A practical guide to keeping 17 physiological systems running and restoring them when they slip. It combines a mechanism-first framework (find the limiting factor, restore the mechanism, don't supplement blindly) with the doses and field-ready emergency steps that make it usable.

Tier 1: Cellular energy and gradients

1. ATP–phosphocreatine (ATP–PCr) buffer

Role: Creatine kinase hands a phosphate from phosphocreatine to ADP, regenerating ATP in the first seconds of maximal effort.

• Maintain: Creatine monohydrate 3–5 g/day, taken consistently, is the best-supported sports supplement here. It is optional, not required. Enough total food and sleep matter more.
• Fix: Rest 3–5 minutes between maximal sets or sprints to resynthesize phosphocreatine. To fill stores quickly (vegetarians, or after a long gap), load 20 g/day in 4 doses for 5–7 days, then 3–5 g/day. Skipping the load works too; it just takes several weeks.
• Escalate: "ATP–PCr crisis" is not a real field diagnosis. Collapse or weakness that persists outside the effort needs a look for heat illness, electrolyte loss, low glucose, muscle injury or medication effects. Chest pain, fainting or numbness is cardiac until proven otherwise: lay the person flat, call emergency services, and start CPR and use an AED if they stop responding. Don't push them to keep moving or give stimulants.

2. Mitochondrial respiration and fuel oxidation (Krebs cycle + OxPhos)

Role: The electron transport chain builds a proton gradient that ATP synthase uses to make ATP. The Krebs cycle feeds it from carbohydrate, fat and some amino acids.

• Maintain: Adequate total calories, zone 2 aerobic training 2–4 times a week (built up gradually), iron and B vitamins from food, no smoking or toxic exposures. CoQ10 100–200 mg/day is optional; it has not been shown to boost nutrient-replete people.
• Fix: Cut the workload, then find the actual constraint: under-fuelling, anaemia, thyroid disease, medication, infection, or a heart or lung problem. Replace documented deficits only: iron if ferritin is low, B12, thiamine (especially with heavy alcohol use), riboflavin. Add L-carnitine 1–2 g only if dietary intake is low. Rebuild with gradual aerobic loading, not maximal efforts.
• Escalate: Persistent exercise intolerance, unexplained weakness or neurologic symptoms need testing. People with a known fatty-acid oxidation or mitochondrial disorder should avoid prolonged fasting and follow their written metabolic plan. For carbon monoxide or severe hypoxia, see the emergency section.

3. Na⁺/K⁺ pump, ion gradients and membrane potential

Role: The pump uses ATP to move 3 sodium ions out and 2 potassium ions in, setting cell volume and electrical excitability.

• Maintain: Potassium-rich foods (potatoes, beans, bananas, yogurt, leafy greens), sodium matched to sweat losses, and magnesium glycinate or citrate. Keep supplemental magnesium at or under 350 mg/day (the US upper limit for supplements; more causes diarrhoea). Magnesium from food doesn't count toward that cap.
• Fix: For cramps, weakness or twitching after heavy sweating or GI fluid loss, drink an oral rehydration solution (ORS) or electrolyte drink, eat something salty, and take 200–350 mg magnesium. Get potassium from food and drinks, not high-dose pills. For diarrhoea, use a commercial ORS mixed exactly per the packet, sipping often. ORS replaces losses through intestinal sodium–glucose transport; it does not repair the pump. Cramps alone don't identify which electrolyte is off.
• Escalate: Palpitations, fainting, paralysis or confusion, or any of these with kidney disease or severe dehydration, need emergency care and blood tests (sodium, potassium, magnesium, calcium, kidney function). Both low and high potassium are dangerous. Keep the person resting; start CPR and use an AED if they arrest. Never give potassium or salt pills.

4. Calcium transport and signalling

Role: Pumps and channels keep resting cytosolic calcium extremely low so brief calcium spikes can trigger contraction and secretion.

• Maintain: Meet calcium and vitamin D needs through food and sensible sun. Avoid megadoses. Calcium control also depends on magnesium, phosphate, the kidneys and parathyroid hormone.
• Fix: Twitching or cramps don't mean low calcium. If a problem is suspected, test calcium (sometimes ionized), magnesium, phosphate, kidney function, vitamin D and PTH, then correct the identified cause (deficiency, medication, parathyroid or kidney disorder).
• Escalate: Severe spasms, seizures, confusion or palpitations need urgent care. Both low and high calcium are treated under medical monitoring.

