You’re Treating the Wrong Problem | Dr. Chris Masterjohn EP 231
In a Nutshell
Dr. Chris Masterjohn debunks the serotonin-mood myth, revealing SSRIs and benzodiazepines as misunderstood mitochondrial disruptors that block serotonin-melatonin conversion, force constant stimulation, and cause severe, protracted withdrawal mimicking Parkinson's via energy deficits in Complex I-IV. Mitochondrial dysfunction underlies aging (1% yearly decline), chronic illnesses, inflammation, SSRI damage, mold toxicity, and supplement intolerances like sulfur/methylation overloads from high red meat/low-carb diets—fix via Maidome testing (mito.me) for personalized nutrient cocktails (e.g., carnitine, folinic acid, microdosed creatine) over mega-doses. Top supports: nutrition (organ meats, unfortified yeast), sunlight/exercise/sleep cycles, cholestyramine for toxins, and avoiding synthetics like SS-31; rest breaks vicious energy budget cycles from burnout or insults like COVID/Lyme.
These notes were generated by AI and may contain inaccuracies.
The idea that serotonin primarily acts in the brain on neurons to boost mood is nonsense, stemming from an SSRI marketing campaign in the 80s. Chris Masterjohn has a PhD in nutritional sciences and uses it to help people harness nutrition for vibrant health. Mitochondrial function declines 1% per year with age, the major driver of aging.
SSRIs and benzodiazepines are mitochondrial drugs in ways prescribers do not understand. They force constant stimulation without cycling between stimulation, rest, and recovery.
Host's dad has been very ill; SSRIs and withdrawal treated with clonazepam neurologically injured him, resembling Parkinson's but not. Family has chronic health issues back to great-grandparents.
Chris Masterjohn runs Maidome, a mitochondrial testing company. His work shows all health and disease driven by mitochondria's ability to convert food energy into ATP for body maintenance, repair, and distribution. Time split between new research, reanalyzing centuries-old research, and developing strategies with or without testing.
Testing focuses on actionable, unique insights, not just good/bad. Measures specific engines in the electron transport chain with nutritional implications (e.g., vitamins like CoQ10). Mitochondrial cocktails target specific roles; testing reveals unique needs.
All-meat diet (lion diet) transformed host's, dad's, and mom's health. Later research links benefits to ketosis or other factors. Got sick again in Miami from black mold, symptoms recurred despite unchanged diet, suggesting mitochondrial impact from both food reactions and mold.
Many factors negatively impact mitochondria, causing diverse symptoms.
Host's history: inflammatory disease in youth, Enbrel at 8 years old led to mental problems, SSRIs, diet fixed it, SSRI withdrawal catastrophe, red meat and carbohydrate restriction turning points, mold toxins.
Enbrel blocks TNF-alpha. Pattern: mitochondrial dysfunction causes toxic metabolite buildup from incomplete food processing; fixed by carnitine (made in body or from red meat). TNF-alpha signals carnitine import. Inflammatory disorders responding to TNF-blockers often precede mental health issues on the drug because TNF serves a purpose in carnitine delivery.
Blocking TNF stops inflammation (e.g., arthritis, psoriasis, Crohn's) but worsens mitochondrial function, depleting brain energy for mental health control.
Persistent cough led to research on T-cells failing to resolve inflammation. Active T-cells fuel on carbohydrate and glutamine; lion diet removes carbs, calms T-cells, provides carnitine from red meat, addressing childhood inflammation.
Over 10 years off SSRIs, which were more detrimental than mold or other exposures. Reactions lessened but feels best on meat. Dad neurologically injured by SSRIs and clonazepam withdrawal.
Family struggles with supplements (e.g., CoQ10, B vitamins) causing excess energy/agitation. Intolerance to most, except folinic acid. Suggests inability to tolerate helpful mitochondrial supports.
Supplement intolerance often idiosyncratic, but none tolerated points to issue. Folinic acid tolerance suggests secondary sulfur toxicity explaining glutathione intolerance.
Red meat, low-carb diet high in sulfur amino acids (e.g., methionine, cysteine); body makes carbs from them. Sulfur interwoven with methylation (methylfolate vs. folinic acid). Excess methylation breaks down sulfur amino acids, causing mitochondrial/neurotoxicity, agitation, restlessness, insomnia, restless legs.
Host experienced severe insomnia from methylfolate, folic acid; B1 less bad but still issues. Mom on same diet fine; host and dad share SSRI history and prior B-vitamin intolerance (dad's 10 years pre-SSRI).
B vitamins interact with methylation/sulfur metabolism; excess aggravates catabolism, causing insomnia, anxiety, restlessness. Red meat low-carb predisposes. Work within diet to gently boost nutrients.
Supplement-intolerant: analyze diet micronutrients, gently increase via food (not mega-doses). 200mg reaction doesn't mean no need for 2mg from diet.
Maidome testing avoids trendy mega-dosing pitfalls (e.g., high-dose thiamine 1000-2000mg helped fatigue but caused neuromuscular issues like imbalance; testing showed pathway block, food-based B vitamins + PT resolved).
