Does it really do anything for cellular energy?

What this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.

1. 01NAD+ / B ComplexBlendLimited. People have taken it in a published study, but fewer than 100 of them. 5 completed trials, 34 people given it.8 reported

   34 people given it2 trials

   • The vitamin drip did not beat salt water. Thirty four adults with fibromyalgia were given either the vitamin mixture or a plain fluid drip every week for two months. Both groups felt better. Neither group felt better than the other, at two months or at four. Sitting for an hour with a needle in your arm does something on its own, and that is what this trial measured. It is the closest thing to a controlled test of the drip NAD+ is sold alongside.

     The numbers 34 adults with fibromyalgia randomised to weekly infusions of the Myers cocktail or to lactated Ringer's solution for eight weeks. Both groups improved, but there was no statistically significant difference between them on any outcome at eight or sixteen weeks. This is the closest thing to a controlled trial of the intravenous vitamin cocktail that NAD+ is sold alongside, and it did not beat saline.

     Journal of Alternative and Complementary Medicine, 2009· 34 people

   • The first look at NAD+ given by drip in people, and it measured chemistry rather than benefit. Blood was sampled through a six hour infusion. Nothing rose in the blood for the first two hours, which suggests the body takes it up or breaks it down quickly. Nobody was tested for energy, thinking, sleep or anything else a clinic sells this for. No B vitamins were given. This is a starting point for researchers, not evidence that a drip does anything for you.

     The numbers The first human data on intravenous NAD+. Plasma NAD+ and its metabolites did not rise during the first two hours of the infusion, consistent with rapid tissue uptake or breakdown. The study measured the metabolome only. No efficacy outcome of any kind was assessed, and no B vitamins were given.

     Frontiers in Aging Neuroscience, 2019· number of people not given

   What people using it report

   • Chest tightness, cramping, flushing and nausea during the NAD+ part of the drip. Clinics handle it by slowing the drip down. This is the effect people are least ready for.

   Also measured in animals or in the lab

   • In a lab. Three forms of B12 were tested for how well they hold up against heat, light, acid and other vitamins. Methylcobalamin, the form sold as the best one, broke down the most. Cyanocobalamin held up best. Vitamin C, which broke it down, is a routine part of the drips NAD+ is added to.

     The numbers Direct comparison of cyanocobalamin, hydroxocobalamin and methylcobalamin under heat, UV, pH and co-existing vitamins. Methylcobalamin was the least stable, losing 48 to 76 percent alongside other water-soluble vitamins, 70 to 76 percent with ascorbic acid and 79 percent at pH 3; cyanocobalamin was the most stable. Ascorbic acid is a routine component of the infusions NAD+ is added to.

     International Journal for Vitamin and Nutrition Research, 2020· lab (cells in a dish)

2. 02CotadutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 6 completed trials, 1,221 people given it.

   0 people given it1 trial1 found nothing

   • found nothingPeople lost weight on cotadutide because they ate less, not because they burned more. This small study followed 12 people on the drug and 7 on a dummy for six weeks. The drug group lost four percent of their body weight against one and a half percent on the dummy. They ate far less food. Energy burned, measured properly, did not change at all. Nineteen people is a very small number for a question this specific. AstraZeneca funded it.

     The numbers Phase 2a energy balance study; 12 cotadutide and 7 placebo completers over 42 days. Weight change minus 4.0 percent against minus 1.4 percent (P equals 0.011); energy intake fell 41.3 percent against placebo; energy expenditure by doubly labelled water did not differ (1.0 percent, P equals 0.784). Weight loss was driven by eating less, not by burning more. Funded by AstraZeneca.

     Diabetes, Obesity and Metabolism, 2024· number of people not given

3. 03Peptide YYPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 12 people given it.3 reported

   0 people given it1 trial1 found nothing

   • found nothingCopying the hormone mix that follows stomach bypass surgery cut food intake by about a third. Obese volunteers wore a pump under the skin for about ten and a half hours, delivering three gut hormones at post-surgery levels, or a dummy infusion. Each person tried both, in turn, and did not know which was running. They ate roughly 32% less on the hormones. Resting energy burn did not change, so the whole effect was on appetite. Public money paid for the work.

