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Longevity and Healthy Aging

Longevity and healthy aging (habits, supplements and tests studied for aging well) · also called Longevity, healthy aging, healthspan, anti-aging, longevidad, envejecimiento saludable

Longevity research asks what helps people live longer and stay healthy as they age. The strongest evidence points to everyday habits: not smoking, being active, eating a Mediterranean-style diet, sleep and social ties. For supplements such as vitamin D, omega-3, NMN and resveratrol, trials have found no clear benefit for living longer. No product has been proven to slow human aging, so be careful with bold claims.

General information, not medical advice. Last substantive update · Not medically reviewed. A named clinician has not signed off on this page. How this page is made

About Longevity and Healthy Aging

Longevity is a research field, not a treatment. The best-supported actions are everyday habits, led by not smoking and staying active. Supplements have mostly not shown a benefit for living longer, and some antioxidant vitamins slightly raised death rates in pooled trials. Biological-age tests are research tools.

What "longevity" research is, and what this page covers

Longevity research looks at what helps people live longer and stay well as they age. Two different things are measured. One is living longer (deaths during follow-up). The other is stand-in markers, such as a blood test or a DNA "age clock", that scientists use because trials cannot wait 40 years.

This page covers natural approaches: everyday habits, foods and supplements. It does not cover prescription medicines. Some longevity clinics sell prescription medicines for aging; those are not supplements and fall outside this page.

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Habits with the most evidence

Not smoking has the clearest effect. A US study of 202,248 adults found smokers had about three times the death rate and lost at least ten years of life expectancy, and people who quit by their early 30s regained about ten years.

Physical activity is linked with lower death rates in a pooled analysis of 661,137 adults, and most of the gain came at modest levels. A five-year trial in 1,567 older Norwegian adults did not find a clear difference in deaths between supervised exercise and following activity guidelines, though few people died and the control group was already active.

A review of reviews found a Mediterranean-style diet linked with lower overall mortality, heart disease and diabetes. Short and long sleep were linked with higher death rates in pooled studies, and strong social ties with better survival. These are observational links, so they show association, not proof that changing a habit changes the outcome.

In two large US cohorts, people with five low-risk habits together had about a quarter of the death rate of people with none. That result is from health professionals and is partly modelled.

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What supplement trials found

The VITAL trial gave vitamin D3 or marine omega-3 or placebo to 25,871 generally healthy adults for about five years. Neither lowered cancer, major heart events or deaths overall. Omega-3 was linked with fewer heart attacks, a secondary result. A pooled analysis of older trials suggested a very small fall in deaths with vitamin D3, mainly in older people in care, but its authors warned about weaknesses.

A multivitamin was not linked with lower death risk in 390,124 US adults. A Cochrane review of antioxidant vitamin trials found no support for them and some harm signals from beta-carotene and vitamin E.

NAD precursors: small trials show NR and NMN raise NAD+ and that NMN improved muscle insulin sensitivity in postmenopausal women with prediabetes. A 15-trial review of NMN did not find broad benefit and found no clear safety problems in short trials. No trial on lifespan or age-related disease was read.

Resveratrol: ten small trials in older adults gave mixed results, and high amounts raised some cardiovascular risk markers in one group.

The NCCIH says omega-3 supplement side effects are usually mild and that, for some conditions, evidence for benefit from eating seafood is stronger than for omega-3 supplements.

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Biological-age tests, clocks and clinic programmes

DNA methylation "clocks" estimate biological age from a blood sample. In one 3-year trial, omega-3 slowed three of four clocks by about 3 to 4 months. The abstract does not show that anyone was healthier or lived longer.

A 2019 expert review says key challenges remain in understanding how the clocks work and how useful they are as biomarkers. A clinic score is not proof that a treatment works. Ask what the test measures and whether trials show that acting on it helps people.

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How to read a longevity claim

Ask four questions. Was it in people, or only in cells, worms or mice? Did it measure living longer or staying healthier, or only a lab marker? Was it a trial with a comparison group, or only a link in a population study? Was it the same product and amount you are being sold?

The evidence labels on this page are our own judgement from the abstracts read. High means a very large, consistent effect. Against means a good trial found no benefit. Insufficient means too little human data to say.

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At a glance

Traditional uses history, not proof

  • Healthy aging is a modern research topic, not a single traditional remedy
  • Habits such as being active, eating well, sleeping and staying connected are the parts with the most human evidence

Studied for research

  • Not smoking and quitting, high certainty for large survival gains
  • Regular physical activity and living longer, moderate certainty
  • Mediterranean-style diet, moderate certainty
  • Sleep length and social ties, low certainty (observational)
  • Vitamin D and marine omega-3 for cancer, heart events and death in healthy older adults, trial found no benefit
  • Multivitamins and antioxidant vitamins, no benefit found, some harm signals
  • NAD precursors (NMN, NR) and resveratrol, insufficient evidence for aging
  • Biological-age clocks as trial markers, very low certainty

Main compounds

  • Vitamin D3
  • Marine omega-3 fatty acids
  • Nicotinamide riboside (NR)
  • Nicotinamide mononucleotide (NMN)
  • Resveratrol
  • Beta-carotene and vitamin E (antioxidant vitamins)

Common forms

  • Everyday habits (activity, eating pattern, sleep, social contact)
  • Single supplements and multivitamins
  • NAD-precursor and polyphenol supplements
  • Biological-age and blood test panels
  • Longevity clinic programmes

Research links: Pooled analysis: leisure-time physical activity and mortality (661,137 adults) · US study: smoking, quitting and life expectancy · VITAL trial: vitamin D and cancer and heart disease (25,871 adults) · VITAL trial: marine omega-3 and heart disease and cancer · 2026 meta-analysis: oral NMN safety and metabolic outcomes (15 trials) · Research Library · Genes & Biomarkers Library

What it is and its history

Accepted scientific name
Longevity and healthy aging (a research topic, not a substance)
Common names
Longevity (English); Healthy aging (English); Healthspan and lifespan research (English); Longevidad (Spanish); Envejecimiento saludable (Spanish)
Family or group
Topic overview: habits, supplements and tests that are studied in relation to living longer and aging well.
Look-alikes and adulterants
Name: Biohacking; Note: A broader do-it-yourself health culture; has its own page.; Name: Longevity clinic programmes; Note: Commercial packages of tests and treatments; the claims are covered in the clinics guide.; Name: Anti-aging products; Note: Marketing term; the evidence for individual products is covered in the guides.
Sustainability and conservation
Not assessed.

What is inside, and how it may work

What it contains and how those compounds act in cells and animals. Laboratory and animal mechanisms are not proven effects in people.

Main compounds

CompoundFamilyWhere it is concentratedActivity studiedLevel of evidence
Vitamin D3 (cholecalciferol)vitaminTested in the VITAL trial and in pooled trials for cancer, heart events and death. 12 5Human data
Marine omega-3 fatty acidsfatty acidFish oil and similar sourcesTested in VITAL and in DO-HEALTH. 13 3Human data
Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN)NAD+ precursorsRaise NAD+ in small human trials; no outcome trials read. 14 18 17Human data
ResveratrolpolyphenolNot stated in the sources readTen trials in older adults, mixed results. 16Human data

Mechanisms, receptors and pathways

Target or pathwayGene or receptorWhat was foundLevel
NAD+ productionNot specifiedThe NMN trial abstract states that in rodents obesity and aging impair NAD+ production and that NMN availability limits NAD+ production in mammals. In postmenopausal women with prediabetes, NMN raised muscle insulin sensitivity. 18Rodent (background) and human (trial)
DNA methylation age clocksCpG sitesClocks use methylation at a set of CpG sites to estimate age; the review says much research aims to use them to test longevity interventions and discusses challenges. 2Expert review

Absorption, metabolism and elimination

Absorption
Not found.
Distribution
Not found.
Metabolism
Not found.
Elimination
Not found.
Bioavailability
Not found.

Isolated compounds versus whole extracts

NCCIH says that for some conditions the evidence for benefit from eating seafood is stronger than for omega-3 supplements, partly because other nutrients in seafood may matter and seafood eaters tend to have healthier lifestyles. The Mediterranean-diet umbrella review looked at whole eating patterns, not pills. A habit or a whole diet is not the same as a supplement of one ingredient.

Nutritional composition

The National Institute on Aging (content reviewed April 23, 2021) says most if not all of your daily vitamins and minerals should come from food, and that a healthy lifestyle matters whether or not supplements are used. This is a published statement, not advice for any one person.

12benefits and uses looked at
20studies and sources checked
High certaintybest evidence rating found
2lab markers tracked in trials

1 high certainty2 moderate certainty1 mixed findings3 low certainty1 very low certainty2 not enough evidence2 evidence against

What was looked at

The 12 benefits and uses checked for Longevity and Healthy Aging, each with how strong the evidence is. Tap one to open it.

Lab markers tracked in the studies

All-cause mortality (death from any cause)DNA methylation ("epigenetic") age clocks

What is Longevity and Healthy Aging good for?

The main things studied for living longer and aging well, and how strong the human evidence is for each. Habits are mostly observational; supplement trials are small, short or null. Each result is for the exact study described.

