Carbon dioxide molecular structure
Carbon dioxide molecular structure

Carbon dioxide (CO₂) is a gas cells make when they burn fuel with oxygen, especially glucose (blood sugar). Efficient burning in the mitochondria yields CO₂, water, and energy (ATP).

Retained CO₂ firms blood vessels, helps deliver oxygen to tissues, protects proteins, and opposes leaky low-energy states. Sugar oxidation makes more CO₂ than fat oxidation does.[1]

Oxidation of sugar is metabolically efficient in many ways, including sparing oxygen consumption. It produces more carbon dioxide than oxidizing fat does, and carbon dioxide has many protective functions, including increasing Krebs cycle activity and inhibiting toxic damage to proteins.

— Ray Peat[2]

The Krebs cycle is the main aerobic path that turns fuel fragments into CO₂ inside mitochondria.

Directly measuring CO₂ inside living cells has been difficult; a 2026 study introduced CarboSenR2, a fluorescent molecular sensor validated as sensitive across the physiological and pathophysiological CO₂ range, and used it to reveal mitochondria-associated CO₂ microdomains within cells.[3]

Respiration, calcium, and PTH

Respiration and CO₂ push against parathyroid hormone (PTH). PTH raises blood calcium by drawing from bone and gut when the mineral signal is wrong. Steady CO₂ production belongs with thyroid, progesterone, and adequate salt in the same protective set.[4]

Respiration and carbon dioxide are the basic antagonists of the PTH.

— Ray Peat[5]

Hyperventilation

Hyperventilation is over-breathing. It dumps CO₂. Two minutes of it already raises leakage from blood into the lungs and lifts serotonin and histamine (inflammatory signals).[6]

Simply hyperventilating for a couple of minutes will increase leakage from the blood into the lungs; hyperventilation decreases carbon dioxide, and increases serotonin and histamine.

— Ray Peat[7]

Chronic respiratory alkalosis (blood too alkaline from low CO₂) raised serum phosphate and PTH and lowered calcium in human work (Krapf et al.) cited in the phosphate essay.[8][9]

Altitude

At altitude, oxygen pressure falls. Slight CO₂ retention improves oxygen unloading into tissues (Bohr effect: CO₂ helps hemoglobin release oxygen). Adapted high-altitude workers make less lactic acid at the same work rate (lactate paradox). Retained CO₂ calms cell excitation and supports burning lactate through oxidation.[10]

A 2025 hypothesis paper builds directly on the Bohr effect to explain aging: falling mitochondrial CO2 output weakens oxygen release from hemoglobin, and the resulting tissue hypoxia (via HIF-1 stabilization) further suppresses mitochondrial function, closing a self-reinforcing "aging spiral" that stays reversible only until cellular energy drops below the threshold needed for cell division.[11]

Breathing pure oxygen lowers the oxygen content of tissues; breathing rarefied air, or air with carbon dioxide, oxygenates and energizes the tissues.

— Ray Peat[12]

Stress, shock, inflammation, aging, and organ failure are, in important ways, respiratory problems.

— Ray Peat[13]

100% oxygen and hard over-breathing waste CO₂, raise alkalosis, and raise lactic acid.[10] Low CO₂ production from hypothyroidism lets lactate enter blood even at rest as adrenaline compensates; excess lactate then displaces CO₂ and drives more ventilation.[10]

Mountain sickness (lung and brain swelling) follows ascent faster than adaptation. Acetazolamide retains CO₂ and causes mild acidosis; it is standard prevention. Retinal bleeding at 10,000 feet without adaptation marks silent stress in other organs too.[10] Long-term high-altitude populations show lower cancer and heart mortality in the data that essay reviews.[10]

Mountain sickness and acclimatization

Mountain sickness, including pulmonary and cerebral edema, can follow ascent faster than adaptation allows. Acetazolamide retains CO₂ and causes mild acidosis, which is why it is used for prevention. Retinal bleeding at 10,000 feet without adaptation suggests similar silent stress in other organs.[10] Gradual acclimatization raises T3 output and can correct hypothyroidism, while sudden ascent produces hyperventilation and can cause lung and brain swelling.[14]

Long-term altitude data

People who live at very high altitudes show lower cancer and heart disease incidence in the data reviewed by Ray Peat. Lower cosmic radiation was raised as a possible contributor, but the radiation explanation conflicts with the lower cancer rates observed at higher elevations. Linus Pauling had assumed that Denver would be more dangerous than sea level because of stronger cosmic rays and sunlight there, yet cancer of all kinds is less common at higher altitude.[15][16]

The two largest studies of altitude and cataracts found fewer cataracts at higher elevation, and cataracts appeared later in life the higher people lived.[17]

Mitochondria, T3, and neuroprotection

Altitude adaptation raises T3 activity and stimulates new mitochondria formation, a mechanism connected with neurological recovery, including recovery from the low-thyroid state associated with learned helplessness.[18] In Russian research described in an interview, animals kept at high altitude for a few months retained roughly twice as many mitochondria for the rest of their lives after returning to low altitude and were more efficient at producing energy.[19] In a modern human study, total skeletal-muscle mitochondrial volume density increased after high-altitude exposure, driven by a preferential rise in intermyofibrillar mitochondria, even though whole-body weight, composition, and muscle fiber area stayed the same.[20]

