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Salmon, spinach, berries, broccoli, nuts, seeds and tomatoes laid out on a white tableSupplement evidence

Supplement evidence tiers

Common longevity supplements, sorted by how strong the human evidence behind each one actually is. Not a rating, and never advice for you.

31 ingredients3 evidence tiersRule adopted 15 Oct 2026

Every source checked 15–31 Oct 2026

Three tiers, not a rating

How much you can trust the evidence behind each one, not which is "best". Pick a tier to jump to it.

How we decide the tiers

Every ingredient is checked against the same written rule, using the sources linked on its entry. Rule adopted 15 Oct 2026.

1. What counts as evidence, strongest first

RankType of evidenceWhat it is, in plain EnglishWhat it can tell usCan support
1Systematic review or meta-analysis (e.g. Cochrane)Researchers gather every good trial on a question and pool the resultsThe most reliable answer we haveTier 1 or 2
2Randomised controlled trialPeople are given the supplement or a dummy pill at random, then comparedWhether the supplement itself causes a changeTier 2 (needs 2+ trials that agree)
3Observational studyResearchers track what people already take and how they fareA link, not proof: people who take supplements often live healthier lives anywayContext only, never enough on its own
4Animal or cell studyTested in mice, worms or a lab dishWhy scientists are interested; often doesn't carry over to peopleTier 3 only
–Brand claims, press releases, influencersWhat the seller or a promoter saysNothing about whether it worksNever used as evidence

2. How that sorts into tiers

TierDoes the body need it?Strongest evidence it hasWhat the tier meansExamples
1: Strong evidence (for the stated purpose)Yes: official daily amounts exist, and national surveys show many people fall shortMeta-analyses of human trials showing a benefitFills a common gap, with strong evidence that it helpsVitamin D, magnesium
2: Moderate or mixed evidenceNot necessarilyA meta-analysis or 2+ human trials, but the effect is small or mixed, or only on a blood markerReal effects in people, but not proven to improve long-term healthCreatine, omega-3, TMG
3: Early or limited evidenceNoMostly animal or cell studies, or small, short human trialsInteresting science, not yet shown to work in peopleNMN, glycine, fisetin

The fine print

  • A blood marker isn't a health outcome. TMG reliably lowers homocysteine, but trials haven't shown fewer heart attacks. Each entry says which one it has.
  • Raising the supplement's own level in the blood doesn't count. That only shows it's absorbed.
  • At least one trial must not be paid for by the company selling it.
  • We judge the evidence for what the ingredient is sold for. Each entry lists every main claim with its own evidence, and the tier comes from the best-supported claim.
  • Each entry grades the evidence by purpose and by who was studied, because the same ingredient can be well supported for one use and not another. Vitamin D is strong for correcting a deficiency but weak for preventing disease in healthy adults under 75. Grades: Strong (meta-analyses or official guidance agree), Moderate (a meta-analysis or several trials, but the effect is small, mixed or only on a blood marker), Weak (few, small or seller-run trials, or results that disagree), No benefit found (trials looked and found none), Not tested (no human trials for that purpose). A tier describes the evidence, not a recommendation.
  • Genes: we report what official health bodies say about a gene variant, and never pair a gene result with a supplement.
  • Where we look, in this order: Cochrane reviews; official nutrient guidance (NHMRC nutrient reference values); meta-analyses of human trials on PubMed; individual trials; animal and cell studies (Tier 3 only). Never brand sites, press releases, preprints or influencers.
Tier 1 · Strong evidence

Strong evidence (for the stated purpose)

Nutrients the body needs, with official daily amounts, that national surveys show many people fall short of, and with meta-analyses of human trials showing a benefit. Worth ruling out a deficiency before considering anything higher up this page. See the comparison page for blood tests that check these directly, and the glossary for what each blood marker actually measures.

Vitamin D3

Strong evidence

Needed for bones, muscles and the immune system. The skin makes it from sunlight, but low levels are common. In the last national survey, just under 1 in 4 Australian adults were deficient, rising to more than 1 in 3 in winter. See the glossary for what a vitamin D blood test actually measures.

Correcting a shortfall: severe deficiency softens bones (rickets in children, osteomalacia in adults), and supplements correct it. This is what puts it in Tier 1.

Living longer: a 2014 Cochrane review (56 trials, 95,286 people) found vitamin D3 seemed to slightly lower deaths in older people, most of them women over 70.

Bones: a 2026 review in the BMJ (69 trials, about 154,000 people) found vitamin D, with or without calcium, had little or no effect on fractures or falls in people living at home, most of whom weren't at high risk.

