Main Article Content
Oral contraceptives (OCs) are widely used by a significant number of women, often commencing at early adolescence. Whilst most research has investigated the physiological effects of OCs, some studies have identified impacts upon nutritional status of certain vitamins and minerals. In this context, a report published by the World Health Organization (WHO) is relevant, since women who take OCs-especially in less well-developed countries might not always have adequate diet. Furthermore, women whose life style is unhealthy, those with malabsorption pathologies, or have genetic polymorphisms that affect vitamin metabolism might also be at risk of the negative impacts on an individual’s nutrient status. This literature review investigates the effects that oral contraceptives might have upon nutrient status. It identifies potential interactions with Vitamins A, B1, B2, B6, B12, C, and E and folic acid as well as magnesium, zinc, selenium, copper, co-enzyme Q10, and beta-carotene status. It then examines the possible consequences that induced depletion of folic acid might cause with especial focus on neural tubes defects in UK, where food supplementation with this vitamin is not yet mandatory. It suggests that in those using this form of contraception or hormone replacement therapy, it is valid to consider appropriate nutritional supplements as a complementary first line strategy in order to prevent possible vitamin and mineral deficiencies.
Lobo R, Stanczyk F. New knowledge in the physiology of hormonal contraceptives. Am J Obstet Gynecol. 1994;170:1499-1507.
Shulman LP. The state of hormonal contraception today: Benefits and risks of hormonal contraceptives: Combined estrogen and progestin contraceptives. Am J Obstet Gynecol. 2011;205:S9-13.
Mansour D, Inki P, Gemzell-Danielsson K. Efficacy of contraceptive methods: A review of the literature. Eur J Contracept Reprod Health Care. 2010;15(Suppl 2): S19-31.
Bitzer J, Simon J. Current issues and available options in combined hormonal contraception. Contraception. 2011;84: 342-356.
Gallo M, Nanda K, Grimes D, Lopez L, Schulz K. 20 microg versus >20 microgestrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev. 2011;1:CD003989.
Theuer RC. Effect of oral contraceptive agents on vitamin and mineral needs: A review. J Reprod Med. 1972;8:13-19.
Berg G, Kohlmeier L, Brenner H. Effect of oral contraceptive progestins on serum copper concentration. Eur J Clin Nutr. 1998;52:711-715.
Ghayour-Mobarhan M, Taylor A, New SA, Lamb DJ, Ferns GA. Determinants of serum copper, zinc and selenium in healthy subjects. Ann Clin Biochem. 2005; 42:364-375.
Tamura T, Picciano MF. Folate and human reproduction. Am J Clin Nutr. 2006;83: 993-1016.
Prevention of neural tube defects: Results of the medical research council vitamin study. Mrc Vitamin Study Research Group. Lancet. 1991;338:131-137.
Prasad AS, Oberleas D, Moghissi KS, Stryker JC, Lei KY. Effect of oral contraceptive agents on nutrients: Ii. Vitamins. Am J Clin Nutr. 1975;28:385-391.
Wilson SM, Bivins BN, Russell KA, Bailey LB. Oral contraceptive use: Impact on Folate, Vitamin B(6), and Vitamin B(1)(2) Status. Nutr Rev. 2011;69:572-583.
Mooij PN, Thomas CM, Doesburg WH, Eskes TK. Multivitamin supplementation in oral contraceptive users. Contraception. 1991;44:277-288.
Tyrer LB. Nutrition and the pill. J Reprod Med. 1984;29:547-550.
Ahmed F, Bamji MS, Iyengar L. Effect of oral contraceptive agents on vitamin nutrition status. Am J Clin Nutr. 1975;28: 606-615
Thorp VJ. Effect of oral contraceptive agents on vitamin and mineral requirements. J Am Diet Assoc. 1980;76: 581-584.
Briggs MH, Briggs M. Thiamine status and oral contraceptives. Contraception. 1975; 11(2):151-154.
Vir SC, Love AH. Effect of oral contraceptive agents on thiamin status. International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin-und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition. 1979;49(3):291-295.
Lewis CM, King JC. Effect of oral contraceptives agents on thiamin, riboflavin, and pantothenic acid status in young women. The American Journal of Clinical Nutrition. 1980;33(4):832-838.
Ahmed F, Bamji MS. Vitamin supplements to women using oral contraceptives (studies of vitamins B1, B2, B6 and A). Contraception. 1976;14(3):309-318.
Newman LJ, Lopez R, Cole HS, Boria MC, Cooperman JM. Riboflavin deficiency in women taking oral contraceptive agents. The American Journal of Clinical Nutrition. 1978;31(2):247-249.