Sudden relocation and suicide risk

The mortality data for people already adapted to altitude does not describe sudden relocation. Cross-sectional and longitudinal human data associate moving to altitudes of roughly 900 meters or higher with increased depression, anxiety, and suicidal ideation. In one cohort of medical students, moving to at least 3,000 feet was linked to higher depression scores and more suicidal ideation. Marines showed depression- and anger-like scores comparable to psychiatric outpatients after a month of altitude training, with effects persisting up to three months. Proposed mechanisms include chronic hypobaric hypoxia altering serotonin metabolism and brain bioenergetics. Gradual acclimatization and sudden shock have different effects.[21]

Mortality and obesity data

Statistics for New Mexico showed improvement in mortality for every increase of altitude within the state, from below sea level up to around 12,000 feet.[22]

A US cohort of incident dialysis patients found altitude inversely associated with all-cause mortality. Patients who started dialysis above 1,828 meters had 15% lower mortality than patients near sea level after adjustment for demographics and comorbidities, with five-year survival of 42.7% versus 34.8%.[23]

An ecological study of 3,108 US counties found adult obesity fell as elevation rose, from 5.18% lower at 500 to 999 meters to 35.28% lower at 2,500 meters and above compared with counties under 500 meters. Physical inactivity and smoking explained part of the gap, leaving a 17.54% difference at the highest elevations after adjustment.[24] Colorado has the highest mean elevation of any US state and, as of 2024 CDC data, the lowest adult obesity rate of any state at 25.0%.[25]

CO₂ and insulin

CO₂ binds to insulin and alters its conformation, a possible mechanism for why thyroid hormone affects diabetes: thyroid raises CO₂ production.[26]

It is known to bind to insulin, affecting its conformation. I think this is likely to explain some of the effects of the thyroid hormone in diabetes, since thyroid increases the production of carbon dioxide.

— Ray Peat[27]

Therapeutic CO₂ (intermittent hypercapnia)

Carbon dioxide is increasingly used to prevent inflammation and edema, for example to prevent adhesions in abdominal surgery and to protect the lungs during mechanical ventilation, and it inhibits inflammatory cytokines and prostaglandins.[28]

The therapeutic effects of increasing carbon dioxide are being more widely recognized in recent years. ... But still very few biologists recognize its role as a fundamental, universal protective factor.

— Ray Peat[29]

In a rotenone-induced mouse model of Parkinson's disease, high CO₂ inhalation restored exploratory behavior, locomotor activity, and motor coordination lost to the toxin. The proposed mechanism is transient brain acidification triggering mitophagy, the targeted clearance of damaged mitochondria that mitochondrial dysfunction in Parkinson's disease is thought to block.[30]

The first human follow-up came in 2025: a trial gave Parkinson's patients and healthy older adults three 10-minute sessions of intermittent hypercapnia (cycling brief periods of elevated CO₂) and measured cerebrospinal fluid (CSF) flow with MRI. The CO₂ pulses drove vasomotion, the rhythmic widening and narrowing of blood vessels that pumps CSF through the brain's clearance system, and increased CSF inflow in both groups, though the effect was smaller in Parkinson's patients than in healthy controls.[31] The mechanism mirrors what already happens during deep sleep, when natural CSF clearance of misfolded proteins peaks; the researchers were testing whether it could be reproduced deliberately while awake.[31] The approach was feasible and well tolerated, and the authors propose it as a candidate for future clinical trials targeting toxic protein clearance in Parkinson's disease.[31]

In the embryonic state, damaged tissues regenerate quickly. The metabolism of an embryo or fetus is highly oxidative, converting glucose rapidly to carbon dioxide and water.

— Ray Peat[32]

A mouse study posted as a preprint, not yet peer reviewed, found that mTOR signaling in newborn neurons falls within minutes of the first breath as CO₂ is exhaled, through a rise in pH inside the cells and the kinase SNRK. In adult mice, CO₂ inhalation or deletion of the SNRK gene restored mTOR in retinal ganglion cells and allowed their axons to regenerate after injury.[33]

In a randomized crossover study in healthy adults, breathing 2.5% CO₂ through an open mask all night raised sleep efficiency and deep sleep without changing blood gases, while a higher dose disturbed sleep.[34]

Carbon dioxide protects nerves and muscles against excessive excitation. It inhibits lactic acid formation, and lipid peroxidation (measured in the blood) can be completely suppressed by a pC02 of about 90 mm, which isn't high enough to produce acidosis.

— Ray Peat[35]

CO₂ foot bathing and ischemic wounds

In a 77-year-old man with diabetes, arteriosclerosis obliterans, and an MRSA plantar ulcer with osteolytic destruction of the second-toe metatarsophalangeal joint, daily artificial carbon dioxide foot bathing (1000-1300 ppm CO₂ at 37 °C for 15 minutes) plus povidone-iodine sugar ointment, after limited plantar incision without sequestrectomy or systemic antibiotics, accompanied wound closure and bone and joint remodeling by 6 months. At 1 year 5 months, radiographs showed regeneration of a joint-like structure and normal walking.[36]

In an open-label multicenter randomized trial in people with non-healing diabetic foot ulcers, weekday sessions with the lower body sealed in a CO₂-filled plastic wrap, added to standard care, healed about two-thirds of ulcers within a month against few with standard care alone, and no adverse effects were reported.[37]

Bathing in carbon dioxide in a bathtub or a bag lets the skin absorb CO₂; that raised tissue level turns off inflammatory processes and suppresses wasteful lactic acid production, which can help a wounded, sick, or aged person restore energy.[38]

