The episode features Chris Masterjohn, PhD, a nutrition researcher with 21 years of experience specializing in mitochondrial function and metabolic health. Host Joe Rogan explores evidence-based nutrition science, debunking common myths and examining the biochemical mechanisms underlying health and disease.

The conversation begins with the tryptophan-turkey myth before diving deep into mitochondrial energy production as the foundation of all health outcomes. Masterjohn presents his thesis that mitochondrial dysfunction drives aging and that individuals have significant control over this process through diet, supplementation, and lifestyle choices.

Major topics include the controversial role of seed oils in atherosclerosis, the importance of creatine beyond muscle building, optimal exercise strategies based on longevity data from professional athletes, and the critical but overlooked role of thyroid function and iodine status in modern health.

The discussion emphasizes a food-first, pharmaceutical-last approach to health optimization, with detailed exploration of specific supplements like CoQ10, methylene blue, and natokinase, along with practical testing strategies for personalized nutrition interventions.

The Tryptophan Myth and Digestive Biology

"Turkey is not that high in tryptophan - even whey protein is higher in tryptophan than turkey is, and tryptophan doesn't make you tired" - Chris. The myth originated from journalists in the 1980s looking for explanations for post-Thanksgiving fatigue.

Overeating activates the parasympathetic nervous system, called the "rest and digest system," which is biologically wired to make you sleepy after consuming large amounts of food, similar to lions resting after a kill.

"We are biologically wired to be alert when we need to work to get our food, and then we're wired to eat that food, feel like we've gotten our fill, and now we can rest" - Chris

Mitochondria as the Root of Health and Aging

"The crowning thesis of my work so far is that we really want to be thinking about mitochondrial function at the root of all health and disease" - Chris. Deep sleep's primary function is giving mitochondria rest to restore energy reserves.

Sleep deprivation study showed subjects taking 20 grams of creatine through the night performed significantly better on brain puzzles because creatine acts as the "power grid" distributing mitochondrial energy throughout cells.

Mitochondrial function declines at an average rate of 1% per year from age 18 through age 70-80, resulting in half the baseline energy production by age 70, but age only explains 25% of this variation.

"75% of mitochondrial decline is under your control" - Chris. The goal is to make mitochondrial function decline only 10% by age 70 instead of the average 50% through lifestyle optimization.

Aging creates a vicious cycle where mitochondria have slightly less energy for self-repair after each stress event (illness, injury, overtraining), leading to progressively worse function over time.

Creatine Beyond Muscle Building

"Almost every cell and every tissue has the creatine system" - Chris. Creatine is distributed throughout the body including the retina, stomach acid production, and sperm motility, not just muscles.

Traumatic brain injury research showed 20 grams of creatine daily for six months doubled the rate of healing, demonstrating significant neurological benefits beyond athletic performance.

"If you're not eating one or two pounds of meat per day, you should probably be taking creatine" - Chris. Red meat eaten rare retains more creatine than white meat cooked well done.

Most brain research uses doses around 20 grams daily because muscles take first priority for creatine absorption, requiring higher doses to reach the brain effectively.

The theoretical vegan diet providing adequate creatine would require half a kilogram of tofu and half a kilogram of tempeh daily, which is impractical and potentially digestively damaging.

Red Light Therapy and Vision Improvement

Joe Rogan reported stopping macular degeneration and reversing some vision loss after 1.5-2 years using a red light bed combined with lutein and zeaxanthin supplementation from Pure Encapsulations Macular Support.

"Red light energizes cytochrome c oxidase, which is complex four of the mitochondrial energy production engines, and orders the water structure inside mitochondria to make those engines produce energy more easily" - Chris

Recent study showed blasting people's chests with red light improved their vision systemically, demonstrating that benefits don't require direct eye exposure due to coordinated whole-body energy metabolism.

Lutein and zeaxanthin are best sourced from egg yolks, especially from chickens fed marigolds which are super high in these compounds. The egg yolk fat enhances absorption.

Morning sunlight provides red and infrared wavelengths without burning risk, allowing 1-2 hours of safe exposure. Afternoon sun requires more caution due to UV intensity.

