Advertisement

Dietary Intakes of Vitamin B-2 (Riboflavin), Vitamin B-6, and Vitamin B-12 and Ovarian Cycle Function among Premenopausal Women

Published:December 23, 2019DOI:https://doi.org/10.1016/j.jand.2019.10.013

      Abstract

      Background

      Riboflavin, vitamin B-6, and vitamin B-12 are key players in one-carbon metabolism as enzymatic cofactors, and deficiency of these nutrients may influence reproductive outcomes possibly through affecting reproductive hormones.

      Objective

      The goal was to investigate associations between dietary intakes of riboflavin, vitamin B-6, and vitamin B-12, and menstrual function among premenopausal women.

      Design

      This was a secondary analysis of a prospective cohort study conducted at the University at Buffalo during 2005 to 2007.

      Participants/setting

      Participants were 259 healthy, regularly menstruating women (aged 18 to 44 years) with self-reported menstrual cycles between 21 and 35 days, who were not trying to conceive, and who had not used hormonal contraception during the past 3 months.

      Main outcome measures

      Intakes of B vitamins were assessed via 24-hour dietary recalls four times per menstrual cycle for two cycles. Serum reproductive hormones and plasma homocysteine were measured eight and three times, respectively, per cycle for two cycles. Anovulatory cycles were determined by progesterone concentrations ≤5 ng/mL (15.9 nmol/L) and no observed serum luteinizing hormone peak during the mid or late luteal phase visit.

      Statistical analysis

      Weighted linear mixed regressions were used to evaluate associations between cycle-averaged B vitamin intakes and hormones and homocysteine, and generalized linear regressions for associations with anovulation. Models were adjusted for age, race, body mass index, physical activity, alternate Mediterranean diet score, intakes of total energy, protein, fiber, and folate, and percentage of energy intake from fat.

      Results

      Higher intakes of riboflavin (per 0.1 mg increase in intake) were inversely correlated with estradiol (−0.87%, 95% CI −1.67 to −0.06) and homocysteine levels (−0.61%, 95% CI −1.10 to −0.12). Higher vitamin B-6 intakes were suggestive of higher follicle-stimulating hormone, although the results were not statistically significant (0.63% difference, 95% CI −0.03 to 1.29, per 0.1 mg increase in intake; P=0.06). Small increases in testosterone and decreases in homocysteine were found with vitamin B-12 intake. No associations were observed between intake of B vitamins and a risk of sporadic anovulation.