Japanese physiology work on bathing in carbonated water sits behind the clinical foot-bath practice: warm water holds less dissolved CO₂ than tissue already carries, yet the body still takes CO₂ up through the skin.[39] A plastic-bag CO₂ bath produces immediate warmth and pink skin; hot springs deliver the same directional uptake against the apparent concentration gradient.[40] Healing mineral waters carry carbon dioxide and carbonates that the body absorbs when bathing in or drinking the water.[41]

Mitochondrial biogenesis in skeletal muscle

Transcutaneous CO₂ application (a topical delivery method) to rat hindlimb muscle raised PGC-1α, SIRT1, and VEGF gene expression, increased mitochondrial number, and shifted fiber type toward slow-twitch, improving endurance running performance over the treatment period.[42] The same delivery method accelerated repair after induced muscle injury in rats, with muscle fibers fully repaired by six weeks versus only partial repair in untreated controls, alongside elevated protein-synthesis gene expression and capillary density.[43] The same hydrogel delivery method also accelerated fracture repair in rats,[44] and improved diabetic chronic wound healing in a double-blind randomized clinical trial.[45]

CO₂, hypoxia, and cancer

CO₂ (hypercapnia) suppresses the hypoxia-inducible factor (HIF)-dependent adaptive response to low oxygen, the same pathway activated in rheumatoid arthritis and implicated in tumor progression.[46] Transcutaneous CO₂ reduced tumor growth in a mouse model optimizing antitumor treatment conditions,[47] suppressed bone destruction from breast cancer metastasis,[48] and decreased the metastatic potential of osteosarcoma cells via reoxygenation.[49]

CO₂, sensory stimulation, and mental fatigue

Carbonation itself, apart from any caloric or caffeine content, blunts cognitive fatigue during sustained mental work. In a randomized crossover trial, 14 regular video gamers played a virtual soccer match for three hours on two separate days, once drinking plain water and once drinking unsweetened, highly carbonated water. Sparkling water blunted the rise in subjective fatigue, raised enjoyment, and preserved flanker-task accuracy (a measure of executive function) relative to plain water, with no difference in heart rate, interstitial glucose, or salivary cortisol between conditions. Players also committed fewer in-game fouls, though scoring and passing were unchanged. The authors attribute the effect to dissolved CO₂ activating TRPA1 receptors on the trigeminal nerve and TRPV1 receptors in the pharynx and brainstem, a sensory route distinct from CO₂'s metabolic and vascular roles.[50]

What supports CO₂

In acidotic predialysis CKD, raising serum total CO₂ with oral sodium bicarbonate accompanied rises in free and total T3 (and free T4 and TSH), with the CO₂ change correlating with T3 change.[51]

Thyroid, progesterone, steady glucose oxidation, salt, niacinamide (Vitamin B3), and aspirin support CO₂ production or retention in the stress and glycemia writing.[1][52]

Elevated CO₂ selectively inhibits interleukin-6 and TNF-α expression and reduces phagocytosis in macrophages.[53] A brief 10-minute CO₂ inhalation pre-treatment prevented LPS-induced lung injury in mice by downregulating Toll-like receptor 4.[54]

Over-breathing, PUFA-driven lipolysis (free fat release), and gut endotoxin (bacterial wall toxin) lower the CO₂ story. See Buteyko method, Randle cycle, Tissue leakiness.

Bicarbonate from dissolved CO₂ can shift iron-driven free-radical chemistry toward milder forms that hit guanine in DNA, a buffering role under metabolic stress in recent work.[55]

Oral bicarbonate raised tumor CO₂ and slowed growth in rodent models of acidosis-driven cancer cell behavior.[56]

Colonoscopy insufflation

Insufflating the colon with CO2 instead of room air during colonoscopy lowers post-procedure stress and discomfort. In a randomized, double-blind trial of 100 patients, CO₂ insufflation cut post-examination abdominal fullness and pain, shortened recovery time, and produced a lower total rise in salivary alpha-amylase (a stress marker) compared to air insufflation, with the benefit most pronounced in longer examinations.[57] CO2 diffuses across the gut wall far faster than room air's mostly nitrogen content, so it clears through normal respiration instead of lingering to distend the bowel.

Bone as a carbonate reservoir

About 80% of the body's total carbonate sits in bone, built into the mineral's carbonated-apatite structure.[58] During metabolic acidosis, bone releases this carbonate, along with phosphate, sodium, and potassium, to buffer the acid load, at the cost of bone mineral content.[59] Cultured bone measurably loses carbonate content under metabolic (low-bicarbonate) acidosis specifically, not under respiratory acidosis from elevated CO2 alone.[60]

In rats with disuse osteoporosis from hindlimb suspension, daily CO₂ applied through the skin sped up healing of a broken thigh bone on X-ray and in tissue, and raised early bone-forming signals.[61] In one inherited form of marble-bone disease, patients lack carbonic anhydrase II, the enzyme that turns CO₂ into acid inside the cells that dissolve bone.[62]

Alkalosis

Alkalosis is high blood pH from low CO2 (overbreathing) or metabolic base excess. Hyperventilation syndromes appear with anxiety. Peat defined hyperventilation as breathing enough to produce respiratory alkalosis from CO2 loss, with lactic acid produced in turn as a response to that alkalosis.[63] Calm breathing helps; medical care when severe. See Buteyko Breathing, Anxiety, Baking soda.