Guideline: for people without a known reason to take vitamin D, the Endocrine Society’s 2024 guideline suggests against routine vitamin D blood tests, and against doses above the recommended intake in healthy adults under 75. It suggests vitamin D for children and teens, adults 75 and older, during pregnancy, and for adults with high-risk prediabetes. All of these are conditional recommendations.

Evidence by purpose

  • StrongCorrecting a deficiency (rickets, osteomalacia) · People with low levels
  • WeakLowering the risk of disease, at doses above the recommended intake · Healthy adults under 75The Endocrine Society (2024) suggests against it
  • ModerateLowering the risk of death · Adults 75 and olderThe Endocrine Society (2024) suggests it: a conditional recommendation, moderate-certainty evidence
  • No benefit foundFractures and falls · People living at home, most not at high riskBMJ review, 2026
Typical form
softgel / drops
Sample dosage
1000–4000 IU D3/dayThe NHMRC's nutrient reference values set the adult upper level of intake at 80 mcg (3,200 IU) a day. The top of this range is above that level. NHMRC nutrient reference values: vitamin D, upper level, checked 3 Nov 2026.

Sources: NHMRC nutrient reference values: vitamin D · ABS: Australian Health Survey biomedical results, 2011–12 · Cochrane review of 56 trials, 2014 · Meta-analysis of 69 trials, BMJ 2026 · Endocrine Society vitamin D guideline, 2024

Checked 31 Oct 2026

Taken by 5 of the 5 experts who publish a stack (Huberman, Sinclair, Patrick, Johnson and Hyman). Where the experts agree

In 7 of the 9 all-in-ones we compare:AgeMateMelroseIM8DoNotAge®The OneKeeperTmrw

Magnesium (glycinate/threonate)

Strong evidence

Involved in over 300 processes in the body, including muscle, nerve and blood sugar control. About 1 in 3 Australians don't get enough from food, according to the last national nutrition survey.

Blood pressure: a 2016 meta-analysis of 34 trials found it lowered blood pressure by about 2 points, at around 300mg a day for a month or more.

Forms: magnesium oxide is cheap but more likely to upset the stomach. Glycinate and threonate are often sold as better absorbed, but there's little evidence that they work better for health.

Evidence by purpose

  • StrongCorrecting a shortfall · People whose diet falls shortOfficial daily amounts, NHMRC
  • ModerateBlood pressure · AdultsAbout 2 points lower in a 2016 meta-analysis
  • WeakBetter health from glycinate or threonate than other forms · Adults
Typical form
capsule / powder
Sample dosage
200–400mg/dayThe NHMRC's nutrient reference values set the adult upper level of intake for magnesium from supplements at 350 mg a day (magnesium in food isn't counted). The top of this range is above that level. NHMRC nutrient reference values: magnesium, upper level, checked 3 Nov 2026.

Sources: NHMRC nutrient reference values: magnesium · ABS: usual nutrient intakes, 2011–12 · Meta-analysis of 34 trials, Hypertension 2016

Checked 15 Oct 2026

Taken by 3 of the 5 experts who publish a stack (Huberman, Patrick and Hyman). Where the experts agree

Everyday vitamins & minerals

Essential nutrient

Ten basics that turn up again and again in the all-in-ones: vitamin C, B12, folate, B6, thiamine, biotin, niacin, zinc, chromium and choline. The body needs each of them, and official health bodies set a daily amount for all ten. Extra on top of a diet that already covers them hasn't been shown to add much, which is why stacks tend to include them as "cover the bases" rather than as the headline.

Show all 10 +Hide –

Evidence by purpose

  • StrongPreventing or correcting a deficiency · People who are lowOfficial daily amounts for all ten, NHMRC
  • WeakExtra on top of a diet that already covers them · Most adults

Vitamin C

An antioxidant the body can't make for itself. It's needed to build collagen (in skin, blood vessels and gums) and helps the body absorb iron from plant foods. Real deficiency is rare where people eat fresh fruit and vegetables, and the body passes out most of any extra in urine.

Source: NHMRC nutrient reference values: vitamin C

Checked 15 Oct 2026
In 6 of the 9 all-in-ones we compare:AgeMateMelroseAG1IM8The OneBlueprint

Vitamin B12

Needed to make red blood cells and to keep nerves working. It comes almost only from animal foods, so vegans run low more often, and older adults absorb it less well, as do people on some long-term medicines such as metformin and acid-reducing drugs.

Source: NHMRC nutrient reference values: vitamin B12

Checked 15 Oct 2026
In 5 of the 9 all-in-ones we compare:AgeMateMelroseAG1IM8The One

Folate (vitamin B9)

Needed to make DNA and new cells. Low intake around conception and early pregnancy raises the risk of neural tube defects, which is why bread-making flour in Australia has folic acid added. A high intake of folic acid can hide the signs of a low B12.