Sanpitak N, Chayutimonkul L. Oral contraceptives and riboflavine nutrition. Lancet. 1974;1:836-837.
Bamji M, Prema K, Jacob C, Rani M, Samyukta D. Vitamin supplements to Indian women using low dosage oral contraceptives. Contraception. 1985;32: 405-416.
Roe DA, Bogusz S, Sheu J, McCormick DB. Factors affecting riboflavin requirements of oral contraceptive users and nonusers. The American Journal of Clinical Nutrition. 1982;35(3):495-501.
Zencirci B. Comparison of the effects of dietary factors in the management and prophylaxis of migraine. J Pain Res. 2010; 3:125-130.
Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther. 1982;4:423-440.
Prasad AS, Lei KY, Moghissi KS, et al. Effect of oral contraceptives on nutrients. III. Vitamins B6, B12 and folic acid. Am J Obstet Gynecol. 1976;125:1063-1069.
Butterworth CE. Interactions of nutrients with oral contraceptives and other drugs. J Am Diet Assoc. 1973;62:510-4.
Haspels AA, Bennink HJ, Schreurs WH. Disturbance of tryptophan metabolism and its correction during oestrogen treatment in postmenopausal women. Maturitas. 1978; 1:15-20.
Rose DP. The influence of oestrogens on tryptophan metabolism in man. Clin Sci. 1966;31:265-272.
Lussana F, Zighetti Ml, Bucciarelli P, Cugno M, Cattane M. Blood levels of homocysteine, folate, vitamin B6 and B12 in women using oral contraceptives compared to non-users. Thromb Res. 2003;112:37-41.
Lumeng L, Cleary Re, Li Tk. Effect of oral contraceptives on the plasma concentration of pyridoxal phosphate. Am J Clin Nutr. 1974;27:326-333.
Morris Ms, Picciano Mf, Jacques Pf, Selhub J. Plasma pyridoxal 5'-phosphate in the US population: The National Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr. 2008;87:1446-1454.
Leklem Je, Brown Rr, Rose Dp, Linkswiler Hm. Vitamin B6 requirements of women using oral contraceptives. Am J Clin Nutr. 1975;28:535-541.
Leklem Je. Vitamin B-6 requirement and oral contraceptive use--a concern? J Nutr. 1986;116:475- 477.
Van der Vange N, van der Berg H, Kloosterboer HJ, Haspels AA. Effects of seven low-dose combined contraceptives on vitamin B6 status. Contraception. 1989; 40:377-84.
Miller LT. Do oral contraceptive agents affect nutrient requirements--vitamin B-6? The Journal of Nutrition. 1986;116(7): 1344-1345.
Trowbridge M Jr., Wadsworth R, Moffitt E. Malabsorption associated with gluten enteropathy, do oral contraceptives interfere with folate metabolism? J Maine Med Assoc. 1968;59:240-242.
Paton A. Oral contraceptives and folate deficiency. Lancet. 1969;1:418.
Ryser J, Farquet J, Petite J. Megaloblasticanemia due to folic acid deficiency in a young woman on oral contraceptives. Acta Haematol. 1971;45: 319-324.
Whitehead N, Reyner F, Lindenbaum J. Megaloblastic changes in the cervical epithelium. Association with oral contraceptive therapy and reversal with folic acid. JAMA. 1973;226:1421-1424.
Shojania AM. Oral contraceptives: Effect of folate and vitamin B12 metabolism. Can Med Assoc J. 1982;126:244-247.
Shojania A M, Hornady G, Barnes P. Oral contraceptives and serum-folate level. Lancet. 1968;1:1376-1377.
Pritchard J, Scott D, Whalley P. Maternal folate deficiency and pregnancy wastage. IV. Effects of folic acid supplements, anticonvulsants, and oral contraceptives. Am J Obstet Gynecol. 1971;109:341-346.
Castren OM, Rossi RR. Effect of oral contraceptives on serum folic acid content. J Obstet Gynaecol Br Commonw. 1970; 77:548-550.
Green T, Houghton L, Donovan U, Gibson R, O’connor D. Oral contraceptives did not affect biochemical folate indexes and homocysteine concentrations in adolescent females. J Am Diet Assoc. 1998;98:49-55.
Shere M, Bapat P, Nickel C, Kapur B, Koren G. Association between use of oral contraceptives and folate status: A systematic review and meta-analysis. Journal of Obstetrics and Gynaecology Canada. 2015;37(5):430-8.
Castano PM, Aydemir A, Sampson-Landers C, Lynen R. The folate status of reproductive-aged women in a randomised trial of a folate-fortified oral contraceptive: Dietary and blood assessments. Public health nutrition. 2014;17(6):1375-1383.