Baking soda

Sodium bicarbonate molecular structure
Sodium bicarbonate molecular structure

Baking soda is sodium bicarbonate, an alkaline salt used in cooking, as a simple antacid, and as a practical partner for dissolving aspirin in water. It serves short acid-base and sodium jobs and is not meant as a large daily dose.

Dosing

Taking baking soda after a very large meal carries a rare risk of stomach rupture, about half of reported cases linked to eating disorders.[64]

For breaking an anxiety or panic attack, half a teaspoon of baking soda in a couple of ounces of water will sometimes make a difference, and "it doesn't hurt to take a teaspoon."[65]

With aspirin and food

A pinch of baking soda in hot water helps aspirin tablets dissolve and fizz so the clear liquid can be taken with food. That use is about avoiding undissolved tablet contact with the stomach, not about alkalizing the whole body for its own sake. See Aspirin.

With a protein meal, bicarbonate slows stomach acid for a few minutes. Digestion pauses, then continues. That is a short buffer effect, not proof that stomach acid should be chronically neutralized.[66]

Sodium and acid-base

Bicarbonate protects against many toxic effects of ammonia, and more carbon dioxide steers ammonia into urea synthesis and away from polyamine formation.[67] In a crisis, baking soda in water can help raise carbon dioxide, but rebreathing into a paper bag works better.[68]

In predialysis chronic kidney disease with metabolic acidosis (serum total CO₂ ≤ 22 mM), oral sodium bicarbonate titrated to raise total CO₂ to ≥ 24 mM over 8–12 weeks raised free T3, total T3, free T4, and TSH, while free T3 fell further in untreated controls; percentage rise in total CO₂ tracked the T3 changes, and GFR held in the bicarbonate arm but fell in controls. See Thyroid, CO2.[51]

Baking soda is a sodium load and an alkaline load. Small culinary amounts sit inside ordinary salt and food chemistry. Large chronic doses change acid-base balance and sodium balance and need a reason. People with kidney disease, high blood pressure under medical care, or low stomach acid problems should not invent a bicarbonate protocol from a wiki page. See Sodium, Salt, Harm reduction.

Baking soda does not replace CO2 retention, thyroid, or sugar oxidation. Those raise bicarbonate the biological way, through respiration and metabolism, not through a box of powder.

Splenic anti-inflammatory signal

In rats, drinking sodium bicarbonate for a few days shifted spleen, blood, and kidney macrophages from the inflammatory M1 type toward the regulatory M2 type, and raised regulatory T cells, compared with salt water carrying the same sodium. A small group of healthy young adults showed a similar macrophage shift in blood within hours of one 2 g dose. Blocking stomach acid secretion in rats stopped the response, and so did simply handling the spleen during surgery. In the authors' model, the signal reaches the spleen through nerve-like cells lining its outer capsule, using cholinergic signals, rather than through a direct nerve route. These are immune cell markers in healthy people, not a measured drop in disease or symptoms.[69]

Athletic performance

An umbrella review rated moderate-quality evidence that sodium bicarbonate raises peak and mean power in the Wingate test and Yo-Yo test performance, with lower-quality evidence for events of about 45 seconds to 8 minutes.[70]

Sodium bicarbonate loading before a single maximal-effort event is one of the better-studied acute uses of the buffering effect. In a randomised, double-blind, placebo-controlled trial, 9 elite male swimmers ingested sodium bicarbonate (300 mg/kg body mass), a placebo, or nothing 60-90 minutes before a 200 m freestyle time trial on three separate occasions. Mean 200 m time was faster after sodium bicarbonate (1:52.2) than after placebo (1:54.0) or control (1:53.7), alongside higher pre-exercise blood bicarbonate, pH, and base excess, and higher post-swim blood lactate. The gain came from acute buffering, since there was no training period.[71] The effect is acute and event-specific; it says nothing about chronic megadosing, see above.

In sepsis and critical illness

These are hospital findings with intravenous sodium bicarbonate under ICU monitoring, and baking soda by mouth is a different thing. In a retrospective cohort of septic patients with acute moderate lactic acidosis, IV sodium bicarbonate was linked to lower ICU and hospital mortality, including in the septic shock subgroup.[72]

The benefit does not generalize to all acidotic septic patients. A separate cohort found sodium bicarbonate infusion was not associated with improved survival in septic patients with metabolic acidosis overall; a mortality benefit appeared only in the subgroup with severe acidosis and stage 2-3 acute kidney injury.[73] Both studies are observational cohorts, not randomized trials, so the numbers describe an association in specific acidosis subgroups, not a general "sepsis cure."

Bath and sleep

A sodium bicarbonate bath acts on skin and circulation and has little direct effect on stomach acid or blood pH. In a small randomized pilot trial, healthy adults who took a short sodium bicarbonate bath after dinner for a week slept longer than those who showered or bathed in tap water, and reported better sleep satisfaction and lower salivary alpha-amylase (a stress marker) than the shower group.[74] The trial was small and short, and the authors call it a feasibility pilot, not a treatment for diagnosed insomnia. See Sleep.

Carbon monoxide

Carbon monoxide molecular structure
Carbon monoxide molecular structure

Carbon monoxide binds hemoglobin tighter than oxygen and is toxic in inhaled smoke. Cells also produce tiny amounts in heme breakdown. Heme oxygenase breaks heme down into biliverdin, iron, and carbon monoxide. This endogenous carbon monoxide adds to oxidative stress and makes blood vessel linings more permeable, letting fats and fibrinogen enter cells.[75] Practical harm reduction for inhaled CO is smoke avoidance and working detectors. Not a supplement.

