Health claims & Studies

Fertility

Hou E, Zhao Y, Hang J, Qiao J. Metabolomics and correlation network analysis of follicular fluid reveals associations between l-tryptophan, l-tyrosine and polycystic ovary syndrome. Biomed Chromatogr. 2021 Mar;35(3):e4993. doi: 10.1002/bmc.4993. Epub 2020 Nov 5. PMID: 32986877

Polycystic ovary syndrome (PCOS) is a disorder that affects women of reproductive age. This study examined metabolic differences in plasma and follicular fluid from 32 PCOS patients without obesity or insulin resistance (IR) and 31 healthy women. The study found that increased levels of l-tryptophan and l-tyrosine were significantly positively associated with serum androgen levels in PCOS patients. These findings suggest that disorders of amino acid metabolism, especially tryptophan and tyrosine metabolism, may play a role in the development of PCOS in predisposed women without obesity and IR.

Hou E, Zhao Y, Hang J, Qiao J. Metabolomics and correlation network analysis of follicular fluid reveals associations between l-tryptophan, l-tyrosine and polycystic ovary syndrome. Biomed Chromatogr. 2021 Mar;35(3):e4993. doi: 10.1002/bmc.4993. Epub 2020 Nov 5. PMID: 32986877

Kikuchi AM, Tanabe A, Iwahori Y. A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning. J Diet Suppl. 2021;18(3):316-333. doi: 10.1080/19390211.2020.1746725. Epub 2020 Apr 10. PMID: 32272859

Intake of L-tryptophan, a precursor of serotonin, may decrease anxiety and increase positive mood in healthy individuals, according to a systematic review of 11 RCTs. Taking 0.14-3 g of TRP per day in addition to the usual meal can be expected to improve mood, but further studies are needed to determine the optimum amount of TRP intake.

Kikuchi AM, Tanabe A, Iwahori Y. A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning. J Diet Suppl. 2021;18(3):316-333. doi: 10.1080/19390211.2020.1746725. Epub 2020 Apr 10. PMID: 32272859

Garner TB, Hester JM, Carothers A, Diaz FJ. Role of zinc in female reproduction. Biol Reprod. 2021 May 7;104(5):976-994. doi: 10.1093/biolre/ioab023. PMID: 33598687; PMCID: PMC8599883

Zinc plays a critical role in female germ cell growth, fertility, and pregnancy. Zinc is necessary for meiotic arrest, oocyte maturation, egg activation, and preimplantation embryo development. Zinc deficiency during pregnancy can hinder fetal development. Zinc supplementation should be considered for reproductive-age women at risk of deficiency.

Garner TB, Hester JM, Carothers A, Diaz FJ. Role of zinc in female reproduction. Biol Reprod. 2021 May 7;104(5):976-994. doi: 10.1093/biolre/ioab023. PMID: 33598687; PMCID: PMC8599883

Ng SW, Norwitz SG, Taylor HS, Norwitz ER. Endometriosis: The Role of Iron Overload and Ferroptosis. Reprod Sci. 2020 Jul;27(7):1383-1390. doi: 10.1007/s43032-020-00164-z. Epub 2020 Feb 19. PMID: 32077077

Iron deficiency is a well-known risk factor for many reproductive disorders. However, paradoxically, these disorders can be more commonly observed under conditions of iron excess. In women's health, specifically in endometriosis, abnormal eutopic endometrium and dysregulated iron homeostasis may cause too much iron. This can result in localized iron overload and inflammation in endometriotic lesions. The association between endometriosis and high cholesterol levels may be explained by an interaction between the mevalonate cholesterol biosynthetic pathway and ferroptosis signaling, which allows endometrial tissues to survive and expand into endometriotic lesions.

Ng SW, Norwitz SG, Taylor HS, Norwitz ER. Endometriosis: The Role of Iron Overload and Ferroptosis. Reprod Sci. 2020 Jul;27(7):1383-1390. doi: 10.1007/s43032-020-00164-z. Epub 2020 Feb 19. PMID: 32077077

Ni Z, Li Y, Song D, Ding J, Mei S, Sun S, Cheng W, Yu J, Zhou L, Kuang Y, Li M, Cai Z, Yu C. Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity. Cell Death Dis. 2022 Jul 4;13(7):579. doi: 10.1038/s41419-022-05037-8. PMID: 35787614; PMCID: PMC9253011

Endometriosis-related infertility is caused by follicle dysplasia and reduced oocyte quality. Iron overload in ovarian follicular fluid is associated with oocyte maturation disorder. This study identified the mechanism underlying ferroptosis in ovarian granulosa cells and oocyte maturation failure in EMs, and found that granulosa cells undergoing ferroptosis further suppressed oocyte maturation by releasing exosomes. Vitamin E and iron chelators were found to be effective in alleviating EMs-related infertility models.

