Fasting and Health

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Chief

Chief of Sinners.
Fasting - in several forms (time-restricted eating, intermittent fasting, periodic prolonged fasting) - produces reproducible short-term benefits for body weight and cardiometabolic risk factors and activates conserved cellular pathways (AMPK, mTOR, sirtuins, autophagy) that plausibly link to improved healthspan and longevity. Strong evidence for lifespan extension exists in many animal models; human data show promising effects on biomarkers of aging and metabolic health but do not yet prove extended human lifespan. Fasting can be used safely by many adults if done sensibly, but it carries real risks for specific groups and must be implemented with attention to hydration, protein needs, medications and safe re-feeding.

About Upton Sinclair’s The Fasting Cure​

Upton Sinclair’s early-20th-century pamphlet/documents describe many enthusiastic case reports and personal experience with multi-day fasts, recommend daily enemas, lots of water, daily baths, careful re-feeding (heavily promoting milk as a post-fast diet), and argue that many chronic ailments result from “autointoxication” relieved by fasting. Sinclair collected many testimonials and framed fasting as a universal cure; he also warned about two main hazards: psychological fear and unsafe breaking of fasts. This material is useful historically and for early practical tips, but it reflects the era’s medical ideas and anecdotal evidence rather than modern randomized trials.

What modern science says (evidence summary - key, high-quality findings)​

Effects on weight and cardiometabolic risk​

Biomarkers of aging and longevity signals​

  • Caloric restriction (CR) (sustained reduced calorie intake) in humans (CALERIE trial) produced favorable changes in multiple aging-related biomarkers (insulin sensitivity, body composition, some inflammatory markers) and an apparent slowing of some measures of biological aging; but CR is difficult to sustain and long-term effects on human mortality remain unproven.
  • Mechanistic biomarkers (DNA methylation clocks, pace-of-aging metrics) showed favorable shifts in controlled CR interventions - proof-of-principle that human physiology can move toward a “younger” profile.

Mechanistic evidence (cellular maintenance)​

  • Fasting and nutrient-restriction reliably activate conserved nutrient-sensing pathways - AMPK, mTOR inhibition, and sirtuin (SIRT1) signaling - which in turn upregulate autophagy, mitochondrial quality control, stress resistance and DNA-repair processes. These mechanisms explain how periods without external nutrients can promote cellular renewal and resilience in animals and cell systems. Reviews of autophagy and nutrient signaling summarize these pathways.

Clinical cautions and harms​

  • Most randomized trials report only modest adverse events (headache, lightheadedness) in generally healthy adults when fasting protocols are supervised; however there are important contraindications: pregnancy, breastfeeding, active eating disorders, some psychiatric disorders, certain older adults, and people on medications that raise risk of hypoglycemia or volume depletion (e.g., insulin, sulfonylureas, some antihypertensives). There are also concerns about disordered eating risk in vulnerable people.

How fasting probably produces benefits - concise mechanistic model​

  1. Energy/nutrient sensing: Reduced feeding lowers insulin and amino-acid signals → mTOR inhibition and AMPK activation.
  2. Autophagy induction: mTOR downregulation and SIRT1 activation upregulate autophagy → removal of damaged proteins/organelles, improved cellular function.
  3. Metabolic switch: After glycogen is used, tissues oxidize fatty acids and produce ketones (β-hydroxybutyrate), which are signaling metabolites that support mitochondrial function, reduce inflammation and may protect neurons. (Mechanistic reviews and trials document metabolic switching during fasting.)
  4. Systemic effects: Improved insulin sensitivity, reduced inflammation, lowered blood pressure and improved lipid profiles lead to lower cardiometabolic risk - plausible contributors to longer healthspan.

Evidence strength - what’s solid and what’s tentative​

  • Solid / well-supported: modest weight loss; improved insulin sensitivity and some cardiometabolic markers in short-to-medium term; activation of nutrient-sensing/autophagy pathways in animals and cells.
  • Plausible but not proven in humans: direct extension of human lifespan (strong animal evidence but human mortality data are lacking). Biomarker improvements (CALERIE) are encouraging but not the same as demonstrated lifespan increases.
  • Uncertain / mixed: which fasting protocol is best (IF vs TRE vs periodic prolonged fast vs chronic CR); effects in older adults, pregnant people or those with complex comorbidity; long-term adherence and real-world cardiovascular outcomes. Recent umbrella reviews show heterogeneity; benefits are often modest and depend on context.

Practical, evidence-backed guidance to use fasting safely for healthspan​

Start with the goals: (A) weight/metabolic improvement, (B) cellular maintenance/biomarkers, or (C) periodic “deep” reset. Your plan will differ.