Fruzzetti F. Beyaz®: An oral contraceptive fortified with folate. Women's Health. 2012; 8(1):13-9.
Butterworth CE, Hatch KD, Gore H, et al. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr. 1982;35:73-82.
Check WA. Folate for oral contraceptive users may reduce cervical cancer risk. J Am Med Assoc. 1980;244:633-4.
Wertalik L, Metz E, Lobuglio A, Balcerzak S. Decreased serum B 12 levels with oral contraceptive use. JAMA. 1972;221:1371-1374.
Sutterlin M, Bussen S, Rieger L, Dietl J, Steck T. Serum folate and vitamin b12 levels in women using modern oral contraceptives (Oc) Containing20 Microg Ethinyl Estradiol. Eur J Obstet Gynecol Reprod Biol. 2003;107:57-61.
Riedel B, BjorkeMonsen A, Ueland P, Schneede J. Effects Of Oral Contraceptives And Hormone Replacement Therapy On Markers Of Cobalamin Status. Clin Chem. 2005;51: 778-781.
Shojania Am, Wylie B. The effect of oral contraceptives on vitamin B12 metabolism. Am J Obstet Gynecol. 1979;135:129- 134.
Veninga KS. Effects of oral contraceptives on vitamins B6, B12, C, and folacin. J Nurse Midwifery. 1984;29:386-390.
Hielt K, Brynskov J, Hippe E, et al. Oral contraceptives and the cobalamin (vitamin B12) metabolism. Acta Obstet Gynecol Scand. 1985;64:59-63.
Grace E, Emans SJ, Drum DE. Hematologic abnormalities in adolescents who take oral contraceptive pills. J Pediatrics. 1982;101:771-774.
Barone C, Bartoloni C, Ghirlanda G, Gentiloni N. Megaloblasticanemia due to folic acid deficiency after oral contraceptives. Haematologica. 1979;64: 190-195.
McArthur JO. Biological variability and impact of oral contraceptives on vitamins B6, B12 and folate status in women of reproductive age. Nutrients. 2013;5:3634-3645.
Adams MJ Jr., Khoury MJ, Scanlon KS, Stevenson RE, Knight GJ, Haddow JE, et al. Elevated midtrimester serum methylmalonic acid levels as a risk factor for neural tube defects. Teratology. 1995; 51:311-317.
Gardyn J, Mittelman M, Zlotnik J, Sela BA, Cohen AM. Oral contraceptives can cause falsely low vitamin B(12) levels. Acta Haematol. 2000;104:22-24.
Bush AI. The metallobiology of Alzheimer's disease. Trends Neurosci. 2003;26:207-214.
Dante G, et al. Vitamin and mineral needs during the oral contraceptive therapy: A systematic review. Int J Reprod Contracept Obstet Gynecol. 2014;3(1):1-10.
Basnayake S, de Silva SV, Miller PC, Rogers S. A trial of daily vitamin supplementation as a means of reducing oral contraceptive side effects and discontinuation in Sri Lanka. Contraception. 1983;27:465-472.
Palmery A, Saraceno A, Vaiarelli G. Carlomagno oral contraceptives and changes in nutritional requirements. European Review for Medical and Pharmacological Sciences. 2013;1804-1812.
Webb JL. Nutritional effects of oral contraceptive use: A review. J Reprod Med. 1980;25:150-156.
WHO. Advances in methods on fertility regulation. World Health Organization; 1975.
Hudiburgh N, Milner A. Influence of oral contraceptives on ascorbic acid and triglyceride status. J Am Diet Assoc. 1979; 75:19-22.
Zal F, Mostafavi-Pour Z, Amini F, Heidari A. Effect of vitamin E and C supplements on lipid peroxidation and GSH-dependent antioxidant enzyme status in the blood of women consuming oral contraceptives. Contraception. 2012;86:62-66.
Weininger J, King JC. Effect of oral contraceptives on ascorbic acid status of young women consuming a constant diet. Nutr Rep Int. 1977;15:255-264.
Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas. 2002;42:129-135.
Aftergood L, Alfin-Slater RB. Oral contraceptive alpha- tocopherol interrelationships. Lipids. 1974;9:91-96.
Akinsanya M, Adeniyi T, Ajayi G, Oyedele M. Effects of vitamin E and folic acid on some antioxidant enzymes activities of female Wistar rats administered combined oral contraceptives. African J Biochem Res. 2010;4:238-242.
Brigg M. Letter: Vitamin E status and oral contraceptives. Am J Clin Nutr. 1975;28: 436.