Genes (MTHFR): some DNA tests report variants in the MTHFR gene, which can mean slightly higher homocysteine and lower folate in the blood. The US CDC says people with these variants can process all types of folate, including folic acid, and that the claim they need a special form such as methylfolate is not true. In folic acid trials, people with the common variant ended up with the same homocysteine levels as everyone else. A blood test for homocysteine, folate and B12 measures actual levels; see the comparison page.

Sources: NHMRC nutrient reference values: folate · CDC: MTHFR gene variants and folic acid · Meta-analysis of MTHFR and folic acid trials, Eur J Nutr 2017

Checked 15 Oct 2026
In 5 of the 9 all-in-ones we compare:AgeMateMelroseAG1IM8The One

Vitamin B6

Helps the body use protein and make brain messengers such as serotonin. Most people get enough from food. Too much can cause nerve damage (peripheral neuropathy: tingling, burning or numbness in the hands and feet). Australia's medicines regulator, the TGA, says it has been reported even at low doses and is more likely when someone takes more than one product containing B6, which is easy to do without noticing. TGA safety alert · checked 15 Oct 2026

Source: NHMRC nutrient reference values: vitamin B6

Checked 15 Oct 2026
In 3 of the 9 all-in-ones we compare:AG1IM8The One

Thiamine (vitamin B1)

Helps turn carbohydrates into energy and keeps nerves working. Deficiency is mostly seen with heavy alcohol use. Bread-making flour in Australia has thiamine added, so most diets cover it.

Source: NHMRC nutrient reference values: thiamin

Checked 15 Oct 2026
In 4 of the 9 all-in-ones we compare:AgeMateAG1IM8The One

Biotin (vitamin B7)

Helps the body use fats, carbohydrates and protein. Deficiency is rare. Worth knowing for anyone getting blood tests: high-dose biotin can make some lab results (such as thyroid tests) read falsely high or low, and the US FDA has warned about it, which is why labs often ask about supplements beforehand.

Source: NHMRC nutrient reference values: biotin

Checked 15 Oct 2026
In 4 of the 9 all-in-ones we compare:AgeMateAG1IM8The One

Niacin (vitamin B3)

Helps turn food into energy and is a building block of NAD+, the same molecule NMN and NR aim to raise (see the NMN / NR card). Deficiency is rare. High doses of the nicotinic acid form cause skin flushing and can strain the liver; the niacinamide form doesn't cause flushing.

Source: NHMRC nutrient reference values: niacin

Checked 15 Oct 2026
In 2 of the 9 all-in-ones we compare:AG1IM8

Zinc

Needed for the immune system, wound healing, and taste and smell. Meat and shellfish are the richest sources. Taking a lot for a long time can block copper absorption and lead to a copper deficiency.

Source: NHMRC nutrient reference values: zinc

Checked 15 Oct 2026
In 4 of the 9 all-in-ones we compare:AgeMateAG1IM8The One

Chromium

A trace mineral involved in how insulin works. Trials of chromium supplements for blood sugar have found small, inconsistent effects, and deficiency is rare.

Source: NHMRC nutrient reference values: chromium

Checked 15 Oct 2026
In 3 of the 9 all-in-ones we compare:MelroseAG1IM8

Choline

An essential nutrient (not strictly a vitamin, but usually grouped with them). It's used to build cell membranes and acetylcholine, a brain messenger, and the liver needs it to process fat. Eggs and meat are the main sources, and many people eat less than the recommended amount.

Source: NHMRC nutrient reference values: choline

Checked 15 Oct 2026
In 6 of the 9 all-in-ones we compare:AgeMateMelroseAG1IM8The OneKeeper
Tier 2 · Moderate evidence

Moderate or mixed evidence

Real, measurable effects in people: a meta-analysis, or at least two trials with at least one not paid for by the seller. But the effect is small or mixed, or shows up only in a blood marker, and none is proven to improve long-term health. Reasonable to consider once the basics are covered, not before.

Omega-3 (EPA/DHA)

Moderate evidence

Fats found mainly in oily fish. One of the most-studied supplements, with more mixed results than its reputation suggests. Australia sets an adequate daily intake for these fats. Quality and concentration vary a lot between brands.

Heart: the 2020 Cochrane review (86 trials, about 163,000 people) found little or no effect on deaths or heart events overall, a slight drop in coronary heart disease, and lower triglycerides. A 2019 analysis of 13 large trials found small drops in heart attacks and heart deaths.

Brain: a Cochrane review found no benefit for memory and thinking in healthy older people.

Mood: a 2019 meta-analysis found products that are mostly EPA (60% or more) eased symptoms of depression; mostly-DHA products didn't.