     The numbers Single-blind randomised placebo-controlled crossover in obese volunteers: a 10.5-hour ambulatory subcutaneous infusion of GLP-1, oxyntomodulin and PYY at doses matching post-gastric-bypass levels (PYY 0.4 pmol/kg/min) cut food intake by a mean 32 percent with no change in resting energy expenditure. Non-US government funded.

     Journal of Clinical Endocrinology and Metabolism, 2017· number of people not given

4. 04OxyntomodulinPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 13 people given it.

   nobody was given it1 watch-only study

   • People ate less, and they did not burn more. 15 healthy young men got oxyntomodulin, GLP-1, glucagon, the last two together, or salt water before a meal, on separate days. Every hormone cut how much they ate, by about the same amount. Giving GLP-1 and glucagon together added nothing. Oxygen use, which is how energy burn is measured, did not shift on any of them. The weight effect comes from eating less, not from burning more.

     The numbers The trial that separates the appetite claim from the energy expenditure claim by running oxyntomodulin against its two component signals and against the combination. Read this before believing the raises-your-metabolism half of the story.

     Journal of Clinical Endocrinology and Metabolism, 2015· number of people not givenobserved only, nobody was given it

5. 05NAD+ with glutathioneBlendLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 21 people given it.5 reported

   nobody was given it1 watch-only study

   • Swallowing nicotinamide riboside does raise NAD in the blood, and that is all this study set out to show. Healthy volunteers took it, everyone knew they were taking it, and there was no comparison group. Blood NAD roughly doubled, and the rise matched how much of the compound got into the blood. No side effects were reported. Here is the limit. Blood NAD is a marker, not a benefit. Nothing here says anyone felt better, performed better or lived longer.

     The numbers Oral nicotinamide riboside was well tolerated with no adverse events. Significant increases from baseline to steady state were seen for both NR at p = 0.03 and NAD+ at p = 0.001, with NAD+ rising by 100%. Change in NR and change in NAD+ correlated at R squared 0.72. This is the surrogate that the NAD field rests on: blood NAD can be raised.

     PLoS One, 2017· number of people not givenobserved only, nobody was given it

   What people using it report

   • Chest tightness, nausea, cramping and flushing during a fast NAD+ drip, which go away when the drip is slowed. Nearly everyone reports this.

Vitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.

1. 01NRPTSupplementModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 176 people given it.3 reported

   144 people given it2 trials1 found nothing

   • The pills raise NAD in the blood, and that is all this trial measured. 120 healthy adults aged 60 to 80 took a dummy pill, the recommended dose, or double, every day for eight weeks, and nobody involved knew which. NAD rose about 40 percent on the normal dose and about 90 percent on the double, and stayed up for the full eight weeks. Nothing rose on the dummy. No serious side effects. Nobody measured whether anyone felt or functioned better. Elysium Health, which sells the product, paid for it.

     The numbers The pivotal trial. 120 healthy adults aged 60 to 80 randomised to placebo, recommended dose NRPT, or double dose, taken daily for 8 weeks. Whole blood NAD rose approximately 40 percent at the recommended dose and approximately 90 percent at double dose after 4 weeks compared with placebo and baseline, and the increase was sustained through the full 8 weeks. Placebo NAD did not rise. No serious adverse events. The endpoints are blood NAD and safety; no functional or clinical outcome was assessed. Funded by Elysium Health, which sells the product as Basis, and conducted by an independent contract research organisation, KGK Synergize. Six authors are Elysium employees and shareholders. A correction was published in the same journal in 2018.

     npj Aging and Mechanisms of Disease, 2017· 120 people

   • found nothingThe pills raised NAD in patients with sudden kidney injury, and nothing about their kidneys changed. 24 hospital patients took rising doses of the combination or a dummy for two days. The kidney injury itself halved NAD in the untreated patients, which is a finding in its own right. Pooled across doses the supplement lifted NAD by about a third, though results jumped around between individuals and only one dose step stood out alone. Kidney and liver blood tests were unchanged. Two authors work for Elysium Health.