Regular physical activity and living longerModerate certaintyLarge studies following hundreds of thousands of adults found that people who were physically active had lower rates of death over the next 14 years, and most of the gain came at modest levels. A five-year trial in older adults did not show a clear difference in deaths, mostly because few people died and the comparison group was already active. Not smoking, and quitting smokingHigh certaintySmoking cut life expectancy by at least ten years in a large US study, and people who quit earlier got most of those years back. This is the clearest and largest effect of any habit in this review. Mediterranean-style eating patternModerate certaintyA big review of reviews found that people who ate closer to a Mediterranean-style diet had lower overall death rates and less heart disease, diabetes and some cancers. For many other outcomes the evidence was weak. Sleep length and living longerLow certaintyIn pooled studies, people who slept very little and people who slept a lot both had a higher risk of death than people in the middle. This does not show that changing sleep length changes life span. Social ties and survivalLow certaintyPeople with stronger social ties were more likely to survive over follow-up in a pooled analysis of 148 studies. Being ill may also make social ties weaker, so the direction of cause is not settled. Several healthy habits togetherLow certaintyTwo very large US cohorts found that people who combined five habits (never smoking, healthy weight, regular activity, moderate alcohol and a good diet) had far lower death rates and a projected 12 to 14 more years of life at age 50 than people with none of them. Vitamin D and marine omega-3 for cancer, heart disease and death in generally healthy older adultsEvidence againstA large trial of more than 25,000 generally healthy older adults found that neither vitamin D nor marine omega-3 lowered cancer, major heart events or deaths from any cause over about five years. Omega-3 was linked with fewer heart attacks, a secondary result that may be chance. Vitamin D3 and survival in older people (pooled trials)Mixed findingsA pooled analysis of 56 trials found a very small fall in deaths with vitamin D3, mainly in older people living independently or in care. The authors warned that dropout and missing outcomes weaken confidence, and it was published before the large VITAL trial. Omega-3, vitamin D and exercise and "biological age" clocksVery low certaintyIn one 3-year trial in older adults, omega-3 slowed three of four DNA methylation "clocks" a little, equal to a few months. The clocks are research tools. The trial did not show that anyone was healthier or lived longer. NAD precursors: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN)Not enough evidenceSmall human trials show NR raises NAD+ and that NMN may improve muscle insulin sensitivity in postmenopausal women with prediabetes. No trial shows that either slows human aging, prevents disease or extends life. Resveratrol in older adultsNot enough evidenceA review of 10 randomised trials in older adults found mixed results: some muscle and function gains when combined with exercise, no advantage over placebo in people with diabetes or artery disease, and some higher cardiovascular risk markers at high doses. It does not show that resveratrol slows aging. Multivitamins for living longerEvidence againstAmong 390,124 US adults followed up to 27 years, people who took multivitamins did not have a lower risk of death than non-users. Studies of antioxidant vitamins also found no support for them (see Safety).

Benefits, one by one

Each card is a research question, not a promise. Tap a goal to filter. Open a card to see the studies, doses and limits.

Regular physical activity and living longer

Moderate certainty

Large studies following hundreds of thousands of adults found that people who were physically active had lower rates of death over the next 14 years, and most of the gain came at modest levels. A five-year trial in older adults did not show a clear difference in deaths, mostly because few people died and the comparison group was already active.

2 studiesNot applicable (lifestyle or diet, not a product)

Studies, doses and limits

What the trials found

A pooled analysis of six cohorts (661,137 adults, 116,686 deaths) found lower death rates at every level of reported leisure-time activity, with the benefit levelling off at about three to five times the recommended minimum and no harm seen at ten times the minimum. A randomised trial in 1,567 older Norwegian adults (Generation 100) found no clear difference in all-cause deaths over five years between supervised exercise and following activity guidelines.

Results

Strong link in observation, not proven cause. The one randomised trial read was inconclusive for deaths.

Effect sizes as reported

Cohort: hazard ratio 0.80 to 0.61 for rising activity. Trial: high-intensity vs control hazard ratio 0.63 (95% CI 0.33 to 1.20).

Why this rating

Moderate (not high) because the cohort result is large and consistent but self-reported and observational, while the only randomised trial read was inconclusive. The pooled study states benefits compared with no activity at all.

Who was studied

Adults aged 21 to 98 in the cohorts; adults aged 70 to 77 in the trial.

Limits

Self-reported activity; fitter people may differ in other ways; the trial had few deaths and a control group that was already active.

Why researchers looked

Exercise is the habit most often linked to longer life in population studies, so researchers asked how much seems to matter and whether it really lowers deaths.

Proposed mechanism Proposed mechanism

Proposed: activity improves heart and lung fitness, blood sugar control and muscle; these routes are proposed, not shown by the studies read here.

A proposed mechanism does not show that the effect happens in people.

The studies read here did not report on harms of exercise. If you have a health condition, ask a clinician before starting something new.

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Not smoking, and quitting smoking

High certainty

Smoking cut life expectancy by at least ten years in a large US study, and people who quit earlier got most of those years back. This is the clearest and largest effect of any habit in this review.

1 studiesNot applicable (lifestyle or diet, not a product)

Studies, doses and limits

What the trials found

A US study of 113,752 women and 88,496 men followed to 2006 found current smokers died at about three times the rate of people who never smoked, losing at least a decade of life. People who stopped at ages 25 to 34 gained about 10 years, at 35 to 44 about 9 years and at 45 to 54 about 6 years.

Results

Very large difference in survival; quitting before age 40 removed about 90 percent of the extra risk of death.

Effect sizes as reported

Hazard ratio for death 3.0 in women (99% CI 2.7 to 3.3) and 2.8 in men (2.4 to 3.1).

Why this rating

High because the effect is very large, matches decades of other work and shows a clear pattern with quitting age, even though the data are observational and a trial of smoking cannot be done.

Who was studied

US adults aged 25 and older.

Limits

Self-reported smoking; observational by necessity; the study ends in 2006.

Why researchers looked

Smoking is the biggest preventable cause of early death, so the question was how many years it costs now and how much quitting gives back.

Proposed mechanism Proposed mechanism

Not examined in the abstract read.

A proposed mechanism does not show that the effect happens in people.

Quitting help exists; a doctor or pharmacist can explain the options.

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Mediterranean-style eating pattern

Moderate certainty

A big review of reviews found that people who ate closer to a Mediterranean-style diet had lower overall death rates and less heart disease, diabetes and some cancers. For many other outcomes the evidence was weak.

1 studiesA pattern of eating, not a product. Foods named in the abstract are n…

Studies, doses and limits

What the trials found

An umbrella review of 13 meta-analyses of observational studies and 16 meta-analyses of randomised trials (over 12.8 million people, 37 outcomes) found robust evidence for lower overall mortality, heart disease, coronary heart disease, heart attack, overall cancer, brain-degenerating disease and diabetes with greater adherence. Evidence for most single cancers and for inflammation markers was only suggestive or weak.

Results

Link with lower overall deaths and several diseases; weaker for individual cancers and blood markers.

Effect sizes as reported

Not given as one number in the abstract.

Why this rating

Moderate because the signal is consistent across many analyses and includes trials, but most of the underlying evidence is observational, the diet was measured many different ways and the abstract gives no certainty rating or funding detail.

Form and dose studied

A pattern of eating, not a product. Foods named in the abstract are not listed; this review did not test any supplement.

Who was studied

General adult populations across many studies.

Limits

Diet was defined differently across studies; a review of reviews inherits the weaknesses of the studies it combines.

Why researchers looked

Researchers wanted to know whether one eating pattern is linked to living longer, and by how much.

Proposed mechanism Proposed mechanism

Proposed: more vegetables, fruit, olive oil, fish and whole grains and less processed food may help blood vessels and blood sugar. The review did not test this.

A proposed mechanism does not show that the effect happens in people.

Food allergies, medicines and medical conditions can change what is suitable; a dietitian can help.

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Sleep length and living longer

Low certainty

In pooled studies, people who slept very little and people who slept a lot both had a higher risk of death than people in the middle. This does not show that changing sleep length changes life span.

1 studiesNot applicable (lifestyle or diet, not a product)

Studies, doses and limits

What the trials found

A meta-analysis of 16 prospective studies (27 cohort samples, 1,382,999 people, 112,566 deaths) found short sleep went with a 12 percent higher risk of death and long sleep with a 30 percent higher risk, with differences between studies.

Results

Higher risk at both ends of the range, in questionnaire-based studies.

Effect sizes as reported

Short sleep relative risk 1.12 (95% CI 1.06 to 1.18); long sleep 1.30 (1.22 to 1.38).

Why this rating

Low because sleep was self-reported by questionnaire, the studies differed a lot, and illness could explain some of the long-sleep result. No trial of changing sleep length to live longer was read.

Who was studied

Adults in prospective cohorts, follow-up 4 to 25 years.

Limits

Self-reported sleep; heterogeneity between studies; cause not shown.

Why researchers looked

Sleep is a daily habit that may track overall health, so researchers pooled studies to see if sleep length predicts death.

Proposed mechanism Proposed mechanism

Not examined in the abstract read; long sleep may reflect illness rather than cause it, which the abstract does not settle.

A proposed mechanism does not show that the effect happens in people.

Ongoing sleep problems or loud snoring with pauses in breathing are worth discussing with a clinician.

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Social ties and survival

Low certainty

People with stronger social ties were more likely to survive over follow-up in a pooled analysis of 148 studies. Being ill may also make social ties weaker, so the direction of cause is not settled.

1 studiesNot applicable (lifestyle or diet, not a product)

Studies, doses and limits

What the trials found

A meta-analysis of 148 studies (308,849 people) found a 50 percent greater likelihood of survival with stronger social relationships, strongest for broad measures of social integration and weaker for simply living alone versus with others.

Results

A link of similar size to other well-known risk factors, according to the authors.

Effect sizes as reported

Odds ratio 1.50 (95% CI 1.42 to 1.59); 1.91 (1.63 to 2.23) for complex integration measures; 1.19 (0.99 to 1.44) for living alone.

Why this rating

Low because these are observational studies, social ties were measured in many ways, and illness could reduce social contact rather than the other way round. No trial of increasing social ties to extend life was read.

Who was studied

Adults across 148 studies; results held across age, sex and health status according to the abstract.

Limits

Observational; measures of social ties varied; reverse cause is possible.

Why researchers looked

Loneliness and isolation have been proposed as health risks, so researchers pooled studies on social relationships and survival.

Proposed mechanism Proposed mechanism

Not examined in the abstract read.

A proposed mechanism does not show that the effect happens in people.

Not applicable.

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Several healthy habits together

Low certainty

Two very large US cohorts found that people who combined five habits (never smoking, healthy weight, regular activity, moderate alcohol and a good diet) had far lower death rates and a projected 12 to 14 more years of life at age 50 than people with none of them.

1 studiesNot applicable (lifestyle or diet, not a product)

Studies, doses and limits

What the trials found

The Nurses Health Study and Health Professionals Follow-up Study (123,219 people, up to 34 years, 42,167 deaths) found people with all five low-risk habits had about one quarter of the all-cause death rate of people with none, and a projected life expectancy at 50 that was about 14.0 years longer for women and 12.2 years longer for men.

Results

Large projected gain; the figures are estimates built from two cohorts and national statistics.

Effect sizes as reported

All-cause hazard ratio 0.26 (95% CI 0.22 to 0.31); 14.0 extra years in women (11.8 to 16.2); 12.2 in men (10.1 to 14.2).

Why this rating

Low because it is observational, the cohorts are mostly white health professionals, habits were self-reported and life expectancy is modelled. The direction is clear but the exact gain for any one person is not.

Who was studied

US adults, mostly health professionals.

Limits

Observational; limited diversity in the cohorts; modelled life expectancy.

Why researchers looked

Habits tend to go together, so researchers asked what happens when people combine several at once.

Proposed mechanism Proposed mechanism

Not examined in the abstract read.

A proposed mechanism does not show that the effect happens in people.

The five-habit set is a research definition (it includes moderate alcohol); it is not advice to drink.

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Vitamin D and marine omega-3 for cancer, heart disease and death in generally healthy older adults

Evidence against

A large trial of more than 25,000 generally healthy older adults found that neither vitamin D nor marine omega-3 lowered cancer, major heart events or deaths from any cause over about five years. Omega-3 was linked with fewer heart attacks, a secondary result that may be chance.

2 studiesSupplement trial results are for the exact product and amount tested …

Studies, doses and limits

What the trials found

The VITAL trial (25,871 generally healthy adults, median 5.3 years) compared vitamin D3 with placebo and marine omega-3 with placebo. Vitamin D: cancer hazard ratio 0.96, major cardiovascular events 0.97, death from any cause 0.99. Omega-3: major cardiovascular events 0.92, cancer 1.03, death from any cause 1.02, heart attack 0.72. No excess of high blood calcium, bleeding or other serious harm was seen.

Results

No benefit on the main outcomes. Neither is shown to help healthy older adults live longer.

Effect sizes as reported

Vitamin D: cancer HR 0.96 (95% CI 0.88 to 1.06); death HR 0.99 (0.87 to 1.12). Omega-3: events HR 0.92 (0.80 to 1.06); death HR 1.02 (0.90 to 1.15).

Why this rating

Rated "against" for the main outcomes because a large, well-run randomised trial found no benefit, with narrow confidence intervals. The heart-attack finding is a secondary outcome and is labelled as such.

Form and dose studied

Supplement trial results are for the exact product and amount tested and do not carry over to other products. Studied: vitamin D3 and marine omega-3 capsules; amounts appear only in the studies table.

Who was studied

Generally healthy adults aged 50 or older (men) and 55 or older (women) in the US, not selected for low vitamin D.

Limits

Median 5.3 years of follow-up; healthy people; the trial says nothing about people who are deficient in vitamin D or have a diagnosed condition. A one-trial result, though a very large one.

Why researchers looked

Both supplements are widely taken, and observational studies had suggested benefits, so a big randomised trial was run to test them.

Proposed mechanism Proposed mechanism

Not examined: the trial tested outcomes, not mechanisms.

A proposed mechanism does not show that the effect happens in people.

No excess harm in the trial. See the Safety tab for kidney-stone and high-calcium signals in other vitamin D work.

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Vitamin D3 and survival in older people (pooled trials)

Mixed findings

A pooled analysis of 56 trials found a very small fall in deaths with vitamin D3, mainly in older people living independently or in care. The authors warned that dropout and missing outcomes weaken confidence, and it was published before the large VITAL trial.

2 studiesSupplement trial results are for the exact product and amount tested …

Studies, doses and limits

What the trials found

A Cochrane review of 56 randomised trials (95,286 people, mostly women over 70, mean 4.4 years) found a relative risk of death of 0.97 for all vitamin D forms and 0.94 for vitamin D3. Vitamin D2, alfacalcidol and calcitriol did not significantly change deaths. About 150 people would need to take D3 for five years to prevent one extra death, said the authors, who also say the evidence has weaknesses.

Results

Small possible benefit for D3 in older adults that later large trials of healthy adults did not repeat.

Effect sizes as reported

All forms RR 0.97 (95% CI 0.94 to 0.99); vitamin D3 RR 0.94 (0.91 to 0.98).

Why this rating

Mixed because pooled older trials point to a small gain for vitamin D3 in older adults, while the later VITAL trial in generally healthy adults found none, and the review itself warns about dropout and reporting bias.

Form and dose studied

Supplement trial results are for the exact product and amount tested and do not carry over to other products. D3 appeared better than D2 and active forms in this review.

Who was studied

Mostly women over 70, many living in care; 48 of 56 trials were in healthy people.

Limits

Dropout above 8 percent; many trials did not report mortality; searches ran to 2012.

Why researchers looked

Because vitamin D is cheap and common, researchers asked whether pooled small trials could show an effect on survival.

Proposed mechanism Proposed mechanism

Not examined in the abstract.

A proposed mechanism does not show that the effect happens in people.

Pooled with calcium, D3 was linked to more kidney stones. See Safety.

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Omega-3, vitamin D and exercise and "biological age" clocks

Very low certainty

In one 3-year trial in older adults, omega-3 slowed three of four DNA methylation "clocks" a little, equal to a few months. The clocks are research tools. The trial did not show that anyone was healthier or lived longer.

1 studiesSupplement trial results are for the exact product and amount tested …

Studies, doses and limits

What the trials found

A post hoc analysis of 777 DO-HEALTH participants found omega-3 alone slowed the PhenoAge, GrimAge2 and DunedinPACE clocks, and the three treatments (vitamin D, omega-3, exercise) together showed an additive benefit on PhenoAge. Standardised effects were 0.16 to 0.32 units, about 2.9 to 3.8 months over 3 years.

Results

Small change in a research marker; no evidence in this paper of fewer diseases or longer life.

Effect sizes as reported

Standardised effects 0.16 to 0.32 units (2.9 to 3.8 months).

Why this rating

Very low because it is a post hoc analysis in a subset, the outcome is a surrogate marker and the clocks themselves are still being validated (see Evidence).

Form and dose studied

Supplement trial results are for the exact product and amount tested and do not carry over to other products.

Who was studied

777 older adults in the DO-HEALTH trial.

Limits

Post hoc; surrogate outcome; no confidence intervals in the abstract; consumer clock tests are not the same as the research clocks used here.

Why researchers looked

DNA methylation clocks estimate biological age from a blood sample, so they are used as quick stand-ins for aging in trials.

Proposed mechanism Proposed mechanism

Not examined in the abstract: the clocks read chemical tags on DNA, and the trial asks whether treatments shift them.

A proposed mechanism does not show that the effect happens in people.

No safety signal in this abstract.

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NAD precursors: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN)

Not enough evidence

Small human trials show NR raises NAD+ and that NMN may improve muscle insulin sensitivity in postmenopausal women with prediabetes. No trial shows that either slows human aging, prevents disease or extends life.

3 studiesSupplement trial results are for the exact product and amount tested …

Studies, doses and limits

What the trials found

A 2 x 6 week crossover trial of NR in healthy middle-aged and older adults found it was well tolerated and raised NAD+ metabolism. A 10-week trial of NMN in postmenopausal women with prediabetes and overweight or obesity found better muscle insulin sensitivity and signalling. A 2026 meta-analysis of 15 NMN trials found no increase in adverse events and no clear effect on weight, blood sugar, cholesterol or systolic blood pressure, with a slight fall in diastolic pressure.