Evidence by purpose

  • WeakDeaths and heart events overall · AdultsLittle or no effect overall, Cochrane 2020
  • ModerateTriglycerides (a blood fat) · AdultsA blood marker
  • No benefit foundMemory and thinking · Healthy older people
  • ModerateSymptoms of depression, mostly-EPA products · People with depression
Typical form
fish oil / algae oil
Sample dosage
1–2g combined EPA+DHA/day

Sources: NHMRC nutrient reference values: fats · Cochrane review of 86 trials, 2020 · Meta-analysis of 13 trials, J Am Heart Assoc 2019 · Cochrane review on thinking and memory, 2012 · Meta-analysis on depression, Transl Psychiatry 2019

Checked 15 Oct 2026

Taken by 4 of the 5 experts who publish a stack (Huberman, Patrick, Johnson and Hyman). Where the experts agree

Not in any of the 9 all-in-ones we compare

Vitamin K2

Moderate evidence

Vitamin K helps the body use calcium to build bone. K2 is one form of it (leafy greens supply another, K1), and true deficiency is rare in adults, which is why it isn't in Tier 1. It's popular because bone loss is one of the big risks of ageing: a broken hip in later life is a serious event.

Bones: a 2022 meta-analysis of 16 trials in women after menopause found better bone density in the spine; fewer fractures showed up only after one study was left out. Many of those trials used a high-dose form (MK-4, 45mg a day) that Japan prescribes as an osteoporosis medicine. In healthy women after menopause, a 3-year trial of 180mcg a day of MK-7 (244 women, sponsored by NattoPharma, which sells that MK-7) slowed bone loss at the spine and the neck of the thigh bone, though not across the whole hip. A 1-year trial in early menopause found no difference. No trial has tested whether starting earlier in life makes a difference.

Note: vitamin K changes how warfarin, a blood-thinning medicine, works. Anyone taking warfarin should talk to their doctor before taking it.

Evidence by purpose

  • ModerateSpine bone density · Women after menopauseMany trials used a high-dose prescription form
  • WeakFewer fractures · Women after menopauseOnly after one study was left out
Typical form
softgel / drops, often combined with D3
Sample dosage
90–180mcg/day (MK-7)

Sources: NHMRC nutrient reference values: vitamin K · Meta-analysis of 16 trials, Front Public Health 2022 · 3-year randomised trial, Osteoporos Int 2013 · 1-year randomised trial, Osteoporos Int 2010

Checked 15 Oct 2026

Taken by 4 of the 5 experts who publish a stack (Sinclair, Patrick, Johnson and Hyman). Where the experts agree

In 8 of the 9 all-in-ones we compare:AgeMateMelroseAG1IM8DoNotAge®The OneKeeperTmrw

Creatine monohydrate

Moderate evidence

The body makes some creatine and gets more from meat and fish. It isn't a nutrient most people fall short of, which is why it sits in Tier 2 even though the muscle evidence is good.

Muscle: taken alongside resistance training (not instead of it), a meta-analysis of trials in older adults found more lean mass, about 1.4kg, and more strength than training alone. See our research page for more.

Brain: a 2024 meta-analysis of 16 trials (492 people) found small gains in memory, attention and processing speed, mostly in people with a health condition, and no change in overall thinking. Europe's food safety authority, EFSA, reviewed the evidence in 2024 and found a cause-and-effect link with better thinking hadn't been established.

Evidence by purpose

  • ModerateMuscle mass and strength, alongside resistance training · Older adults
  • WeakMemory and thinking · Mostly people with a health condition
Typical form
powder
Sample dosage
3–5g/day

Sources: Meta-analysis of trials in older adults, Open Access J Sports Med 2017 · Meta-analysis of 16 trials on thinking, Front Nutr 2024 · EFSA opinion on creatine and thinking, 2024

Checked 15 Oct 2026

Taken by 4 of the 5 experts who publish a stack (Huberman, Patrick, Johnson and Hyman). Where the experts agree

In 3 of the 9 all-in-ones we compare:MelroseThe OneBlueprint

CoQ10

Moderate evidence

Supports mitochondrial energy production; often taken alongside statins, which are known to deplete natural CoQ10 levels. One trial in people with heart failure found fewer serious heart events; outside heart failure, human evidence is mostly on blood markers such as cholesterol.