     The numbers NCT03176628. 24 hospitalised patients with acute kidney injury received escalating doses of NRPT or placebo twice daily for 2 days across four dose steps up to 1000 mg NR with 200 mg pterostilbene. Acute kidney injury itself reduced whole blood NAD by 50 percent at 48 hours in placebo patients (P=0.05). Pooling all steps, NRPT increased NAD by 37 percent at 48 hours (P=0.002), but only one individual step reached significance and interindividual variability was considerable. Creatinine, eGFR, electrolytes, liver function tests and blood counts were unchanged. Three of 20 patients on NRPT reported minor gastrointestinal effects. Two authors are Elysium Health employees.

     BMC Nephrology, 2020· 24 people

2. 02NMNSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 94 people given it.6 reported

   80 people given it1 trial1 found nothing

   • found nothingNMN raised NAD in the blood and added a little to how far people could walk, and did nothing for blood sugar handling. Eighty healthy middle aged adults took one of three daily doses or a dummy for two months, and nobody involved knew which. Walking distance in six minutes improved modestly. Insulin resistance did not budge. Most people took it without trouble. Two months is short, walking distance is easy to improve, and nobody was followed long enough to see whether anything lasted.

     The numbers 60-day RCT in 80 adults: 300 to 900 mg/day raised blood NAD and modestly improved six-minute walk distance; well tolerated; HOMA-IR unchanged.

     GeroScience, 2023· 80 people

3. 03MIB-626SupplementModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 107 people given it.1 reported

   42 people given it2 trials1 found nothing

   • found nothingThe tablet raised NAD in very sick patients and made no difference to them. 42 adults in hospital with COVID-19 and sudden kidney injury took MIB-626 or dummy tablets twice a day for two weeks. NAD in the blood roughly doubled by the end. Kidney blood tests came out the same in both groups. So did inflammation markers and how ill people were. The authors want the drug tried as a drip instead. Two authors work for the manufacturer and a third consults for it.

     The numbers NCT05038488. 42 adults hospitalised with COVID-19 and acute kidney injury randomised 3:2 to MIB-626 1.0 g or placebo tablets twice daily for 14 days. Blood NAD rose gradually from 16.0 to 25.5 to 42.6 micrograms per millilitre at baseline, day 5 and day 14, and NAD metabolites rose rapidly by day 3. Serum creatinine, cystatin C and serum markers of acute kidney injury did not differ between groups. Serum CRP, IL-6 and TNF alpha and indices of disease severity also did not differ. The authors attribute the absence of clinical effect to the slow rise in NAD and call for studies of parenteral administration. Two authors are employees of Metro International Biotech and a third is a consultant to the company.

     FASEB BioAdvances, 2025· 42 people

   • This trial shows the tablet raises NAD in the blood, and nothing beyond that. 32 overweight or obese adults aged 55 to 80 took MIB-626 once a day, twice a day, or a dummy tablet for two weeks, and nobody involved knew which. NMN in the blood was clearly higher by the end, and NAD rose more on the bigger dose. Sex, weight and age made no difference. What was measured here was blood chemistry and safety, not how anyone felt or functioned.

     The numbers Randomised, double-blind, placebo-controlled pharmacokinetic trial. 32 overweight or obese adults aged 55 to 80, block randomised and stratified by sex, given MIB-626 1000 mg once daily, twice daily, or placebo for 14 days. Blood NMN on day 14 was significantly higher than placebo, with mean AUClast 1.7-fold and 3.7-fold above baseline for the once and twice daily schedules, and there were substantial dose-related increases in blood NAD. Changes were unrelated to sex, BMI or age. Very little unmodified NMN was excreted in urine. The endpoints are blood metabolites and safety.