Renaud S, Ciavatti M, Perrot L, Berthezene F, Dargent D, Condamin P. Influence of vitamin E administration on platelet functions in hormonal contraceptive users. Contraception. 1987; 36:347-358.
Seelig MS. Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment. Magnes Res. 1990;3:197-215.
Seelig MS. Interrelationship of magnesium and estrogen in cardiovascular and bone disorders, eclampsia, migraine, and premenstrual syndrome. J Am Coll Nutr. 1993;12:442-458.
Muneyyirci-Delale O, Nacharaju VL, Dalloul M, et al. Serum ionized magnesium and calcium in women after menopause: Inverse relation of estrogen with ionized magnesium. Fertil Steril. 1999;71:869-872.
Stanton MF, Lowenstein FW. Serum magnesium in women during pregnancy, while taking contraceptives, and after menopause. J Am Coll Nutr. 1987;6:313-319.
Akinloye O, Adebayo T, Oguntibeju O, Oparinde D, Ogunyemi E. Effects of contraceptives on serum trace elements, calcium and phosphorus levels. West Indian Med J. 2011;60:308-315.
Hameed A, Majeed T, Rauf S, Ashraf M, Jalil M, Nasrullah M, Hussan A, Noreen R. Effect of oraland injectable contraceptives on serum calcium, magnesium and phosphorus in women. J Ayub Med Coll Abbottabad. 2001;13:24-25.
Olatunbosun D, Adeniyi F, Adadevoh BK. Effect of oral contraceptives on Serum magnesium levels. Int J Fertil. 1974;19: 224-226.
Blum M, Kitai E, Ariel Y, Schnierer M, Bograd H. Oral contraceptive lowers serum magnesium. Harefuah. 1991;121:363-364.
Cowan JA. Introduction to the biological chemistry of magnesium. ed. J.A. Cowan. New York. VCH; 1995.
Halsted JA, Hackley BM, Smith JC Jr. Plasma-zinc and copper in pregnancy and after oral contraceptives. Lancet. 1968;2: 278-279.
King JC. Do women using oral contraceptive agents require extra zinc? J Nutr. 1987;117:217-219.
Briggs MH, Briggs M, Austin J. Effects of steroid pharmaceuticals on plasma zinc. Nature. 1971;232:480-481.
Prema K, Ramalakshmi Ba, Babu S. Serum copper and zinc in hormonal contraceptive users. Fertil Steril. 1980;33: 267-271.
Fallah S, Sani FV, Firoozrai M. Effect of contraceptive pill on the selenium and zinc status of healthy subjects. Contraception. 2009;80:40-43.
Chilvers DC, Jones MM, Selby PL, et al. Effects of oral ethinyloestradiol and norethisterone on plasma copper and zinc complexes in post-menopausal women. Hormone Metab Res. 1985;17:532-535.
Smith JC, Brown ED. Effects of oral contraceptive agents on trace element metabolism - a review. In: Prasad AS (ed). Trace Elements in Human Health and Disease. Essential and Toxic Elements. New York: Academic Press. 1976;2:315-345.
Vir SC, Love AH. Zinc and copper nutriture of women taking oral contraceptive agents. Am J Clin Nutr. 1981;34:1479-1483.
Hinks LJ, Clayton BE, Lloyd RS. Zinc and copper concentrations in leukocytes and erythrocytes in healthy adults and the effect of oral contraceptives. J Clin Pathol. 1983;36:1016-1021.
Powell-Beard L, Lei KY, Shenker L. Effect of long-term oral contraceptive therapy before pregnancy on maternal and fetal zinc and copper status. Obstet Gynecol. 1987;69:26-32.
Liukko P, Erkkola R, Pakarinen P, et al. Trace elements during 2 years' oral contraception with low-estrogen preparations. Gynecol Obstet Invest. 1988; 25:113-117.
Thane CW, et al. Oral contraceptives and nutritional status in adolescent British girls. Nutrition Research. 2002;22:449-462.
Gambacciani M, Cappagli B, Lazzarini V, Ciaponi M, Fruzzetti F, Genazzani AR. Longitudinal evaluation of perimenopausal bone loss: Effects of different low dose oral contraceptive preparations on bone mineral density. Maturitas. 2006;54:176–180.
Kleerekoper M, Brienza RS, Schultz LR, Johnson CC. Oral contraceptive use may protect against low bone mass. Henry Ford Hospital Osteoporosis Cooperative Research Group. Arch. Intern. Med. 1991; 151:1971–1976.
Kuohung W, Borgatta L, Stubblefield P. Low-dose oral contraceptives and bone mineral density: An evidence-based analysis. Contraception. 2000;61:77–82.
