A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia.

BACKGROUND: Infant DNA methylation profiles are associated with their mother's periconceptional nutritional status. DNA methylation relies on nutritional inputs for one-carbon metabolic pathways, including the efficient recycling of homocysteine. This randomised controlled trial in nonpregnant women in rural Gambia tests the efficacy of a novel nutritional supplement designed to improve one-carbon-related nutrient status by reducing plasma homocysteine, and assesses its potential future use in preconception trials. METHODS AND FINDINGS: We designed a novel drink powder based on determinants of plasma homocysteine in the target population and tested it in a three-arm, randomised, controlled trial. Nonpregnant women aged between 18 and 45 from the West Kiang region of The Gambia were randomised in a 1:1:1 allocation to 12 weeks daily supplementation of either (a) a novel drink powder (4 g betaine, 800 µg folic acid, 5.2 µg vitamin B12, and 2.8 mg vitamin B2), (b) a widely used multiple micronutrient tablet (United Nations Multiple Micronutrient Preparation [UNIMMAP]) containing 15 micronutrients, or (c) no intervention. The trial was conducted between March and July 2018. Supplementation was observed daily. Fasted venepuncture samples were collected at baseline, midline (week 5), and endline (week 12) to measure plasma homocysteine. We used linear regression models to determine the difference in homocysteine between pairs of trial arms at midline and endline, adjusted for baseline homocysteine, age, and body mass index (BMI). Blood pressure and pulse were measured as secondary outcomes. Two hundred and ninety-eight eligible women were enrolled and randomised. Compliance was >97.8% for both interventions. At endline (our primary endpoint), the drink powder and UNIMMAP reduced mean plasma homocysteine by 23.6% (-29.5 to -17.1) and 15.5% (-21.2 to -9.4), respectively (both p < 0.001), compared with the controls. Compared with UNIMMAP, the drink powder reduced mean homocysteine by 8.8% (-15.8 to -1.2; p = 0.025). The effects were stronger at midline. There was no effect of either intervention on blood pressure or pulse compared with the control at endline. Self-reported adverse events (AEs) were similar in both intervention arms. There were two serious AEs reported over the trial duration, both in the drink powder arm, but judged to be unrelated to the intervention. Limitations of the study include the use of a single targeted metabolic outcome, homocysteine. CONCLUSIONS: The trial confirms that dietary supplements can influence metabolic pathways that we have shown in previous studies to predict offspring DNA methylation. Both supplements reduced homocysteine effectively and remain potential candidates for future epigenetic trials in pregnancy in rural Gambia. TRIAL REGISTRATION: Clinicaltrials.gov Reference NCT03431597.

Obstructive Sleep Apnea Awareness among Primary Care Physicians in Africa.

Rationale: Obstructive sleep apnea (OSA) is a significant health problem among adults and children globally, resulting in decreased quality of life and increased costs of healthcare. For optimal clinical care, primary care physicians should be familiar with OSA and confident in their ability to screen, diagnose, and manage this condition.Objectives: To assess the knowledge, attitudes, and practices of primary care physicians in Kenya, Nigeria, and South Africa regarding OSA in adults and children.Methods: We conducted a multicenter cross-sectional survey in Kenya (Nairobi), Nigeria (Edo State), and South Africa (Cape Town) between April 2016 and July 2017. At least 40 participants were randomly selected from a register of primary care physicians at each site. Potential participants were contacted to receive online/paper-based, validated OSA Knowledge and Attitudes (OSAKA) and OSAKA in Children (OSAKA-KIDS) questionnaires related to adults and children, respectively. The median percentage knowledge scores and proportions of favorable attitude were computed and current diagnostic and referral practices were documented.Results: The median OSAKA knowledge scores were 83.3% (interquartile range [IQR], 77.8-88.9), 66.7% (IQR, 55.6-77.8), and 61.1% (IQR, 55.6-77.8) among South African, Kenyan, and Nigerian physicians, respectively. For OSAKA-KIDS, the median knowledge scores were 61.1% (IQR, 50.0-72.2), 64.2% (IQR, 35.3-93.2), and 58.3% (IQR, 44.4-66.7) among South African, Kenyan, and Nigerian physicians, respectively. Most physicians (90-94%) considered adult and pediatric OSA very/extremely important. Fewer physicians agreed/strongly agreed that they were confident about OSA diagnosis (55%), management (25%), and continuous positive airway pressure (18%) use in adults. Even fewer physicians agreed/strongly agreed that they were confident about pediatric OSA diagnosis (35%), management (21%), and continuous positive airway pressure use (18%). South African physicians mainly prescribed polysomnography (51%) and overnight oximetry (22%), whereas 49% of Nigerian physicians and 65% of Kenyan physicians commonly requested lateral cervical radiography.Conclusions: Primary care physicians in South Africa, Nigeria, and Kenya considered OSA to be important but had modest knowledge about OSA in adults and children, and had a low perceived confidence in adult and pediatric management. Focused educational interventions during undergraduate training and continuing professional development programs may improve primary physicians' knowledge about OSA and its diagnosis and management.