Five Essential Mitochondrial Optimization Strategies

Creatine optimization is first priority for anyone not consuming 1-2 pounds of meat daily, with dosing adjusted based on meat type (red vs white) and cooking method (rare vs well done).

Morning sunlight exposure is critical for mitochondrial wake-up signaling. "If you don't have morning sunlight, you are going to have your mornings full of suboptimal energy metabolism that is initiating that vicious cycle of aging" - Chris

Comprehensive nutrition is third priority: 93% of Americans are deficient in at least one nutrient, 30% have verifiable blood markers of deficiency, and 6% have markers of two or more deficiencies.

Nose-to-tail eating is essential - incorporate liver, heart, kidney, and bone broth. Chris personally eats 60% ground beef blended with liver, heart, and kidney for comprehensive nutrient coverage.

Diverse exercise training is fifth priority: "You really want to be hitting strength, endurance, mobility, agility, balance, proprioception, reaction time, and cognitive exercise" - Chris. Each type trains mitochondria in different tissues.

Gymnasts Live Longest: Exercise Insights

2024 study analyzing hundreds of professional athletes adjusted for population mortality rates found gymnasts and pole vaulters live eight years longer than the general population, while cyclists gain only two years.

"Sumo wrestlers are 10 years below" average lifespan. Sports with high injury rates, especially impacts to hands and martial arts, showed mortality close to general population despite fitness benefits.

The commonality between gymnasts and pole vaulters isn't height (gymnasts are short, pole vaulters are tall) but coordination, explosive movement, skill training, and time spent upside down.

Rodent study showed stretching prevents tumor growth, potentially through mechanical effects on T cell activation. T cells need to push off their environment to activate, and cancers modify extracellular environment to compromise this.

"You don't want to get sucked into just optimizing VO2 max" - Chris. The lesson from gymnasts is identifying all the movements you cannot do and incorporating them into training, not just cardiorespiratory fitness.

Chris personally converted workouts to gymnastic versions: "Why would I overhead press when I could try to do wall push-ups now? My hope is by next year I'll be able to do handstand push-ups."

CoQ10: Dosing, Benefits, and Individual Variation

CoQ10 is naturally made in the body and most abundant in heart tissue. "Heart is the best" food source - Chris recommends eating heart before supplementing.

Heart disease literature shows dose-response curve: 100-200mg daily improves blood pressure, glucose, and insulin in average person, but 400mg actually worsens these markers with huge individual variability.

Case study: Client named Jacqueline lost her period at age 28 for 10 years. Mitochondrial testing showed specific CoQ10 need. "Two weeks into taking 700-800 milligrams, she got her period back after 10 years" - Chris

Some people report insomnia, racing heart, or palpitations at just 100mg, demonstrating hypersensitivity. "It's not common, but all the people with uncommon stuff always ask me about it" - Chris

CoQ10 sits about two-thirds through the mitochondrial electron transport pathway, acting like a ferry across a river. Too much creates traffic jams and accidents in the mitochondria.

"If you're going to supplement with CoQ10, I'm kind of like, you should play around with it. You very well may benefit from 100-200 milligrams a day. But my food-first pharma-last approach is: did you eat heart today?" - Chris

Methylene Blue: Detours and Blockages

"Methylene blue is a very nonspecific rewirer of how your mitochondria produce energy" - Chris. It was originally patented as clothing dye that wouldn't wash out, then became the first pharmaceutical drug.

Methylene blue acts like "shady taxis at the airport" - creating detour signs throughout mitochondria. Helpful if main pathways are blocked, but creates chaos if pathways are functioning normally.

Clinical Alzheimer's trials use 200mg doses, but consumer products on Amazon contain as little as 0.5mg. Around 10mg daily provides some monoamine oxidase inhibitor effects (antidepressant action).

"I wouldn't even take methylene blue without testing showing that I need it" - Chris. One client's energy dropped from 50% to 5% on just 0.5-1mg daily due to worsening mitochondrial function.

Animal experiments show methylene blue only improves ATP production when specific mitochondrial inhibitors are present. Without blockages, it makes mitochondria less efficient at converting food to usable energy.

