CRON-WEB's Definitive Guide to Supplementation


What is “life extension”?

CR [calorie restriction] “has been repeatedly shown to increase life span and delay the onset of age-associated pathologies in laboratory mice and rats.”[1] “For more than 60 years the only dietary manipulation known to retard aging was caloric restriction, in which a variety of species respond to a reduction in energy intake by demonstrating extended median and maximum life span.”[2]

No confirmed evidence for life-extending effects of any drug or supplement in normal, healthy mammals.

Animal Studies

Human Studies


Randomized, Controlled Trials

Heart disease


 “Well, it Can’t Hurt, and it Might Help” Mistake

Vitamin A (Retinol/Retinyl Esters)

Excess Zn or Zn:Cu

Excess Mn

Unbalanced alpha-tocopherol?

Synthetic beta-carotene (below)?

Should we supplement? What, and how much?

Tier I: Supplementation Necessities

This is what we know. Everything beyond this is increasingly speculative.

 “You can’t win if you don’t play” lottery logic is very bad thinking for the life extensionist. Killing yourself with supplements is just too damned stupid for words. If you’re going to take a supplement, insist on meaningful evidence that it will help you. Human RCTs in healthy people with clinical endpoints > epidemiology with clinical endpoints > studies in vivo in healthy people and rodents showing health benefits/favorable surrogate endpoints. Make-the-case mechanistic arguments, inbred genetic fuckup rodents, or animals exposed to massive doses of hideous toxins may mean nothing at all.

Bad-Evidence Supplementation Schemes:

Tier II: Disease Risk Reduction in the Healthy?

The Supplement Paradox: massive epidemiological support for fruit and vegetable intake – and intake of many of the nutrients they contain – and lower cancer &CVD risk. Yet supplements keep failing! Why??

[Tautology]: Supplements fail to reflect the key aspects of healthy diets.

[Inference]: Supplement programs which better reflect healthy diets are more likely to yield risk reduction.

How to identify ‘healthy diets’? What are their key (supplementable) components? How can supplements better reflect them?

Best current long-term, healthy human evidence is epidemiology, testing  independent variables and clinical endpoints.

How do Supplements and Good Diets Differ?

Tier III: Slowing Aging?

Even if we get full lifestyle benefits, so what? Average person's longevity gain from the eradication of cancer <=3.2 years of life. Ischemic heart disease? <=3.55 years. Both together <= 7.83 years. Both, plus all circulatory diseases and diabetes:15.3 years. (And, hint: we’re already living pretty healthily …).

Retarding aging to extend life span. Logically includes healthspan!

Only one proven intervention: CR [CRON] – and that in rodents! Hence, warning: maximum speculation follows!!

What factors are associated across mammalian species, and within mammalian spp AL [ad lib] vs CR, with slower aging and extended maximum lifespan?

Only 2 AFAIK [as far as I know]: