Heart and circulation
Does it move blood pressure?
Reported in almost every metabolic trial, often as a secondary result nobody advertises.
1,196
people in trials
23
human studies
1
compounds, animal or cell only
10
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.
- 608 people4 human studies1 found nothing
found nothingThe Nattokinase Atherothrombotic Prevention Study (NAPS, NCT02080520), the only large, long, placebo-controlled Western academic RCT of nattokinase: 265 adults without cardiovascular disease, median age 65.3, 2,000 FU/day for a median of 3 years, with carotid ultrasound every 6 months. No significant difference from placebo in the rate of change of carotid intima-media thickness, carotid arterial stiffness, blood pressure, or any coagulation, fibrinolysis, inflammatory or metabolic marker measured.
Clinical Hemorheology and Microcirculation, 2021 · 265 people
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
Randomized, double-blind, placebo-controlled trial, 86 adults with pre-hypertension or stage 1 hypertension (73 completed), 2,000 FU/day for 8 weeks: net change versus placebo of -5.55 mmHg systolic (95% CI -10.5 to -0.57) and -2.84 mmHg diastolic (95% CI -5.33 to -0.33), with a matching fall in plasma renin activity.
Hypertension Research, 2008 · 86 people
North American RCT, 79 hypertensive adults (74 completed), 100 mg/day (about 2,000 FU) of vitamin K2-depleted nattokinase (NSK-SD) for 8 weeks, sponsored by the product's US distributor: diastolic blood pressure fell from 87 to 84 mmHg versus a flat placebo group (p<0.05), with a larger drop in men (86 to 81 mmHg, p<0.006); a fall in von Willebrand factor was seen in women only at p<0.1.
Integrated Blood Pressure Control, 2016 · 79 people
What people using it report
- Commercial capsules are almost universally standardized around 2,000 FU (about 100 mg of NSK-SD or an equivalent extract) per capsule, matching the dose used in most of the published blood pressure trials. A pharmacist-run survey of the Long COVID and ME/CFS community, published by PharmD Martha Eckey, found respondents commonly took more than that, in the 4,000 to 12,000 FU per day range, with 4,000 FU taken twice daily on an empty stomach described as a frequently reported 'sweet spot.'
- Outside the Long COVID community, the goals people describe are cardiovascular prevention in a general sense (better circulation, arterial health, blood pressure) and, in a smaller but vocal group, an attempt to address suspected microclots. In the Long COVID and ME/CFS survey specifically, respondents were taking it for fatigue, brain fog, and other post-viral symptoms tied to a microclot hypothesis that has not been established in controlled trials; about 60% of survey respondents reported some benefit, most within 2 weeks.
- 213 people5 human studies3 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
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 nothingTen adults aged 72 on average, open-label, 1 to 2 g per day for four weeks. Peak post-meal glucose fell from 185 to 166 mg/dL (p = .003), three-hour glucose AUC from 469 to 428 (p = .001) and the Matsuda index rose from 3.1 to 3.8 (p = .03). Fasting glucose, weight, blood pressure and lipids were unchanged. Ten people, no placebo arm, so it is hypothesis-generating.
Journals of Gerontology Series A, 2012 · 10 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
- 184 people2 human studies
109 hospitalised patients randomised to tolvaptan or carperitide. Symptoms and plasma BNP improved similarly in both groups. Blood pressure was lower after carperitide, and fewer adverse events such as worsening heart failure and hypotension requiring discontinuation occurred with tolvaptan (p = 0.027).
Journal of Clinical Pharmacology, 2013 · 109 people
75 patients with acute heart failure given 0.0125 micrograms per kilogram per minute of carperitide for 6 hours. Lower baseline plasma ANP (r = -0.35, p = 0.002) and lower vasopressin (r = -0.54, p < 0.001) predicted a larger diuretic response; baseline blood pressure, renal function and prior loop diuretic use did not.
ESC Heart Failure, 2022 · 75 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
- 37 people2 human studies2 found nothing
found nothing37 adults aged 40 to 80 with systolic pressure 125 to 160 mmHg, 100 mg (-)-epicatechin a day for 4 weeks in crossover. Flow-mediated dilation: +1.1 percentage points, 95 percent CI -0.1 to 2.3, p = 0.07, not significant. Fasting insulin fell 1.46 mU/L (p = 0.03) and HOMA-IR fell 0.38 (p = 0.04). No change in blood pressure, arterial stiffness or lipids. Funding not stated in the abstract retrieved.
American Journal of Clinical Nutrition, 2015 · 37 people
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
- 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
- 23 people1 human study1 found nothing
found nothing23 women randomised double-blind to 250 mg of a 10 percent Coleus forskohlii extract twice daily (n equals 7) or placebo (n equals 12) for 12 weeks. No significant differences in fat mass, fat-free mass or body fat percentage. Non-significant trends toward mitigating gains in body mass (p equals 0.10) and scanned mass (p equals 0.08). Treated participants reported less hunger and fullness. No clinically significant changes in blood lipids, liver or muscle enzymes, thyroid hormones, insulin, heart rate or blood pressure. The authors concluded it does not appear to promote weight loss but may help mitigate weight gain.
Journal of the International Society of Sports Nutrition, 2005 · 23 people
- 8 people2 human studies1 found nothing
The safety-relevant human study, in eight healthy male volunteers given a 60-minute infusion of human galanin at 80 pmol/kg per minute or saline. Galanin lowered supine plasma noradrenaline from 0.84 to 0.33 nmol/L and blunted the noradrenaline response to standing from 1.68 to 0.44 nmol/L, while enhancing the adrenaline response to standing. It raised supine heart rate from 70 to 99 beats per minute and the standing heart rate from 82 to 107, and blunted the systolic and diastolic blood pressure responses to standing. A substantial autonomic effect in healthy young men.