Evidence by purpose

  • WeakSerious heart events · People with heart failureOne trial
  • ModerateCholesterol and triglycerides · AdultsSmall changes in blood markers
Typical form
softgel (ubiquinol form)
Sample dosage
100–200mg/day

Sources: Randomised trial, 420 people with heart failure (Q-SYMBIO), JACC Heart Fail 2014 · Meta-analysis of 50 trials on blood fats, J Clin Endocrinol Metab 2022

Checked 15 Oct 2026
In 5 of the 9 all-in-ones we compare:AG1IM8DoNotAge®KeeperTmrw(ubiquinol)

Taurine

Moderate evidence

An amino acid of growing research interest for metabolic and cardiovascular health; a 2026 review pooling 34 human trials found small improvements in blood sugar, blood fats and blood pressure. Those are markers; whether taurine lowers rates of heart disease or diabetes hasn't been tested.

Evidence by purpose

  • ModerateBlood sugar, blood fats and blood pressure · AdultsSmall changes in markers
  • Not testedRates of heart disease or diabetes · Adults
Typical form
powder / capsule
Sample dosage
1–3g/day

Sources: Meta-analysis of 34 trials, Nutr Rev 2026

Checked 15 Oct 2026
In 4 of the 9 all-in-ones we compare:IM8(amount undisclosed)KeeperBlueprintTmrw

Curcumin

Moderate evidence

The active compound in turmeric, studied for anti-inflammatory effects.

Note: curcumin is poorly absorbed on its own in most human trials: bioavailability-enhanced formulations (e.g. with piperine or as a phytosome) show meaningfully different results to plain turmeric extract. This matters more here than for most Tier 2 entries.

Evidence by purpose

  • ModerateInflammation markers such as CRP · AdultsBlood markers; results depend on the form
Typical form
capsule (look for bioavailability-enhanced)
Sample dosage
500–1000mg/day

Sources: Meta-analysis on inflammation markers, Cytokine 2023

Checked 15 Oct 2026
In 1 of the 9 all-in-ones we compare:IM8(turmeric, amount undisclosed)

TMG (trimethylglycine, betaine)

Moderate evidence

A methyl donor the body uses to turn homocysteine back into methionine. Trials show it reliably lowers blood homocysteine, by about 1.3 µmol/L on average in a 2021 meta-analysis, but lowering homocysteine hasn't been shown to prevent heart disease events. It's often paired with NMN on the theory that NMN uses up the body's methyl groups. That idea hasn't been tested for health outcomes.

Note: at around 4g a day or more, betaine has been linked to higher cholesterol in trials. Most longevity products use well under that (0.5–1g).

Evidence by purpose

  • ModerateLowering homocysteine · AdultsA blood marker
  • Not testedPreventing heart disease events · Adults
  • Not testedOffsetting NMN’s use of methyl groups · People taking NMN
Typical form
powder / capsule
Sample dosage
500–2000mg/day

Sources: Meta-analysis on heart markers, Crit Rev Food Sci Nutr 2021

Checked 15 Oct 2026
In 3 of the 9 all-in-ones we compare:DoNotAge®KeeperTmrw

L-theanine

Moderate evidence

An amino acid found naturally in tea leaves. Small human trials suggest it can modestly reduce feelings of stress and improve some measures of sleep quality and attention, often studied alongside caffeine. There is no evidence on ageing or lifespan itself; it turns up in longevity products mainly for calm and sleep, and sits at the thin end of this tier.

Evidence by purpose

  • ModerateStress, sleep and attention · AdultsSmall effects
  • Not testedAgeing or lifespan · People
Typical form
capsule / powder
Sample dosage
100–400mg/day

Sources: Meta-analysis on sleep, 18 trials, Sleep Med Rev 2025 · Meta-analysis of 31 trials, Mol Psychiatry 2026

Checked 15 Oct 2026

One expert's pick: Andrew Huberman is the only one of the 5 who publish a stack to take it. Where the experts agree

In 5 of the 9 all-in-ones we compare:AgeMateMelroseThe OneBlueprintTmrw(amount undisclosed)

Rhodiola rosea

Moderate evidence

A herb traditionally used as an "adaptogen", meaning it is claimed to help the body cope with stress. Human trials have looked mainly at fatigue, stress and mental performance, but reviews describe them as small and of mixed quality, with inconsistent results. Lifespan effects have been reported only in worms and flies, not in people.

Evidence by purpose

  • WeakFatigue, stress and mental performance · AdultsSmall trials, mixed quality and results
  • Not testedLifespan · PeopleReported only in worms and flies
Typical form
capsule (root extract)
Sample dosage
200–600mg/day

Sources: Systematic review of 11 trials, BMC Complement Altern Med 2012

Checked 15 Oct 2026
Tier 3 · Early evidence

Early or limited evidence

The most speculative tier on this page: mostly animal or cell studies, or small, short human trials, often paid for by the seller. These target specific cellular ageing pathways with real scientific interest, but this is where marketing claims most often outrun the research.