Ni Z, Li Y, Song D, Ding J, Mei S, Sun S, Cheng W, Yu J, Zhou L, Kuang Y, Li M, Cai Z, Yu C. Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity. Cell Death Dis. 2022 Jul 4;13(7):579. doi: 10.1038/s41419-022-05037-8. PMID: 35787614; PMCID: PMC9253011

Petraglia F, Dolmans MM. Iron deficiency anemia: Impact on women's reproductive health. Fertil Steril. 2022 Oct;118(4):605-606. doi: 10.1016/j.fertnstert.2022.08.850. PMID: 36182259.

Iron deficiency and iron deficiency anemia are prevalent among women, especially during reproductive age, and can have adverse health consequences. Heavy menstrual bleeding, pregnancy, and postpartum period are major causes. Despite being underdiagnosed and undertreated, this article provides an overview of iron metabolism, pathogenetic mechanisms of heavy menstrual bleeding, and treatment options for iron deficiency anemia and uterine disorders

Petraglia F, Dolmans MM. Iron deficiency anemia: Impact on women's reproductive health. Fertil Steril. 2022 Oct;118(4):605-606. doi: 10.1016/j.fertnstert.2022.08.850. PMID: 36182259.

Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Iron intake and risk of ovulatory infertility. Obstet Gynecol. 2006 Nov;108(5):1145-52. doi: 10.1097/01.AOG.0000238333.37423.ab. PMID: 17077236

A prospective cohort study found that consumption of iron supplements and nonheme iron from other sources may decrease the risk of ovulatory infertility in premenopausal women without a history of infertility. Heme iron intake was not associated with ovulatory infertility.

Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Iron intake and risk of ovulatory infertility. Obstet Gynecol. 2006 Nov;108(5):1145-52. doi: 10.1097/01.AOG.0000238333.37423.ab. PMID: 17077236

Razavi M, Jamilian M, Kashan ZF, Heidar Z, Mohseni M, Ghandi Y, Bagherian T, Asemi Z. Selenium Supplementation and the Effects on Reproductive Outcomes, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome. Horm Metab Res. 2016 Mar;48(3):185-90. doi: 10.1055/s-0035-1559604. Epub 2015 Aug 12. PMID: 26267328.

Selenium supplementation for 8 weeks among women with polycystic ovary syndrome (PCOS) had beneficial effects on reproductive outcomes, DHEA, hs-CRP, and MDA levels. The study was conducted on 64 women aged 18-40 years old with PCOS, and the participants were randomly assigned to 2 groups receiving either 200 μg selenium daily or placebo for 8 weeks. After 8 weeks of intervention, pregnancy rate in the selenium group was higher than in the placebo group, and alopecia and acne decreased following the consumption of selenium supplements compared with placebo.

Razavi M, Jamilian M, Kashan ZF, Heidar Z, Mohseni M, Ghandi Y, Bagherian T, Asemi Z. Selenium Supplementation and the Effects on Reproductive Outcomes, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome. Horm Metab Res. 2016 Mar;48(3):185-90. doi: 10.1055/s-0035-1559604. Epub 2015 Aug 12. PMID: 26267328.

Chuong CJ, Dawson EB. Zinc and copper levels in premenstrual syndrome. Fertil Steril. 1994 Aug;62(2):313-20. doi: 10.1016/s0015-0282(16)56884-8. PMID: 8034078.

This study aimed to determine whether changes in peripheral zinc and copper levels are associated with symptoms of premenstrual syndrome (PMS). The results showed that zinc values were significantly lower during the luteal phase in PMS patients compared to the follicular phase and controls. Copper levels were higher during the luteal phase in PMS patients compared to controls. The zinc:copper ratio was significantly lower in PMS patients during the luteal phase, indicating reduced availability of zinc in the body. The study concludes that zinc deficiency occurs in PMS patients during the luteal phase, and the availability of zinc is further reduced by elevated copper.

Chuong CJ, Dawson EB. Zinc and copper levels in premenstrual syndrome. Fertil Steril. 1994 Aug;62(2):313-20. doi: 10.1016/s0015-0282(16)56884-8. PMID: 8034078.

Grieger JA, Grzeskowiak LE, Wilson RL, Bianco-Miotto T, Leemaqz SY, Jankovic-Karasoulos T, Perkins AV, Norman RJ, Dekker GA, Roberts CT. Maternal Selenium, Copper and Zinc Concentrations in Early Pregnancy, and the Association with Fertility. Nutrients. 2019 Jul 16;11(7):1609. doi: 10.3390/nu11071609. PMID: 31315178; PMCID: PMC6683068.

Lower maternal plasma concentrations of zinc and selenium were associated with longer time to pregnancy and increased risk of subfertility in Australian women. No association was found between copper and time to pregnancy or subfertility. Further research is needed to support recommendations for increasing maternal trace element intake in women planning a pregnancy.

Grieger JA, Grzeskowiak LE, Wilson RL, Bianco-Miotto T, Leemaqz SY, Jankovic-Karasoulos T, Perkins AV, Norman RJ, Dekker GA, Roberts CT. Maternal Selenium, Copper and Zinc Concentrations in Early Pregnancy, and the Association with Fertility. Nutrients. 2019 Jul 16;11(7):1609. doi: 10.3390/nu11071609. PMID: 31315178; PMCID: PMC6683068.