5. Glycolysis, glucose entry and glycogen

Role: Glycolysis turns glucose into pyruvate and ATP. Glycogen is the quick-access reserve in muscle and liver.

• Maintain: Carbohydrate matched to real workload, with thiamine, niacin and magnesium from whole foods. In hard exercise lasting over an hour, take 30–60 g carbohydrate per hour.
• Fix: After ordinary exertion, eat a normal carbohydrate meal. If another hard session is coming within hours, use 1.0–1.2 g/kg/hour for the first 4 hours; most people don't need that rate for routine recovery. If measured glucose is low and the person is alert and can swallow, use the 15–15 rule: 15 g fast carbohydrate, recheck in 15 minutes, repeat if still low, then eat a balanced meal.
• Escalate (severe "bonk"): If the person can't stand, is disoriented, or stays confused after resting, call emergency services. Give 30–50 g liquid carbohydrate only if they are fully alert and able to swallow. Give nothing by mouth if they are drowsy or semi-conscious.

Tier 2: Redox, chemistry and substrates

6. Antioxidant and redox defence (NAD⁺/NADH, NADPH, glutathione)

Role: Redox couples carry electrons for energy, antioxidant defence and repair. Glutathione is built from glutamate, cysteine and glycine.

• Maintain: Enough protein, cruciferous and allium vegetables, colourful plants, a couple of Brazil nuts a few times a week for selenium, sleep, little alcohol, no smoking. This is a regulated network, not a tank you fill with antioxidants.
• Fix: Remove the pressure first: alcohol, smoke, infection, a drug or toxin exposure. NAC 600–1,200 mg once or twice daily with glycine 3 g is a popular glutathione-support stack, but evidence is limited to selected trials (such as GlyNAC in older adults). Treat it as optional. Avoid megadoses of vitamins C and E around training, which can blunt adaptations.
• Escalate (paracetamol/acetaminophen or toxin overdose): Call Poison Control and emergency services right away, even if the person feels fine. NAC is a true antidote here, but it is given by hospital protocol (IV or timed oral doses), not improvised at home. Note the time and amount taken and bring the packaging. Don't induce vomiting unless Poison Control says to.

7. Acid–base balance

Role: Buffers, transporters, lungs and kidneys hold blood and cellular pH in range. Exercise-related acidity resolves as workload falls.

• Maintain: Fruit and vegetables, adequate protein and hydration. Lungs and kidneys do the resting regulation.
• Fix (exercise): Lower the intensity, do an easy cooldown, breathe slowly. Performance tools for specific hard efforts: sodium bicarbonate 0.2–0.3 g/kg with a meal 60–120 minutes beforehand (trial it in training first; GI upset is common), and beta-alanine 3.2–6.4 g/day for 4+ weeks (split doses to limit harmless tingling). These are not treatments for illness.
• Escalate: Deep, rapid breathing with confusion, severe weakness, chest pain, fever or diabetes means urgent care. Causes include diarrhoea, kidney failure, ketoacidosis, lactic acidosis and toxins, and treatment depends on blood chemistry. Don't self-treat with baking soda. Don't use paper-bag breathing (dangerous in pulmonary embolism or DKA). Coach 4-second-in, 6-second-out breathing only when there is an obvious panic trigger and no physical illness.

8. Enzyme cofactors and micronutrient catalysis

Role: Thiamine, riboflavin, niacin, magnesium, iron, B12 and folate each run specific reactions.

• Maintain: A varied diet. Watch the risk factors: heavy alcohol use, GI disease, vegan diets (B12), and medicines such as metformin or acid blockers (B12). A multivitamin fills small gaps but can't fix malabsorption or a real deficiency.
• Fix: Pick the nutrient from history and symptoms, test where it will guide treatment, replace at a recognised dose and duration, then recheck. Iron for confirmed deficiency: 30–60 mg elemental iron every other day with vitamin C. B12 route (pills vs injections) depends on the cause. If a deficiency keeps returning, look for ongoing loss or malabsorption instead of escalating doses. Skip high-dose iron or fat-soluble vitamins without a clear indication, and don't take iron just because you're tired.
• Escalate: Suspected thiamine deficiency in a high-risk person (a heavy drinker with confusion or unsteadiness) needs prompt medical treatment.

