Does it move blood pressure?

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. 01PT-141PeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 4 completed trials, 2,355 people given it.9 reported

   397 people given it1 trial

   • Bremelanotide raises blood pressure a little and slows the heart, for a short while after each shot. 397 premenopausal women wore blood pressure monitors around the clock. At the label dose the top blood pressure number ran about 3 mmHg higher than on the dummy in the four hours after the shot, with peaks usually lasting under 15 minutes. Heart rate fell about 4.6 beats per minute. 26 women stopped for blood pressure rises, about equally in every group, dummy included.

     The numbers 397 premenopausal women: ambulatory systolic pressure rose 3.1 to 3.2 mmHg versus placebo at 1.75 mg in the first four hours, with peaks usually under 15 minutes, and heart rate fell 4.6 to 4.7 beats per minute. 26 participants discontinued for prespecified blood pressure rises, similarly across all groups.

     Journal of Hypertension, 2017· 397 people

2. 02ANPPeptideModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 188 people given it.4 reported

   184 people given it2 trials

   • Head to head against a water tablet called tolvaptan, this drug came off slightly worse. 109 people in hospital with heart failure got either tolvaptan or carperitide. Symptoms and a blood test for heart strain improved about equally on both. Blood pressure ran lower on carperitide. More people on carperitide had to stop because their heart failure got worse or their blood pressure dropped. Just over a hundred people is a small study for a comparison like this.

     The numbers 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 peoplepoints the wrong way

   • This looked for who passes more water on the drug, and found two blood tests that predict it. 75 people in hospital with heart failure got a low dose of carperitide through a drip for six hours. Those who started with lower levels of their own natriuretic hormone, and lower vasopressin, produced the most urine. Blood pressure, kidney function and previous water tablets predicted nothing. Everyone here got the drug, so there is no comparison group and no way to know what would have happened anyway.

     The numbers 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

3. 03ElamipretidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 487 people given it.6 reported

   71 people given it1 trial1 found nothing

   • found nothingElamipretide was tested in failing hearts and it changed nothing. Seventy one people with a weak heart pump got a dummy injection or one of two elamipretide doses, daily for four weeks. Ultrasound scans of how much blood the heart held and how much it pushed out looked the same in all three groups. The trial was small and short, so it could only have caught a fairly large effect. It did not find one.

     The numbers 71 patients randomized to placebo, 4 mg or 40 mg daily for 28 days: no significant change in left ventricular end systolic volume or ejection fraction versus placebo (4 mg p = 0.90, 40 mg p = 0.28). Tolerability was similar across the three arms.

     Journal of Cardiac Failure, 2020· 71 people

4. 04GalaninPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 21 people given it.

   8 people given it2 trials1 found nothing

   • Galanin has a real effect on the body's automatic controls, and this is the study that shows it. Eight healthy young men were infused for an hour, or given salt water instead. On galanin, the stress chemical noradrenaline fell by more than half while they lay down, and barely rose when they stood up. Their resting heart rate went from about 70 beats a minute to about 99. Their blood pressure response to standing was blunted. That is a substantial change.

     The numbers 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 time galanin was given to people, it set off a surge of growth hormone. Ten healthy volunteers were infused for an hour at one of two rates. Growth hormone climbed many times over, further at the higher rate. The hormone behind milk production rose a little. Stress and thyroid hormones did not move, and neither did heart rate or blood pressure. The only complaints were a passing bitter taste and extra saliva. Sugar cleared from the blood more slowly, with insulin unchanged.

     The numbers The 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· number of people not given

5. 05VIPPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.2 reported

   0 people given it1 trial

   • A small, early study in a serious lung condition, with everyone knowing what they were getting. People with high blood pressure in the lungs breathed in VIP. Pressures in the lung circuit improved and they could walk further. All of them were short of VIP to begin with, which is the best case there is for giving it back. There was no dummy group and nobody was kept in the dark, so how much of this was the drug is unknown.

     The numbers Small open study: inhaled VIP improved hemodynamics and exercise capacity in primary pulmonary hypertension patients deficient in VIP.

     Journal of Clinical Investigation, 2003· number of people not given

6. 06Thymalin with epitalonBlendStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 1,106 people given it.7 reported

   0 people given it1 trial

   • This is the study the thymalin story rests on, and it is not built to carry that weight. 266 older people were followed for six to eight years, and given thymalin and epithalamin in the first two or three. Infections and deaths were reported at about half the rate of a comparison group, and several age-related diseases as less common. The problem is this. The paper does not say anyone was grouped by chance or kept unaware of their treatment. And no other team has repeated it.

     The numbers 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· number of people not given

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

1. 01ResveratrolSupplementModerate. At least one finished study in people, and at least 100 people who took it. 14 completed trials, 403 people given it.7 reported

   213 people given it5 trials3 found nothing

   • found nothingThe longest and largest diabetes trial of resveratrol found nothing that counted. 192 patients took 40 mg, 500 mg or a dummy pill every day for six months. An inflammation marker fell further on resveratrol, but not by enough to call real. Weight, waist, blood pressure, blood sugar, insulin and a string of other markers did not change. Cholesterol and triglycerides rose slightly on the high dose. Patients earlier in their diabetes did show a real fall in inflammation.

     The numbers The 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

   • 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 nothingTen older adults took resveratrol for a month and their blood sugar after meals came down. The peak reading fell by about a tenth, the total sugar load over three hours fell, and their response to insulin improved. Fasting sugar, weight, blood pressure and cholesterol did not move. There was no comparison group, and everyone knew what they were taking. So this raises a question rather than answering one.

     The numbers Ten 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 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

2. 02TaurineSupplementModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 120 people given it.5 reported

   120 people given it1 trial

   • Taurine can move blood pressure in people who are already on the high side of normal. 120 adults took 1.6 grams a day, or a dummy pill, for 12 weeks. The top number of their blood pressure, measured in the clinic, fell 7.2 points on taurine against 2.6 on the dummy. This is a blood pressure study, not an ageing study.

     The numbers 120 prehypertensive adults randomised to 1.6 g/day taurine or placebo for 12 weeks. Mean clinic systolic reduction 7.2 mmHg against 2.6, diastolic 4.7 against 1.3. Not an ageing endpoint.

     Hypertension, 2016· 120 people

3. 03PterostilbeneSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 80 people given it.4 reported

   80 people given it1 trial

   • It pushed blood pressure down and bad cholesterol up. 80 adults with raised cholesterol took pterostilbene at 125 mg twice a day, at 50 mg twice a day, at 50 mg with grape extract, or a dummy, for 6 to 8 weeks. On pterostilbene alone, bad cholesterol rose 17.1 units. Adding grape extract removed that rise. On the high dose, the upper blood pressure number fell 7.8 points and the lower one 7.3. Raising bad cholesterol in people who already have too much is a real trade-off.

     The numbers 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

4. 04EpicatechinSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 44 people given it.1 reported

   37 people given it2 trials2 found nothing

   • found nothingPure epicatechin did not improve blood vessel function, and the small insulin change is easy to over-read. 37 adults aged 40 to 80 with raised blood pressure took 100 mg a day for four weeks, and each also took a dummy for four weeks, in turn. Artery widening improved slightly, too little to separate from chance. Fasting insulin fell a little. Blood pressure, artery stiffness and cholesterol did not budge. No funding was stated in the abstract retrieved.

     The numbers 37 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 nothingA food-sized dose of pure epicatechin did nothing. 48 overweight or obese non-smokers with features of metabolic syndrome took 25 mg a day for two weeks, and each took a dummy for two weeks as well, in turn. Nothing moved: not blood pressure, glucose, insulin, triglycerides, or any cholesterol measure. The authors conclude that whatever cocoa does, epicatechin alone does not explain it. Two weeks is short, and the dose was deliberately a dietary one.

     The numbers 48 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· number of people not given

5. 05ForskolinSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 53 people given it.5 reported

   23 people given it1 trial1 found nothing

   • found nothingThe same supplement was tested in women and it did not work. 23 mildly overweight women took a 10 percent Coleus forskohlii extract twice a day or a dummy for 12 weeks, seven on the extract. Fat mass, lean mass and body fat percentage came out the same in both groups. Slight leanings toward less weight gain were too weak to call. Blood fats, liver enzymes, thyroid, insulin, heart rate and blood pressure were unchanged. Seven people is too few to spot anything but a huge effect.

