The burden of hypertension in Sub-Saharan African countries is rising. Low-cost and effective interventions are needed to mitigate these alarming trends. No evidence is available on the use of dietary nitrate for treating hypertension in African populations. The objectives of this study are to assess the feasibility and efficacy of using beetroot and folate as a combined dietary intervention to treat Tanzanian adults with pre- and mild to moderate hypertension. This was a three-arm double-blind, placebo-controlled, parallel randomised clinical trial conducted within the Hai Demographic Surveillance Site in the Kilimanjaro region in Tanzania. 48 participants were randomised to one of three groups for a 60-day intervention period. Group 1: Combined dietary intervention (beetroot juice and folate), Group 2: Single dietary intervention (beetroot juice and placebo capsule), and Group 3: Control group (placebo beetroot juice and placebo capsule). The primary outcome of the trial was to evaluate the feasibility of the study in a low-income setting. Trial assessments included resting clinic and ambulatory 24-hr blood pressure measurements, lifestyle and dietary questionnaires and collection of biological samples. Our cohort included 8 (16.7%) males and 40 (83.3%) females with mean age 60.7 years (SD 6.5). The mean (SD) BMI, clinic systolic blood pressure and ambulatory systolic blood pressure at baseline were 27.6 kg/m2 (5.4), 151.0 (19.4), and 140.4 (15.0) mmHg, respectively. Eight (16.7%) participants were classified as pre-hypertensive, 20 (41.7%) as stage-1 hypertensive, and 20 (41.7%) as stage-2 hypertensive. Overall, the results support the feasibility of a study of this nature within a hypertensive African population.

Introduction

Hypertension is associated with a significant risk of cardiovascular morbidity and mortality worldwide [1]. The United Republic of Tanzania is a developing country within the East African region of Sub-Saharan Africa. Research indicates that current Tanzanian management strategies are struggling to control the burgeoning hypertension epidemic [2]. A recent study conducted by our group established a ‘rule of sixths’ in a cohort of hypertensive patients, where 2/6th of the cohort were previously diagnosed, 1/6th of those with a diagnosis were on treatment, and only 1/6th of those on treatment were adequately controlled [3].

Optimal control of hypertension remains challenging and the rising prevalence of hypertension in Tanzania calls for effective interventions. The need to develop a low-cost intervention that is both acceptable to local communities and effective either alone or alongside current medication is urgently warranted. Dietary interventions may be a valuable potential solution. The Dietary Approach to Stop Hypertension (DASH) diet is one of the best proven non-pharmacologic interventions for the prevention of hypertension [4] and the high inorganic nitrate content in the DASH diet may be responsible for this effect [5]. Recent studies have shown that dietary nitrate supplementation can reduce blood pressure and improve endothelial dysfunction [[6], [7], [8]]. Proposed mechanisms involve the generation of nitrite and subsequently nitric oxide, which promotes vasodilation to lower blood pressure [9].

Beetroot is a vegetable that is easily grown and naturally rich in dietary nitrate [10]. Studies utilising beetroot juice as a nitrate supplement have shown promising effects on reducing blood pressure [11]. One trial in healthy participants showed a reduced systolic and diastolic pressure of 10.4  mmHg and 8.0 mmHg respectively following a single dose after 3 h [9]. Similar benefits were seen in a sample of African-American women [12]. Additionally, folic acid is associated with mechanisms controlling the regulation of vascular tone (i.e., Nitric Oxide Synthase coupling, reduction of homocysteine) and its supplementation has been associated with improvements in endothelial function and blood pressure [[13], [14], [15]].

Poor adherence to medical treatment and lack of health infrastructures are key factors contributing to the poor control of hypertension in Tanzania [[16], [17], [18], [19]]. Dietary supplementation could potentially address these issues. Firstly, individuals may be more willing to take dietary supplements over anti-hypertensives due to the reduced side-effect profile and cultural perceptions of Western medicine, which could improve adherence to treatment. Secondly, using dietary supplements as an additional source of anti-hypertensive therapy may help alleviate the burden on already resource-limited healthcare systems, where a consistent supply of medication can often be unfeasible and expensive compared to obtaining dietary nitrate from foods that can be grown locally and sustainably. As beetroot and folate induce beneficial effects on BP via different mechanisms, a combined intervention may yield greater benefits compared to the consumption of each individually. To our knowledge, a combined dietary intervention focussed on folic acid and inorganic nitrate has not been conducted, especially in an African setting. Therefore, the aim of our study was to determine the feasibility of using beetroot and folate to lower blood pressure, and its efficacy for use in this setting.

Methods

Study design

Our study was a three-arm, placebo-controlled, double blind, randomised clinical trial (RCT) that was conducted in the Hai Demographic Surveillance Site (DSS) in the Kilimanjaro region of Northern Tanzania. Participants were assessed at Hai District Hospital and Kware village dispensary and samples were processed and stored at the Kilimanjaro Clinical Research Institute (KCRI). Recruitment started in March 2018, with trial assessments beginning in May and finishing in August.

In order to measure the effects of dietary intervention, we utilised clinic and ambulatory blood pressure measurements to examine changes in systolic and diastolic blood pressure. Blood and saliva samples were collected to evaluate compliance to the interventions (folic acid and nitrate) and measure biomarkers of nitric oxide production. The study comprised of four phases: (1) Recruitment, (2) Screening, (3) Randomisation and Baseline, and (4) Intervention. Eligible participants were randomised into one of three groups for an intervention period of 60 days:

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Group 1–Combined Intervention Group (High-Nitrate Beetroot and Folic Acid)

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Group 2–Single Intervention Group (High-Nitrate Beetroot and Placebo)

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Group 3–Control Group (Nitrate-Depleted Beetroot and Placebo)

The feasibility and acceptability of the intervention was evaluated through one-to-one qualitative interviews and participant compliance to the interventions and measurement protocols.