Results

Raises a biochemical marker; health benefits not shown; short trials.

Effect sizes as reported

Meta-analysis: no clear effect on weight, BMI, fasting glucose, HbA1c, lipids or systolic blood pressure.

Why this rating

Insufficient because the human trials are short and small, measure markers not outcomes, and the largest summary found broad metabolic benefit "not evident". No trial of lifespan or age-related disease was read.

Form and dose studied

Supplement trial results are for the exact product and amount tested and do not carry over to other products.

Who was studied

Healthy middle-aged and older adults (NR); postmenopausal women with prediabetes (NMN); adults in 15 NMN trials.

Limits

Short trials; surrogate outcomes; the prediabetes result may not apply to healthy people; many products and amounts.

Why researchers looked

In rodents, aging and obesity impair NAD+ production, so researchers asked whether giving a precursor helps people.

Proposed mechanism Proposed mechanism

Proposed: NMN is a rate-limiting step in making NAD+ in mammals, so a supplement could raise NAD+. Whether this helps people is not shown.

A proposed mechanism does not show that the effect happens in people.

See Safety for tolerability in short trials.

14 18 17

Resveratrol in older adults

Not enough evidence

A review of 10 randomised trials in older adults found mixed results: some muscle and function gains when combined with exercise, no advantage over placebo in people with diabetes or artery disease, and some higher cardiovascular risk markers at high doses. It does not show that resveratrol slows aging.

1 studiesSupplement trial results are for the exact product and amount tested …

Studies, doses and limits

What the trials found

The 2024 systematic review included 10 randomised trials. Resveratrol with exercise improved exercise adaptation and muscle function in healthy older adults and physical performance in people with limited function. In overweight people it helped cognition but at high doses some cardiovascular risk markers rose. Not better than placebo for diabetes or peripheral artery disease. No important side effects were reported.

Results

Mixed and varied; no sign that resveratrol extends human life.

Effect sizes as reported

No pooled numbers in the abstract.

Why this rating

Insufficient because the ten trials are small and differ in groups and products, results are mixed, and no trial of lifespan was read.

Form and dose studied

Supplement trial results are for the exact product and amount tested and do not carry over to other products.

Who was studied

Healthy older adults and older adults with Alzheimer disease, diabetes, peripheral artery disease or overweight.

Limits

No pooled numbers in the abstract; different products and doses.

Why researchers looked

Resveratrol has drawn interest for possible benefits against chronic diseases, and older adults are a group where it might matter, so researchers tested it in them.

Proposed mechanism Proposed mechanism

Not examined in the abstract read. No trial read shows that resveratrol extends human life.

A proposed mechanism does not show that the effect happens in people.

The abstract says optimal amounts, long-term effects and drug interactions still need to be tested.

16

Multivitamins for living longer

Evidence against

Among 390,124 US adults followed up to 27 years, people who took multivitamins did not have a lower risk of death than non-users. Studies of antioxidant vitamins also found no support for them (see Safety).

1 studiesSelf-reported daily multivitamin use; formulas vary.

Studies, doses and limits

What the trials found

Pooled analysis of three US cohorts (390,124 adults, 164,762 deaths): multivitamin use was not linked to lower all-cause mortality (hazard ratio 1.04 in each half of follow-up). The authors mention an earlier US Preventive Services Task Force review that found insufficient evidence from trials.

Results

No mortality benefit found.

Effect sizes as reported

HR 1.04 (95% CI 1.02 to 1.07) first half; 1.04 (0.99 to 1.08) second half.

Why this rating

Rated "against" for living longer because a very large cohort study with careful adjustment found no benefit, and there was no signal of benefit in the abstract. It is observational, so it cannot settle the question alone.

Form and dose studied

Self-reported daily multivitamin use; formulas vary.

Who was studied

Adults aged around 62 without cancer or chronic disease at baseline.

Limits

Observational; multivitamin products differ.

Why researchers looked

About one in three US adults uses a multivitamin, often to prevent disease, so researchers asked if it lowers death rates.

Proposed mechanism Proposed mechanism

Not examined.

A proposed mechanism does not show that the effect happens in people.

See Safety for antioxidant vitamin findings.

11

Connections to the rest of health

How Longevity and Healthy Aging connects to the rest of our health knowledge graph. Every link says what kind of connection it is. A safety link (for example to the liver) is a warning, not a benefit. A study that merely mentions a topic never creates a benefit link.

Explore every connection: goals, body systems, organs, symptoms, genes

A. Wellness goals

Connected toKind of connectionEvidence statusContextStudies
Healthy Aging Moderate certainty Regular physical activity and living longer: Large studies following hundreds of thousands of adults found that people who were physically active had lower rates of death over the next 14 years, and most of the gain came at modest levels. A five-year trial in older adults did not show a clear difference in deaths, mostly because few people died and the comparison group was already active. 1 15
Healthy Aging High certainty Not smoking, and quitting smoking: Smoking cut life expectancy by at least ten years in a large US study, and people who quit earlier got most of those years back. This is the clearest and largest effect of any habit in this review. Several healthy habits together: Two very large US cohorts found that people who combined five habits (never smoking, healthy weight, regular activity, moderate alcohol and a good diet) had far lower death rates and a projected 12 to 14 more years of life at age 50 than people with none of them. 9 10 11
Healthy Aging Moderate certainty Mediterranean-style eating pattern: A big review of reviews found that people who ate closer to a Mediterranean-style diet had lower overall death rates and less heart disease, diabetes and some cancers. For many other outcomes the evidence was weak. 7
Healthy Aging Low certainty Sleep length and living longer: In pooled studies, people who slept very little and people who slept a lot both had a higher risk of death than people in the middle. This does not show that changing sleep length changes life span. Social ties and survival: People with stronger social ties were more likely to survive over follow-up in a pooled analysis of 148 studies. Being ill may also make social ties weaker, so the direction of cause is not settled. 6 8 5 12
Healthy Aging Evidence against Vitamin D and marine omega-3 for cancer, heart disease and death in generally healthy older adults: A large trial of more than 25,000 generally healthy older adults found that neither vitamin D nor marine omega-3 lowered cancer, major heart events or deaths from any cause over about five years. Omega-3 was linked with fewer heart attacks, a secondary result that may be chance. Omega-3, vitamin D and exercise and "biological age" clocks: In one 3-year trial in older adults, omega-3 slowed three of four DNA methylation "clocks" a little, equal to a few months. The clocks are research tools. The trial did not show that anyone was healthier or lived longer. 12 13 3 14 18 17
Healthy Aging Not enough evidence Resveratrol in older adults: A review of 10 randomised trials in older adults found mixed results: some muscle and function gains when combined with exercise, no advantage over placebo in people with diabetes or artery disease, and some higher cardiovascular risk markers at high doses. It does not show that resveratrol slows aging. 16

B. Body systems

Connected toKind of connectionEvidence statusContextStudies
Whole Body Biological association Moderate certainty Studied for: Regular physical activity and living longer Studied for: Not smoking, and quitting smoking 1 15 9 7 10 5 12 3 16 11
Nervous System Biological association Low certainty Studied for: Sleep length and living longer Studied for: Social ties and survival 6 8
Cardiovascular System Biological association Evidence against Studied for: Vitamin D and marine omega-3 for cancer, heart disease and death in generally healthy older adults 12 13
Metabolic System Biological association Not enough evidence Studied for: NAD precursors: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) 14 18 17

E. Health conditions

Connected toKind of connectionEvidence statusContextStudies
Healthy aging Observational and trial evidence Habits such as not smoking and being active show the strongest links with longer life; supplements read here do not. Habits show the strongest links with longer life; supplements read here do not.
Preparation or compound: Lifestyle habits and selected supplements
9 1 12

I. Biomarkers

Connected toKind of connectionEvidence statusContextStudies
All-cause mortality (death from any cause) Biological association Moderate certainty Measured in trials: lower in people with more activity, non-smokers, closer Mediterranean-style eaters and stronger social ties (observational). A lab change is not the same as a health benefit. 1 9 15
DNA methylation ("epigenetic") age clocks Biological association Very low certainty Measured in trials: small slowing with omega-3 in one trial; unproven meaning. A lab change is not the same as a health benefit. 3

K. Biological pathways

Connected toKind of connectionEvidence statusContextStudies
NAD+ production Preliminary mechanism Rodent (background) and human Proposed target of NAD+ precursors; trials read measure markers, not lifespan. 18

L. Active compounds

Connected toKind of connectionEvidence statusContextStudies
Vitamin D3 (cholecalciferol) Biological association Human Tested in the VITAL trial and in pooled trials for cancer, heart events and death. 12 5
Marine omega-3 fatty acids Biological association Human Tested in VITAL and in DO-HEALTH.
Preparation or compound: Fish oil and similar sources
13 3
Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) Biological association Human Raise NAD+ in small human trials; no outcome trials read. 14 18 17
Resveratrol Biological association Human Ten trials in older adults, mixed results. 16

Each connection is stored with the ingredient, the connected record, the kind of connection, the evidence status, the supporting studies, the preparation or compound involved, and a review date (last reviewed October 31, 2026).