NMN / NR (NAD+ precursors)

Early evidence

Aim to raise NAD+, a molecule involved in cellular energy metabolism that declines with age. Human trials show it raises NAD+ in the blood, which shows it's absorbed, but that alone doesn't count under our rule. A review of 12 trials found most clinically relevant measures unchanged, and a 2025 review found no effect of NMN or NR on muscle mass or strength in people over 60.

Regulatory status in Australia: since 10 Dec 2025, NMN is a TGA-permitted ingredient in listed medicines, but only under conditions: oral use, no more than 500 mg a day, 12 weeks or less, adults only (not in pregnancy or breastfeeding), and a single approved ingredient supplier until Dec 2027. NAD, NAD+ and NADH themselves are not permitted. The TGA's safety alert (last updated 3 Feb 2026) warns that NAD/NMN products not on the Australian Register of Therapeutic Goods are likely being supplied illegally, so look for an AUST L number. TGA ingredient update · TGA safety alert · checked 27 Sep 2026

Evidence by purpose

  • Not gradedRaising NAD+ in the blood · AdultsShows absorption only
  • WeakClinical measures · AdultsMost unchanged in a review of 12 trials
  • No benefit foundMuscle mass and strength · People over 60
Typical form
capsule / powder
Sample dosage
250–500mg/day

Sources: Meta-analysis of 12 trials, Crit Rev Food Sci Nutr 2024 · Meta-analysis on muscle, J Cachexia Sarcopenia Muscle 2025

Checked 15 Oct 2026

Taken by 2 of the 5 experts who publish a stack (Sinclair and Hyman). Where the experts agree

In 6 of the 9 all-in-ones we compare:AgeMateMelroseDoNotAge®The OneKeeperTmrw

Urolithin A

Early evidence

Targets mitophagy (cellular "cleanup" of damaged mitochondria). It has more human data than most of this tier: two randomised trials, in adults aged 40–64 and over 65, found better muscle endurance or strength. Both were run by Amazentis, the company that sells it as Mitopure. Our rule needs at least one trial not paid for by the seller before an ingredient moves up, so it stays here for now.

Evidence by purpose

  • WeakMuscle endurance or strength · Adults 40 and olderTwo trials, both run by the seller
Typical form
capsule
Sample dosage
500–1000mg/day

Sources: Randomised trial, ages 40–64, Cell Rep Med 2022 (Amazentis) · Randomised trial, ages 65+, JAMA Netw Open 2022 (Amazentis)

Checked 15 Oct 2026
In 1 of the 9 all-in-ones we compare:Tmrw(amount undisclosed)

Spermidine

Early evidence

Studied for its role in autophagy, the body's cellular recycling process. Most of the evidence is from animals. The largest human trial so far, 12 months in 100 older adults with memory concerns, found no improvement in memory compared with a placebo. Interesting mechanism, not yet a proven outcome.

Evidence by purpose

  • No benefit foundMemory · Older adults with memory concerns12-month trial, 100 people
Typical form
capsule (often wheat-germ derived)
Sample dosage
1–5mg/day

Sources: 12-month randomised trial, 100 older adults, JAMA Netw Open 2022

Checked 15 Oct 2026

Taken by 2 of the 5 experts who publish a stack (Sinclair and Johnson). Where the experts agree

In 4 of the 9 all-in-ones we compare:IM8(amount undisclosed)DoNotAge®KeeperTmrw

Resveratrol

Early evidence

A polyphenol found in grape skins and red wine, made famous by lab studies suggesting it activates sirtuins, a family of proteins linked to ageing. It extended lifespan in mice on a high-fat diet, but the US National Institute on Aging's lifespan program found no lifespan gain in normal mice. Human trials are mixed, and the body absorbs and breaks it down quickly. Meta-analyses find a small drop in blood pressure at high doses (300mg or more a day), mainly in people with diabetes, and no effect on CRP, an inflammation marker. It's sold for ageing, not blood pressure, and our rule judges the evidence for what an ingredient is sold for.

Evidence by purpose

  • Not testedAgeing or lifespan · PeopleNo lifespan gain in normal mice (NIA)
  • ModerateBlood pressure, at 300mg a day or more · Mainly people with diabetesSmall drop
  • No benefit foundCRP, an inflammation marker · Adults
Typical form
capsule / powder
Sample dosage
150–1000mg/day

Sources: NIA mouse lifespan program, J Gerontol 2013 · Meta-analysis on blood pressure, Crit Rev Food Sci Nutr 2019 · Meta-analysis on CRP and heart markers, Int J Cardiol 2015

Checked 15 Oct 2026

Taken by 2 of the 5 experts who publish a stack (Sinclair and Hyman). Where the experts agree

In 5 of the 9 all-in-ones we compare:MelroseDoNotAge®The OneKeeperIM8(amount undisclosed)

Fisetin

Early evidence

A flavonoid found in strawberries and apples. In mouse studies it acted as a "senolytic", clearing out senescent cells (old cells that stop dividing but keep releasing inflammatory signals), and extended lifespan in one study of older mice. The US National Institute on Aging's lifespan program later tested it and found no lifespan gain. Human trials are small and still under way, so there is no human outcome data yet.

