Re: Flawed Clinical Trial Finds No Effect of Nigella on Blood Pressure in Elderly Patients with Hypertension

Nigella (Black Cumin; Nigella sativa, Ranunculaceae) Hypertension Elderly Date: 10-15-2018 HC# 031833-602 Rizka A, Setiati S, Lydia A, Dewiasty E. Effect of Nigella sativa seed extract for hypertension in elderly: a double-blind, randomized controlled trial. Acta Med Indones. October 2017;49(4):307-313. Hypertension can lead to cardiovascular complications and is the number one cause of death in the elderly. Reducing blood pressure in persons older than 60 years significantly reduces mortality and cardiovascular events. In Indonesia, home to these authors, the prevalence of hypertension in the elderly is high and the condition is poorly controlled in this population. Nigella (black cumin; Nigella sativa, Ranunculaceae) seed has been used to treat various diseases for hundreds of years. In animal models, nigella has been shown to have diuretic effects, decrease sympathetic activities, improve lipid levels, and increase the production of nitric oxide. These effects are potentially beneficial for the treatment of hypertension. The authors conducted a double-blind, randomized, and controlled trial to assess the efficacy of an undefined extract of nigella seed in decreasing blood pressure in elderly patients with hypertension. The study was conducted from June 2011 to September 2011 at the Geriatric, Renal-Hypertension, and Internal Medicine Outpatient Clinics at Cipto Mangunkusumo National Hospital in Jakarta, Indonesia. Eligible patients were 60 years or older with hypertension, which was defined as systolic blood pressure (SBP) ˃ 140 mm Hg and/or diastolic blood pressure (DBP) ˃ 90 mm Hg. The exclusion criteria were decreased renal or liver function, severe dementia, depression, orthostatic hypertension, malignant hypertension, use of more than three antihypertensive agents at maximum doses, and refusing to participate in the study. The patients were randomly assigned to take two capsules daily of either nigella (n=38) or placebo (n=38) for 28 days. Each nigella capsule contained 300 mg nigella extract of unknown composition, identity, quality, and strength. Each placebo capsule contained flour and had a similar color, weight, and smell as a nigella capsule. The source of the nigella and the chemical characteristics of the extract were not reported. Unused capsules were returned on the last day of the study. The patients were advised to continue any antihypertensive medications, their usual lifestyle and dietary activities, smoking habits, and use of supplements. At baseline and on day 28, the patients were interviewed and underwent physical and laboratory examinations. Five patients in the nigella group did not complete the study because of nausea (3 patients), trauma emergency surgery (1 patient), and forgetfulness (1 patient). Of the dropouts in the placebo group, one was due to nausea, and one was due to forgetfulness. A total of 33 patients in the nigella group (25 females and 13 males) and 36 patients in the placebo group (30 females and 8 males) completed the study. From baseline to the end of the study, SBP decreased by 14.6 mm Hg in the nigella group and by 13.3 mm Hg in the placebo group (P=0.36). Mean decrease in DBP was 3.9 mm Hg in the nigella group and 0.8 mm Hg in the placebo group (P=0.35). Six patients in the nigella group reported nausea and gastric discomfort, including one who reported vomiting and two others who reported difficulty defecating. Two other studies of the effects of nigella on blood pressure were conducted in young adults.1,2 In one of those studies,2 the primary outcome was improvement in lipid profiles, with change in blood pressure reported as a secondary outcome. Significant decreases in blood pressure with the use of nigella were reported in both studies. The authors suggest that the lack of significant therapeutic effects compared with placebo in elderly patients with hypertension might be due to rigidity of arteries, which plays an important role in the pathogenesis of hypertension in the elderly. Another potential explanation is that 66% of the patients in the nigella group were elderly females, in whom blood pressure is harder to control compared with elderly men.3 The small change in DBP could be explained by the fact that 60% of patients in the nigella group had isolated systolic hypertension, a condition in which SBP is high and DBP is normal or low. Acknowledged limitations of this study include the failure to measure fluctuations in blood pressure during the study period, relatively short study duration, small sample size, and heterogeneity in SBP/DBP characteristics. Furthermore, the authors failure to adequately describe the composition, identity, purity, quality, and strength of the investigational product causes the results to be of questionable value. The experiment is not reproducible due to this significant flaw. The authors conclude that nigella did not significantly reduce blood pressure in elderly patients with hypertension. Sources of funding for the study were not reported. The article did not include a conflict of interest declaration. —Shari Henson References 1Dehkordi FR, Kamkhah AF. Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundamen Clin Pharmacol. August 2008;22(4):447-452. 2Qidwai W, Hamza HB, Qureshi R, Gilani A. Effectiveness, safety, and tolerability of powdered Nigella sativa (kalonji) seed in capsules on serum lipid levels, blood sugar, blood pressure, and body weight in adults: results of a randomized, double-blind controlled trial. J Altern Complement Med. June 2009;15(6):639-644. 3Lloyd-Jones DM, Evans JC, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community. JAMA. July 2005;294(4):466-472. Peer Review Comments No conclusions can be made from this study, which should not have made it through peer review process due to the completely inadequate description of the investigational product in the materials and methods section. No information is provided on the method of authentication of the raw material that was used to make the extract (i.e., how done and by whom) and the lot number(s). No information is provided whether a voucher specimen (i.e., retention sample) was retained and, if so, where it is kept or deposited, and the reference number. The quality of the starting raw material used to make the extract is not disclosed. The type and concentration of extraction solvent used (e.g., 80% ethanol, 100% H2O, 90% glycerine, etc.) to make the extract is not stated. The drug-to-extract (DER) concentration ratio of the extract is not stated. There was no description of the type of extract. If a standardized extract, the quantity of active/marker constituents per dosage unit form was not disclosed. The composition of the extract ingredient itself is lacking. No information is provided as to whether the daily single dose of 300 mg of nigella extract is composed of 100% nigella seed extractive matter or whether the extract also contains any added materials, such as binders, fillers, flow agents or other excipients (e.g. cellulose, maltodextrin). All components of the investigational product should be listed (extractive and excipients).