The evidence

The research centre for Longevity and Healthy Aging. Every record here was checked against PubMed or the publisher's page; we never list a study we have not verified.

Evidence by outcome

Bars show how many studies we found for each outcome, not how well it works. People are added up across trials only (reviews are not added, to avoid double counting).

How we rate evidence

High certainty

Several well-run trials or reviews agree; further research is unlikely to change the picture much.

Moderate certainty

Good trials point the same way, but some doubt remains.

Low certainty

Small, short or inconsistent trials. The finding could change with better research.

Very low certainty

Very little or very weak human data. Treat as a possibility only.

Mixed findings

Trials or reviews disagree with each other.

Not enough evidence

Not enough human research to say either way.

Evidence against

Good research found no benefit, or found harm.

We take the reviewers' own risk-of-bias and GRADE statements where they exist, and otherwise judge from study size, design, consistency, directness and whether a product matches what is sold. Many publications do not make evidence high. Method note: We searched PubMed, re-read the abstract of every review, trial and cohort study cited, and read in full the National Institute on Aging and NCCIH pages named here. Only abstracts were read for PubMed papers.

Study library: every study we checked 20
StudyDesignPeopleProduct, dose, lengthResult
Arem 2015
Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship.
JAMA Intern Med · PMID 25844730 · DOI
Pooled cohort analysis
661137
6 US and European cohorts, adults (median age 62) followed a median 14.2 years; 116,686 deaths
Leisure-time moderate-to-vigorous physical activity (self-reported)
Reported in metabolic-equivalent hours per week, not given in the abstract in plain units Median follow-up 14.2 years · vs People reporting no leisure-time activity
Compared with no leisure-time activity, people reporting less than the recommended minimum had 20 percent lower mortality risk, those at 1 to 2 times the minimum 31 percent lower, and 2 to 3 times the minimum 37 percent lower. The extra benefit levelled off at 3 to 5 times the minimum (39 percent lower). No evidence of harm was seen at 10 or more times the minimum.
Hazard ratios 0.80, 0.69, 0.63, 0.61 for rising activity; 0.69 at 10 or more times the minimum (0.78 to 0.82; 0.67 to 0.70; 0.62 to 0.65; 0.59 to 0.62; 0.59 to 0.78)
Methods, limits and funding

Outcomes: All-cause mortality (also heart disease and cancer deaths)

Limitations: Observational: activity was self-reported and fitter people may differ in other ways, so the result shows a link, not proof that activity causes longer life.

Funding and conflicts: PubMed record lists US National Institutes of Health research support; no conflict-of-interest statement in the record read.

Read: abstract

Bell 2019
DNA methylation aging clocks: challenges and recommendations.
Genome Biol · PMID 31767039 · DOI
Expert review
human and other vertebrates
Not applicable (review of DNA methylation clock research) DNA methylation ("epigenetic") age clocks
The review says epigenetic clocks measure chronological age very accurately in humans and other vertebrates and that much research aims to use them to quantify biological aging and test longevity interventions. It lays out key challenges in understanding how clocks work and how useful they are as biomarkers, and raises ethical issues in predicting an individual's aging trajectory.
Methods, limits and funding

Outcomes: Clock mechanisms, biomarker use, ethics

Limitations: Expert review; no pooled numbers; written in 2019.

Funding and conflicts: No funding or conflict statement in the record read.

Read: abstract

Bischoff-Ferrari 2025
Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial.
Nat Aging · PMID 39900648 · DOI
Randomised controlled trial
777
Older adults in the DO-HEALTH trial (post hoc analysis of 777 participants)
Vitamin D, marine omega-3 and a home exercise programme, alone and combined, measured with four DNA methylation clocks of biological aging
Vitamin D 2,000 IU a day and omega-3 1 g a day (as studied) 3 years · vs Placebo and no exercise programme
Omega-3 alone slowed three of the four clocks. All three treatments together showed an additive benefit on one clock (PhenoAge). The standardised effects were small, equal to 2.9 to 3.8 months on the clocks over 3 years.
Standardised effects 0.16 to 0.32 units (about 2.9 to 3.8 months) (Not given in the abstract)
Methods, limits and funding

Outcomes: DNA methylation clocks PhenoAge, GrimAge, GrimAge2 and DunedinPACE

Limitations: A post hoc analysis in a subset; clock changes are surrogate markers and the abstract does not show that they mean fewer illnesses or longer life.

Funding and conflicts: No funding or conflict statement in the abstract read.

Read: abstract

Bjelakovic 2012
Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.
Cochrane Database Syst Rev · PMID 22419320 · DOI
Systematic review meta analysis
296707
78 randomised trials; 26 in healthy people (215,900) and 52 in people with stable disease; mean age 63
Antioxidant supplements: beta-carotene, vitamin A, vitamin C, vitamin E, selenium, alone or combined
Varied; the abstract notes higher vitamin A amounts went with higher mortality 28 days to 12 years (mean 3 years) · vs Placebo or no treatment
Across all trials antioxidant supplements had no significant effect on death in the main (random-effects) analysis. In the 56 trials at low risk of bias, they raised mortality slightly (relative risk 1.04). In those trials beta-carotene and vitamin E raised mortality, while vitamin A, vitamin C and selenium did not significantly change it. The authors found no evidence to support antioxidant supplements for prevention.
All trials RR 1.02; low-risk-of-bias trials RR 1.04; beta-carotene RR 1.05; vitamin E RR 1.03 (0.98 to 1.05; 1.01 to 1.07; 1.01 to 1.09; 1.00 to 1.05)
Methods, limits and funding

Outcomes: Death from any cause

Limitations: Published 2012 with searches to 2011; mixed populations (healthy and ill); combined products; the abstract notes the result differs with the statistical model used.

Funding and conflicts: Cochrane review; the abstract does not give a funding statement.

Read: abstract

Bjelakovic 2014
Vitamin D supplementation for prevention of mortality in adults.
Cochrane Database Syst Rev · PMID 24414552 · DOI
Systematic review meta analysis
95286
56 randomised trials with usable mortality data (159 identified), mostly women over 70; 48 trials in healthy people
Vitamin D3, D2 and active forms (alfacalcidol, calcitriol)
Varied; not summarised in the abstract Weighted mean 4.4 years · vs Placebo or no treatment
All forms pooled gave a very small fall in deaths (relative risk 0.97). Vitamin D3 alone gave a small fall (0.94) mainly in older people living independently or in care; D2 and the active forms did not. The authors warn that dropout, missing outcomes and other weaknesses limit confidence. Vitamin D3 with calcium raised kidney stones (relative risk 1.17), and alfacalcidol and calcitriol raised high blood calcium.
All forms 0.97; D3 0.94; D3 and cancer death 0.88; kidney stones 1.17 (0.94 to 0.99; 0.91 to 0.98; 0.78 to 0.98; 1.02 to 1.34)
Methods, limits and funding

Outcomes: Death from any cause; adverse events

Limitations: Published 2014 with searches to 2012, so it predates the large VITAL trial; high dropout and selective reporting could bias results; the authors call for more placebo-controlled trials.

Funding and conflicts: Cochrane review; the abstract does not give a funding statement.

Read: abstract

Cappuccio 2010
Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies.
Sleep · PMID 20469800 · DOI
Systematic review meta analysis
1382999
16 prospective studies (27 cohort samples), 112,566 deaths, follow-up 4 to 25 years
Habitual sleep length, reported by questionnaire
4 to 25 years · vs Middle (typical) sleep length
Short sleep went with a 12 percent higher risk of death and long sleep with a 30 percent higher risk. The studies differed from each other considerably.
Relative risk 1.12 (short sleep) and 1.30 (long sleep) (1.06 to 1.18; 1.22 to 1.38)
Methods, limits and funding

Outcomes: All-cause mortality

Limitations: Sleep was self-reported. Long sleep may be a sign of illness, not a cause, and the studies were quite different from each other. The abstract does not say if the authors judged cause.

Funding and conflicts: PubMed record lists non-US-government research support; no conflict statement in the record read.

Read: abstract

Dinu 2018
Mediterranean diet and multiple health outcomes: an umbrella review of meta-analyses of observational studies and randomised trials.
Eur J Clin Nutr · PMID 28488692 · DOI
Umbrella review
12800000
13 meta-analyses of observational studies and 16 meta-analyses of randomised trials covering 37 health outcomes, over 12.8 million people in total
Mediterranean-style eating pattern (adherence measured in many different ways)
Varied · vs Lower adherence or usual diet
The authors found robust evidence that closer adherence to a Mediterranean-style diet went with lower overall mortality, heart disease, coronary heart disease, heart attack, overall cancer, brain-degenerating disease and diabetes. For most single cancers and for inflammation and metabolic markers the evidence was only suggestive or weak. Nothing was found for LDL cholesterol or bladder, endometrial and ovarian cancers.
Not summarised as one number in the abstract (Not given in the abstract)
Methods, limits and funding

Outcomes: Overall mortality, heart disease, cancers, diabetes, brain-related disease, blood markers

Limitations: Mostly observational studies; the diet was defined in many ways; a review of reviews cannot fix the weaknesses of what it summarises.