Liu SL, Lebrun CM. Effect of oral contraceptives and hormone replacement therapy on bone mineral density in premenopausal and perimenopausal women: A systematic review. Br. J. Sports Med. 2006;40:11–24.
Garnero P, Sornay-Rendu E, Delmas PD. Decreased bone turnover in oral contraceptive users. Bone. 1995;16:499–503.
Zittermann A. Decreased urinary calcium loss and lower bone turnover in young oral contraceptive users. Metabolism. 2000;49: 1078–1082.
Goulding A, McChesney R. Oestrogen-progestogen oral contraceptives and urinary calcium excretion. Clin. Endocrinol. 1977;6:449–454.
Hartard M, Kleinmond C, Kirchbichler A, Jeschke D, Wiseman M, Weissenbacher ER, Felsenberg D, Erben RG. Age at first oral contraceptive use as a major determinant of vertebral bone mass in female endurance athletes. Bone. 2004; 35:836–841.
Cobb KL, Kelsey JL, Sidney S, Ettinger B, Lewis CE. Oral contraceptives and bone mineral density in white and black women in CARDIA. Coronary Risk Development in Young Adults. Osteoporos. Int. 2002;13: 893–900.
Hartard M, Bottermann P, Bartenstein P, Jeschke D, Schwaiger M. Effects on bone mineral density of low-dosed oral contraceptives compared to and combined with physical activity. Contraception. 1997; 55:87–90.
Burr DB, Yoshikawa T, Teegarden D, Lyle R, McCabe G, McCabe LD, Weaver CM. Exercise and oral contraceptive use suppress the normal age-related increase in bone mass and strength of the femoral neck in women 18-31 years of age. Bone. 2000;27:855–863.
Weaver CM, Teegarden D, Lyle RM, McCabe GP, McCabe LD, Proulx W, Kern M, Sedlock D, Anderson DD, Hillberry BM, et al. Impact of exercise on bone health and contraindication of oral contraceptive use in young women. Med. Sci. Sports Exerc. 2001;33:873–880.
Teegarden D, Legowski P, Gunther CW, McCabe GP, Peacock M, Lyle RM. Dietary calcium intake protects women consuming oral contraceptives from spine and hip bone loss. J. Clin. Endocrinol. Metab. 2005;90:5127–5133.
Babić Z, Tariba B, Kovačić J, Pizent A, Varnai V, Macan J. Relevance of serum copper elevation induced by oral contraceptives: A meta-analysis Contraception. 2013;87:790–800.
Prabhudas R. Palan, Felix Strube, Juraj Letko, Azra Sadikovic, Magdy S. Mikhail. Effects of oral, vaginal, and transdermal hormonal contraception on serum levels of coenzyme Q10, vitamin E, and total antioxidant activity. Obstetrics and Gynecology International; 2010. Article ID 925635, 4 pages.
Palan PR, Connell K, Ramirez E, et al. Effects of menopause and hormone replacement therapy on serum levels of coenzyme Q10 and other lipid-soluble antioxidants. Biofactors. 2005;25(1-4): 61-6.
Knopp RH, Zhu X, Bonet B. Effects of estrogens on lipoprotein metabolism and cardiovascular disease in women. Atherosclerosis. 1994;110:S83-91.
Palan PR, Romney SL, Vermund SH, Mikhail MG, Basu J. Effects of smoking and oral contraception on plasma β-carotene levels in healthy women. American Journal of Obstetrics & Gynecology. 1989;161(4):881-885.
United Nations Department of Economic & Social Affairs, Population Division. World Contraceptive Use; 2012.
World Health Organization Department of Reproductive Health and Research (WHO/RHR), Johns Hopkins Bloomberg School of Public Health Center for Communication Programs (CCP), Knowledge for health project. Family planning: A global handbook for providers (2011 Update). Baltimore and Geneva: CCP and WHO. 2011;388.
Office for National Statistics. Opinions Survey Report No. 41. Contraception and Sexual Health; 2008-09.
Rashed A. Trends and patterns of hormonal contraceptive prescribing for adolescents in primary care in the UK. King’s College London; 2013.
Singh S, Sedgh G, Hussain R. Unintended pregnancy: Worldwide levels, trends, and outcomes. Stud Fam Plann. 2010;41(4): 241–250.
Khosravi A, Najafi F, Rahbar MR, et al. Health indicators in I.R. Iran. Tehran: Ministry of Health and Medical Education; 2009. Available:http://behdasht.gov.ir/uploads/291_1041_simayeisalamat.Pdf
Moosazadeh M, Nekoei-Moghadam M, Emrani Z, Amiresmaili M. Prevalence of unwanted pregnancy in Iran: A systematic review and meta-analysis. Int J Health Plann Manage. 2014;29(3):277–290.