     The numbers 23 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

6. 06NMNSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 94 people given it.6 reported

   0 people given it1 trial1 found nothing

   • found nothingA high dose NMN tablet raised NAD in the blood and moved weight and cholesterol, but not muscle. 30 overweight or obese adults took MIB-626, 1000 mg twice a day, or a dummy pill, for 28 days. Weight fell 1.9 kg. The lower blood pressure number and LDL cholesterol fell too. Strength, tiredness, fitness and stair climbing power did not change. Neither did the body's response to insulin. The maker paid for it.

     The numbers 30 overweight or obese adults aged 45 and over randomised 2:1 to MIB-626 (microcrystalline NMN) 1000 mg twice daily or placebo for 28 days. Weight -1.9 kg, diastolic BP -7.01 mmHg, LDL -18.73 mg/dL versus placebo. Muscle strength, fatigability, aerobic capacity and stair-climbing power did not differ. Insulin sensitivity unchanged. Funder: Metro International Biotech.

     Journal of Clinical Endocrinology and Metabolism, 2023· number of people not given

7. 07MIB-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

   0 people given it1 trial1 found nothing

   • found nothingThe tablet moved some body measurements and left every measure of physical function untouched. 30 overweight or obese adults aged 45 and over took MIB-626 or a dummy tablet for four weeks. Weight fell by about two kilograms. Blood pressure and cholesterol both came down. Strength, stamina, how quickly muscles tired and stair climbing power did not change. Insulin sensitivity, liver fat and belly fat did not change either. The manufacturer helped fund it. This study looked at many things at once, so treat any single result as a hint.

     The numbers Randomised 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· 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. 01NattokinaseBiologicStrong. At least two finished studies in people, and at least 1,000 people who took it. 9 completed trials, 1,795 people given it.6 reported

   608 people given it4 trials1 found nothing

   • found nothingThe one long, careful, independent trial found nothing. 265 adults without heart disease took nattokinase or a dummy pill for a median of three years, with neck artery scans every six months. The artery wall thickened at the same rate in both groups. Stiffness, blood pressure, and every clotting, inflammation and metabolic marker measured came out the same. A trial this long would have found a real effect on plaque if there was one to find.

     The numbers The 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

   • In a better built trial, nattokinase alone moved one blood fat and nothing else. 178 patients with stable heart disease, already on their usual medicines, took nattokinase, red yeast rice, both, or a dummy pill for 90 days. Nattokinase alone lowered LDL, the harmful cholesterol, compared with the dummy. Total cholesterol, triglycerides and good cholesterol did not budge. The combination improved every blood fat, and blood pressure as well.

     The numbers 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

   • Nattokinase lowered blood pressure a little. 86 adults with borderline or mild high blood pressure took it or a dummy pill for eight weeks. The top number came down about 5 points more than on the dummy, and the bottom number by nearly 3. A hormone that helps set blood pressure fell at the same time, which fits. A few points is real, and it is modest.

     The numbers 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

   • A second trial found a smaller blood pressure effect, and the distributor paid for it. 79 adults with high blood pressure took nattokinase or a dummy for eight weeks. The lower blood pressure number fell by about 3 points while the dummy group stayed flat. Men did better than women. A clotting marker fell in women only, and weakly. The company that sells the product in the United States funded the study, which is disclosed in the paper.

     The numbers 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

   • Store capsules almost all hold about 2,000 FU, roughly 100 mg of NSK-SD or a similar extract. That matches the dose in most of the published blood pressure trials. A survey of the Long COVID and ME/CFS community, published by pharmacist Martha Eckey, found people often took more, from 4,000 to 12,000 FU a day. 4,000 FU twice a day on an empty stomach was often called the sweet spot.
   • Outside Long COVID, people take it for heart health in general: better circulation, artery health and blood pressure. A smaller, vocal group takes it for suspected microclots. In the Long COVID and ME/CFS survey, people took it for tiredness, brain fog and other after-virus symptoms, based on a microclot idea no controlled trial has proven. About 60% said they got some benefit, mostly within 2 weeks.
2. 02MifepristoneSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 320 people given it.4 reported

   50 people given it1 trial

   • In Cushing's syndrome, where cortisol is the problem, blocking its receptor with mifepristone improved blood sugar, blood pressure and weight over six months. 50 adults took part, and there was no dummy pill group. Tiredness, nausea, headache and low potassium were common. This is the approved use, not a study of ageing.