Funding and conflicts: No funding or conflict statement in the record read.

Read: abstract

Holt-Lunstad 2010
Social relationships and mortality risk: a meta-analytic review.
PLoS Med · PMID 20668659 · DOI
Systematic review meta analysis
308849
148 studies, 308,849 people
Strength of social relationships (many ways of measuring)
Varied · vs Weaker social relationships
People with stronger social relationships had a 50 percent greater likelihood of survival, and the link was strongest for broad measures of social integration. Living alone versus with others was a weaker marker.
Odds ratio 1.50 for survival (stronger vs weaker ties); 1.91 for complex integration measures; 1.19 for living alone (1.42 to 1.59; 1.63 to 2.23; 0.99 to 1.44)
Methods, limits and funding

Outcomes: Survival / mortality

Limitations: Observational: people who are ill may also have fewer social ties, so the direction of cause is not settled by this review.

Funding and conflicts: PubMed record lists non-US-government research support; no conflict statement in the record read.

Read: abstract

Jha 2013
21st-century hazards of smoking and benefits of cessation in the United States.
N Engl J Med · PMID 23343063 · DOI
Prospective cohort study
202248
113,752 women and 88,496 men aged 25 or older in the US National Health Interview Survey (1997 to 2004), deaths followed to 2006
Current smoking, former smoking and quitting at different ages
Deaths followed to the end of 2006 · vs People who had never smoked
Current smokers died at about three times the rate of people who never smoked. Smokers lost at least ten years of life expectancy. Those who quit between ages 25 and 34 gained about 10 years, at 35 to 44 about 9 years, and at 45 to 54 about 6 years compared with those who kept smoking. Quitting before age 40 cut the extra risk of death by about 90 percent.
Hazard ratio for death 3.0 in women and 2.8 in men (current vs never smokers) (99% CI 2.7 to 3.3 (women); 2.4 to 3.1 (men))
Methods, limits and funding

Outcomes: Death from any cause; life expectancy

Limitations: Smoking was self-reported, and the survey could not follow people after 2006.

Funding and conflicts: No funding or conflict statement in the record read; PubMed lists US National Institutes of Health research support.

Read: abstract

Li 2018
Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population.
Circulation · PMID 29712712 · DOI
Prospective cohort study
123219
78,865 women (Nurses Health Study) and 44,354 men (Health Professionals Follow-up Study), mostly health professionals, followed up to 34 years
Five lower-risk habits: never smoking, healthy body weight, regular moderate-to-vigorous activity, moderate alcohol and a high-quality diet
Up to 34 years; 42,167 deaths · vs People with none of the five habits
People with all five habits had about one quarter of the death rate of people with none. Projected life expectancy at 50 was about 14 years longer in women and 12 years longer in men. These are projections from two cohorts combined with national data.
Hazard ratio for all-cause death 0.26 (5 habits vs 0); 14.0 extra years (women) and 12.2 (men) at age 50 (0.22 to 0.31; 11.8 to 16.2; 10.1 to 14.2)
Methods, limits and funding

Outcomes: All-cause, cancer and heart-disease death; projected life expectancy at age 50

Limitations: Mostly white health professionals, habits self-reported, and the life-expectancy figures are modelled estimates.

Funding and conflicts: No funding or conflict statement in the record read; PubMed lists US National Institutes of Health research support.

Read: abstract

Loftfield 2024
Multivitamin Use and Mortality Risk in 3 Prospective US Cohorts.
JAMA Netw Open · PMID 38922615 · DOI
Prospective cohort study
390124
Adults without cancer or chronic disease at the start, from three US cohorts, followed up to 27 years; 164,762 deaths
Self-reported daily multivitamin use
Up to 27 years · vs Non-users
Multivitamin use was not linked to a lower risk of death. The hazard ratio was 1.04 in both halves of follow-up. The authors note that many US adults use multivitamins to stay healthy.
Hazard ratio 1.04 (first half) and 1.04 (second half) (1.02 to 1.07; 0.99 to 1.08)
Methods, limits and funding

Outcomes: All-cause mortality

Limitations: Observational; multivitamin formulas vary and use was self-reported.

Funding and conflicts: PubMed record lists US National Institutes of Health research support; no conflict statement in the record read.

Read: abstract

Manson 2019
Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease.
N Engl J Med · PMID 30415629 · DOI
Randomised controlled trial
25871
Men aged 50 or older and women aged 55 or older in the US, generally healthy, including 5,106 Black participants
Vitamin D3 (cholecalciferol) capsules, in a trial that also tested marine omega-3
Capsule 2,000 IU a day (as studied) Median 5.3 years · vs Placebo
Vitamin D did not lower invasive cancer (793 vs 824 cases), major cardiovascular events (396 vs 409) or deaths from any cause. No excess of high blood calcium or other harm was identified.
Cancer hazard ratio 0.96; major cardiovascular events 0.97; death from any cause 0.99 (0.88 to 1.06; 0.85 to 1.12; 0.87 to 1.12)
Methods, limits and funding

Outcomes: Invasive cancer; major cardiovascular events; death from any cause

Limitations: Participants were generally healthy and not selected for low vitamin D; the trial says nothing about people who are deficient. Median follow-up of 5.3 years may be too short for effects on cancer.

Funding and conflicts: Funded by the US National Institutes of Health and others (as stated in the abstract).

Read: abstract

Manson 2019
Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer.
N Engl J Med · PMID 30415637 · DOI
Randomised controlled trial
25871
Same participants as the vitamin D comparison: generally healthy US adults aged 50 or older
Marine omega-3 fatty acid capsules, in a trial that also tested vitamin D3
Capsule 1 g a day (as studied) Median 5.3 years · vs Placebo
Omega-3 did not lower major cardiovascular events (386 vs 419) or invasive cancer (820 vs 797), nor deaths from any cause. Heart attack, a secondary outcome, was lower (hazard ratio 0.72). No excess bleeding or other serious harm was seen.
Major cardiovascular events hazard ratio 0.92; cancer 1.03; death from any cause 1.02; heart attack 0.72 (0.80 to 1.06; 0.93 to 1.13; 0.90 to 1.15; 0.59 to 0.90)
Methods, limits and funding

Outcomes: Major cardiovascular events; invasive cancer; death from any cause

Limitations: Secondary outcomes can arise by chance; the trial was in generally healthy people and may not apply to people with existing heart disease.

Funding and conflicts: Funded by the US National Institutes of Health and others (as stated in the abstract).

Read: abstract

Martens 2018
Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.
Nat Commun · PMID 29599478 · DOI
Randomised controlled trial
Healthy middle-aged and older adults; the abstract gives no head-count Nicotinamide riboside (NR), a vitamin B3 form that raises NAD+
Capsule Not given in the abstract 2 x 6 weeks, crossover · vs Placebo
NR was well tolerated and raised NAD+ metabolism. The authors say future trials should look at blood pressure and arterial stiffness. The abstract reports no results on health outcomes or on aging itself.
Not given in the abstract (Not given in the abstract)
Methods, limits and funding

Outcomes: NAD+ metabolism; tolerability; early signals for blood pressure and artery stiffness

Limitations: Short, small crossover trial; raising NAD+ in blood is a biochemical marker, not a health result.

Funding and conflicts: PubMed record lists US National Institutes of Health research support; no conflict statement in the record read.

Read: abstract

Stensvold 2020
Effect of exercise training for five years on all cause mortality in older adults-the Generation 100 study: randomised controlled trial.
BMJ · PMID 33028588 · DOI
Randomised controlled trial
1567
Older adults aged 70 to 77 in Trondheim, Norway; mostly in good health and already fairly active
Five years of supervised exercise (high-intensity interval training or moderate continuous training), twice a week
Two sessions a week 5 years · vs Following national physical-activity guidelines
Deaths did not differ between the control group and the two exercise groups combined. Compared with the control group, the high-intensity group had a lower death rate that was not statistically firm, and the moderate group a slightly higher one that was not firm either. The authors note the control group exercised at an intensity between the two groups.
High-intensity vs control hazard ratio 0.63; moderate vs control 1.24; high-intensity vs moderate 0.51 (0.33 to 1.20; 0.73 to 2.10; 0.25 to 1.02)
Methods, limits and funding

Outcomes: All-cause mortality

Limitations: Only 4.7 percent of the control group died, so the trial had little power to see a difference; the control group was already active.

Funding and conflicts: PubMed record lists non-US-government research support; no conflict statement in the record read.

Read: abstract

Yadegar 2024
Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review.
Phytother Res · PMID 38433010 · DOI
Systematic review of randomised trials
Ten randomised trials of resveratrol in older adults, including healthy older adults, people with Alzheimer disease, diabetes, peripheral artery disease and overweight Resveratrol supplements
Varied; the abstract notes some high doses raised cardiovascular risk markers Varied · vs Placebo or exercise alone
Results were mixed. Resveratrol with exercise improved some exercise adaptation and muscle function in healthy older adults and physical performance in people with limited function. In overweight people it helped cognition but at high doses raised some cardiovascular risk markers. In older adults with diabetes and with peripheral artery disease it was not better than placebo. No study reported important side effects. The authors say best amount, long-term effects and drug interactions need well-designed trials.
Not summarised as numbers in the abstract (Not given in the abstract)
Methods, limits and funding

Outcomes: Muscle function, mobility, cognition, blood markers, safety

Limitations: Ten different small trials with different groups and products; the abstract gives no pooled numbers or certainty rating.