      Conclusions

      Higher intakes of riboflavin were associated with a small decrease in serum estradiol among healthy, regularly menstruating women. Higher intakes of riboflavin and vitamin B-12 were associated with lower plasma homocysteine concentrations. Overall, riboflavin, vitamin B-6, and vitamin B-12 that are one-carbon nutrients do not appear to influence the ovarian cycle among premenopausal women.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the Academy of Nutrition and Dietetics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Laanpere M.
        • Altmae S.
        • Stavreus-Evers A.
        • Nilsson T.K.
        • Yngve A.
        • Salumets A.
        Folate-mediated one-carbon metabolism and its effect on female fertility and pregnancy viability.
        Nutr Rev. 2010; 68: 99-113
        • Thaler C.J.
        • Budiman H.
        • Ruebsamen H.
        • Nagel D.
        • Lohse P.
        Effects of the common 677C>T mutation of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene on ovarian responsiveness to recombinant follicle-stimulating hormone.
        Am J Reprod Immunol. 2006; 55: 251-258
        • Hecht S.
        • Pavlik R.
        • Lohse P.
        • Noss U.
        • Friese K.
        • Thaler C.J.
        Common 677C–>T mutation of the 5,10-methylenetetrahydrofolate reductase gene affects follicular estradiol synthesis.
        Fertil Steril. 2009; 91: 56-61
        • Haggarty P.
        • McCallum H.
        • McBain H.
        • et al.
        Effect of B vitamins and genetics on success of in-vitro fertilisation: Prospective cohort study.
        Lancet. 2006; 367: 1513-1519
        • Gaskins A.J.
        • Chiu Y.H.
        • Williams P.L.
        • et al.
        Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies.
        Am J Clin Nutr. 2015; 102: 943-950
        • Steegers-Theunissen R.P.
        • Twigt J.
        • Pestinger V.
        • Sinclair K.D.
        The periconceptional period, reproduction and long-term health of offspring: The importance of one-carbon metabolism.
        Hum Reprod Update. 2013; 19: 640-655
        • Michels K.A.
        • Wactawski-Wende J.
        • Mills J.L.
        • et al.
        Folate, homocysteine and the ovarian cycle among healthy regularly menstruating women.
        Hum Reprod. 2017; 32: 1743-1750
        • Gaskins A.J.
        • Mumford S.L.
        • Chavarro J.E.
        • et al.
        The impact of dietary folate intake on reproductive function in premenopausal women: A prospective cohort study.
        PLoS One. 2012; 7: e46276
        • Chavarro J.E.
        • Rich-Edwards J.W.
        • Rosner B.A.
        • Willett W.C.
        Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility.
        Fertil Steril. 2008; 89: 668-676
        • Wactawski-Wende J.
        • Schisterman E.F.
        • Hovey K.M.
        • et al.
        BioCycle study: Design of the longitudinal study of the oxidative stress and hormone variation during the menstrual cycle.
        Paediatr Perinat Epidemiol. 2009; 23: 171-184
        • Craig C.L.
        • Marshall A.L.
        • Sjostrom M.
        • et al.
        International physical activity questionnaire: 12-Country reliability and validity.
        Med Sci Sports Exerc. 2003; 35: 1381-1395
      1. NDS-R. Version 2005. Nutrition Coordinating Center, Minneapolis, MN2005
        • Gaskins A.J.
        • Rovner A.J.
        • Mumford S.L.
        • et al.
        Adherence to a Mediterranean diet and plasma concentrations of lipid peroxidation in premenopausal women.
        Am J Clin Nutr. 2010; 92: 1461-1467
        • Gorczyca A.M.
        • Sjaarda L.A.
        • Mitchell E.M.
        • et al.
        Changes in macronutrient, micronutrient, and food group intakes throughout the menstrual cycle in healthy, premenopausal women.
        Eur J Nutr. 2016; 55: 1181-1188
        • Sartorius G.
        • Ly L.P.
        • Sikaris K.
        • McLachlan R.
        • Handelsman D.J.
        Predictive accuracy and sources of variability in calculated free testosterone estimates.
        Ann Clin Biochem. 2009; 46: 137-143
        • Sodergard R.
        • Backstrom T.
        • Shanbhag V.
        • Carstensen H.
        Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature.
        J Steroid Biochem. 1982; 16: 801-810
        • Lynch K.E.
        • Mumford S.L.
        • Schliep K.C.
        • et al.
        Assessment of anovulation in eumenorrheic women: Comparison of ovulation detection algorithms.
        Fertil Steril. 2014; 102: 511-518 e2
        • Institute of Medicine, Food and Nutrition Board
        Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline.
        National Academies Press, Washington, DC1998
        • US Departmentt of Agriculture, Agricultural Research Service
        Nutrient intakes from food: Mean amounts consumed per individual, by gender and age.
        • Cole S.R.
        • Hernan M.A.
        Constructing inverse probability weights for marginal structural models.
        Am J Epidemiol. 2008; 168: 656-664
      2. SAS [computer program]. Version 9.4. SAS Institute Inc, Cary, NC2013
        • Miller W.L.
        Minireview: Regulation of steroidogenesis by electron transfer.
        Endocrinology. 2005; 146: 2544-2550
        • Pinto J.T.
        • Cooper A.J.
        From cholesterogenesis to steroidogenesis: Role of riboflavin and flavoenzymes in the biosynthesis of vitamin D.
        Adv Nutr. 2014; 5: 144-163
        • Zondek B.
        • Brzezinski A.
        Inactivation of oestrogenic hormone by women with vitamin B deficiency.
        J Obstet Gynaecol Br Emp. 1948; 55: 273-280
        • Kaya C.
        • Cengiz S.D.
        • Satiroglu H.
        Obesity and insulin resistance associated with lower plasma vitamin B12 in PCOS.
        Reprod Biomed Online. 2009; 19: 721-726
        • Agacayak E.
        • Tunc S.Y.
        • Sak S.
        • et al.
        Levels of neopterin and other inflammatory markers in obese and non-obese patients with polycystic ovary syndrome.
        Med Sci Monit. 2015; 2: 2446-2455
        • Jacques P.F.
        • Bostom A.G.
        • Wilson P.W.
        • Rich S.
        • Rosenberg I.H.
        • Selhub J.
        Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort.
        Am J Clin Nutr. 2001; 73: 613-621
        • Jacques P.F.
        • Kalmbach R.
        • Bagley P.J.
        • et al.
        The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene.
        J Nutr. 2002; 132: 283-288
        • Hoey L.
        • McNulty H.
        • Askin N.
        • et al.
        Effect of a voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults.
        Am J Clin Nutr. 2007; 86: 1405-1413
        • Schatzkin A.
        • Kipnis V.
        • Carroll R.J.
        • et al.
        A comparison of a food frequency questionnaire with a 24-hour recall for use in an epidemiological cohort study: Results from the biomarker-based Observing Protein and Energy Nutrition (OPEN) study.
        Int J Epidemiol. 2003; 32: 1054-1062
        • Subar A.F.
        • Kipnis V.
        • Troiano R.P.
        • et al.
        Using intake biomarkers to evaluate the extent of dietary misreporting in a large sample of adults: The OPEN study.
        Am J Epidemiol. 2003; 158: 1-13
        • Behre H.M.
        • Kuhlage J.
        • Gassner C.
        • et al.
        Prediction of ovulation by urinary hormone measurements with the home use ClearPlan Fertility Monitor: Comparison with transvaginal ultrasound scans and serum hormone measurements.
        Hum Reprod. 2000; 15: 2478-2482

      Biography

      K. Kim is a research fellow, Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.

      Biography

      J. L. Mills is a senior investigator, Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.

      Biography

      K. A. Michels is a postdoctoral fellow, Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.

      Biography

      E. N. Chaljub is a postbaccalaureate fellow, Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.

      Biography

      S. L. Mumford is an investigator, Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.

      Biography

      T. C. Plowden is a clinical research fellow, Epidemiology Branch, Division of Intramural Population Health Research and Program of Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.

      Biography

      J. Wactawski-Wende is a professor and dean of the School of Public Health and Health Professions, University at Buffalo, State University of New York, Buffalo, NY.