Metabolic
Does it move cholesterol or triglycerides?
Lipids measured in blood, which is a laboratory result rather than an event.
53,513
people in trials
14
human studies
1
compounds, animal or cell only
6
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.
- 29,087 people2 human studies
HPS2-THRIVE, NCT00461630. 25,673 adults with vascular disease on statin-based therapy randomised to 2 g extended-release niacin with 40 mg laropiprant or placebo for a median of 3.9 years. LDL was 10 mg/dL lower and HDL 6 mg/dL higher on treatment. Major vascular events occurred in 13.2 percent versus 13.7 percent, rate ratio 0.96 (95 percent CI 0.90 to 1.03, P=0.29). Treatment caused absolute excesses in serious disturbances of diabetes control (3.7 percentage points, P<0.001), new diabetes diagnoses (1.3 points, P<0.001), serious gastrointestinal events (1.0 point), musculoskeletal events (0.7 point), skin events (0.3 point), and unexpectedly infection (1.4 points) and bleeding (0.7 points). Funded by Merck and others.
New England Journal of Medicine, 2014 · 25,673 people
AIM-HIGH, NCT00120289. 3,414 patients with established atherosclerotic cardiovascular disease and LDL below 70 mg/dL, randomised to extended-release niacin 1500 to 2000 mg daily (n=1718) or placebo (n=1696), all on simvastatin plus ezetimibe as needed. Stopped after a mean of 3 years for lack of efficacy. Niacin raised median HDL from 35 to 42 mg/dL, lowered triglycerides from 164 to 122 mg/dL and lowered LDL from 74 to 62 mg/dL. The primary composite endpoint occurred in 282 niacin patients (16.4 percent) and 274 placebo patients (16.2 percent), hazard ratio 1.02 (95 percent CI 0.87 to 1.21, P=0.79). Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories.
New England Journal of Medicine, 2011 · 3,414 people
- 20,536 people1 human study
20,536 UK adults aged 40 to 80 with coronary, other occlusive arterial disease or diabetes, randomised to 40 mg simvastatin daily or placebo. All-cause mortality 12.9 percent versus 14.7 percent (p equals 0.0003). Major vascular events fell 24 percent, from 25.2 percent to 19.8 percent. Benefit held even in participants entering with LDL cholesterol below 3.0 mmol/L. The annual excess risk of myopathy was about 0.01 percent.
Lancet, 2002 · 20,536 people
- 2,909 people1 human study
2,909 participants randomised 2:1 to enlicitide 20 mg or placebo for 52 weeks. LDL cholesterol fell 57.1 percent at week 24 against a 3.0 percent rise on placebo, an adjusted between-group difference of 55.8 percentage points (p < 0.001). Non-HDL cholesterol, apolipoprotein B and lipoprotein(a) also improved. Funded by the manufacturer.
New England Journal of Medicine, 2026 · 2,909 people
- 268 people1 human study
The largest published human trial, run by GSK: 268 people with low HDL took 2.5, 5 or 10 mg or placebo for 12 weeks. HDL cholesterol rose up to 16.9%, triglycerides fell 16.9% and apoB fell 14.9%. Twelve weeks is the longest published human exposure; the rodent carcinogenicity findings that ended development were never published as a primary paper.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2012 · 268 people
- 225 people2 human studies1 found nothing
Double-blind, placebo-controlled RCT, 178 patients with stable coronary artery disease already taking statins, aspirin or beta-blockers, randomized to nattokinase (3,615 FU/day), red yeast rice, the combination, or placebo for 90 days: nattokinase alone significantly lowered LDL-C versus placebo but not total cholesterol, triglycerides or HDL-C. The combination arm improved every lipid and blood pressure measure and raised antithrombin III more than placebo.
Frontiers in Nutrition, 2024 · 178 people
found nothingRCT, 47 patients with hyperlipidemia, nattokinase alone versus nattokinase plus red yeast rice versus placebo for 6 months: the nattokinase-only arm showed no significant lipid change against placebo, while the combination arm improved triglycerides, total cholesterol, LDL-C and HDL-C from month 1. Nattokinase's own lipid contribution cannot be separated from red yeast rice's in the positive result.
Asia Pacific Journal of Clinical Nutrition, 2009 · 47 people
- 192 people1 human study1 found nothing
found nothingThe largest and longest diabetes trial here: 192 patients, 40 or 500 mg per day for six months. CRP fell 5.6% and 15.9% versus placebo but not significantly, and there was no significant change in weight, BMI, waist, blood pressure, fasting glucose, HbA1c, insulin, C-peptide, free fatty acids, liver enzymes, uric acid, adiponectin or IL-6. Total cholesterol and triglycerides rose slightly on 500 mg. Subgroups with shorter diabetes duration did show a significant CRP reduction.
Pharmacological Research, 2016 · 192 people
- 151 people1 human study1 found nothing
found nothingPooled blood lipid data from four placebo-controlled randomised studies, including three of betaine totalling 151 participants. Betaine at 6 g/d for six weeks raised LDL cholesterol by 0.36 mmol/L (95 percent CI 0.25 to 0.46), triacylglycerol by 0.14 mmol/L and the total to HDL ratio by 0.23, with no effect on HDL. Lower doses also raised LDL without significance, and the LDL effect was already evident at two weeks. Folic acid had no effect on lipids. The authors conclude the lipid effects may undo the potential cardiovascular benefit of homocysteine lowering. Funding was 29 percent industrial through a food science consortium, disclosed in the paper.
PLoS Medicine, 2005 · 151 people
- 80 people1 human study
80 adults with total cholesterol at or above 200 mg/dL and/or LDL at or above 100 mg/dL, in four arms for 6 to 8 weeks: pterostilbene 125 mg twice daily, 50 mg twice daily, 50 mg plus grape extract 100 mg twice daily, or placebo. LDL rose 17.1 mg/dL on pterostilbene monotherapy (p = 0.001), an effect not seen with the grape extract combination (p = 0.47) and attenuated by background cholesterol medication. Systolic blood pressure fell 7.8 mmHg (p < 0.01) and diastolic 7.3 mmHg (p < 0.001) on the high dose. Registered as NCT01267227.
Evidence-Based Complementary and Alternative Medicine, 2014 · 80 people
- 36 people1 human study
The cost side, in a different indication. 36 patients with acquired aplastic anaemia on danazol monotherapy at 10 mg per kg per day capped at 600 mg. After 6 months HDL cholesterol fell 30 percent and LDL rose 11 percent, with significant changes in left ventricular mass, ejection fraction and diastolic indices. The authors conclude that danazol causes profound dyslipidaemia and potential cardiac dysfunction.
Blood Cells, Molecules and Diseases, 2025 · 36 people
- 29 people1 human study1 found nothing
found nothing29 healthy Japanese adults aged 40 to 57 with normal to moderately high triglycerides, 20 mg a day for 12 weeks, randomised and double blind. Mean triglycerides did not change. LDL cholesterol fell marginally in the PQQ group, from 136.1 to 127.0 mg/dL, with a clearer fall in the subgroup whose baseline LDL was 140 mg/dL or above. Run by the division of the company that makes BioPQQ.
Journal of Nutritional Science and Vitaminology, 2015 · 29 people
- no headcount stated1 human study1 found nothing
found nothing48 overweight or obese non-smokers aged 20 to 65 with features of metabolic syndrome, 25 mg (-)-epicatechin a day for 2 weeks in crossover. No significant effect on blood pressure, glucose, insulin, HOMA-IR, triglycerides, total, LDL or HDL cholesterol, or oxidised LDL. The authors conclude the cocoa effect cannot be ascribed to epicatechin alone.
American Journal of Clinical Nutrition, 2018 · no headcount in the line
- no headcount stated1 human study1 found nothing
found nothingRandomised 2:1, 30 overweight or obese adults aged 45 and over, MIB-626 two 500 mg tablets twice daily for 28 days. Body weight fell 1.9 kg (95 percent CI -3.3 to -0.5, P=.008), diastolic blood pressure fell 7.01 mmHg (-13.44 to -0.59, P=.034), total cholesterol fell 26.89 mg/dL (P=.004) and LDL fell 18.73 mg/dL (P=.007). Muscle strength, muscle fatigability, aerobic capacity and stair-climbing power did not change. Insulin sensitivity, hepatic fat and intra-abdominal fat did not change in either group. Metro International Biotech, the manufacturer, is a listed funder. This is a physiologic study with multiple outcomes rather than a trial powered on one of them.
Journal of Clinical Endocrinology and Metabolism, 2023 · 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.
- 1 preclinical study
Measured in animals or cells
Interventions Testing Program, three test sites, treatment beginning at 4 months of age. None of the five agents, medium-chain triglyceride oil included, had a statistically significant effect on lifespan of male or female mice by log-rank test at the concentrations tested.
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.
- Measurable biochemical consequences of the procedure are reported in the published crossover trial and are worth knowing before booking one: total cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein A, total protein and albumin all fell, and red cell distribution width and mean corpuscular haemoglobin concentration rose.
Sources: The published trial reports themselves, which is where the adverse event and laboratory-change numbers above come from: the AMBAR primary results in Alzheimer's and Dementia 2020, the Aging Cell 2025 randomised trial and the Scientific Reports 2025 crossover trial. The description of how the procedure is marketed reflects the endpoints those clinics advertise, which are the epigenetic clock measures named in the trials. No clinic, forum post or individual patient account is quoted or relied on.
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 MCT oil as the example, because it states the problem most clearly:
A lifespan null from this programme is a real, expensive, well-powered finding, and it is narrower than it sounds. What was tested was one concentration in the diet, started at one age, in one mouse strain, with death as the endpoint. A null tells you that this dose, in these animals, did not move that endpoint. It does not tell you the compound is inert, that a different dose would also fail, that the mechanism is wrong, or that the reason people actually take it has been refuted. Those are separate questions and most of them were never asked. The failure mode this site is trying to avoid runs in both directions: treating a mouse lifespan positive as proof that a supplement works, and treating a mouse lifespan null as proof that it does nothing.
MCT oil is a good place to say what the ITP test did and did not cover. It fed the oil to mice from 4 months of age and measured when they died. It did not measure body composition trajectories, cognition, or anything about ketosis, and it certainly did not test the ketogenic diet, which is a different intervention involving carbohydrate restriction rather than an added fat.
So the sentence that survives is narrow: adding MCT oil to mouse chow from young adulthood did not extend life. Everything people actually buy MCT oil for, which is ketone elevation, appetite and body composition, was tested elsewhere, in people, with modest positive results.
The Alzheimer's evidence deserves its own caution. A 1.9 point ADAS-Cog difference at day 45 that concentrates in APOE4 non-carriers is a subgroup finding from a single trial by the product's developer. It was enough to support marketing as a medical food, which is a lower regulatory bar than drug approval, and it has not been replicated at the same scale.
The Interventions Testing Program is funded by the National Institute on Aging and run in parallel at three independent laboratories, in Bar Harbor, Ann Arbor and San Antonio. It uses UM-HET3 mice, a four-way genetic cross, so no result can be an artefact of a single inbred background. Both sexes are studied, cohorts are sized to detect roughly a 10 percent shift in lifespan, compounds are fed in the diet from a stated starting age, and the programme commits in advance to publishing negative results alongside positive ones. That last commitment is why this batch can exist at all: almost no other part of ageing research reliably tells you what did not work.
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.