The Journal of Clinical Endocrinology and Metabolism, 1995 · 8 people
found nothingThe first human study. Galanin infused for 60 minutes into healthy volunteers at 7.8 pmol/kg per minute (n=4) or 33.2 pmol/kg per minute (n=6). Plasma growth hormone rose from 2.8 to a mean peak of 48.5 mU/L at the high dose and from 2.5 to 23.5 mU/L at the low dose; prolactin rose from 176 to 274 mU/L. No change in cortisol, TSH, FSH or LH. No change in heart rate or blood pressure at these doses; the only symptoms were a transitory bitter taste and slight hypersalivation. Galanin reduced glucose clearance after an intravenous glucose bolus without significantly affecting plasma insulin.
The Lancet, 1986 · no headcount in the line
- 7 people1 human study1 found nothing
found nothing7 heart failure patients on a left ventricular assist device given oral clenbuterol up-titrated to 720 micrograms a day for 3 months. No serious adverse events or arrhythmias, creatine phosphokinase rose in 4 patients. Ejection fraction did not improve and end-diastolic dimension increased; body weight and lean mass rose and quadriceps maximal voluntary contraction improved from 37.0 to 45.8 kg. Cardiac function did not improve.
The Journal of Heart and Lung Transplantation, 2006 · 7 people
- no headcount stated1 human study
Small open study: inhaled VIP improved hemodynamics and exercise capacity in primary pulmonary hypertension patients deficient in VIP.
Journal of Clinical Investigation, 2003 · 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
- no headcount stated1 human study
266 elderly and older persons assessed over six to eight years, with thymalin and epithalamin applied during the first two to three years. Acute respiratory disease incidence fell 2.0 to 2.4-fold, with reduced clinical ischaemic heart disease, hypertension, deforming osteoarthrosis and osteoporosis against control. Mortality fell 2.0 to 2.1-fold with thymalin, 1.6 to 1.8-fold with epithalamin and 2.5-fold with both, and a separate group treated with both annually for six years had a 4.1-fold lower mortality rate. Single group, no described blinding or randomisation, never replicated.
Neuro Endocrinology Letters, 2003 · no headcount in the line
- no headcount stated1 human study
Analysis of the 154 strokes in TREAT: 5.0 percent of the darbepoetin group and 2.6 percent of the placebo group. Assignment to darbepoetin was an independent predictor (odds ratio 2.1, 95 percent confidence interval 1.5 to 2.9). The doubling could not be attributed to baseline characteristics or to post-randomisation blood pressure, haemoglobin, platelet count or dose, so the risk could not be mitigated by monitoring those.
Circulation, 2011 · 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
Mouse. Clearing senescent cells, including with ABT-263, worsened pulmonary hypertension in several models. A senolytic harm signal in animals, reported here because the benefit signals in animals are quoted constantly and this one is not.
Circulation, 2023 · 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.
- Commercial capsules are almost universally standardized around 2,000 FU (about 100 mg of NSK-SD or an equivalent extract) per capsule, matching the dose used in most of the published blood pressure trials. A pharmacist-run survey of the Long COVID and ME/CFS community, published by PharmD Martha Eckey, found respondents commonly took more than that, in the 4,000 to 12,000 FU per day range, with 4,000 FU taken twice daily on an empty stomach described as a frequently reported 'sweet spot.'
- Outside the Long COVID community, the goals people describe are cardiovascular prevention in a general sense (better circulation, arterial health, blood pressure) and, in a smaller but vocal group, an attempt to address suspected microclots. In the Long COVID and ME/CFS survey specifically, respondents were taking it for fatigue, brain fog, and other post-viral symptoms tied to a microclot hypothesis that has not been established in controlled trials; about 60% of survey respondents reported some benefit, most within 2 weeks.
Sources: A published pharmacist-run survey of the Long COVID and ME/CFS supplement-using community (Martha Eckey, PharmD, writing on Substack), which is the only named, citable source for dosing and outcome patterns used here; the Health Canada licensed natural health product label and the Canadian NHPID ingredient entry, which supply the specific warfarin and bleeding-disorder caution language quoted in the legal status section; Memorial Sloan Kettering's integrative medicine monograph on nattokinase, which was used to cross-check the case reports and mechanism claims against a clinical secondary source; and the case-report and clinical literature cited directly elsewhere on this page. Reddit's r/Supplements and r/Biohackers, and any other Reddit community, could not be retrieved for this entry.
- Headache and, at higher amounts, a raised blood pressure reading.
Sources: The nausea, yawning and stretching appear in the melanotan II controlled trial. The pigment changes and the rest come from forums including r/peptides and from the dermatological review of unregulated alpha-MSH analogue use.
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 Navitoclax as the example, because it states the problem most clearly:
Navitoclax is the clearest case in the senolytic field of a compound whose mechanism defeats its own translation. BCL-xL keeps platelets alive; inhibiting BCL-xL kills senescent cells and drops the platelet count in the same stroke. The phase 1 authors named this explicitly in 2010. Every subsequent oncology trial has reported the same toxicity, which is tolerable when the alternative is progressive cancer and not tolerable as a preventive given to well people.
That is why DT2216, a degrader designed to route BCL-xL for destruction through an E3 ligase that platelets barely express, exists at all. It is also why the widely repeated claim that senolytics rejuvenate stem cells should always be read with its species label attached: the rejuvenation was in mice. No senolytic has improved a clinical outcome in a randomised trial in humans, and the drug with the strongest animal senolytic data is the one least likely to be tested for it.
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.