Funding and conflicts: No funding or conflict statement in the abstract read.

Read: abstract

Yang 2026
Safety and Metabolism-Related Outcomes of Oral Nicotinamide Mononucleotide Supplementation in Adults: A Systematic Review and Meta-Analysis.
Nutrients · PMID 42514320 · DOI
Systematic review meta analysis
Fifteen parallel randomised trials of oral NMN in adults, ten contributing to safety analyses Oral NMN or NMN-related supplements
250 to 2,000 mg a day across trials 14 days to 24 weeks · vs Placebo, blank, lifestyle control or same background intervention
NMN did not raise overall, serious or withdrawal-related adverse events or liver enzymes in short trials. No clear effect on weight, BMI, fasting glucose, HbA1c, lipids or systolic blood pressure. Diastolic blood pressure fell slightly. The authors call broad metabolic benefit not evident and say larger, longer trials are needed.
Not given as numbers in the abstract (Not given in the abstract)
Methods, limits and funding

Outcomes: Adverse events, liver enzymes ALT and AST, body weight, blood sugar, cholesterol, blood pressure

Limitations: Short trials (up to 24 weeks); the abstract gives no head-count and no certainty ratings for individual outcomes.

Funding and conflicts: No funding or conflict statement in the abstract read; registered in PROSPERO.

Read: abstract

Yoshino 2021
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.
Science · PMID 33888596 · DOI
Randomised controlled trial
Postmenopausal women with prediabetes who were overweight or obese; the abstract gives no head-count Nicotinamide mononucleotide (NMN) supplement
Capsule Not given in the abstract 10 weeks · vs Placebo
Muscle insulin sensitivity and muscle insulin signalling rose with NMN and did not change with placebo. Genes for muscle remodelling were up-regulated.
Not given in the abstract (Not given in the abstract)
Methods, limits and funding

Outcomes: Insulin-stimulated glucose disposal in muscle (clamp test) and muscle gene activity

Limitations: A 10-week study in one specific group; the abstract does not report weight, blood sugar control or any ageing outcome. The result applies to postmenopausal women with prediabetes, not healthy adults.

Funding and conflicts: PubMed record lists US National Institutes of Health research support; no conflict statement in the record read.

Read: abstract

s-nccih-omega3
NCCIH: Omega-3 Supplements: What You Need To Know (last updated November 2024)
· Source
Official guidance
n/a

Methods, limits and funding

Read: full-text

s-nia-supplements
National Institute on Aging: Dietary supplements for older adults (content reviewed April 23, 2021)
· Source
Official guidance
n/a

Methods, limits and funding

Read: full-text

What we do not know yet

  • No trial read shows that any supplement extends human life or slows aging itself.
  • Evidence for habits is mostly observational; the one randomised exercise trial read did not show a clear difference in deaths.
  • Clock-based results (DNA aging clocks) have not been shown to predict health or life span.
  • Human NMN, NR and resveratrol trials are small and short.
  • Other compounds in longevity marketing (spermidine, CoQ10, taurine, glycine with NAC, and others) were not reviewed here.
  • No safety data on multi-supplement stacks, clinic programmes or contaminant testing of longevity products were read.
  • Pregnancy, breastfeeding and children: no source read.
  • The abstracts of several pooled analyses give no funding statement, so funding is not stated for them.

How new research is added

New studies are found by a saved PubMed search and placed in a review queue before the page changes.

Lab markers

What changed in blood or saliva tests during trials. A changed number is not the same as feeling or being healthier, and we give no "normal ranges".

Other 2

●

All-cause mortality (death from any cause)

Lower in people with more activity, non-smokers, closer Mediterranean-style eaters and stronger social ties (observational) in trials

The share of people who die from any cause during a study. It is the clearest outcome for living longer.

Moderate certainty
Results and what it means

Why it was measured

To see whether a habit or product is linked to longer life.

Statistical vs. clinical meaning

The best single measure of living longer, but cohort links are not proof of cause and trials rarely last long enough to show a difference.

Safety implication

None reported in these abstracts.

StudyResultPeopleProduct
1Hazard ratio 0.61 to 0.80 across rising activity levels versus none661,137 adults, 6 cohortsLeisure-time activity
9Current smokers had about three times the death rate (hazard ratio 3.0 women, 2.8 men)202,248 US adultsSmoking vs never smoking
15No clear difference in deaths between exercise groups and guideline control over 5 years1,567 adults aged 70 to 77Supervised exercise training

1 9 15

●

DNA methylation ("epigenetic") age clocks

Small slowing with omega-3 in one trial; unproven meaning in trials

Research tests that estimate biological age from chemical tags on DNA in a blood sample.

Very low certainty
Results and what it means

Why it was measured

To check whether a treatment appears to slow aging without waiting decades for deaths.

Statistical vs. clinical meaning

A research marker. It has not been shown that changing a clock changes health or life span.

Safety implication

None reported in the abstract.

StudyResultPeopleProduct
3Omega-3 alone slowed PhenoAge, GrimAge2 and DunedinPACE; effects equal to about 2.9 to 3.8 months over 3 years777 older adults, 3 yearsOmega-3, vitamin D, exercise alone and combined

3

Safety

What studies and official sources say about side effects, medicines and who should check first. Each point shows what kind of evidence it comes from.

Main points to know 4
  • No product has been proven to slow human aging. No trial read in preparing this page shows that any supplement, test-guided programme or clinic treatment slows human aging or extends life. The best randomised trial of vitamin D and marine omega-3 in generally healthy older adults found no lower rate of cancer, major heart events or death. Claims of "reversing" or "slowing" aging usually rest on animal or cell studies, small trials or lab markers. Randomised trial and pooled analyses 12 13 17 16
  • Antioxidant vitamin supplements: no support, and some harm signals. A Cochrane review of 78 trials (296,707 people) found no evidence to support antioxidant supplements for prevention. In the trials at low risk of bias beta-carotene and vitamin E slightly raised the risk of death, and the authors say higher amounts of vitamin A might too. The National Institute on Aging says large doses of antioxidant supplements will not prevent chronic disease and some studies show harm. Systematic review and official guidance 4 20
  • Supplements are not approved or checked before sale. The National Institute on Aging says the FDA does not approve dietary supplements for safety or effectiveness before they are sold, and that being on a shelf does not mean a product is safe, does what the label says or contains what the label states. The Federal Trade Commission investigates ads that misrepresent what supplements do, and some private groups run seals of approval. Official guidance 20
  • Biological-age tests and clinic panels are still research tools. Reviewers of DNA methylation "age clocks" describe key challenges in understanding how the clocks work and how useful they are as biomarkers, and call for more study in different tissues, over time and in diverse groups. Scores from a consumer test should not be read as proof that a treatment is working. Some longevity clinics also sell prescription medicines; those are not supplements and are not covered here. Expert review 2
Side effects 5
EffectHow oftenSeverity and recoveryEvidence
Higher death rates with some antioxidant vitamins (beta-carotene, vitamin E)
Trials used a range of amounts and products. Food sources were not tested in these trials.
Relative risk 1.05 for beta-carotene and 1.03 for vitamin E in low-risk-of-bias trials; small differences across hundreds of thousands of people.Death (small increase in risk)
Not assessed
Systematic review of randomised trials 4
Kidney stones with vitamin D3 plus calcium; high blood calcium with the active forms of vitamin D
Alfacalcidol and calcitriol are prescription forms of vitamin D; mentioned only because they were in the review.
Vitamin D3 with calcium: relative risk 1.17 for kidney stones (4 trials). Alfacalcidol and calcitriol: relative risk 3.18 for high blood calcium (3 trials, 710 people). VITAL found no excess high blood calcium with vitamin D3 alone.Not assessed in the abstract
Not assessed
Systematic review and randomised trial 5 12
Mild stomach upset, taste and bad breath with omega-3 supplements
VITAL found no excess of bleeding or other serious harm with marine omega-3 in generally healthy adults.
No rate found in the page read.Usually mild
Not assessed
Official guidance 19 13
Some cardiovascular risk markers rose at high resveratrol amounts
No important side effects were reported in the review overall. Authors say long-term effects need study.
From one subgroup of overweight people in the 10-trial review; no rate given.Not assessed
Not assessed
Systematic review of randomised trials 16
NMN in short trials: no increase in side effects or liver enzymes
Long-term safety has not been established; the authors call for larger, longer trials.
Fifteen trials, ten in safety analyses, up to 24 weeks.No clear increase in adverse events
Not assessed
Meta-analysis 17
Liver

The only liver data read are from NMN trials: a 2026 meta-analysis found no significant rise in ALT or AST liver enzymes in short trials of up to 24 weeks. No liver data were read for the other topics on this page. People with liver disease should ask a clinician before trying any supplement. 17

How often. No case reports were searched for this overview.

Monitoring. No agency monitoring advice was read.