Ali MM, Cleland JG, Shah IH. Causes and consequences of contraceptive discontinuation: Evidence from 60 demographic and health surveys. Cairo: WHO; 2012.
Ponce de Leon R, Juarez-Perez MA, Grubb GS. Effect of vitamin B6 on the side effects of a low-dose combined oral contraceptive. Contraception. 1997;55(4): 245–248.
Mohammad-Alizadeh-Charandabi S, Mirghafourvand M, Froghy L, Javadzadeh Y, Razmaraii N. The effect of multivitamin supplements on continuation rate and side effects of combined oralcontraceptives: A randomised controlled trial. The European Journal of Contraception and Reproductive Health Care. 2015;20:361–371.
Zolfaghari SS. The relationship between folic acid, vitamin B12, and vitamin B6 intakes and depression in women who Use hormonal oral contraceptives thesis presented to the Department of Family and Consumer Sciences California State University, Long Beach B.S., 2005, University of California, Irvine December 2015 ProQuest Number: 1604887.
Westhoff CL, Heartwell S, Edwards S, Zieman M, Stuart G, Cwiak C, et al. Oral contraceptive discontinuation: Do side effects matter? American Journal of Obstetrics and Gynecology. 2007;196(4) 412:e1- e7.
Oakley D, Sereika S, Bogue EL. Oral contraceptive pill use after an initial visit to a family planning clinic. Family Planning Perspectives. 1991;150–154.
Rosenberg MJ, Waugh MS, Meehan TE. Use and misuse of oral contraceptives: Risk indicators for poor pill taking and discontinuation. Contraception. 1995; 51(5):283–288.
Rosenberg MJ, Waugh MS. Oral contraceptive discontinuation: A prospective evaluation of frequency and reasons. American Journal of Obstetrics and Gynecology. 1998;179(3):577–82. PMID: 9757954.
Berenson AB, Rahman M. Changes in weight, total fat, percent body fat, and central-to-peripheral fat ratio associated with injectable and oral contraceptive use. American Journal of Obstetrics and Gynecology. 2009;200(3):329.e1-8.
De Melo N, Aldrighi J, Faggion D, Reyes V, Souza J, Fernandes C, et al. A prospective open-label study to evaluate the effects of the oral contraceptive Harmonet1 (gestodene75/EE20) on body fat. Contraception. 2004;70(1):65–71.
Gallo M, Lopez L, Grimes D, Schulz K, Helmerhorst F. Combination contraceptives: Effects on weight (Review). Cochrane Database of Systematic Reviews. 2014;1:78.
Picardo CM, Nichols M, Edelman A, Jensen JT. Women's knowledge and sources of information on the risks and benefits of oral contraception. Journal of the American Medical Women's Association (1972). 2002;58(2):112–116.
García OP, Long KZ, Rosado JL. Impact of micronutrient deficiencies on obesity. Nutrition Reviews. 2009;67(10):559–572.
Aasheim ET, Hofsø D, Hjelmesæth J, Birkeland KI, Bøhmer T. Vitamin status in morbidly obese patients: A cross-sectional study. The American Journal of Clinical Nutrition. 2008;87(2):362–9.
Kimmons JE, Blanck HM, Tohill BC, Zhang J, Khan LK. Associations between body mass index and the prevalence of low micronutrient levels among US adults. Medscape General Medicine. 2006; 8(4):59.
Park B, Kim J. Oral contraceptive use, micronutrient deficiency, and obesity among premenopausal females in Korea: The necessity of dietary supplements and food intake improvement. PloS One. 2016; 11(6):e0158177.
Kowalska K, Milnerowicz H. Pro/antioxidant status in young healthy women using oral contraceptives Environmental Toxicology and Pharmacology. 2016;43:1–6.
Kamp F, Soares T, Rodrigues L, Donangelo C. Effect of oral contraceptive use and zinc supplementation on zinc, iron and copper biochemical indices in young women e-SPEN. The European e-Journal of Clinical Nutrition and Metabolism. 2011;6:253-258.
Bernstein P, Pohost G. Progesterone, progestins, and the heart. Rev Cardiovasc Med. 2010;11:228-236.
Kiriwat O, Petyim S. The effects of transdermal contraception on lipid profiles, carbohydrate metabolism and coagulogram in Thai women. Gynecol Endocrinol. 2010;26:361-365.
Grigoryan OR, Grodnitskaya EE, Andreeva EN, Shestakova MV, Melnichenko GA, Dedov II. Contraception in perimenopausal women with diabetes mellitus. Gynecol Endocrinol. 2006;22:198-206.