     Journals of Gerontology Series A, 2023· number of people not given

4. 04ResveratrolSupplementModerate. At least one finished study in people, and at least 100 people who took it. 14 completed trials, 403 people given it.7 reported

   11 people given it3 trials2 found nothing

   • This is the strongest good human result resveratrol has, and it rests on eleven men. Obese but otherwise healthy men took 150 mg a day for a month, and also spent a month on a dummy pill. Their resting metabolism slowed the way it does when people eat less. Liver fat, blood sugar, triglycerides, a liver enzyme and inflammation markers all fell. Blood pressure improved. Muscle samples showed the cell's energy machinery switched on.

     The numbers Eleven healthy obese men, randomised double-blind crossover, 150 mg per day for 30 days. Sleeping and resting metabolic rate fell; muscle AMPK was activated with higher SIRT1 and PGC-1alpha protein and improved mitochondrial respiration on a fatty-acid substrate; intrahepatic lipid, circulating glucose, triglycerides, ALT and inflammation markers fell; systolic blood pressure and HOMA improved. The strongest positive mechanistic human result in the literature, in eleven men.

     Cell Metabolism, 2011· 11 people

   • found nothingRun again at a high dose, the same idea produced nothing. Twenty-four obese but otherwise healthy men took high-dose resveratrol or a dummy pill for four weeks. The main measure was how well their bodies answered insulin, using the most exacting test there is. It drifted slightly worse in both groups. Blood pressure, energy burned at rest, fat burning, fat around the organs and inflammation markers did not move. The authors say this casts doubt on resveratrol for metabolic problems.

     The numbers The direct contradiction of the trial above. Twenty-four obese but otherwise healthy men, parallel-group, four weeks of high-dose resveratrol. Insulin sensitivity by hyperinsulinaemic euglycaemic clamp, the primary outcome, deteriorated insignificantly in both arms. No effect on blood pressure, resting energy expenditure, lipid oxidation, ectopic or visceral fat, or inflammatory and metabolic biomarkers. The authors say the result raises doubt about resveratrol as a supplement in metabolic disorders.

     Diabetes, 2013· number of people not given

   • found nothingResveratrol did nothing in healthy postmenopausal women, right down to the mechanism. They took 75 mg daily for 12 weeks, and blood tests confirm it reached them. The most exacting test of insulin response found no change in liver, muscle or fat. Body composition, resting metabolism, blood fats and inflammation markers were unchanged. The proteins resveratrol is supposed to act on were unmoved in muscle and fat too. There is no hidden effect being missed here.

     The numbers Seventy-five mg per day for 12 weeks in nonobese postmenopausal women. Plasma resveratrol rose, but a two-stage hyperinsulinaemic euglycaemic clamp with labelled tracers found no change in liver, muscle or adipose insulin sensitivity, and no change in body composition, resting metabolic rate, lipids or inflammatory markers. The putative targets AMPK, SIRT1, NAMPT and PPARGC1A were unmoved in muscle and fat, so the null went all the way down to the mechanism.

     Cell Metabolism, 2012· number of people not given

   Also measured in animals or in the lab

   • In a dish. Sinclair's team answered back. They found that natural target proteins with certain water-avoiding patches let SIRT1 be switched on without any tag, using one key spot on the enzyme. The question is narrower now, but it is not closed, and both sides had money at stake.

     The numbers The answer from Sinclair, Vlasuk and the Sirtris team. Specific hydrophobic motifs in native SIRT1 substrates such as PGC-1alpha and FOXO3a permit activation without any fluorophore, and a single residue, Glu230, in a structured N-terminal domain is required by every activator scaffold tested. In cells reconstituted with an activation-defective SIRT1 the metabolic effects of these compounds disappeared. A 2010 Sirtris paper had already shown activation of unlabelled natural-amino-acid peptides. The question is narrower now than in 2010 but it is not closed, and both sides had commercial interests.