A — Gentle, widely used, first-step: Time-Restricted Eating (TRE)​

  • Typical protocol: eat during an 8–10 hour window (e.g., 10:00–18:00) and fast ~14–16 hours. Trials show TRE can produce weight loss and improve BP and glucose in some people.
  • Practical tips: keep calories similar at first (don’t binge in the window), prioritise protein and vegetables, avoid late-night eating (finish ≥2–3 hours before bed), hydrate during fasting window.

B — Intermittent energy restriction (5:2 / alternate-day) or Intermittent Fasting (IF)​

  • 5:2: two non-consecutive low-calorie days (~500–600 kcal) per week; other days normal eating. IF trials show comparable weight loss to continuous calorie restriction for many.
  • Use when: you tolerate short calorie-restricted days; monitor energy, mood and work performance.

C — Periodic prolonged fasting (≥48–72 hours) - advanced, used occasionally​

  • May be used for metabolic “resets” or under medical supervision; most mechanistic autophagy studies use longer fasts, but prolonged fasts carry higher risk and require medical oversight. Sinclair’s historical approach favored multi-day fasts with enemas and milk re-feeding - note the historical context and avoid unsupervised prolonged fasting.
  • If you try this: do it under clinician supervision, stop medication risks reviewed, ensure hydration and electrolyte monitoring, and adopt a careful re-feeding plan 👇.

Re-feeding after prolonged fast (critical safety step)​

  • Re-feeding syndrome is a real risk after prolonged starvation. Modern guidance: start with small, easily digested portions, prioritise fluids and electrolytes, then slowly add protein and complex carbs over days. Historically Sinclair recommended orange juice and then milk in stages; modern practice favours small broths, diluted juices, and gradual re-introduction of whole foods with attention to electrolytes and blood glucose. Get medical guidance for fasts >48 hours.

Practical safety checklist before you start​

  • Medical review if you have diabetes, are on medications (especially insulin, sulfonylureas, diuretics, antihypertensives), pregnant/breastfeeding, elderly, or have a history of eating disorders.
  • Start slow (shift to 12–14 h fasts → 14–16 h → consider 18–20 h if tolerated). Track energy, mood, sleep, menstrual cycle and work performance.
  • Stay hydrated (water, mineral water, plain tea). Consider electrolyte supplementation on longer fasts. Sinclair emphasized water and baths historically; hydration remains essential.
  • Aim to preserve muscle: when practicing prolonged or frequent fasting, ensure adequate protein intake in feeding windows and include resistance exercise to preserve lean mass. (Fasting alone can reduce fat mass but prolonged deficits without protein/strength work can reduce muscle.)

Implementation example - a 12-week, pragmatic longevity-oriented plan​

  1. Weeks 0–2: switch to TRE 12:12 (e.g., 08:00–20:00) and focus on whole foods, protein at each meal. Hydrate.
  2. Weeks 3–6: tighten to TRE 10:14 or 16:8 if tolerable (e.g., 10:00–18:00). Add 2 resistance sessions/week. Monitor weight and fasting glucose.
  3. Weeks 7–10: try one 24-hour fast (dinner-to-dinner) once every 1–2 weeks if feeling well. Keep electrolytes.
  4. Week 11–12: reassess biomarkers (fasting glucose, lipids, BP), body composition; adjust. Consider clinician-supervised prolonged fast only if clear indication and with medical support.

Research gaps & what to watch for​

  • Which fasting pattern (TRE vs IF vs CR) is best for human longevity remains unresolved. Large, long-term randomized mortality trials are infeasible; surrogate biomarkers (DNA-methylation clocks, inflammatory profiles) are being used as proxies and show promise (CALERIE & follow-ups).
  • Individual variability is large - genetics, baseline metabolic health, circadian timing and meal quality matter. Emerging personalized approaches will refine recommendations.

Final position (practical verdict)​

  • Use fasting (especially TRE and measured IF) as a pragmatic tool to improve weight, metabolic health and activate cellular renewal pathways that are plausibly linked to improved healthspan. Evidence supports short-to-medium term benefits and mechanistic plausibility for longevity, but human lifespan extension has not been proven.
  • Do not take prolonged, unsupervised fasting lightly (Sinclair’s era treatments and enthusiastic case reports are historically interesting but are not a substitute for modern clinical oversight). If you consider prolonged fasts, consult a clinician, check medications, and have a re-feeding plan.
  • Finally, fasting is one tool among many (quality diet, regular exercise, sleep, stress management, avoiding smoking, vaccinations and access to healthcare) that together build longevity - fasting is best used as part of a comprehensive lifestyle approach.
 
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