This is a safety connection. It is not evidence that Longevity and Healthy Aging supports liver health.

Medicines and supplements 4
WithWhy it mattersImportanceEvidenceWhat to do
Calcium supplements and vitamin D3
supplement
In four pooled trials, vitamin D3 combined with calcium was linked to more kidney stones (relative risk 1.17).Systematic review of randomised trials Low certainty 5Ask a doctor or pharmacist about combining vitamin D and calcium, especially after kidney stones.
Prescription medicines (general)
prescription
Not found.The resveratrol review says drug interactions still need study. No interaction study was read for NMN, NR, omega-3 or vitamin D with any medicine. The National Institute on Aging page read does not discuss interactions. A medicine interaction checker, or a pharmacist, is the next stop.Absence of evidence Not enough evidence 16Absence of a study is not proof of safety. Show a doctor or pharmacist every supplement you take.
Blood-thinning medicines and omega-3
prescription
Not found.VITAL saw no excess of bleeding in generally healthy adults, but did not test people taking blood thinners. No source read addressed this combination.Absence of evidence Not enough evidence 13Ask a doctor or pharmacist before adding omega-3 if you take blood-thinning medicines.
Several supplements taken together ("stacks")
supplement
Not found.No trial read tested multi-supplement longevity stacks for safety. Trials read tested one or two products at a time.Absence of evidence Not enough evidence Combining products multiplies the unknowns. Ask a pharmacist.
Who should check first 5
SituationAdviceEvidence
Taking prescription medicinesShow a doctor or pharmacist every supplement before starting. Do not stop or change a prescribed medicine because of a longevity claim. (General safety guidance, not from a source read.)General safety guidance
History of kidney stonesVitamin D3 plus calcium was linked to more kidney stones in pooled trials. Ask a doctor first.Systematic review of randomised trials 5
Diabetes, artery disease or other long-term conditionsIn the resveratrol review, older adults with diabetes or peripheral artery disease did not do better than on placebo, and high amounts raised some cardiovascular risk markers in one group. Ask a clinician before using supplements for aging.Systematic review of randomised trials 16
Pregnancy, breastfeeding and childrenNo source read covers longevity products in pregnancy, breastfeeding or children. Ask a doctor or pharmacist.Absence of evidence
Anyone considering a costly clinic programme, genetic or biological-age testAsk what the test measures, whether trials show that acting on it helps people, and what the programme costs. Discuss it with your own doctor. (General guidance, not from a source read.)General safety guidance 2
Overdose, product quality and regulators

Summary. Healthy habits such as activity, not smoking and a balanced eating pattern are not toxic in the sources read. For supplements, the concerns are specific: antioxidant vitamins at high amounts, vitamin D with calcium, and very little long-term data for NAD precursors and resveratrol.

Animal. Not reviewed.

Human doses studied. Amounts appear only inside studies tables.

High dose or long term signals. High-dose resveratrol raised some cardiovascular risk markers in one subgroup; beta-carotene and vitamin E raised death rates in pooled trials; long-term NMN safety is unknown.

Overdose response. Not found.

Genotoxicity. Not researched.

No test of longevity supplements for contaminants was read. The National Institute on Aging says supplements may not contain what the label says and that seal programmes check for harmful ingredients such as lead.

Labels and contents. The National Institute on Aging says the federal government does not regularly test what is in dietary supplements, and that a product on a shelf is not guaranteed to be safe, to do what its label says or to contain what the label states. 20

Private seals. Groups such as U.S. Pharmacopeia and NSF International run seals of approval; to earn one, products must follow good manufacturing practice, contain what is listed and not contain harmful levels of ingredients that do not belong, such as lead. The pages of these programmes were not read. 20

BodyActionDate
National Institute on Aging (US) (United States)States that dietary supplements are not approved by the FDA for safety or effectiveness before sale, that labels may not match contents, that large doses of antioxidant supplements will not prevent chronic disease and may be harmful, and that a healthy lifestyle remains important whether or not supplements are used. source2021-04-23
National Center for Complementary and Integrative Health (US) (United States)Omega-3 page: side effects of omega-3 supplements are usually mild; for some conditions evidence for benefit from seafood is stronger than for omega-3 supplements. source2024-11
When to get medical help
  • Swelling of the lips, face or throat, hives or trouble breathing after a supplement: call emergency services (999 in the UK, 911 in the US). This is general safety guidance, not taken from a source read for this page.
  • Yellow skin or eyes, dark urine or severe stomach pain after starting a new supplement: stop it and see a doctor. General safety guidance, not from a source read.
  • Severe pain in the side or back with nausea, or blood in urine, in someone taking vitamin D with calcium: see a doctor (possible kidney stone). General safety guidance, not from a source read.
  • Chest pain, fainting or sudden weakness: call emergency services; do not wait to try a supplement.

Stop using the product and contact a clinician or emergency service. In the US, Poison Control is 1-800-222-1222.

General information only, not medical advice. Ask a clinician or pharmacist before use, especially with medicines, in pregnancy or with a health condition. See the Natural Remedy Safety guide.

Frequently asked questions

What is longevity and healthy aging?

It is the research field that asks what helps people live longer and stay healthy as they age. It covers habits, foods, supplements and tests. It is not a treatment, and aging is not an approved medical condition.

2

What does the best evidence say helps people live longer?

Not smoking has the largest effect in a US study of 202,248 adults, followed by regular physical activity, a Mediterranean-style diet, sleep and social ties. Most of this is observational, which shows links, not proof.

9 1 7

Does exercise help you live longer?

A pooled analysis of 661,137 adults found lower death rates with more leisure-time activity, with most of the gain at modest levels. A five-year trial in older adults did not show a clear difference in deaths. Ask a clinician about activity that suits you.

1 15

Does vitamin D help you live longer?

In the VITAL trial of 25,871 generally healthy older adults, vitamin D did not lower cancer, major heart events or deaths. An older pooled analysis suggested a very small fall in deaths with vitamin D3, mainly in older people in care, with caveats.

12 5

Does omega-3 help you live longer?

In VITAL, marine omega-3 did not lower major heart events, cancer or deaths overall, though heart attacks were lower in a secondary result. A small trial found omega-3 slowed some DNA aging clocks a few months, which is not the same as living longer.

13 3

Do NMN or NAD supplements slow aging?

No trial read shows that they do. Small trials show NR and NMN raise NAD+, and one showed better muscle insulin sensitivity in postmenopausal women with prediabetes. A 15-trial review found no broad metabolic benefit and no clear short-term safety problem.

14 18 17

Does resveratrol work for aging?

Ten trials in older adults gave mixed results. Some muscle benefits appeared when combined with exercise, it was no better than placebo in diabetes or artery disease, and high amounts raised some heart risk markers in one group.

16

Do multivitamins or antioxidant pills help?

A study of 390,124 US adults found no lower death risk with multivitamins. A Cochrane review found no support for antioxidant supplements and slightly higher death rates with beta-carotene and vitamin E in the best trials.

11 4

Can a biological-age test tell if my supplements are working?

Not reliably. Reviewers say key challenges remain in understanding age clocks and their use as biomarkers. A change in a clock has not been shown to mean fewer illnesses or longer life.

2 3

Is it safe to combine several supplements?

No trial read tested multi-supplement longevity stacks for safety. Vitamin D3 plus calcium was linked to more kidney stones. Show a pharmacist everything you take.

5

Are supplements checked before they are sold?

The National Institute on Aging says the FDA does not approve supplements for safety or effectiveness before sale, and a label may not match the contents. Some private groups run seals of approval.

20

Who should talk to a doctor first?

Anyone taking prescribed medicines, with kidney stones, diabetes, artery or other long-term disease, pregnant or breastfeeding, or thinking of a costly clinic programme should ask a doctor or pharmacist first. Never stop a prescribed medicine because of a longevity claim.

5 16

Explore by health goal

Healthy Aging

Editorial transparency
Written by
AlternativeMed editorial team. Research compiled with AI assistance, then checked against the sources listed.
Medical review
None. This page has not been reviewed by a physician or pharmacist.
First published
2026-10-31
Last substantive update
2026-10-31
How we research
We searched PubMed, re-read the abstract of every review, trial and cohort study cited, and read in full the National Institute on Aging and NCCIH pages named here. Only abstracts were read for PubMed papers.
How we rate evidence
See "How we rate evidence" in the Evidence tab.
Independence
No product is promoted on this page. No affiliate links are shown. Funding is stated only where the abstract or PubMed record gives it.
Sources 20

Each source was opened and checked. Where we read only the abstract, it says so. The small numbers in the text point here.

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  11. Loftfield E, O'Connell CP, Abnet CC, Graubard BI, Liao LM, Beane Freeman LE, Hofmann JN, Freedman ND, Sinha R. Multivitamin Use and Mortality Risk in 3 Prospective US Cohorts.. JAMA Netw Open. 2024. PMID 38922615. DOI 10.1001/jamanetworkopen.2024.18729. (abstract)
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  19. . NCCIH: Omega-3 Supplements: What You Need To Know (last updated November 2024). . . (full-text)
  20. . National Institute on Aging: Dietary supplements for older adults (content reviewed April 23, 2021). . . (full-text)
Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.