Longevity supplements graded A to D on the human evidence

Few longevity supplements have strong human evidence, and none has been shown to make people live longer. Creatine and protein have the best trial support, for muscle and strength when combined with resistance training. Vitamin D and standard fish oil were tested in large trials. They did not prevent heart events, cancer or deaths in people not selected for deficiency. NMN, NR and resveratrol rest mostly on animal data. This page grades each one on human evidence; it is not personal medical advice.

How we grade the evidence

Each grade applies to one stated outcome, because a supplement can be well supported for one thing and unsupported for another.

• A. Consistent evidence from human randomised trials for the stated outcome.
• B. Human trials exist, but they are small, short, mixed, or measure markers rather than events.
• C. Mostly observational human data, or a few low-quality trials.
• D. Mostly animal or cell studies.
• Not supported. Large human trials tested the outcome and found no benefit.

A good grade is not a recommendation. It means the evidence for that outcome is solid. Whether it fits you is a question for your own doctor, who knows your medicines, blood tests and history.

Longevity supplements, graded

Supplement	Outcome	Grade	What the human evidence shows
Creatine	Muscle and strength with resistance training, older adults	A	22 trials, 721 people: about 1.4 kg more lean mass and greater strength
Protein	Muscle and strength with resistance training	A	49 trials, 1,863 people: modest gains; smaller with age; no added gain above about 1.6 g/kg/day
Omega-3, prescription dose (4 g/day)	Lowering very high triglycerides	A	Reductions of 30% or more, per the American Heart Association
Omega-3, prescription dose	Fewer heart events in high-risk, statin-treated patients	B	One large trial positive (pure EPA), one large trial null (EPA plus DHA)
Fish oil, 1 g/day	Preventing heart events or cancer in the general population	Not supported	VITAL, 25,871 people: no effect on either main outcome
Vitamin D	Preventing cancer, heart events, fractures or death in adults not tested for deficiency	Not supported	VITAL and D-Health, over 47,000 people combined: no benefit
Magnesium	Blood pressure	B	34 trials: about 2 mmHg lower systolic pressure
Magnesium	Sleep in older adults	C	3 small trials, low to very low quality
NMN and NR	Raising NAD+ and metabolic markers	B	Small, short trials; NAD+ rises, other effects early
NMN and NR	Slowing ageing or extending life	D	Animal data only
Resveratrol	Longer life	D	Mice on a high-calorie diet; dietary levels not linked with survival in older Italians
Olive polyphenols, as olive oil	Protecting blood lipids from oxidative stress	A	Authorised EU health claim; EUROLIVE trial in 200 men
Olive polyphenols	Longer life	C	Large observational cohorts on olive oil; no supplement trials on ageing outcomes
Metformin	Slowing ageing	Not graded: prescription drug	Proposed TAME trial; blunted exercise gains in two trials in older adults

Creatine and protein: the strongest grades

A meta-analysis of 22 randomised trials included 721 adults with average ages of 57 to 70. Taking creatine during resistance training added 1.37 kg more lean tissue than placebo, plus greater chest and leg press strength (Chilibeck et al., 2017). An earlier meta-analysis also found better chair-stand performance, while noting the limited number of studies (Devries and Phillips, 2014).

For protein, a meta-analysis of 49 trials with 1,863 people found supplements increased strength and muscle gains during resistance training (Morton et al., 2018). The effect shrank with age. Total protein intakes above about 1.6 g per kg of body weight a day added no further gain.

The key word in both cases is training. The supplements added to the effect of lifting weights; they did not replace it.

Vitamin D and fish oil: tested at scale, mostly null

The VITAL trial gave 25,871 US adults vitamin D3 at 2,000 IU a day, omega-3 at 1 g a day, both, or placebo. Over a median 5.3 years, vitamin D did not lower invasive cancer or major cardiovascular events (Manson et al., 2019). A VITAL sub-study found no effect on total, non-vertebral or hip fractures (LeBoff et al., 2022).

Australia's D-Health trial gave 21,315 people aged 60 and over 60,000 IU of vitamin D3 a month for five years. It did not reduce all-cause mortality (Neale et al., 2022). Exploratory analyses even hinted at more cancer deaths, which the authors flagged as a reason for caution.

These trials studied people not selected for low vitamin D. Testing and treating a diagnosed deficiency is a separate medical question for your doctor.