     Science, 2013· lab (cells in a dish)

5. 05EpicatechinSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 44 people given it.1 reported

   7 people given it1 trial

   • In a muscle-wasting disease, epicatechin moved the biology, but nobody went without it. Seven adults with Becker muscular dystrophy who could still walk took 50 mg twice a day for eight weeks, with a muscle sample taken before and after. Markers of mitochondrial building and muscle repair rose, myostatin fell, and heart rate and lactate at set workloads came down. Everybody knew they were taking it and there was no comparison group, so no way to know what would have happened anyway.

     The numbers Open-label, 7 ambulatory adults, 50 mg twice daily for 8 weeks with biceps biopsy before and after. Increased LKB1, AMPK, PGC-1alpha, cristae abundance, follistatin and regeneration markers; myostatin fell; heart rate and lactate at fixed workloads fell. No placebo group.

     Muscle and Nerve, 2021· 7 people

6. 06Nicotinamide RibosideSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 90 people given it.5 reported

   0 people given it3 trials, 1 watch-only1 found nothing

   • Swallowing this form of vitamin B3 really does raise NAD in the blood. In a small human study the level rose by up to nearly three times. That single fact is what the entire NAD supplement industry is built on. Raising a level in the blood is the start of an argument, not the end of it. Nobody in this study got healthier.

     The numbers Oral NR raised blood NAD+ up to 2.7-fold in a human pilot and showed superior hepatic NAD+ kinetics in mice.

     Nature Communications, 2016· number of people not givenobserved only, nobody was given it

   • Six weeks of it was comfortable to take, and it lifted NAD as expected. Adults in middle age and older each did a stretch on the supplement and a stretch without it. What was measured was body chemistry. No symptom, no performance test and no disease outcome was looked at here.

     The numbers Randomized crossover trial: 6 weeks of NR was well tolerated and effectively stimulated NAD+ metabolism.

     Nature Communications, 2018· number of people not given

   • Eight weeks of it was safe in healthy overweight adults, and larger doses raised NAD further. Some people got the supplement and some got a dummy pill. The study was built to check safety and find a dose, and that is what it answered. It was not built to show a benefit, and it did not show one.

     The numbers 8-week dose-ranging RCT supporting safety and dose-dependent NAD+ elevation.

     Scientific Reports, 2019· number of people not given

   • found nothingIn obese men, it did not help. 40 inactive men with a BMI over 30 took 1000 mg twice a day, or a dummy pill, for 12 weeks. A careful test of how their bodies handled insulin showed no change. Neither did how they burned fuel, their body fat or muscle, or the fat in their liver. It was safe. Raising NAD in a mouse and fixing insulin in a man turned out to be different things.

     The numbers 40 obese insulin-resistant sedentary men, BMI over 30, aged 40 to 70, randomised to NR 1000 mg twice daily or placebo for 12 weeks. Insulin sensitivity by hyperinsulinaemic euglycaemic clamp, endogenous glucose production, glucose disposal, resting energy expenditure, lipolysis and body composition did not improve. Safe. NCT02303483.

     American Journal of Clinical Nutrition, 2018· number of people not given

7. 07NAD+SupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.7 reported

   0 people given it1 trial

   • The first time anyone measured what a NAD drip actually does in people, and it measured nothing about whether it helps. Blood was sampled during a six hour infusion. For the first two hours, NAD in the blood did not go up, nor did its breakdown products. The likely explanation is that tissues take it up or destroy it fast. No symptom, no energy measure and no health outcome was recorded. So this tells you where the drug goes, and nothing about what it does.

     The numbers First human data on IV NAD+: no rise in plasma NAD+ or metabolites for the first 2 hours of infusion, consistent with rapid tissue uptake or breakdown; no efficacy outcomes measured.