General rule: if no good reaction to mega-dosing, stop.
Organ meats (liver highest in nearly all B vitamins), unfortified nutritional yeast (avoid fortified to get food-based nutrients).
Host couldn't handle liver early in meat journey despite tolerating other beef; likely B vitamins, vitamin A, or copper overload. Specific folinic tolerance supports B-vitamin issue. Start low (e.g., one liver capsule).
Need to do mitochondrial test; in touch with many doctors.
They ran genetic screening using sequencing.com and third-party sites, revealing methylation problems and COMT issues. B vitamins cause skyrocketing symptoms, making the patient look hospitalized. Comprehensive mitochondrial testing is recommended to interpret whole genome sequencing better, as it identifies specific mitochondrial defects with genetic bases. AI helps but data volume remains overwhelming.
Dad's symptoms resemble previous neurological damage flaring without trigger. People on SSRIs or benzodiazepines report protracted withdrawal lasting years. Randomized controlled trials show withdrawal rare, benign, and self-resolving, but trials last 12 weeks max (one year-long placebo-controlled), while average use is 5 years with no 5-year trials.
Observational literature shows worse outcomes: harder to quit after 2 years, catastrophic after 5-12 years. Among those on SSRIs ≥1 year, 38% tried quitting and restarted due to inability. Many suffer severe, life-destroying withdrawal (lost marriage, job) but dismissed. Long-term use is primary issue; short trials cannot generalize to 5-year experience, similar to fish oil looking good at 12 weeks but poor at 4-6 years.
Pharma knows trials too short but designs them that way. Human metabolism complexity means drugs have unintended effects, often primary mechanisms mislabeled 'off-target.' SSRI science distorted serotonin science: serotonin primarily aids mitochondrial adaptations to oxygen deficits, not just brain mood boosting (80s marketing).
Serotonin's True Role
Serotonin directs blood from poorly oxygenated lung segments to oxygenated ones. Hypoxia includes exercise (relative deficit) or morning metabolic ramp-up. Morning sunlight signals brain serotonin rise for adaptations. Serotonin controls breathing rate via brainstem release during oxygen shortfall. 95% gut serotonin regulates motility: food digestion consumes oxygen; serotonin pushes food to prevent hypoxia. SSRI 2-week nausea from gut serotonin overdose. Serotonin syndrome (MAOI + SSRI) causes hyperventilation.
Serotonin coordinates breathing, mitochondrial energy production, protein synthesis body-wide.
Serotonin is the traffic cop that sends the blood away from the poorly oxygenated parts to the oxygenated parts.
Dad's family depression (crippling, immobile) links to B vitamin issues; SSRIs initially helped breathing ('I can breathe'), sleep, relaxation—life-saving then ruining. Depression tied to inhalation difficulty, misattributed to anxiety.
Breathing rate physiologically controlled by serotonin, which drugs target unknowingly.
SSRI Mechanisms and Withdrawal
SSRIs block neuronal reuptake but actually prevent serotonin cell entry body-wide (brain, tissues, placenta, gut), blocking mitochondrial access. Serotonin enters cells, acts on mitochondrial receptors, converts to melatonin for benefits. SSRIs partially facilitate adaptations but block others.
SSRIs enter cells, activate non-serotonin receptors for cyclical stress responses, forcing constant mitochondrial stimulation (pedal to metal 24/7), leading to addiction-like dysfunction on withdrawal.
Benzodiazepines (e.g., clonazepam) act on GABA (inhibitory); withdrawal overactivates neurons, spiking mitochondrial demand to toxic levels. Clonazepam enters mitochondria, switches them on (dose-dependent).
Dad's SSRI withdrawal catastrophic post-sodium metabisulfite (apple cider preservative): sleepless 2-3 weeks, couldn't walk, green, hunched. Clonazepam normalized sleep, breathing, function.
Sulfur problems common thread. Energetic crisis breaks down sulfur amino acids, producing sulfite (glutamate activator) if pathway incomplete. Apple cider sulfite stimulated glutamate; clonazepam activated GABA—opposing levers.
SSRIs/benzos are mitochondrial drugs with unknown effects; toxicity possible during use, but new-onset dysfunction more common post-withdrawal. Triggers idiosyncratic.
Cases: SSRI withdrawal caused neuromuscular/urinary/electrolyte issues, 17 lbs muscle loss (functional but impaired); another early-20s male bedridden year (month unable to bathroom). Tests differ.
First case: couldn't transport methyl groups to mitochondria due to genetic mutation blocking transporter. Methylation crucial for mitochondrial engines. Protocol: microdosed creatine (100mg increments to 1-5g over months), methylation-centric (accelerated). By 6 weeks: better than years; 6-8.5 months: life back; 1 year: regained 17 lbs muscle, stable.
A lot of people that talk about methylation don't talk about how important it is to actually produce the engines in the mitochondria that make your energy.
Microdosing creatine advised if full doses (scoop) feel off (not agitation like B vitamins).