The omega-3 arm of VITAL also missed both main outcomes: major cardiovascular events and cancer (Manson et al., 2019). Prescription doses are a different story. At 4 g a day, they lower very high triglycerides by 30% or more (Skulas-Ray et al., 2019).

For heart events, the two big prescription trials disagree. REDUCE-IT gave 8,179 statin-treated patients 4 g a day of icosapent ethyl, a purified EPA. Events fell from 22.0% to 17.2% (Bhatt et al., 2019). STRENGTH gave 13,078 similar patients 4 g of EPA plus DHA and found no difference against corn oil (Nicholls et al., 2020). Hence a B. For a comparison with olive products, see olive oil capsules vs fish oil.

Magnesium: modest and honest

A meta-analysis pooled 34 double-blind trials with 2,028 adults. Magnesium, at a median 368 mg a day for three months, lowered blood pressure by 2.00/1.78 mmHg (Zhang et al., 2016). That is real but small, so it earns a B.

For sleep, a review found only three trials in 151 older adults. People fell asleep about 17 minutes faster, but the evidence was rated low to very low quality (Mah and Pitre, 2021). That is a C.

NMN, NR and resveratrol: promising in animals, thin in people

NAD+ boosters are the most marketed longevity supplements. In a six-week crossover trial in healthy middle-aged and older adults, nicotinamide riboside (NR) was well tolerated and raised NAD+ metabolism (Martens et al., 2018). In a 10-week trial, NMN improved muscle insulin sensitivity in postmenopausal women with prediabetes (Yoshino et al., 2021).

Both trials were small and short, and both measured markers. The headline claim, slower ageing, comes from animal research. No human trial has shown longer life or slower ageing.

Resveratrol made headlines when it improved health and survival in mice on a high-calorie diet (Baur et al., 2006). A nine-year study followed 783 Italians aged 65 and over. Resveratrol levels from diet were not linked with death, inflammation, heart disease or cancer (Semba et al., 2014). That study measured diet, not supplements, but it gives no human support for the longevity claim.

Metformin is a drug, not a supplement

Metformin is a prescription diabetes medicine. Researchers have proposed testing it against ageing in a trial called TAME (Barzilai et al., 2016). We do not grade it alongside supplements, because only a prescriber can weigh it for you.

Two trials in older adults give pause. Metformin blunted gains in insulin sensitivity and fitness from 12 weeks of aerobic training (Konopka et al., 2019). It also reduced muscle gains from 14 weeks of resistance training (Walton et al., 2019).

Olive polyphenols: what the evidence supports

In the EU, one health claim is authorised for olive oil polyphenols. Its wording: olive oil polyphenols contribute to the protection of blood lipids from oxidative stress; the effect is obtained with a daily intake of 20 g of olive oil containing at least 5 mg of hydroxytyrosol and its derivatives (EFSA, 2011; European Commission, 2012). See our page on hydroxytyrosol for how that is measured.

A key trial behind it, EUROLIVE, gave 200 healthy men 25 mL a day of olive oils differing only in polyphenol content. Over three-week periods, oxidised LDL and other oxidative stress markers fell as polyphenol content rose (Covas et al., 2006). That earns an A, for a marker outcome, in the same way prescription omega-3 earns an A for triglycerides.

For longer life, the grade drops to C. Two US cohorts followed over 92,000 adults for 28 years. Those eating more than half a tablespoon of olive oil a day had 19% lower all-cause mortality than those who rarely ate it (Guasch-Ferré et al., 2022). But this was observational. Olive oil showed no significant difference when compared with other vegetable oils combined.

Two caveats apply. Most of this evidence is for olive oil eaten as food, not for capsules or extracts. And no trial has tested olive polyphenol supplements on ageing outcomes. For a closer look, see do olive oil supplements actually work?

What about supplements for men over 40?

The same grades apply. For men over 40 who lift weights, creatine and enough protein have the best evidence for keeping muscle and strength. The supplement does not replace the training.

Vitamin D and fish oil have not prevented heart events or cancer in large trials of men and women over 50. Metformin is a prescription drug, not a supplement. Anything sold as an anti-ageing pill should be judged on human trials, not mouse studies.

Before starting anything, talk to your own doctor, especially if you take medicines. Our older article on supplements for chronic inflammation covers olive oil and inflammation in more depth. For the eating pattern behind all of this, see eating for longevity the Mediterranean way.

For transparency: Pomoni makes Phenolia Daily, a capsule providing 12 mg of olive polyphenols per two-capsule serving, calculated from the extract's certificate of analysis.

Sources

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