     Frontiers in Aging Neuroscience, 2019· number of people not given

   What people using it report

   • Route is the main division in the discussion. A clinic drip, a do it yourself shot under the skin, and pills that the body turns into NAD+ are treated as three different things rather than as interchangeable, and people are frequently corrected for conflating them.
8. 08NMNHSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.1 reported

   0 people given it1 trial

   • This is the human trial the reduced form does not have. 32 overweight or obese adults aged 55 to 80 took an oral NMN tablet once or twice a day for two weeks, or a dummy tablet, and nobody involved knew which. NMN in the blood ended clearly above the dummy group, and NAD rose more on the bigger dose. Those are blood chemistry results, not health results. Nothing like this exists for NMNH, so anyone selling it is borrowing this evidence.

     The numbers Included as the human benchmark NMNH does not have. A randomised double-blind placebo-controlled trial in 32 overweight or obese adults aged 55 to 80 established what the oxidised form does in people at 1000 mg once or twice daily for 14 days: blood NMN significantly above placebo at day 14 and substantial dose-related increases in blood NAD. Nothing comparable exists for the reduced form.

     Journals of Gerontology Series A, 2023· number of people not given

Approved drugs, biologics and hormones that have been measured for this. They are here because leaving them out would misrepresent the evidence, and they are below the peptides because that is not what most people come here to read.

1. 01Metformin plus rapamycinSmall moleculePreliminary. Studied in people, but no published study has had people take it. 2 registered with no result.2 reported

   0 people given it1 trial

   • The one trial testing this pair cannot tell the two drugs apart. 30 people are enrolled by AgelessRx, an online company that prescribes these drugs, and it is no longer signing people up. Every group stacks rapamycin and metformin together with low-dose naltrexone, NAD+ up the nose, glutathione on the skin and a house-brand supplement. With six things given at once, no result could be traced to either drug. Nothing has been posted.

     The numbers 30 participants, sponsor AgelessRx (a telehealth prescriber), active not recruiting. Arms combine rapamycin 2 to 6 mg weekly, metformin 500 mg daily, low-dose naltrexone, intranasal NAD+, topical glutathione and a proprietary supplement; primary endpoints VO2 max, a cognitive composite and an inflammation index. Cannot isolate either drug. No results posted.

     ClinicalTrials.gov, 2025· number of people not given

Peptides and blends

1. 01CartalaxPeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 4 lab studies, no human study.8 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In a dish. Aging cartilage cells gave off more aging and inflammation signals. Both Cartalax and a cartilage extract pushed those signals back toward normal. These were cells, not joints, and nobody measured a real health result.

     The numbers Cell culture. The senescence-associated secretory phenotype of chondrocytes was characterised by raised p16, p21 and p53, raised TNF-alpha and IL-1-alpha, and lowered Sirt1. Both the AED peptide and a cartilage polypeptide complex normalised the synthesis of those molecules. Chondrocytes in culture, not joints, and no clinical endpoint was measured.

     Advances in Gerontology, 2023· lab (cells in a dish)

2. 02SS-20PeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 4 animal studies, 1 lab study, no human study.6 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. Mice were given a toxin that mimics Parkinson's disease. SS-31 fully protected their dopamine brain cells at higher doses. SS-20, which cannot mop up free radicals, also gave real protection. Both kept mitochondria working in lab tests.

     The numbers MPTP-treated mice, a Parkinson's model. SS-31 gave dose-dependent complete protection against loss of striatal dopamine and of tyrosine hydroxylase positive neurons in the substantia nigra. SS-20, which the paper states has no intrinsic ability to scavenge reactive oxygen species, also showed significant neuroprotection. Both prevented MPP+ induced inhibition of oxygen consumption, ATP production and mitochondrial swelling in isolated mitochondria. Mice and cultured cells.

     Antioxidants and Redox Signaling, 2009· animal study

3. 035-amino-1MQ with SLU-PP-332BlendAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 2 animal studies, no human study.7 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In a dish and in mice, this type of molecule blocked the NNMT enzyme cleanly and got into cells easily. In fat cells in a dish, it raised NAD+ inside the cells. In mice made fat on a high fat diet, a strong version reversed the weight gain. This was cells and mice. No person was given it.