9. Amino-acid metabolism and the urea cycle

Role: The liver converts amino-acid nitrogen to urea for excretion. Inherited urea-cycle disorders can send ammonia up fast during illness or catabolism.

• Maintain: Protein of about 1.2–2.0 g/kg for active adults, steady hydration, moderate alcohol, and no prolonged fasting while ill.
• Fix: After a heavy-protein day with no symptoms, just return to balanced eating and normal fluids. Feeling off after a big steak is not hyperammonaemia. L-citrulline 3–6 g/day is a performance supplement, not an ammonia treatment, and temporary protein cuts or "extra hydration" are not a home fix.
• Escalate: Unexplained vomiting, unusual sleepiness, confusion, ataxia or combativeness, especially with liver disease or a known metabolic disorder, needs emergency care. Tell clinicians hyperammonaemia is a concern, because ammonia can rise quickly and cause brain swelling. Hospital care is ammonia measurement, anti-catabolic calories, nitrogen-scavenging drugs and sometimes dialysis. People with a diagnosed urea-cycle disorder should start their written emergency plan. Bystanders: keep the person calm and seated, watch the airway, give no amino acids or protein, and don't force fluids.

Tier 3: Building and protecting cell components

10. Nucleotide synthesis and DNA maintenance

Role: Cells make and recycle purines and pyrimidines for ATP, RNA and DNA, and repair DNA damage.

• Maintain: Enough folate, B12 and niacin, no tobacco, UV protection. More folic acid isn't better.
• Fix: For macrocytosis, low blood counts or neurologic symptoms, test B12 before treating folate alone (folate can mask B12 deficiency). Correct the deficiency and its cause: diet, absorption or medication.
• Escalate: Persistent unexplained cytopenias, neurologic symptoms or suspected inherited disease need a specialist, not a supplement stack.

11. Protein synthesis and proteostasis

Role: Ribosomes build proteins, chaperones fold them, and the proteasome and autophagy recycle damaged ones. All of it costs energy.

• Maintain: About 1.6 g/kg/day protein across 3–4 meals of 25–40 g (roughly 2.5–3 g leucine per meal), plus resistance training 2–3 times a week. Healthy adults over 65 generally target 1.0–1.2 g/kg/day, and 1.2–1.5 g/kg/day with illness. Sleep and low alcohol protect quality control.
• Fix: After illness, injury, an energy deficit or muscle loss, restore calories first (protein can't compensate for a sustained calorie shortfall), then raise protein to 1.8–2.2 g/kg/day across 4 meals. Use whey or essential amino acids, 20–40 g, if appetite is low, and reload muscle progressively. Individualise targets for kidney or liver disease. There are no supplement shortcuts for folding or autophagy; fasting and marketed "autophagy activators" are not treatment.
• Escalate (rhabdomyolysis): Cola- or tea-coloured urine with severe muscle pain and swelling after extreme effort or a crush injury needs emergency care for labs and IV fluids to protect the kidneys. Stop exercising, rest somewhere cool, and sip water only if fully alert. Don't count on water alone to treat a severe case. No NSAIDs.

12. Membrane lipids, vesicle trafficking and synaptic release

Role: Membrane composition and calcium-triggered vesicle fusion drive neurotransmitter release.

• Maintain: Omega-3 (1–2 g EPA+DHA/day, mainly worthwhile if you rarely eat fish), choline 400–550 mg/day (eggs, liver), magnesium from food, and 7–9 hours of sleep. Extra supplements won't improve release in a nutrient-replete person.
• Fix: Sleep is the real reset. For acute fatigue, 100–200 mg caffeine with a carbohydrate-and-electrolyte meal helps alertness (it doesn't reset the machinery). If symptoms persist, check B12, electrolytes, glucose and medication effects.
• Escalate (seizure): Clear the area, roll the person onto their side, and time it. Call emergency services if it lasts over 5 minutes, recurs, happens in water, or is their first. Give prescribed rescue midazolam or diazepam only if trained. Never restrain them or put anything in their mouth.

