Metabolic
Does it really do anything for cellular energy?
The single most over-claimed area in the supplement half of this catalogue, and the one with the widest gap between a cell-culture result and a human one.
318
people in trials
22
human studies
11
compounds, animal or cell only
7
trials found nothing
Measured in people
Ranked by how many people, which is a fact about the evidence and not a judgement about the compound. The one at the top is the most studied, which is not the same as the best. Counts are never added across compounds, because the same person can appear in more than one trial.
- 144 people2 human studies1 found nothing
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 nothingNCT03176628. 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
- 80 people1 human study1 found nothing
found nothing60-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
- 42 people2 human studies1 found nothing
found nothingNCT05038488. 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
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 · no headcount in the line
- 34 people2 human studies
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 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 · no headcount in the line
Also measured, in animals or cells
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 · in vitro
What people using it report
- Chest tightness, cramping, flushing and nausea during the NAD+ portion of the drip, which clinics manage by slowing the infusion rate. This is the effect people are least prepared for.
- 11 people3 human studies2 found nothing
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 nothingThe 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 · no headcount in the line
found nothingSeventy-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 · no headcount in the line
Also measured, in animals or cells
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 · in vitro
- 7 people1 human study
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
- no headcount stated3 human studies
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 · no headcount in the line
Randomized crossover trial: 6 weeks of NR was well tolerated and effectively stimulated NAD+ metabolism.
Nature Communications, 2018 · no headcount in the line
8-week dose-ranging RCT supporting safety and dose-dependent NAD+ elevation.
Scientific Reports, 2019 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
A randomised trial in otherwise healthy cigarette smokers examining cardiovascular effects of a purpose-designed SIRT1 activator. This is among the few randomised human trials of a sirtuin-activating compound, and the compound did not go on to approval.
Journal of the American Heart Association, 2013 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
What people using it report
- Chest tightness, nausea, cramping and flushing during a fast NAD+ infusion, resolving when the drip rate is slowed. This is close to universal.
- no headcount stated1 human study1 found nothing
found nothingPhase 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 · no headcount in the line
- no headcount stated1 human study1 found nothing
found nothingSingle-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 · no headcount in the line
Measured in animals or cells, not yet in people
These are separated from the trials above rather than ranked against them, because they answer a different question. A result in a rat is a real result and a reason somebody ran the study; it is not a measurement of what happens in you. Where the human work is missing, the reason is usually money rather than failure, and that is set out at the bottom of this page.
- 2 preclinical studies
Measured in animals or cells
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
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
- 2 preclinical studies
Measured in animals or cells
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
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
- 1 preclinical study
Measured in animals or cells
Oral spermidine extended mouse lifespan and preserved cardiac function through enhanced cardiac autophagy and mitophagy.
Nature Medicine, 2016 · animal
- 1 preclinical study
Measured in animals or cells
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 · in vitro
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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 · in vitro
- 1 preclinical study
Measured in animals or cells
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.
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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
What people using these actually report
Uncontrolled self-reports, gathered from clinic write-ups, regulatory complaint records and public forums, and reproduced here as written. They are the best guide on this page to what people actually do, what they expect, and what goes wrong, and they cannot show that anything works, because nobody was measured against a placebo and the people who saw no effect mostly stopped posting. Both halves of that are true at once. The negative reports are kept in for the same reason.
- Chest tightness, cramping, flushing and nausea during the NAD+ portion of the drip, which clinics manage by slowing the infusion rate. This is the effect people are least prepared for.
Sources: The infusion reactions and the price complaints come from IV clinic write-ups and user forums and are not trial data. The B6 neuropathy signal comes from published case reports and from the cell work cited on this page. The fatigue improvement in genuine deficiency comes from clinical literature. The Myers cocktail trial is the only controlled comparison here, and it is the reason to treat the post-drip lift as unproven rather than as a finding.
- Chest tightness, nausea, cramping and flushing during a fast NAD+ infusion, resolving when the drip rate is slowed. This is close to universal.
Sources: Drip clinic patient accounts, forums and clinic write-ups. Uncontrolled self-reports in a setting with an unusually strong expectation effect, since the appointment is expensive, attended and supervised.
Why the trial record looks like this
A missing trial is usually a missing sponsor. Nobody runs a nine-figure programme on a molecule they cannot own, so the compounds with the thinnest human records are often the oldest and most freely available ones rather than the weakest. Taking Rilmenidine as the example, because it states the problem most clearly:
There are two separate evidence questions about any repurposed drug and they have different answers. The first is whether the drug does what it was licensed to do, which here is settled by randomised trials with hard clinical endpoints. The second is whether it slows ageing in humans, which no trial has tested. The strength of the first answer says nothing about the second. A reader who takes the licensed indication as partial proof of the ageing claim has made the central error of this field.
Rilmenidine is the clearest case here of the gap between a mechanism working and an animal benefiting. Two independent mouse experiments showed that the drug induces autophagy and mitophagy exactly as advertised, measured directly in spinal cord tissue, and that the treated animals then deteriorated faster than controls. In one of them the reported harm included a truncated lifespan. That is not a tolerability signal, it is evidence that this particular intervention is context dependent in a way the worm data cannot reveal.
The honest summary is that rilmenidine has a genuinely interesting invertebrate longevity result with a defined receptor, a plausible caloric restriction mimetic signature in mouse tissue, no mammalian lifespan study in normal ageing, and two mammalian studies in disease models where it caused harm. The autophagy induction is the selling point and it is also the mechanism the authors blame for the damage.
A compound appears here only when a citation on its own page states this outcome and reports a result for it; naming it is not enough. Human, animal and cell work are counted separately and never merged. Participant counts are read from the study lines and deliberately undercount. Nothing here is advice, and nothing here is a recommendation to take or to avoid anything.