Any hypoxic tissue, including inflammation of any kind, expresses heme oxygenase and so produces carbon monoxide; in the short term this may help healing, but when it cannot be switched off the process becomes self-sustaining.[76] Estrogen promotes heme oxygenase, carbon monoxide raises cortisol by stimulating ACTH release, and inhibiting carbon monoxide formation promotes bile flow.[77]

Carbon monoxide from heme breakdown inhibits cell respiration and increases reliance on the glycolysis that produces lactic acid, which may help rebuild the "cancer field" around metastatic cells.[78] Cancer, brain aging, atherosclerosis and arthritis all involve excess carbon monoxide, and chemicals that turn off heme oxygenase have halted cancer growth in experiments.[79]

Cytochrome oxidase is especially sensitive to stress, estrogen and carbon monoxide; thyroid hormone raises its expression and the absorption of the copper it needs.[80]

Lungs

Lungs exchange oxygen and carbon dioxide. Breathing pattern, as well as lung structure, sets blood gas levels; over-breathing lowers CO2 even in perfectly healthy lungs.

Breathing pattern affects the lungs directly

Hyperventilation doesn't just lower blood CO2 generally; within minutes it directly increases fluid leakage from blood vessels into lung tissue itself, alongside raising inflammatory signals:[81] Retained CO2, by contrast, firms blood vessels and helps oxygen delivery to tissue rather than just being a waste gas to exhale as fast as possible.

Lung disease itself can push blood gases in either direction depending on the specific condition (some patterns retain CO2, others lose it), so the practical marker isn't lung disease status alone but the breathing pattern layered on top of it. Chronic hyperventilation is common enough to matter clinically on its own: using a validated screening questionnaire, one hospital found 25 of 100 consecutive allergy-clinic patients and 23 of 100 routine ENT-clinic patients met criteria for hyperventilation syndrome, with no significant difference between the two groups, suggesting a breathing-pattern problem that runs well beyond any single diagnosis.[82]

Practice

Nasal, unhurried breathing supports CO2 retention better than mouth-breathing or deliberate over-breathing practices. Smoking damages lung structure directly, independent of breathing pattern. Bacterial endotoxin in house dust is another inhaled exposure; in a US national survey, adults with more endotoxin in bedroom dust more often had asthma and wheeze (cross-sectional survey).[83] See CO2, Mouth breathing for the fuller framework and citations.