Isotopic labeling tracks external vs. cell-made serotonin entry. Isolated mitochondria: serotonin incubation spikes melatonin (absent without). Receptor blockers confirm specificity. Multiple angles converge.
Medical diagnoses predict treatment response; all models false, some useful (distort reality). Parkinson's-like symptoms from many causes; new term needed.
For dad (neurological injury, not psych/Parkinson's): do mito test, identify blocked pathways, slowly rebuild.
The term parkinsonism distinguishes diseases causing Parkinson-like symptoms from actual Parkinson's disease. The primary animal model for Parkinson's uses rotenone, a fish poison and specific inhibitor of Complex I in the mitochondrial electron transport chain—tested in their mitochondrial test. Whether it's true Parkinson's or parkinsonism doesn't matter because neuromuscular dysfunction results from mitochondrial dysfunction: insufficient energy production impairs control over energy allocation.
Everyone knows energy is needed for activity, but resting and sleeping also require energy to direct it properly—like trucks burning gas to deliver Tesla batteries and gasoline. Parkinsonism symptoms illustrate this:
- Tremor: inability to control whether the hand is relaxed or active, stuck in between.
- Rigidity: inability to control when muscles are flexed or relaxed, stuck in between.
- Parkinson patients often can't complete strong movements; they contract constantly without need but can't deliver controlled contractions.
The top 20% of energy controls the bottom 80%. Losing it, especially in brain areas controlling movement, causes these symptoms. Categorizing diseases has value, but medicine misses that combining half of two diseases creates a "rare undiagnosable disease." Viewing health as a continuum focuses on underlying biochemistry and fixes, not rigid diagnoses.
Maidome operates outside medical diagnosis, helping people understand their biochemistry to self-improve. Specialists and diagnoses have their place, but many feel unwell with no doctor answers. Test when you've hit the wall of your knowledge—doing everything right but needing missing pieces. For the host's knowledgeable dad, testing provides those pieces.
Chronic conditions like autoimmunity and mental illness manifest differently but can be treated similarly. Example: In the hospital, idiopathic arthritis patients were next to lupus; a rash would shift classification. Splitting research by slight differences ignores shared symptoms.
Top five for mitochondal health:
- Good nutrition.
- Sunlight.
- Exercise.
- Sleeping cycle.
- Robust fasting-feeding cycle for mitochondrial regeneration (no strong opinion on specific fasting).
Biohacking devices replace missing nature:
- Morning sunlight provides red light and near-infrared; use red light saunas or near-infrared saunas if benefiting more than sun without burning.
- Get morning sun (not all at noon for vitamin D)—stay out hours without burning in most places.
- Traditional saunas benefit health, likely via sweating toxins and lowering core body temperature. Genetic mutations can overheat enzymes; sauna cools the body, countering effects.
Empirically judge what works: have a strategy, evaluate with intuition or data, avoid mindless use.
SS-31, touted as a mitochondrial peptide, showed no benefit in the largest study—doubled risk of side effects like headaches. Subgroup with mitochondrial DNA mutations hinted benefit, but needs RCT. On first principles, synthetic peptides conceived by biochemists (targeting antioxidants to mitochondria) are unexciting until proven; nature-inspired ones work better.
Mitochondrial peptides like MOTS-c and humanin are produced naturally in response to exercise. Beneficial for old, out-of-shape people breaking vicious cycles to start exercising—not for younger, capable people who should exercise to produce them naturally.
Host distrusts synthetics after childhood meds and SSRI damage; food and organs seem better. Binders helped post-mold illness; cholestyramine (still used occasionally) made a huge difference, alongside meat.
Cholestyramine originally a cholesterol-lowering drug, used in 1984 trial "proving" cholesterol causes heart disease. Binds bile acids for excretion; liver pulls cholesterol from blood and ramps up synthesis to replace it (unlike statins). In cholesterol synthesis pathway (30-40 steps, branching), end products include CoQ10 and heme A—essential for mitochondrial engines (Complex III and IV).
Mold toxins are mitochondrial toxins; cholestyramine removes them via bile. Additionally, depleting bile acids ramps the pathway, boosting mitochondrial components independently. Host started full dose, got walloped with mold symptoms (re-exposure theory), titrated up slowly. Likely also acute cholesterol deficit tanked cellular/mitochondrial membranes until pathways adapted.
Dad has CIRS, sensitive to mold buildings. High-performers hit by long COVID, Lyme, chronic illness may suffer stress-induced mitochondrial dysfunction from burnout—not resting properly.
Mitochondria decline 1% per year with age—major aging driver. They fuel body-wide production, maintenance, repair, distribution—including their own. Daily energy budget requires rest/recovery after insults (COVID, Lyme, injuries, trauma) to avoid bankruptcy.
Normal aging: mitochondria miss 1% needed maintenance, function drops 0.01%. Insults compound; without rest, vicious cycle accelerates. High-performers refusing rest push into deficits earlier, turning insults into permanent mitochondrial damage.
Host ordering test at mito.me. Dr. Masterjohn at chrismasterjohnphd.substack.com (newsletter), mito.me (testing), all platforms.
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