     The numbers 50 adults with endogenous Cushing's syndrome, after failed treatment, were given mifepristone 300 to 1,200 mg daily for 24 weeks, open-label, at 17 US centres. In the diabetes or impaired glucose tolerance group 60% had a glucose AUC response; HbA1c fell from 7.43% to 6.29% and fasting glucose from 149 to 105 mg/dL. In the hypertension group 38% had a diastolic pressure response. Mean weight change -5.7%; 87% judged clinically improved. Fatigue, nausea, headache, low potassium, arthralgia, vomiting, oedema and endometrial thickening were common.

     The Journal of Clinical Endocrinology and Metabolism, 2012· 50 people

3. 03DanazolHormoneLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 63 people given it.5 reported

   36 people given it1 trial

   • This is what danazol costs, measured in a different illness. 36 patients with acquired aplastic anaemia took danazol on its own, 10 mg per kilogram a day up to a cap of 600 mg. After six months, good cholesterol had fallen 30 percent and bad cholesterol had risen 11 percent. The size of the heart's main pumping chamber changed, as did how well it pumped and relaxed. The authors conclude the drug causes severe blood fat changes and possible heart damage. Different condition, same drug, similar dose.

     The numbers 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

4. 04ErythropoietinBiologicStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 4,641 people given it.6 reported

   0 people given it1 trial

   • The stroke harm was real and there is no way to screen for it. Researchers went through all 154 strokes in the earlier trial. Five in every hundred on darbepoetin had a stroke, against about two and a half on the dummy injection. Being assigned the drug predicted stroke on its own. It could not be explained away by who the patients were at the start, nor by their blood pressure, blood counts, platelets or dose afterwards. So monitoring those things does not make the drug safer.

     The numbers 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· number of people not given

5. 05ClenbuterolSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 11 people given it.5 reported

   nobody was given it1 watch-only study1 found nothing

   • found nothingClenbuterol built leg muscle in heart failure patients and did nothing for their hearts. 7 people supported by a mechanical heart pump took rising oral doses for three months, up to a very high daily amount. Body weight and lean mass rose, and thigh strength improved from about 37 to about 46 kilograms of force. The pumping fraction did not improve and the heart chamber got larger. No serious side effects or rhythm problems appeared, though a muscle enzyme rose in four patients.

     The numbers 7 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 peopleobserved only, nobody was given it

   What people using it report

   • Hand tremor bad enough to interfere with writing, insomnia, heavy sweating, headache, breathlessness during training, raised blood pressure and a sense of dull thinking all appear repeatedly.

Peptides and blends

1. 01FOXO4-DRIPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 74 people given it.8 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice and rats, this is the result that cuts the other way, and it is usually left out. In mice, clearing worn-out cells from lung blood vessels, with FOXO4-DRI among the tools, raised pressure in the lung circulation. It thickened the right side of the heart and stripped out lining cells the lung depends on. In rats, a related cell-clearing drug helped slightly at one week and made things worse by three. The authors warn that clearing these cells may worsen blood flow through the lungs.

     The numbers Senescent cell clearance in mice, including with FOXO4-DRI, raised right ventricular systolic pressure and the hypertrophy index, increased vessel remodelling and markedly reduced lung pulmonary endothelial cells. In monocrotaline rats, ABT263 slightly reduced pulmonary hypertension at one week and aggravated it at three. The authors conclude senolytic interventions may worsen pulmonary haemodynamics.

     Circulation, 2023· animal studypoints the wrong way

Other compounds

1. 01NavitoclaxSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 137 people given it.2 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. Clearing worn-out cells, including with navitoclax, made high blood pressure in the lungs worse in several mouse models. That is a harm signal. It is listed here because the good results in animals get quoted all the time and this one does not.

     The numbers 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 studypoints the wrong way