Minozzi M, Costantino D, Guaraldi C, Unfer V. The effect of a combination therapy with myo-inositol and a combined oral contra¬ceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome. Gynecol Endocrinol. 2011;27:920-924.
Plu-Bureau G, Hugon-Rodin J, Maitrot-Mantelet L, Canonico M. Hormonal contraceptives and arterial disease: An epidemiologi¬cal update. Best Pract Res Clin Endocrinol Metab. 2013;27:35-45.
Dilbaz B, Ozdegirmenci O, Caliskan E, Dilbaz S, Haberal A. Effect of etonogestrel implant on serum lipids, liver function tests and hemoglobin levels. Contraception. 2010;81:510-514.
Scharnagl H, Petersen G, Nauck M, Teichmann AT, Wieland H, Marz W. Double-blind, randomized study comparing the effects of two monophasic oral contraceptives containing ethinylestra-diol (20 microg or 30 microg) and levonorgestrel (100 microg or 150 microg) on lipoprotein metabolism. Contraception. 2004;69:105-113.
Skouby SO, Endrikat J, Dusterberg B, Schmidt W, Gerlinger C, Wessel J, et al. A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microgethinylestradiol combined with 100 mi¬croglevonorgestrel. Contraception. 2005;71:111-117.
Torkzahrani S, Heidari A, Mostafavi-pour Z, Ahmadi M, Zal F. Amelioration of lipid abnormalities by vitamin therapy in women using oral contraceptives. Clinical and Experimental Reproductive Medicine. 2014;41(1):15-20.
NDNS. Results from Years 7-8 (combined) of the Rolling Programme (2014/2015 – 2015/16): UK Public Health England.
Morris JK, Rankin J, Draper ES, Kurinczuk JJ, Springett A, Tucker D, Wellesley D, Wreyford B, Wald NJ. Prevention of neural tube defects in the UK: A missed opportunity. Archives of Disease in Childhood. 2016;101(7):604-607.
Lim U, Wang SS, Hartge P, Cozen W, Kelemen LE, Chanock S, Davis S, Blair A, Schenk M, Rothman N, Lan Q. Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER case-control study. Blood. 2007; 109(7):3050-3059.
Ogino S, Wilson RB. Genotype and haplotype distributions of MTHFR 677C> T and 1298A> C single nucleotide polymorphisms: A meta-analysis. Journal of Human Genetics. 2003;48(1):1.
Malinow MR, Nieto FJ, Kruger WD, Duell PB, Hess DL, Gluckman RA, Block PC, Holzgang CR, Anderson PH, Seltzer D, Upson B. The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes. Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17(6):1157-1162.
Yang QH, Botto LD, Gallagher M, Friedman JM, Sanders CL, Koontz D, Nikolova S, Erickson JD, Steinberg K. Prevalence and effects of gene-gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the United States: findings from the third National Health and Nutrition Examination Survey DNA Bank–. The American Journal of Clinical Nutrition. 2008;88(1):232-246.
Yadav U, Kumar P, Yadav SK, Mishra OP, Rai V. Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: An updated meta-analysis. Metab Brain Dis. 2015;30:7–24.
To QG, Chen TT, Magnussen CG, To KG. Workplace physical activity interventions: A systematic review. American Journal of Health Promotion. 2013;27(6):113-123.
Pfeiffer CM, Caudill SP, Gunter EW, Osterloh J, Sampson EJ. Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999–2000. The American Journal of Clinical Nutrition. 2005;82(2):442-450.
Hickling S, Hung J, Knuiman M, Jamrozik K, McQuillan B, Beilby J, Thompson P. Impact of voluntary folate fortification on plasma homocysteine and serum folate in Australia from 1995 to 2001: A population based cohort study. Journal of Epidemiology & Community Health. 2005; 59(5):371-376.
Williams LJ, Mai CT, Edmonds LD, Shaw GM, Kirby RS, Hobbs CA, Sever LE, Miller LA, Meaney FJ, Levitt M. Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United States. Teratology. 2002 Jul;66(1):33-39.
De Wals P, Tairou F, Van Allen MI, Uh SH, Lowry RB, Sibbald B, Evans JA, Van den Hof MC, Zimmer P, Crowley M, Fernandez B. Reduction in neural-tube defects after folic acid fortification in Canada. New England Journal of Medicine. 2007; 357(2):135-142.
Mallard SR, Gray AR, Houghton LA. Periconceptional bread intakes indicate New Zealand's proposed mandatory folic acid fortification program may be outdated: Results from a postpartum survey. BMC Pregnancy and Childbirth. 2012;12(1):8.
