superiority of within-subject variance being <<< between subject population variance. But, that’s mitigated by larger sample sizes Let’s discuss n-of-1 and give Nick the benefit of the doubt (he can easily just concede this is what he meant, but he hasn’t). Do you really think it’s practical to self-experiment? How would that work? You’d spend 10 years to reach the same effect size through self trial-and-error to learn that stroke is a black box warning lol? Theres a reason we don’t do n-of-1 for guidelines, it’s theoretically sensible and practically pointless because patients will get one or two trials before it’s too late

N = 1 studies as proxy for evidence is probably less scientific

@joshwhiton It’s a simplification and has amore detailed diagram earlier but the point of this one is to conceptually communicate the results to people without science backgrounds.

.@ChrisMasterjohn this chart from Mitome. What energy does complex IV produce? Not ATP. Does it mean proton pumping? Complex I & III do that too.

@YounisJoseph @nicknorwitz Maybe you should read the textbook on EBM written by the cofounder of EBM who cofounded the GRADE group that is essentially the global authority on guideline development before making comments like this.

@nicknorwitz That’s why case studies aren’t the gold standard for guidelines btw because n = 1 = case study. Lowest tier of evidence

@InsularEntropy “Clonaxepam inhibits the mitochondrial sodium-calcium exchanger” isn’t “circular logic.”

@ChrisMasterjohn I’m well aware that mito cocktails are not a solution at all for chronic akathisia. The problem with mitochondrial dysfunction being viewed as a root cause is that it is circular logic. Anyways, I appreciate any help in solving the Akathisia situation because it’s deadly.

“Mitochondrial dysfunction” does not explain our drug injuries. Nobody has ever put their severe and chronic akathisia into permanent remission by supplementing their way out of this w/ mito cocktails.

What's Wrong With Jordan Peterson's Health? Jordan Peterson’s health has been suffering tremendously. Mikhaila, his daughter, saw that what was ailing him was affecting so many systems of his body that it had to all be connected and began to wonder if it was a form of mitochondrial dysfunction. In trying to research whether mitochondrial dysfunction could be driven by the turning points in his health problems like SSRI withdrawal, benzodiazepine withdrawal, and toxic mold, she found my work and reached out to me. This is the conversation that we had:

Here is a summary of what I think is going on: Mikhaila shares half of Jordan’s genes and has been more detailed about her own health journey going back to childhood, so we start with her. She had juvenile arthritis symptoms starting at 2 and a diagnosis at 7. She went on Enbrel, a “biologic” (a pseudoscientific regulatory term) that opposes the action of the inflammatory mediator tumor necrosis alpha (TNF-alpha); and on methotrexate, which inhibits folate and adenosine metabolism. Methotrexate raises adenosine, which inhibits T cell proliferation. Its inhibition of folate metabolism is thought to be more relevant to cancer but its adenosine-mediated inhibition of T cell proliferation is thought to be more relevant to autoimmune arthritis. The next year, at age 8, she was diagnosed with depression and put on SSRIs. My hypothesis is that she has an underlying block in mitochondrial metabolism leading to CoA sequestration, which occurs when CoA-requiring pathways fail to complete properly. This leads to secretion of TNF-alpha as part of a cellular stress response. TNF-alpha serves to increase carnitine transport into the cell. The carnitine then trades places with CoA, detoxifying the metabolic intermediates and carrying them out into the urine, allowing CoA metabolism to continue. Blocking the TNF-alpha is a double-edged sword. On the one hand, the elevated TNF-alpha will interact with genetic predispositions to certain types of immune dysfunction and with suboptimal joint mechanics to produce an autoimmune disease. Blocking the TNF offers relief from the autoimmunity, but then in doing so makes the cells that were releasing it as a stress signal unable to mitigate their CoA sequestration. This may lead to a plethora of side effects, and for Mikhaila this was depression. I do not discount that inhibition of folate metabolism by methotrexate could have messed with her methylation system, but Mikhaila remains very intolerant of methylfolate and thrives on a low-folate all-meat diet, and I do not think any of her health problems are explained merely by a methylation deficit. Her first major advance was going on an elimination diet that eventually morphed into the red meat carnivore “Lion Diet.” T cells are fueled by glucose and glutamine during active inflammation, and when they transition to resolving inflammation a major drop in glucose and glutamine is a central hallmark of the metabolic shift. The zero-carb nature of the Lion Diet helps resolve T cell inflammation and displaces the need for methotrexate. The large amount of red meat provides carnitine, which addresses CoA sequestration from the point of carnitine supply, relieving the need of cells to secrete TNF-alpha to signal carnitine demand. The carnitine in the red meat thereby helps relieve the need for the Enbrel. Since her elimination diet gave her the first relief of depression she had experienced, it led her to go off the SSRIs. Going off SSRIs produced 2.5 years of new-onset neurological dysfunction, which I contend was new-onset mitochondrial dysfunction. This may have interacted or blended with the mitochondrial dysfunction that initially led to the arthritis, or it may have just been a completely new acquired mitochondrial disorder thrown on top of the existing problems. Throughout this story, various exposures to toxic mold occurred that made her problems worse, including one in 2022 that gave her a whole new list of problems that only moving away from the mold was able to solve. Mold toxins are mitochondrial toxins, so exposure to them would cause a third layer of mitochondrial dysfunction. Jordan had been on SSRIs for over twelve years, but when he saw Mikhaila cure her depression with the early precursor to the Lion Diet, he followed her approach. Having gotten rid of his own depression, he too went off SSRIs around the same time as she did. This led to akathisia, a catastrophically debilitating movement disorder. I contend that this is SSRI withdrawal-induced new-onset mitochondrial dysfunction. He then had a terrible reaction to apple cider that had sodium metabisulfite as a preservative. This led him to be unable to sleep for two or three weeks. He became green and hunched over, and couldn’t walk. For this he was placed on clonazepam, a benzodiazepine. Sulfite has to be converted to sulfate, which requires the mineral molybdenum and the transfer of electrons from the sulfite to the mitochondrial respiratory chain. Mitochondrial dysfunction will prevent sulfite clearance. Zero-carb diets will increase endogenous sulfur production and diets that lack liver and legumes are low in molybdenum. The mitochondrial dysfunction induced by the SSRI withdrawal would inhibit sulfur clearance and the diet that helped Jordan and Mikhaila cure their depression would keep the sulfur-detoxification system maximally occupied. If sulfite is not quickly metabolized to sulfate, it converts to S-sulfocysteine, which is a neurotransmitter that activates glutamate receptors. Sulfite itself is mitochondrially toxic, so if it crosses a critical threshold it can elicit a storm of excess sulfur catabolism and impaired sulfur clearance that keeps S-sulfocysteine levels high. That vicious cycle could explain why the sleep loss lasted 2-3 weeks. Clonazepam directly opposes S-sulfocysteine in that it binds to GABA receptors making GABA more powerfully activate them, which counteracts the S-sulfocyteine’s activation of glutamate receptors. Peterson stayed on clonazepam for three years and then tried going off of it, but this caused an even worse case of akathisia than he experienced from SSRI withdrawal. It lasted three years, and it made him suicidal. Clonazepam can alter calcium signaling in mitochondria in opposite ways depending on the preexisting state of the mitochondrial function. Possible effects of withdrawal include a catastrophic energetic supply/demand imbalance and precipitation of calcium causing damaging deposits that jam up the mitochondrial infrastructure. It is very possible that the clonazepam was causing progressive mitochondrial dysfunction the entire time he was on it and that it only became apparent once the GABA breaks on energy demand were removed by withdrawal. He briefly restarted an SSRI during this time but it didn’t help and it made him so fatigued he needed four extra hours of sleep per day. Ultimately, the final version of the all-meat Lion Diet helped Jordan recover from akathisia. More recently, however, his parents died and he had been cleaning out their moldy basement preparing for a big move, and this led to an attack of pneumonia and sepsis and a return of his akathisia. The mitochondrial toxins in the mold thus became his third acquired mitochondrial disorder, the first two from withdrawal from SSRIs and benzodiazepines. Jordan and Mikhaila share a lot in their health history but her mom has none of these problems and has never been on SSRIs. Thus, it is very likely there are genetic predispositions to these problems that Jordan and Mikhaila share. The Lion Diet is overall extremely helpful but could probably benefit from specific strategies around managing sulfur metabolism. I will do what I can to help them, starting with looking at their mitochondrial function. I think more specific data will provide insights that they can use to convert the vicicous mitochondrial cycles to virtuous mitochondrial cycles and I hope and pray for Jordan’s robust and lasting recovery.

For the full article, click the link in my profile and click on my web site. It's the first article.

There are thousands of genetic variants and uncountable experiences and exposures that can drive what disease or health looks like for each one of us. For one person, disease is diabetes. For another, it’s heart disease. For another, it’s cancer. For yet another, it’s a neurological disease. And for yet another, it’s chronic fatigue. For one person, peak health is athletic achievements. For another, it’s business. For yet another, it’s leadership and the formation of harmony within a community. And for yet another, it’s contemplation of eternal truths and their articulation in art or writing or speech. But whether we experience health or disease and how much of each we experience comes down to how much usable energy we can extract from food and to what extent we can use the top layer of abundant energy to fuel the commitment of the bulk of the energy toward our health and highest purpose. Living in accordance with the first law can be achieved at many levels: one level applies to how we manage our own health; another applies to how a physician may manage the health of others; yet another applies to the scientists who study how the many things we could be exposed to impact our health. For example, using or prescribing mitochondrially toxic antibiotics for acne before giving the skin enough vitamin B5 to allow its mitochondria to clear away the fatty acids that are fueling the growth of those bacteria violates the first law. Consider high cholesterol. Training the liver’s mitochondria to produce abundant energy through fasting and intense exercise will improve the ability of the liver to fuel the energy-intensive clearance of cholesterol from the blood. To do this before resorting to strategies focused exclusively on micromanaging the production of the cholesterol transporters with fiber, ezetimibe, seed oils, and statins is to live in accordance with the first law. A scientist trying to solve the protracted withdrawal syndromes of benzodiazepines and SSRIs by focusing exclusively on neurotransmitters does not walk in the way of the first law. To walk in its way, the scientist must consider how these drugs distribute through the entire body, entering cells in every tissue and altering their mitochondria.

The Five Laws of Mitochondrial Health Living in accordance with these laws keeps us on the path to vibrant health.