A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia
| Autor: | Andrew M. Prentice, Philip T. James, Matt J. Silver, Kabiru Ceesay, Bakary Sonko, Nuredin Mohammed, Fatai M. Akemokwe, Ebrima A. Sise, Ousubie Jawla |
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| Rok vydání: | 2019 |
| Předmět: |
B Vitamins
Homocysteine Physiology Maternal Health Riboflavin Blood Pressure 030204 cardiovascular system & hematology Biochemistry Vascular Medicine law.invention chemistry.chemical_compound 0302 clinical medicine Randomized controlled trial Pregnancy law Medicine and Health Sciences Clinical endpoint 030212 general & internal medicine Political science 2. Zero hunger DNA methylation Organic Compounds Obstetrics and Gynecology Vitamins General Medicine Middle Aged Micronutrient Chromatin Body Fluids 3. Good health Nucleic acids Chemistry Vitamin B 12 Blood Physical Sciences Medicine Epigenetics Female Gambia Metabolic Pathways Anatomy DNA modification Chromatin modification Research Article Chromosome biology Adult Cell biology medicine.medical_specialty United Nations Adolescent Nutritional Status Blood Plasma Social sciences Young Adult 03 medical and health sciences Folic Acid Internal medicine Genetics medicine Humans Vitamin B12 business.industry Organic Chemistry Chemical Compounds Biology and Life Sciences DNA medicine.disease Betaine B vitamins Metabolism chemistry Dietary Supplements Women's Health Gene expression business Body mass index |
| Zdroj: | PLoS Medicine, Vol 16, Iss 8, p e1002870 (2019) PLoS Medicine |
| ISSN: | 1549-1676 1549-1277 |
| Popis: | 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. Philip Thomas James and colleagues reveal a potential, unique link between mother’ nutritional input and an offspring’s methylation status. Author summary Why was this study done? At conception, the methylation marks on DNA from sperm and egg are erased and then re-established in the very early embryo. This DNA methylation relies on nutritional inputs for one-carbon metabolic pathways, including the efficient recycling of homocysteine, an absence of which might interfere with normal fetal development. We sought to test nutritional supplements that could reduce homocysteine and thereby optimise methylation pathways in women at the time of conception. What did the researchers do and find? We designed a novel drink powder containing betaine, folic acid, and vitamins B12 and B2 and tested its efficacy in reducing plasma homocysteine. Efficacy was tested in nonpregnant rural Gambian women in a randomised controlled trial, in which we also tested the UNIMMAP supplement that contains 15 micronutrients but no betaine. Both our novel supplement and UNIMMAP reduced homocysteine after 5 and 12 weeks of supplementation, with the novel drink powder showing a significantly enhanced efficacy. What do these findings mean? This trial demonstrates that it is feasible to lower homocysteine levels even in women whose homocysteine levels are only marginally elevated. Our novel supplement would be a potential candidate for future trials of preconceptional supplements aimed at optimising offspring DNA methylation. |
| Databáze: | OpenAIRE |
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