Chris Masterjohn, PhD

4 days ago | [YT] | 161

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…

1 week 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-…

3 weeks 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

4 weeks 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…

1 month ago | [YT] | 35

Chris Masterjohn, PhD

Are Antidepressants Just Treating Protein Deficiency?

This one amino acid outperforms antidepressant drugs in clinical trials but protein itself would be even better.

Getting protein up to 120 grams per day for women and 160 grams per day for men would likely massively outperform antidepressant drugs just by itself, and these targets form a central foundation of the Depression Protocol.

While this relates to much more than tryptophan, getting enough tryptophan is certainly part of it, so we start by looking at the randomized controlled trials of this one powerful little amino acid.

Click through to read the analysis here:

chrismasterjohnphd.substack.com/p/are-antidepressa…

1 month ago | [YT] | 30

Chris Masterjohn, PhD

The Science Behind The Depression Protocol

🚨Free to read TODAY ONLY! 🚨

The Depression Protocol contains the practical how-tos to beat depression without SSRIs or other drugs.

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 free today only and is reserved for Masterpass members starting 4PM Eastern tomorrow.

Click through to read it while it's still free!

chrismasterjohnphd.substack.com/p/the-science-behi…

1 month ago | [YT] | 11

Chris Masterjohn, PhD

Placebos are more effective than drugs for depression.

Before you stop me and say "false, drugs outperform placebos," you are correct, they do.

But placebos are 40% effective and drugs 54% effective, which means that 74% of the drug's effect is explained by the placebo effect.

In order to properly understand this you have to realize that every treatment *is* a placebo.

The point of comparing it to the placebo is to subtract the proportion of its impact explained by the placebo effect.

So, 74% of a drug's effect is placebo, and 26% of it is biochemical.

That means that the placebo effect is 2.8 times more powerful than the pharmacological effect of the drug's biochemistry!

1 month ago | [YT] | 50

Chris Masterjohn, PhD

Beat From Depression Without SSRIs or Other Drugs

The ultimate how-to guide to obtain resilient mental health while boosting mitochondrial function instead of strangling it.

The first-line treatment for depression in modern society is SSRIs, but long-term SSRI use can cause sexual dysfunction, it can cause severe mitochondrial dysfunction in a rare subset of people, and years-long SSRI use leads to severe withdrawal syndromes becoming common and often leads to new-onset mitochondrial function that lasts years.

While 80% of psychiatrists would put a depressed person on an SSRI, only 40% of them would put themselves on an SSRI if they were depressed.

Even psychiatrists do not understand how SSRIs work: they thing they are mood-boosting drugs that offer some kind of normalization or reset to the neurotransmitter effect of serotonin, but in fact they act through the whole body, have enormous impacts on mitochondrial function, interfere with the necessary benefits of intracellular serotonin and mitochondrial melatonin to mitochondrial energy production, and themselves enter cells where they can have disparate but sometimes powerful impacts on the sigma-1 receptor (beneficial but meant to be activated cyclically, not chronically) and themselves can act as mitochondrial poisons once they reach the mitochondria.

To make matters far worse, many people are prescribed SSRIs by general practitioners, who lack both an understanding of how SSRIs work and also lack the expertise to do a thorough psychological evaluation of the person.

It may surprise you that SSRIs do not have a randomized controlled trial basis to justify the way they are used clinically, nor do they even have superior randomized controlled trial results to drug-free approaches!

For example, there are 52 trials in adults with SSRIs with the average lasting eight weeks, most lasting no longer than twelve weeks, and the longest lasting a year, and zero evidence justifying the average clinical use lasting five years.

While SSRIs have 52 trials and about 10,000 total subjects studied, supplements have 192 trials with just under 17,000 total subjects studied.

Psychotherapeutic approaches had 198 trials in adults with over 15,000 total subjects studied over a decade ago and have far more now.

Exercise approaches in adults have over 218 trials with just over 14,000 subjects studied.

So, just three classes of drug-free approaches to depression combined have twelve times as many clinical trials in adults as SSRIs have with almost five times as many total people studied.

What may surprise you even more — often a single supplement outperforms an SSRI when it is almost certain that a depressed person actually needs multiple corrections to their nutritional status.

This is often true in the average person without doing any testing, when individualizing correction of nutritional status would certainly provide superior results.

Nevertheless, these trials are not all of equal quality, and interpreting them is best done with biochemical and physiological expertise in how the treatments work to assemble how they can best be synergistically combined in different people.

Further, even some herbal medicines have impacts very similar to SSRIs and carry some of the same risks. Thus, understanding how the herbal medicines work and comparing their trials to the SSRI trials is necessary for safe implementation of a protocol.

To help you do this for yourself, or, if you are a health care practitioner, for your patients, I have analyzed the research and produced a 17-page how-to guide, How to Heal From Depression Without SSRIs or Other Drugs.

This synthesizes the best of a scientific and mechanistic understanding of how depression is caused and how to heal from it with an evidence-based analysis of the hundreds of randomized controlled trials showing human outcomes of improvement in depression.

This is not a review of the evidence. I will review the evidence in a separate article. This is strictly a step-by-step how-to guide.

It provides three approaches:

A five-page guide to “throwing the kitchen sink” at it for people who need fast results.

A three-page guide to “try it and see if it works” for people who want to engage the middle of the road approach between quick results and quality results.

A nine-page guide to “optimize it” for the people who want to invest time and money in a slow-and-steady-wins-the-race approach to secure the highest quality results for the long-term.

Click here to get the guide:

chrismasterjohnphd.substack.com/p/beat-from-depres…

2 months ago | [YT] | 34