Supplements tested on top of a prescribed drug

Three randomized trials added beetroot juice to existing antihypertensive therapy and they disagree. In 20 people with treated but uncontrolled hypertension over seven days, ambulatory blood pressure fell by about 8 mmHg systolic and 4 mmHg diastolic against placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received.. A one-week trial in treated hypertensive individuals found no effect and concluded that raising dietary nitrate may not be effective in this group. A four-week trial in older adults with hypertension found nitrate metabolism changed while vascular function and blood pressure did not. The positive trial is the smallest and the shortest of the three.

Background therapy. Prescribed antihypertensive therapy was continued unchanged in all arms of all three trials; nitrate-rich or nitrate-depleted beetroot juice was added.

Kerley et al. (The British Journal of Nutrition, 2018; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 29553033): 7-day double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends. randomized placebo-controlled crossover A trial design in which each participant receives both the treatment and the comparison, one after the other, and serves as their own control. trial in treated, uncontrolled hypertension. Bondonno et al. (The American Journal of Clinical Nutrition, 2015; PMID 26135348): randomized controlled trial People are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect. finding no blood pressure effect in treated hypertensive individuals. Fejes et al. (Food & Function, 2024; PMID 38546454): 4-week trial in older adults with hypertension finding nitrate metabolism changed while vascular function and blood pressure did not.

A systematic review A review that searches for every study on a question using a method set in advance, then assesses them together. of berberine in hypertension examined the combination of berberine with amlodipine and found it was not significantly better than amlodipine alone at reducing either systolic or diastolic blood pressure. The review rates the whole body of evidence as low quality and heterogeneous, and reports that the heterogeneity How much the results of the pooled trials differ from each other. High heterogeneity makes a combined estimate less reliable. prevented a meaningful meta-analysis A study that pools the numbers from several trials into one combined estimate., so this is a null result from weak evidence rather than a firm demonstration of no effect. It is recorded because the pair is widely assumed to work and the assumption has been tested.

Background therapy. Amlodipine was given in both arms; berberine was added in one of them.

Suadoni and Atherton (Complementary Therapies in Clinical Practice, 2021; PMID 33461163): systematic review of 7 controlled trials, 614 participants, of berberine for hypertension.

A meta-analysis of 11 randomized trials totaling 1,386 patients found berberine added to simvastatin lowered triglycerides (mean difference -0.33 mmol/L, 95 percent CI -0.46 to -0.20) and total cholesterol (-0.36, 95 percent CI -0.60 to -0.12) more than simvastatin alone. LDL Low-density lipoprotein cholesterol, the cholesterol fraction most closely tied to plaque in the arteries., the lipid endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. that carries the cardiovascular claim, is not reported for the combination. The review rates the quality and quantity of its own included studies as unsatisfactory, and the trials were drawn largely from the Chinese-language databases SinoMed, CNKI and WanFang.

Background therapy. Simvastatin was continued in both arms across the pooled trials; berberine was added to it.

Zhang et al. (The American Journal of Chinese Medicine, 2019; PMID 31094214): systematic review and meta-analysis of 11 randomized trials of berberine alone or combined with statins in hyperlipidemia.

In 420 patients with moderate to severe chronic heart failure randomized on top of standard therapy, the two-year composite major adverse cardiovascular event rate was 15 percent with CoQ10 and 26 percent with placebo (hazard ratio How often an event happened in the treated group compared with the control group over the same period. A ratio of 0.80 means 20 percent fewer events. 0.50, 95 percent CI 0.32 to 0.80). Cardiovascular mortality was 9 percent versus 16 percent and all-cause mortality 10 percent versus 18 percent. The trial's own primary short-term endpoints at 16 weeks, NYHA class, six-minute walk distance and NT-proBNP, showed no significant change, so what moved was the long-term outcome measure and not the intermediate ones.

Background therapy. Standard heart failure therapy was continued in both arms; CoQ10 100 mg three times daily or matching placebo was added to it.

Mortensen et al. (Journal of the American College of Cardiology: Heart Failure, 2014; PMID 25282031): randomized double-blind multicenter trial, CoQ10 or placebo added to standard therapy in chronic heart failure over two years.

53 overweight and obese women with polycystic ovary syndrome were randomized to metformin alone or metformin plus myo-inositol and D-chiro-inositol for six months. Menstrual cycle regularity and the PCOSQ quality-of-life score improved significantly more in the combination arm. The hormonal and metabolic measures, including HOMA-IR, testosterone, lipids and ovarian volume, did not differ between groups, and pregnancy rates were equal. What separated the arms were the symptom and questionnaire endpoints; the objective ones did not move.

Background therapy. Metformin was given in both arms; myo-inositol and D-chiro-inositol were added in one of them.

Nazirudeen et al. (Clinical Endocrinology, 2023; PMID 37265016): randomized controlled trial comparing myoinositol with metformin against metformin monotherapy in polycystic ovary syndrome.

Monacolin K, the active constituent of red yeast rice, is chemically identical to lovastatin. Taking red yeast rice alongside a prescribed statin is not a supplement added to a drug; it is the same drug class twice, once in an amount the label does not state.

Background therapy. None. The entry exists to record why this combination is not an adjunct question.

Rigillo et al. (Phytotherapy Research, 2025; PMID 39511729): comparative evaluation of the safety and efficacy of red yeast rice against lovastatin.