Evidence by purpose

  • Not testedAgeing or lifespan · PeopleNo lifespan gain in the NIA mouse program
Typical form
capsule
Sample dosage
100–500mg/day

Sources: Mouse study, EBioMedicine 2018 · NIA mouse lifespan program, GeroScience 2024

Checked 15 Oct 2026

Taken by 3 of the 5 experts who publish a stack (Sinclair, Johnson and Hyman). Where the experts agree

In 3 of the 9 all-in-ones we compare:KeeperIM8(amount undisclosed)Tmrw

Quercetin

Early evidence

A flavonoid found in onions, apples and capers. It is best known as a senolytic when combined with dasatinib, a prescription cancer drug, in small pilot studies; on its own, the evidence for any ageing benefit is very early. It is also poorly absorbed, which is why some products use special forms of it. On its own, a meta-analysis of 7 trials found a small drop in blood pressure (about 3 points) at more than 500mg a day. It's sold for ageing, not blood pressure, so that doesn't move it up a tier.

Evidence by purpose

  • Not testedAgeing, on its own · People
  • WeakClearing old cells, with the drug dasatinib · People in small pilot studies
  • ModerateBlood pressure, above 500mg a day · AdultsAbout 3 points lower
Typical form
capsule
Sample dosage
500–1000mg/day

Sources: Meta-analysis of 7 trials, J Am Heart Assoc 2016 · Dasatinib + quercetin pilot study, EBioMedicine 2019

Checked 15 Oct 2026

Taken by 2 of the 5 experts who publish a stack (Sinclair and Hyman). Where the experts agree

Ca-AKG (calcium alpha-ketoglutarate)

Early evidence

Alpha-ketoglutarate is a molecule the body makes in its energy cycle, and blood levels fall with age. In a 2020 mouse study, the calcium form extended lifespan and shortened the time spent frail, more strongly in females. Human data so far comes from small studies without a placebo group, so placebo-controlled trials are still needed.

Evidence by purpose

  • WeakAgeing markers · PeopleSmall studies without a placebo group
  • Not testedLifespan and frailty · PeopleExtended lifespan in one mouse study
Typical form
powder / capsule
Sample dosage
1–2g/day

Sources: Mouse study, Cell Metab 2020 · Study of Rejuvant users, no placebo group, Aging 2021

Checked 15 Oct 2026
In 4 of the 9 all-in-ones we compare:DoNotAge®KeeperBlueprintTmrw

Hyaluronic acid (sodium hyaluronate)

Early evidence

A molecule found in skin and joint fluid. Small trials of the oral form suggest modest effects on skin moisture and some joint comfort, which is the evidence most products lean on. Its longevity interest comes from naked mole-rats, which make an unusually large form of it that may help explain their resistance to cancer. That is a mechanism in another species, not a result in people. One of the two main skin trials was run by a company that makes it.

Evidence by purpose

  • WeakSkin moisture and joint comfort · AdultsSmall trials, one run by a maker
Typical form
capsule / powder
Sample dosage
100–200mg/day

Sources: Randomised trial, 40 adults, Nutrients 2021 (Kewpie) · Randomised trial, Skin Res Technol 2023

Checked 15 Oct 2026
In 4 of the 9 all-in-ones we compare:MelroseDoNotAge®The OneBlueprint

Glycine

Early evidence

An amino acid the body makes itself and a building block of collagen and of glutathione, one of the body's main antioxidants. In the US National Institute on Aging's mouse lifespan program, a glycine-rich diet modestly extended lifespan. Human evidence is thin: small sleep studies, mostly from one research group, and small trials from one US group pairing it with NAC (see below), the largest with 24 people. That's why it's in Tier 3.