Tier 4: Whole-body life-support loops

13. Cardiorespiratory perfusion and gas exchange

• Maintain: Zone 2 training plus some interval work, dietary nitrate (beetroot juice delivering 300–600 mg nitrate, or leafy greens), omega-3s.
• Fix: For breathlessness or exercise intolerance, use slow nasal breathing (~6 breaths/minute) and rebuild gradually. If ferritin is confirmed low, take 30–60 mg elemental iron every other day with vitamin C.
• Escalate (anaphylaxis): Hives, facial swelling, wheeze, faintness or low blood pressure after an allergen: use the epinephrine auto-injector (0.3 mg, outer thigh) and call emergency services. A second dose can be given after 5–15 minutes. Lay the person flat with legs raised (let them sit if breathing is the main problem); don't let them stand or sit up suddenly. Start CPR if there is no pulse. For asthma without anaphylaxis, give 4–8 puffs of albuterol via spacer. Chest pain or severe breathlessness always warrants a call.

14. Blood glucose regulation

• Maintain: Fiber, protein-forward meals, a 10–15 minute walk after eating, strength training, consistent sleep, adequate magnesium.
• Fix (high): Post-meal walks, fewer refined carbohydrates, psyllium 5 g before meals. Berberine 500 mg 2–3 times daily with meals has a modest effect and can upset the stomach and interact with medicines; check before combining with diabetes drugs.
• Fix (low): 15 g fast carbohydrate (glucose tablets, juice), recheck in 15 minutes, repeat if needed, then a balanced meal. Follow your diabetes plan if you have one.
• Escalate: If the person is unresponsive, can't swallow, or is seizing, call emergency services and give nasal glucagon (3 mg) or injectable glucagon if trained. Place them in the recovery position. Never put food, drink or gel in their mouth.

15. Coagulation and haemostasis

• Maintain: Vitamin K1 from leafy greens, K2 from fermented foods like natto, limited NSAIDs and alcohol. (Keep vitamin K intake steady if you take warfarin.)
• Fix (minor cuts): Firm direct pressure for 10 uninterrupted minutes, elevate, cold pack for bruising.
• Escalate (severe bleeding): Spurting, rapid, or soaking through dressings means call emergency services now. For a limb, apply a windlass tourniquet 2–3 inches above the wound and tighten until bleeding stops. For groin or armpit wounds, pack deeply with hemostatic gauze and press hard for at least 3 minutes. Never remove a tourniquet or lift gauze to check.

16. Fluid, osmolarity and sodium balance

• Maintain: Drink to thirst, aim for pale urine, and take 500–1,000 mg sodium/hour in long, sweaty efforts.
• Fix: Homemade ORS: 6 level teaspoons sugar plus ½ level teaspoon salt per litre of clean water, sipped at 200–400 mL/hour. After exercise, replace about 1.5× the weight lost. When badly dehydrated, don't rely on plain water alone. For diarrhoea, a commercial ORS mixed exactly per the packet is safer than a home mix.
• Escalate (exercise-associated hyponatremia): Confusion, severe headache, vomiting or swelling after heavy plain-water drinking in endurance events needs emergency care and hospital hypertonic saline. Keep the person lying or sitting and watch the airway. Give no plain water, hypotonic drinks or salt shots. For diarrhoea, seek care for confusion, fainting, inability to keep fluids down, very low urine output or blood in the stool.

17. Thermoregulation

• Maintain: Heat-acclimate over 10–14 days of progressive exposure, wear breathable clothing, pre-hydrate, keep the bedroom cool.
• Fix (overheating): Stop, get into shade, remove excess clothing, cool the neck, armpits and groin, fan the skin, sip sodium-containing fluids.
• Fix (cold): Change into dry insulated clothing, block wind and moisture, drink warm carbohydrate fluids, keep moving.
• Escalate (heat stroke): Core temperature above 40 °C (104 °F), or confusion, slurred speech or collapse in the heat: start cooling immediately and call emergency services. Submerge the torso in an ice-and-water tub (0.5–15 °C); if there is no tub, apply ice packs to neck, armpits and groin while fanning and continuously wetting the skin with cold water. Cool first, transport second. Don't force fluids on a confused or vomiting person.

Fast reference: disturbance to first move

Emergency bridge: what to do until help arrives