     The numbers Methylquinolinium NNMT inhibitors showed high membrane permeability and high selectivity, not inhibiting related methyltransferases or NAD salvage pathway enzymes. In cultured adipocytes they reduced intracellular 1-methylnicotinamide and increased intracellular NAD+. A potent inhibitor reversed high fat diet-induced obesity in diet-induced obese mice. Cells and mice, with no human exposure.

     Biochemical Pharmacology, 2018· animal study

Supplements

1. 01SpermidineSupplementModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 130 people given it.4 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice, spermidine given by mouth made them live longer and kept their hearts working better. It did this by boosting clean-up inside heart cells.

     The numbers Oral spermidine extended mouse lifespan and preserved cardiac function through enhanced cardiac autophagy and mitophagy.

     Nature Medicine, 2016· animal study

2. 02Ginsenoside Rg3SupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 24 people given it.

   1 animal or lab study

   Measured in animals or in the lab

   • In a dish. The 20(S) form brought worn-out human skin cells back to a younger state by restoring their energy supply and changing growth and repair signals. The 20(R) form did not. This is bringing worn-out cells back, not clearing them.

     The numbers Cultured human dermal fibroblasts. 20(S)-Rg3 reversed replicative senescence by restoring ATP and the NAD+ to NADH ratio and modulating Akt, mTOR and sirtuin signalling; the 20(R) isomer did not. Reversal of senescence, not clearance of senescent cells.

     Journal of Ginseng Research, 2020· lab (cells in a dish)

3. 03Alpha-ketobutyrateSupplementPreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.3 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In worms. Adding alpha-ketobutyrate made normal worms live longer. It worked through a long chain: more NAD+, the worm's sirtuin gene, more active peroxisomes that burn fats, hydrogen peroxide as a signal, and finally the worm's version of NRF2 turning on cleanup genes. In a dish, skin cells also aged more slowly. This paper has no data from mice or people.

     The numbers Supplementing alpha-ketobutyrate extended lifespan in wild-type Caenorhabditis elegans. The mechanism traced through lactate dehydrogenase LDH-1 raising NAD+ production, SIR-2.1 mediating enhanced peroxisome function and biogenesis, raised acox-1.2 expression driving peroxisomal fatty acid beta-oxidation and hydrogen peroxide formation, and SKN-1 (the worm NRF2) driving autophagic and lysosomal gene expression. The paper also reports delayed cellular senescence in fibroblast cells through a SIRT1 to ACOX1 to hydrogen peroxide to NRF2 route. Worms and cells; no mammal lifespan data in this paper.

     Nature Communications, 2023· animal study

4. 04ApigeninSupplementPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.1 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. This is the strongest evidence for blocking CD38, and it did not use apigenin. A strong, precise blocker called 78c reversed the fall in NAD with age. It improved blood sugar control, muscle function, exercise ability and heart function, in mice that aged normally or fast. An author holds a patent on CD38 blockers. 78c is not for sale and has no human data.

     The numbers The strongest evidence for the CD38 strategy, and it was not generated with apigenin. 78c, a highly potent and specific thiazoloquinazolinone CD38 inhibitor, reversed age-related NAD decline and improved glucose tolerance, muscle function, exercise capacity and cardiac function in mouse models of natural and accelerated ageing. The effects depended on tissue NAD levels and were reversed by inhibiting NAD synthesis. A declared conflict: an author holds a patent on the use of CD38 inhibitors for metabolic disease. 78c is not commercially available and has no human data.

     Cell Metabolism, 2018· animal study

Other compounds

1. 01RilmenidineSmall moleculePreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.1 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In worms. Rilmenidine made tiny worms live longer and handle stress better, whether they started young or old. It only worked through one specific receptor and the cell's clean-up system. It added nothing for worms already eating less or on rapamycin. In mice, it changed genes in the liver and kidney to look like eating less, but the mice's lifespan was not measured. Two authors have business interests in longevity.