The Seed Oil Controversy and Atherosclerosis

"Seed oils make your tissues more vulnerable to damage" - Chris. The controversy exists because short-term trials miss effects that take years to manifest as tissue damage accumulates.

LA Veterans Administration Hospital study (longest seed oil trial) showed initial heart disease benefit in first two years, but cancer rates diverged at 2-5 years, widening significantly by 5-7 years with seed oils causing more deaths.

Minnesota Coronary Survey data found in deceased investigator's basement decades later showed seed oil group had double the atherosclerosis despite lowering cholesterol. "Every 35 milligram per deciliter drop in cholesterol was associated with 30% more heart disease."

"It takes you four years just for your tissues to start looking like the seed oil you're eating" - Chris. Switching from butter to corn oil today means tissues won't reflect that change until four years later.

Daniel Steinberg, who chaired the 1984 NIH Consensus Conference leading to Time magazine's anti-cholesterol cover, discovered that polyunsaturated fats in LDL particle membranes drive plaque formation through oxidative damage.

Olive oil emerged as compromise after LA Veterans study suggested seed oils cause cancer: "We already told people to eat corn oil because they can't eat saturated fat, so what are we going to tell them to eat?" - Chris explaining historical context

Hexane residue testing showed all solvent-extracted oils contain residual hexane, with pump spray oils showing massive amounts of unknown chemical solvents. "After I saw that, I was like, I'm never using a pump spray oil" - Chris

Cholesterol, Statins, and Metabolic Signaling

"Higher LDL cholesterol is actually associated with longer lifespans" in elderly populations, though younger people with high cholesterol may have sluggish metabolism indicating poor cholesterol utilization.

Cholesterol clearance from blood is driven by mitochondrial energy production signaling to the hypothalamus about abundance state. Poor mitochondrial function causes the brain to perceive scarcity even with adequate food intake.

"Statins are mitochondrial toxins" - Chris. They inhibit CoQ10 synthesis and other mitochondrial energy production pathways that cannot be supplemented, causing diabetes and further mitochondrial dysfunction.

Atherosclerotic plaque forms when immune system quarantines damaged LDL particles loaded with oxidized seed oils. "The outside is fatty acids, specifically phospholipids. When they get damaged, the immune system recognizes it as a toxin."

Broda Barnes argued in Solved the Riddle of Heart Attacks (1976) that hypothyroidism drives heart disease. Practitioners lowered cholesterol and heart disease risk with thyroid hormone until the 1970s when overdosing deaths ended the practice.

"You should always be trying to optimize mitochondrial function first with natural foods before you try anything else. If you're going to build your house out of pharmaceuticals, do it on a good foundation" - Chris

Thyroid Function and Iodine Requirements

Thyroid hormone is made from tyrosine (from dietary protein) plus iodine. Adequate protein and iodine are the "step one basics of the 101 of the nutrition" for thyroid function.

Seafood is reliably high in iodine because minerals concentrate in oceans, while land-based foods vary 100-fold depending on soil and rainfall patterns around mountains affecting iodine distribution.

"I personally add in a quarter teaspoon of kelp powder to my food. I fortify my own food myself instead of letting the government do it" - Chris recommends eating fish 1-2 times weekly or daily seaweed.

Women with larger breasts can need much more iodine, with fibrocystic breast disease responding to 10-50 times normal iodine intake. Toxic environments with bromine (flame retardants, synthetic materials) increase iodine requirements.

Fluoridated water and toothpaste increase iodine needs. Salt iodization solved deficiency until anti-salt campaigns inadvertently created new deficiency. "I see people walking in with a lump in their throat now" - Midwest cardiologist quoted by Chris

"Every time I've seen a woman who's on thyroid hormone and had them get iodine data, their iodine is low and they've never gotten it tested before" - Chris on medical oversight

Selenium supplementation lowers autoimmune antibodies in Hashimoto's thyroiditis by helping glutathione protect the thyroid from oxidative damage during hormone production. Vitamin C, zinc, copper, manganese, and iron are also critical.

High-Dose Thiamine and Supplement Dangers

Online communities promote 2,000mg daily thiamine (versus 1.3mg RDA), but one client's energy dropped from zero to negative on 1,100mg daily with worsening dizziness and new motor dysfunction.