Yang QH, Carter HK, Mulinare J, Berry RJ, Friedman JM, Erickson JD. Race-ethnicity differences in folic acid intake in women of childbearing age in the United States after folic acid fortification: Findings from the National Health and Nutrition Examination Survey, 2001–2002. The American Journal of Clinical Nutrition. 2007;85(5):1409-1416.
Nagele P, Meissner K, Francis A, Födinger M, Saccone NL. Genetic and environmental determinants of plasma total homocysteine levels: Impact of population-wide folate fortification. Pharmacogenetics and Genomics. 2011;21(7):426.
Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. The National Academies Press, Washington DC; 1998.
Solis C, Veenema K, Ivanov AA, Tran S, Li R, Wang W, Moriarty DJ, Maletz CV, Caudill MA. Folate intake at RDA levels is inadequate for Mexican American men with the methylenetetrahydrofolate reductase 677TT genotype. The Journal of Nutrition. 2008;138(1):67-72.
Stamm RA, Houghton LA. Nutrient intake values for folate during pregnancy and lactation vary widely around the world. Nutrients. 2013;5(10):3920-3947.
Australian Government Department of Health Nutrient Reference Values; 2006. Available:http://www.nrv.gov.au/home
Clinical Guideline. Vitamin and mineral supplementation in pregnancy. Policy developed by: SA Maternal and Neonatal Clinical Network. Govt of South Australia; 2014.
(Approved 19 Dec 2014)
wps/wcm/connect/f53d44004eee83bc8104a36a7ac0d6e4/ Vitamin+mineral+supplementation_Clinical+Guideline_final_Dec14.pdf?MOD=AJPERES&CACHEID=f53d44004eee83bc8 104a36a7ac0d6e4
Colson NJ, Naug HL, Nikbakht E, Zhang P, McCormack J. The impact of MTHFR 677 C/T genotypes on folate status markers: A meta‑analysis of folic acid intervention studies. J Eur J Nutr. 2017;56:247–260.
MRC Vitamin study research group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991;338:131–137.
Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. New England Journal of Medicine. 1992; 327(26):1832-1835.
Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, Mulinare J, Zhao P, Wong LY, Gindler J, Hong SX. Prevention of neural-tube defects with folic acid in China. New England Journal of Medicine. 1999; 341(20):1485-90.
Moore KL, Persaud T. Before We Are Born: Essentials of Embryology and Birth Defects. Philadelphia: WB Saunders Company; 1998.
Department of Health. Folic acid and the prevention of neural tube defects. Report from an Expert Advisory Panel. London: HMSO; 1992.
Brough L, Rees GA, Crawford MA, Dorman EK. Social and ethnic differences in folic acid use during preconception and early pregnancy in the UK: Effect on maternal folate status. The British Dietetic Association Ltd. J Hum Nutr Diet. 2009;22: 100–107.
Bestwick JP, Huttly WJ, Morris JK, Wald NJ. Prevention of neural tube defects: A cross-sectional study of the uptake of folic acid supplementation in nearly half a million women. PLOS ONE. 2014;9(2): e89354.
Hodgetts VA, Morris RK, Francis A, Gardosi J, Ismail KM. Effectiveness of folic acid supplementation in pregnancy on reducing the risk of small‐for‐gestational age neonates: A population study, systematic review and meta‐analysis. BJOG: An International Journal of Obstetrics & Gynaecology. 2015;122(4): 478-90.
National Diet and Nutrition Survey: Years 1 to 9 of the Rolling Programme (2008/2009 – 2016/2017): Time trend and income analyses. Public Health England. Published January 2019 PHE Publications Gateway Number: 2018756.
Wald NJ, Morris JK, Blakemore C. Public health failure in the prevention of neural tube defects: Time to abandon the tolerable upper intake level of folate. Public Health Rev. 2018;39:2.
(Published 2018 Jan 31)
Ericson A, Kallen B, Lofkist E. Environmental factors in the etiology of neural tube defects: A negative study. Environmental Research. 1988;45: 38-47.
Yin Z, Xu W, Xu C, Zhang S, Zheng Y, Wang W, Zhou B. A population-based case-control study of risk factors for neural tube defects in Shenyang, China. Childs Nerv Syst. 2011;27:149–154.
Taylor TN, Farkouh RA, Graham JB, et al. Potential reduction in neural tube defects associated with use of Metafolin-fortified oral contraceptives in the United States. Am J Obstet Gynecol. 2011;205: 460.e1-8.
Czeizel A, Dudás I, Paput L, Bánhidy F Prevention of neural-tube defects with periconceptional folic acid, methylfolate, or multivitamins? Ann Nutr Metab. 2011;58: 263–271.