     The numbers The paper that put rilmenidine into geroscience. Identified by searching for compounds with a caloric-restriction-like expression signature. Increased lifespan in C. elegans when given at young and older ages, with the stress resilience, healthspan and lifespan benefits all dependent on the I1-imidazoline receptor nish-1, on DAF-16 and SKN-1, and on autophagy but not AMPK. Adding it to calorically restricted worms, reduced TORC1 function or rapamycin produced no further gain. Mice treated with rilmenidine showed caloric-restriction-like transcriptional changes in liver and kidney, which is a gene expression finding and not a lifespan finding. Two authors disclose commercial longevity interests.

     Aging Cell, 2023· animal study

   • In mice. In mice bred to get a muscle-wasting nerve disease, rilmenidine switched on cell clean-up in the spinal cord as planned. The harmful protein went down. But the nerve cells died faster and the mice got sicker faster. The authors blame too much clearing of the power plants inside nerve cells.

     The numbers Autophagy and mitophagy were induced in the spinal cord as intended and soluble mutant SOD1 fell, and despite that rilmenidine worsened motor neuron degeneration and symptom progression in SOD1G93A mice. The authors attribute the harm to excessive mitophagy and severe mitochondrial depletion in motor neurons.

     Autophagy, 2018· animal studypoints the wrong way

2. 02AdiponectinBiologicPreliminary. Studied in people, but no published study has had people take it. 3 human studies where nobody was given it.2 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mouse cells and tissues. This paper found adiponectin's two receptors, AdipoR1 and AdipoR2. It showed they carry adiponectin's effects on fat burning and sugar uptake.

     The numbers Identification of AdipoR1 and AdipoR2 and demonstration in mouse cells and tissues that they mediate adiponectin's effects on fatty acid oxidation and glucose uptake through AMPK and PPAR-alpha.

     Nature, 2003· animal study

   • In mice. AdipoRon, a pill-type molecule, switched on both adiponectin receptors. It helped insulin work and improved blood sugar handling in mice on a high-fat diet. It did nothing in mice missing both receptors. It eased diabetes in a diabetic strain and lengthened their shortened lifespan. Mouse only. There is no human data.

     The numbers AdipoRon, an oral small molecule binding AdipoR1 and AdipoR2, activated AMPK and PPAR-alpha, improved insulin resistance and glucose tolerance in mice on a high-fat diet (abolished in double knockouts), ameliorated diabetes in db/db mice and prolonged their shortened lifespan on a high-fat diet. Mouse only; no human data exist.

     Nature, 2013· animal study

3. 03HalofuginoneSmall moleculePreliminary. Studied in people, but no published study has had people take it. 3 human studies where nobody was given it, 1 registered with no result.2 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In obese mice and in pigs. Halofuginone cut how much the animals ate, raised the energy they burned, and caused weight loss. It worked by raising two hormones, FGF21 and GDF15. Mice bred without those hormones did not respond. Note that the paper calls halofuginone FDA-approved for scleroderma. The FDA's approved drug list does not back that up.

     The numbers In diet-induced obese mice and in pigs, halofuginone suppressed food intake, raised energy expenditure and produced weight loss via integrated stress response induction of FGF21 and GDF15; both hormones were required in knockout mice. Animal only. Note that the abstract describes halofuginone as FDA-approved for scleroderma, which the FDA approved drugs database does not support.

     Science Advances, 2025· animal study

4. 04IrisinBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 7 people given it.2 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. This is the first irisin paper. Exercise made mouse muscle release irisin. Irisin made white fat act like brown fat and burn more energy. The mice did better on weight and blood sugar. Public money paid for the work.

     The numbers The original report. In mice, exercise-induced PGC-1alpha raised FNDC5 in muscle; its cleaved product, named irisin, induced UCP1 and a brown-fat programme in white fat, increased energy expenditure and improved obesity and glucose homeostasis. NIH and non-US government funded.

     Nature, 2012· animal study