Evidence by purpose

  • WeakSleep · AdultsSmall studies, mostly one research group
  • WeakOxidative-stress markers, with NAC (GlyNAC) · Older adultsSmall trials, one research group
Typical form
powder
Sample dosage
1–3g/day

Sources: NIA mouse lifespan program, Aging Cell 2019 · Review of the sleep studies, J Pharmacol Sci 2012 · GlyNAC randomised trial, 24 older adults, J Gerontol 2023

Checked 15 Oct 2026
In 6 of the 9 all-in-ones we compare:AgeMateDoNotAge®The OneKeeperBlueprintTmrw

NAC (N-acetylcysteine)

Early evidence

Supplies cysteine, the amino acid that usually limits how much glutathione the body can make. NAC is a long-established medicine (hospitals use it to treat paracetamol overdose). Its longevity interest comes mostly from small "GlyNAC" trials in older adults, where NAC taken with glycine raised glutathione and improved oxidative-stress markers. Those trials are small and come from one research group, so for healthy ageing it sits in Tier 3. Its strongest human evidence is in lung disease: a meta-analysis found fewer flare-ups in chronic bronchitis and COPD.

Note: more antioxidant isn't automatically better. In a 2014 mouse study, NAC sped up the growth of existing lung tumours. That's an animal finding, not a human result, but it's why antioxidants are a less clear-cut "more is better" story than marketing suggests.

Regulatory status in Australia: under the Poisons Standard (June 2026), NAC taken by mouth and labelled with a recommended daily dose of 1 g or less is unscheduled. Oral products labelled above 1 g a day are Schedule 2 (pharmacy medicines), and other forms are Schedule 4 (prescription only). As with any supplement sold here, an AUST L number shows the product is on the Australian Register of Therapeutic Goods. Poisons Standard June 2026 · checked 13 Oct 2026

Evidence by purpose

  • ModerateFewer flare-ups · People with chronic bronchitis or COPD
  • WeakHealthy ageing (GlyNAC) · Older adultsSmall trials, one research group
Typical form
capsule
Sample dosage
500–1000mg/day

Sources: GlyNAC randomised trial, J Gerontol 2023 · Meta-analysis on COPD flare-ups, Eur Respir Rev 2015

Checked 15 Oct 2026
In 1 of the 9 all-in-ones we compare:Keeper
Hands lifting a scoop of powder from a white tub towards a shaker cup

Prefer one product that covers several tiers?

See how 9 all-in-one stacks sold in Australia compare on what's actually dosed inside, price per 30 days and TGA listing.

Compare all-in-ones

Straight answers, sourced

Is anything on this page medical advice?

No. This page describes, at a population level, what a supplement generally does and how strong the evidence behind it is. It never interprets what any of this means for you personally, and never recommends what you specifically should take. A GP reviewing your own blood results can tell you things about your own body, including when a supplement that's fine for most people isn't right for you, that a general page like this can't. See our guide.

How are the three tiers decided?

By a written rule, the same for every ingredient (see how we decide the tiers). Tier 1 is a nutrient with official daily amounts, a shortfall national surveys show is common, and meta-analyses of human trials showing a benefit. Tier 2 has a meta-analysis, or at least two human trials with at least one not paid for by the seller, showing an effect that's real but small or mixed, or only on a blood marker. Tier 3 rests mostly on animal or cell studies, or small, short human trials. We judge each ingredient on what it's sold for, never on popularity or price, and every entry links the reviews or trials it rests on, with the date we checked them. Each entry also grades the evidence separately for each purpose and says who was studied, so a tier describes the evidence, not a recommendation.

Do gene results like MTHFR change which supplements someone needs?

We don't pair gene results with supplements; we report what official health bodies say. For MTHFR, the US CDC says people with common variants can process all types of folate, including folic acid, and that the claim they need a special form such as methylfolate is not true. A blood test measures actual folate, B12 and homocysteine levels, and a GP can say what a result means for you. See the folate entry.

CDC: MTHFR gene variants and folic acid

Checked 15 Oct 2026

Where are the all-in-one products?

On their own page. All-in-one supplements, compared breaks down 9 pre-made stacks sold in Australia using these same three tiers, ingredient by ingredient, alongside price per 30 days and whether each is listed on the Australian Register of Therapeutic Goods.

What about supplement quality scores, like SuppCo's TrustScore?

They measure something different from our tiers. SuppCo's TrustScore rates a product out of 10 on manufacturing standards, third-party certifications, testing and label quality: whether it's well made and contains what it says. It doesn't score whether the ingredients work, which is what our tiers are about, so a product can score highly on quality and still be mostly Tier 3. SuppCo has been owned by Function Health, a US blood-testing company, since May 2026, and it also sells supplements through its own buying club. It doesn't publish how its 30-plus checks are weighted, and its checks are built around US rules, so they don't cover TGA listing. We don't use its scores. On the all-in-ones page we show instead whether each brand publishes its own batch lab reports.

SuppCo: how the TrustScore works · Athletech News: Function acquires SuppCo

Checked 14 Oct 2026

Never ranked for money. No brand can pay to be listed, or for which tier an ingredient sits in.