See also

References

  1. ↑ 1.0 1.1 Ray Peat, "Glycemia, starch, and sugar in context," raypeat.com.
  2. ↑ Glycemia, starch, and sugar in context, Ray Peat newsletter
  3. ↑ Reddan B, Shahen R, Radi R, McCalmont M, Green O, Cummins EP. "Activity-based CO2 sensing using CarboSenR2 provides new insights into cellular metabolism." Redox Biology (2026). Activity-based CO(2) sensing using CarboSenR2 provides new insights into cellular metabolism
  4. ↑ Ray Peat, "Calcium and disease," raypeat.com.
  5. ↑ Calcium and Disease: Hypertension, organ calcification, & shock, vs. respiratory energy, Ray Peat newsletter
  6. ↑ Ray Peat, "Leakiness, aging, and cancer," raypeat.com.
  7. ↑ Leakiness, aging, and cancer, Ray Peat newsletter
  8. ↑ Ray Peat, "Phosphate, activation, and aging," raypeat.com.
  9. ↑ Krapf R, et al. "Chronic respiratory alkalosis induces renal PTH-resistance, hyperphosphatemia and hypocalcemia in humans," Kidney Int. 1992. PMID 1405350.
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 Ray Peat, "Altitude and mortality," raypeat.com.
  11. ↑ Hiki M. "The aging spiral hypothesis: mitochondrial decline, CO2 regulation, and the metabolic collapse of aging," Medical Hypotheses. 2025;205:111817. doi:10.1016/j.mehy.2025.111817.
  12. ↑ Altitude and Mortality, Ray Peat newsletter
  13. ↑ Altitude and Mortality, Ray Peat newsletter
  14. ↑ "Vitamin D, Thyroid, Evolving Consciously, and Much More," Ray Peat interview, ~83:38.
  15. ↑ "Altitude and Mortality," Ray Peat article
  16. ↑ "Politics & Science: Ionizing Radiation in Context, Part 1," Ray Peat interview, 2009-04-20.
  17. ↑ "The Transparency of Life: Cataracts as a Model of Age-Related Disease," Ray Peat article. The studies covered 12,217 patients in one and 30,565 lifelong residents across 105 Himalayan sites in a national Nepal survey; prevalence was 2.7 times higher at sites 185 meters or lower than at sites above 1,000 meters.
  18. ↑ "The dark side of stress (learned helplessness)," Ray Peat article
  19. ↑ "Ask the Herb Doctor: Altitude," Ray Peat interview, ~40:26 (video).
  20. ↑ "Aging, Energy, Progesterone," Ray Peat newsletter
  21. ↑ Kious BM, Kondo DG, Renshaw PF. "Living High and Feeling Low: Altitude, Suicide, and Depression," Harv Rev Psychiatry. 2018;26(2):43-56. Adjusted suicide rates of 17.7 at high altitude versus 4.8 at low altitude per 100,000 across the studies reviewed.
  22. ↑ Ray Peat, "Minimum Beneficial Altitude", p. 376
  23. ↑ Winkelmayer WC, Liu J, Brookhart MA. "Altitude and All-Cause Mortality in Incident Dialysis Patients," JAMA. 2009;301(5). PMID 19190315.
  24. ↑ Merrill RM. "Explaining the Inverse Association between Altitude and Obesity," Journal of Obesity. 2020;2020:1946723.
  25. ↑ "Adult Obesity Prevalence Maps," Centers for Disease Control and Prevention, 2024 data.
  26. ↑ Ray Peat, 1998 Newsletter, quoted in "Ray Peat on insulin", raypeatexplained.com.
  27. ↑ 1998 Newsletter, quoted in raypeatexplained.com
  28. ↑ Ray Peat, "Regeneration and degeneration: Types of inflammation change with aging," raypeat.com.
  29. ↑ Protective CO2 and aging, raypeat.com
  30. ↑ Nadeev AD, Kritskaya KA, Fedotova EI, Berezhnov AV. "«One Small Step for Mouse»: High CO2 Inhalation as a New Therapeutic Strategy for Parkinson's Disease." Biomedicines 10(11) (2022): 2832. «One Small Step for Mouse»: High CO(2) Inhalation as a New Therapeutic Strategy for Parkinson's Disease
  31. ↑ 31.0 31.1 31.2 Erhardt EB, Mayer AR, Lin HC, Pirio Richardson SE, Shaff NA, Vakhtin AA, Caprihan A, van der Horn HJ, Hoffman N, Phillips JP, Grigg-Damberger M, Wang CH, Gough J, Hobson S, Deligtisch A, Suarez Cedeno G, Sugar D, Ryman SG. "The influence of intermittent hypercapnia on cerebrospinal fluid flow and clearance in Parkinson's disease and healthy older adults." NPJ Parkinsons Disease 11 (2025): 334. The influence of intermittent hypercapnia on cerebrospinal fluid flow and clearance in Parkinson's disease and healthy older adults
  32. ↑ Adaptive substance, creative regeneration: Mainstream science, repression, and creativity, raypeat.com
  33. ↑ Song X et al. 2026. "The Onset of Breathing at Birth Switches Off Regenerative Capacity." bioRxiv (preprint, not peer reviewed). doi:10.64898/2026.10.03.756425.
  34. ↑ Liang SF, He BT, Wellman A, Chen YY, Wang Y, Deng XB, Vakulin A, Steier J, Schwartz AR, Luo YM. "Effects of controlled carbon dioxide delivery by a novel device on sleep in healthy subjects." Journal of Applied Physiology 140(3):830–837 (2026). doi:10.1152/japplphysiol.01053.2025. PMID Effects of controlled carbon dioxide delivery by a novel device on sleep in healthy subjects. Randomized crossover, 16 healthy adults, nights at 0%, 2.5%, 3.5% and 5.0% CO₂; sleep efficiency 91.7% at 2.5% vs 78.5% at 5.0%; blood gases normal at 3.5% or less. Paywalled; abstract checked.
  35. ↑ Progesterone, Thyroid, Cancer (newsletter, November 2002)