"People who get miracles are vocal. They make communities on Facebook. So people get the idea that everyone who tries it is benefiting from it" - Chris on selection bias in supplement testimonials.

Mitochondrial testing revealed the client had a blockage where thiamine acts, creating a "train wreck" in her mitochondria from mega-dosing. Lactate testing at home would have caught this within days.

"If you don't have the expertise to run around taking different things that you don't understand, if you don't understand the biochemical pathway of the thing you're mega-dosing, you are not a candidate" - Chris

Food-first approach with nutritional yeast (high in thiamine) would have provided gradual increase with other nutrients preventing imbalance. "Warren Buffett once said diversified portfolio is great protection against ignorance" - Chris applying investment wisdom to nutrition

Natokinase and Blood Clot Prevention

Most heart attacks occur when atherosclerotic plaque ruptures and forms blood clots large enough to block arteries, not from plaques gradually narrowing vessels. Plaque typically grows backward away from blood flow.

Inflammatory process inside plaques, especially from oxidizing seed oils going rancid, degrades collagen. Micro-tears heal with scar tissue buildup, eventually narrowing vessels through repeated breaking and scarring.

Natokinase enzyme from Japanese fermented soybean paste (natto) breaks apart blood clots. Natto also contains high vitamin K2, which protects against calcium deposits weakening plaques. "Actually, just eating natto would be better" - Chris

People with systemic inflammation, genetic clotting defects, or severe atherosclerosis may clot daily. "Every day might be a new day where they can have a heart attack" - taking 2,000 IU natokinase may prevent heart attacks or strokes by degrading clots quickly.

Downside risk is increased bleeding if cut, but upside potential is preventing potentially fatal cardiovascular events in high-risk individuals through faster clot degradation.

Testing Strategy and Energy-to-Anxiety Ratio

"A really good definition of health is you should be abundantly supplied with all the energy you need to fulfill the goals you're trying to fulfill, and you should be adaptable enough to handle things changing" - Chris

"The North Star to know that you are healthy is that your energy-to-anxiety ratio is very high and your libido is very strong" - Chris. These are primary indicators of optimal mitochondrial function.

The last 10% of energy production determines where all energy goes. Declining mitochondrial function may not cause fatigue but instead wastes energy as anxiety, reducing productivity despite feeling wired.

Home testing of glucose, ketones, and lactate provides real-time mitochondrial dysfunction indicators. "If lactate goes down, it's good. If it goes up, it's bad" - Chris recommends this for anyone mega-dosing supplements.

"All medical diagnoses are false, but some are useful" - Chris adapting statistical principle. Medicine thinks in binaries and ignores details that don't change treatment decisions, leaving historical threads unexplored.

Mitochondrial testing is especially important for serious conditions like traumatic brain injury where "you have a six-month window where you need to maximize everything you can" to identify limiting bottlenecks.

Scientific Incentives and Lost Knowledge

Study showed average age of NIH-funded principal investigators increased by one year per year since 1984, suggesting "one group took over the money in 1984 and they've just been giving themselves grants ever since" - Chris

Grand 5-8 year nutrition trials conducted between World War II and 1970s don't exist anymore due to modern incentive structures requiring yearly publications in high-impact journals and preliminary data for grant cycles.

"Scientists concluded in 1969 that the gap in knowledge was we need a trial a lot longer than eight years. And what did we get? Seven to 12-week trials" - Chris on regression in research quality

Time magazine's 1984 "Hold the eggs and butter" cover with frowning face made of bacon and eggs was reversed years later to smiley face with "Scientists labeled fat the enemy. They were wrong." But damage was done.

Sugar industry paid researchers approximately $50,000 in 1960s to shift blame from sugar to fat, fundamentally altering dietary guidelines and ruining public health for decades with relatively small bribe.

Daniel Steinberg, who chaired 1984 NIH Consensus Conference and won Nobel Prize for LDL receptor discovery, showed seed oil PUFAs drive atherosclerosis, but this finding was ignored because "it doesn't change whether I'm going to give you a statin" - Chris