  36. ↑ Hihara M, Fukui M, Mitsui T, Kakudo N, Kuro A. "Osteolytic metatarsal osteomyelitis regenerated by combined treatment of artificial carbon dioxide foot bathing and povidone-iodine sugar ointment: a case report," J Med Case Rep. 2022;16:434. PMID 36404336. doi:10.1186/s13256-022-03654-7.
  37. ↑ Frangež I, Potkonjak M, Veliu S, Metelko Ž, Badanjak A, Križaj J, Ban Frangež H, Poljičanin T, Meloni M, Papanas N, Bulum T. "Transcutaneous Carbon Dioxide Therapy Significantly Accelerates Diabetic Foot Ulcer Healing: A Multicentre Randomised Controlled Trial", Biomedicines. 2026;14(2):422. PMID Transcutaneous Carbon Dioxide Therapy Significantly Accelerates Diabetic Foot Ulcer Healing: A Multicentre Randomised Controlled Trial. Randomized controlled trial, open-label; 115 participants (76 CO₂, 39 control); 50-minute sessions at 99.9% CO₂ every weekday for 4 weeks; healed at 4 weeks 49/76 (64.5%) vs 3/39 (7.7%); OR 35.4, 95% CI 6.68–187.53,.
  38. ↑ Ray Peat, "One Radio Network: What is a virus anyway?", One Radio Network, 21:01
  39. ↑ Ray Peat, "(2010-10) Ray Peat and Bud Weiss - The Biology of Carbon Dioxide", Bud Weiss Interviews, 54:57
  40. ↑ Ray Peat, "Ask the Herb Doctor: Altitude", KMUD, 30:01
  41. ↑ Ray Peat, "Stress and Water."
  42. ↑ Oe K, Ueha T, Sakai Y, Niikura T, Lee SY, Koh A, Hasegawa T, Tanaka M, Miwa M, Kurosaka M. "The effect of transcutaneous application of carbon dioxide (CO₂) on skeletal muscle." Biochem Biophys Res Commun. 2011;407(1):148-52.
  43. ↑ Akahane S, Sakai Y, Ueha T, Nishimoto H, Inoue M, Niikura T, Kuroda R. "Transcutaneous carbon dioxide application accelerates muscle injury repair in rat models." Int Orthop. 2017;41(5):1007-1015.
  44. ↑ Koga T, Niikura T, Lee SY, Okumachi E, Ueha T, Iwakura T, Sakai Y, Miwa M, Kuroda R, Kurosaka M. "Topical cutaneous CO2 application by means of a novel hydrogel accelerates fracture repair in rats," J Bone Joint Surg Am. 2014;96(24):2077-84. PMID 25520342.
  45. ↑ Macura M, Ban Frangez H, Cankar K, Finžgar M, Frangez I. "The effect of transcutaneous application of gaseous CO(2) on diabetic chronic wound healing-A double-blind randomized clinical trial," Int Wound J. 2020;17(6):1607-1614. PMID 32633896.
  46. ↑ Selfridge AC, Cavadas MA, Scholz CC, Campbell EL, Welch LC, Lecuona E, Colgan SP, Barrett KE, Sporn PH, Sznajder JI, Cummins EP, Taylor CT. "Hypercapnia Suppresses the HIF-dependent Adaptive Response to Hypoxia," J Biol Chem. 2016;291(22):11800-8. PMID 27044749.
  47. ↑ Ueha T, Kawamoto T, Onishi Y, Harada R, Minoda M, Toda M, Hara H, Fukase N, Kurosaka M, Kuroda R. "Optimization of antitumor treatment conditions for transcutaneous CO2 application: An in vivo study," Oncol Rep. 2017;37:3688-3694.
  48. ↑ Takemori T, Kawamoto T, Ueha T, Toda M, Morishita M, Kamata E, Fukase N, Hara H, Fujiwara S, Niikura T, Kuroda R, Akisue T. "Transcutaneous carbon dioxide application suppresses bone destruction caused by breast cancer metastasis," Oncol Rep. 2018;40(4):2079-2087. PMID 30066936.
  49. ↑ Harada R, Kawamoto T, Ueha T, Minoda M, Toda M, Onishi Y, Fukase N, Hara H, Sakai Y, Miwa M, Kuroda R, Kurosaka M, Akisue T. "Reoxygenation using a novel CO2 therapy decreases the metastatic potential of osteosarcoma cells," Exp Cell Res. 2013;319(13):1988-1997. PMID 23727023.
  50. ↑ Takahashi S, Kosugi W, Mizuno S, Matsui T. "Sparkling water consumption mitigates cognitive fatigue during prolonged esports play," Computers in Human Behavior Reports. 2026;100943. doi:10.1016/j.chbr.2026.100943.
  51. ↑ 51.0 51.1 Disthabanchong S, Treeruttanawanich A. "Oral sodium bicarbonate improves thyroid function in predialysis chronic kidney disease," Am J Nephrol. 2010;32(6):534-540. PMID 21042013.
  52. ↑ "Ray Peat, PhD Quotes on Therapeutic Effects of Niacinamide"
  53. ↑ Wang N, Gates KL, Trejo H, Favoreto S Jr, Schleimer RP, Sznajder JI, Beitel GJ, Sporn PH. "Elevated CO2 selectively inhibits interleukin-6 and tumor necrosis factor expression and decreases phagocytosis in the macrophage," FASEB J. 2010;24(7):2178-90. PMID 20181940.
  54. ↑ Tang SE, Wu SY, Chu SJ, Tzeng YS, Peng CK, Lan CC, Perng WC, Wu CP, Huang KL. "Pre-Treatment with Ten-Minute Carbon Dioxide Inhalation Prevents Lipopolysaccharide-Induced Lung Injury in Mice via Down-Regulation of Toll-Like Receptor 4 Expression," Int J Mol Sci. 2019;20:6293.
  55. ↑ Fleming AM, Dingman JC, Burrows CJ. "CO2 protects cells from iron-Fenton oxidative DNA damage in Escherichia coli and humans," Proc Natl Acad Sci U S A. 2024;121(49):e2419175121. doi:10.1073/pnas.2419175121. PMID 39602264.
  56. ↑ Rohani N, Hao L, Alexis MS, et al. "Acidification of Tumor at Stromal Boundaries Drives Transcriptome Alterations Associated with Aggressive Phenotypes," Cancer Res. 2019;79(8):1952-1966. doi:10.1158/0008-5472.can-18-1604. PMID 30755444.
  57. ↑ Iida T, et al. "Carbon dioxide insufflation and stress marker," Acta Gastroenterol Belg. 2013;76(2):219-224. Carbon dioxide insufflation reduces the discomfort due to colonoscopy as objectively analyzed by salivary stress markers.
  58. ↑ Green J, Kleeman CR. "Role of bone in regulation of systemic acid-base balance," Kidney Int. 1991;39:9-26. PMID 1706001.
  59. ↑ Bushinsky DA, Krieger NS. "Effects of acid on bone," Kidney Int. 2022;101(6):1160-1170. PMID 35351460.
  60. ↑ Bushinsky DA, Lam BC, Nespeca R, Sessler NE, Grynpas MD. "Decreased bone carbonate content in response to metabolic, but not respiratory, acidosis," Am J Physiol. 1993;265(4 Pt 2):F530-6. PMID 8238381.
  61. ↑ Effects of transcutaneous CO(2) application on fracture healing in a rat fracture model of disuse osteoporosis Male Sprague-Dawley rats, 3 groups; 100% CO₂ with permeable hydrogel 20 min/day, 5 days/week; higher union scores at weeks 3-4 and higher Runx2 and Osterix vs suspension alone. doi:10.1016/j.bone.2026.117948. PMID 42167504.
  62. ↑ Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification Three affected siblings; CA II nearly absent in red cells, about half of normal in carriers. doi:10.1073/pnas.80.9.2752. PMID 6405388.
  63. ↑ Ray Peat, "Altitude and Mortality." "Hyperventilation is defined as breathing enough to produce respiratory alkalosis from the loss of carbon dioxide. Lactic acid is produced in response to the alkalosis of hyperventilation."
  64. ↑ A review found 36 reported cases. Han YJ, Roy S, Siau AMPL, et al. "Binge-eating and sodium bicarbonate: a potent combination for gastric rupture in adults-two case reports and a review of literature," J Eat Disord. 2022;10(1):157. doi:10.1186/s40337-022-00677-9. PMID 36348449.
  65. ↑ Ray Peat, Diving Deeply Into Health; Your Health Questions Answered, One Radio Network.
  66. ↑ Ray Peat, Baking soda email Q&A, raypeatemails.com.
  67. ↑ Ray Peat, "Meat physiology, stress, and degenerative physiology," raypeat.com.
  68. ↑ Ray Peat, email, CO2, raypeatemails.com.
  69. ↑ Ray SC et al. 2018. "Oral NaHCO(3) Activates a Splenic Anti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells," J Immunol. 2018;200(10):3568-3586. doi:10.4049/jimmunol.1701605. PMID 29661827. PMC5940560. Rats: 0.1 M NaHCO3 or equimolar NaCl in drinking water; esomeprazole 20 mg/kg blocked the M1 to M2 shift. Humans: 2 g NaHCO3 (n=11 to 12) or 0.39 g NaCl (n=6) in 250 mL water, blood at 1, 2 and 3 h; Treatment x Time effect on M1 macrophages p=0.0004 and TNFα+ neutrophils p=0.0146; largest falls at 2 to 3 h. Vagotomy reduced spleen mass and capsular acetylcholine esterase staining; its effect on the macrophage response was not reported.
  70. ↑ Grgic J, Grgic I, Del Coso J, et al. "Effects of sodium bicarbonate supplementation on exercise performance: an umbrella review," J Int Soc Sports Nutr. 2021;18(1):71. doi:10.1186/s12970-021-00469-7. PMID 34794476.
  71. ↑ Lindh AM, Peyrebrune MC, Ingham SA, Bailey DM, Folland JP, Sodium bicarbonate improves swimming performance, International Journal of Sports Medicine 29(6):519-523, 2008. PMID: 18004687.
  72. ↑ Adjusted mortality was roughly 35-50% lower. Huang S, et al. Clinical effectiveness of sodium bicarbonate therapy on mortality for septic patients with acute moderate lactic acidosis, Frontiers in Pharmacology 13:1059285, 2023. PMID: 36699087.
  73. ↑ Zhang Z, et al. Effectiveness of sodium bicarbonate infusion on mortality in septic patients with metabolic acidosis, Intensive Care Medicine 44(11):1888-1895, 2018. PMID: 30255318.
  74. ↑ 38 healthy adults, 10-minute bath for 7 days; the bicarbonate group gained about 12 minutes of total sleep time. Tamaoki S, Matsumoto S, Sasa N, Hoei T, Tojo R, Nakamura T, Aoyagi Y, Effects of sodium bicarbonate bath on the quality of sleep: An assessor-blinded, randomized, controlled, pilot clinical trial, Complementary Therapies in Clinical Practice 50:101714, 2023. PMID: 36528983.
  75. ↑ Ray Peat, "Cholesterol, Longevity, Intelligence, and Health." "The heme will be broken down by the enzyme heme oxygenase, into biliverdin, iron, and carbon monoxide, which can contribute to the oxidative stress of the cells. Carbon monoxide makes the blood vessel lining more permeable, allowing fats and fibrinogen to enter the cells."
  76. ↑ Ray Peat, Carbon Monoxide, Estrogen and the Medical Cancer Cult, newsletter.
  77. ↑ Ray Peat, Carbon Monoxide, Stress and Cancer: 1999 Status, newsletter.
  78. ↑ Ray Peat, "The Cancer Matrix," raypeat.com.
  79. ↑ Ray Peat, "Ask the Herb Doctor: Carbon Monoxide", Ask the Herb Doctor, 13:55
  80. ↑ Ray Peat, "Ask the Herb Doctor: Dementia and Progesterone", Ask the Herb Doctor, 27:25
  81. ↑ Ray Peat, "Leakiness, aging, and cancer," raypeat.com. See CO2 for the full quote and context.
  82. ↑ Ogata N, Bapat U, Darby Y, Scadding G. "Prevalence of hyperventilation syndrome in an allergy clinic, compared with a routine ENT clinic,"J Laryngol Otol. 2006;120(11):924-6. doi:10.1017/S0022215106001691.
  83. ↑ Thorne PS, Kulhánková K, Yin M, Cohn R, Arbes SJ Jr, Zeldin DC. "Endotoxin exposure is a risk factor for asthma: the national survey of endotoxin in United States housing," Am J Respir Crit Care Med. 2005;172(11):1371-1377. doi:10.1164/rccm.200505-758OC. PMID 16141442.