ElObeid T, Awad MO, Ganji V, Moawad J. The Impact of Mineral Supplementation on Polycystic Ovarian Syndrome. Metabolites. 2022 Apr 8;12(4):338. doi: 10.3390/metabo12040338. PMID: 35448525; PMCID: PMC9027569

Polycystic ovary syndrome (PCOS) is a common disorder among women of reproductive age. Recent studies suggest that magnesium, zinc, selenium, and chromium supplementation may be beneficial in treating various PCOS phenotypes. This review presents findings from randomized controlled trials and meta-analyses, highlighting the potential health benefits of mineral supplementation. However, further studies are needed to determine appropriate dosage levels due to potential health risks associated with higher doses.

ElObeid T, Awad MO, Ganji V, Moawad J. The Impact of Mineral Supplementation on Polycystic Ovarian Syndrome. Metabolites. 2022 Apr 8;12(4):338. doi: 10.3390/metabo12040338. PMID: 35448525; PMCID: PMC9027569

Chocano-Bedoya PO, Manson JE, Hankinson SE, Willett WC, Johnson SR, Chasan-Taber L, Ronnenberg AG, Bigelow C, Bertone-Johnson ER. Dietary B vitamin intake and incident premenstrual syndrome. Am J Clin Nutr. 2011 May;93(5):1080-6. doi: 10.3945/ajcn.110.009530. Epub 2011 Feb 23. PMID: 21346091; PMCID: PMC3076657.

A case-control study found that high intake of thiamine and riboflavin from food sources was associated with a lower risk of premenstrual syndrome (PMS), while no significant associations were found for niacin, vitamin B-6, folate, and vitamin B-12. B vitamin intake from supplements was not associated with a lower risk of PMS. Further research is needed to evaluate the effects of B vitamins in the development of PMS.

Chocano-Bedoya PO, Manson JE, Hankinson SE, Willett WC, Johnson SR, Chasan-Taber L, Ronnenberg AG, Bigelow C, Bertone-Johnson ER. Dietary B vitamin intake and incident premenstrual syndrome. Am J Clin Nutr. 2011 May;93(5):1080-6. doi: 10.3945/ajcn.110.009530. Epub 2011 Feb 23. PMID: 21346091; PMCID: PMC3076657.

Lee S, Huh I, Kang S, Nam YE, Cho Y, Kamruzzaman M, Hong J, Kwon O, Park T. Meta-Analysis of Randomized Clinical Trials Evaluating Effectiveness of a Multivitamin Supplementation against Oxidative Stress in Healthy Subjects. Nutrients. 2022 Mar 10;14(6):1170. doi: 10.3390/nu14061170. PMID: 35334829; PMCID: PMC8955918.

A meta-analysis of six randomized placebo-controlled trials on the relationship between plant-based multivitamin/mineral supplementation (PMS) and oxidative stress found that PMS can alleviate oxidative stress by providing exogenous oxidant scavengers. The study identified six significant biomarker variables, including vitamins C, B6, and B12, folate, β-carotene, and oxidized LDL, and revealed negative correlations between plasma free radical scavenging nutrients and plasma ox-LDL levels.

Lee S, Huh I, Kang S, Nam YE, Cho Y, Kamruzzaman M, Hong J, Kwon O, Park T. Meta-Analysis of Randomized Clinical Trials Evaluating Effectiveness of a Multivitamin Supplementation against Oxidative Stress in Healthy Subjects. Nutrients. 2022 Mar 10;14(6):1170. doi: 10.3390/nu14061170. PMID: 35334829; PMCID: PMC8955918.

Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms. J Am Coll Nutr. 2000 Feb;19(1):3-12. doi: 10.1080/07315724.2000.10718907. PMID: 10682869.

Calcium is the only dietary supplement that has been shown to significantly reduce symptoms of premenstrual syndrome (PMS) in a large, rigorous, double-blind, placebo-controlled trial. Limited evidence suggests that magnesium, vitamin E, and carbohydrate supplements might also be useful, but more research is needed. Trials of vitamin B6 and evening primrose oil have had conflicting results, and the efficacy of herbal products is uncertain due to a lack of consistent data. Health professionals should be aware of these supplements and counsel patients based on the totality of evidence.

Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms. J Am Coll Nutr. 2000 Feb;19(1):3-12. doi: 10.1080/07315724.2000.10718907. PMID: 10682869.

Rapkin A. A review of treatment of premenstrual syndrome and premenstrual dysphoric disorder. Psychoneuroendocrinology. 2003 Aug;28 Suppl 3:39-53. doi: 10.1016/s0306-4530(03)00096-9. PMID: 12892989

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are diagnosed by the presence of moderate to severe mood and physical symptoms for one to two weeks premenstrually with relief by day 4 of menses. Nonpharmacologic management includes cognitive behavioral relaxation therapy, aerobic exercise, calcium, magnesium, vitamin B(6) L-tryptophan supplementation, or a complex carbohydrate drink. Pharmacologic management includes selective serotonin reuptake inhibitors and serotonergic tricyclic antidepressants. Hormonal therapy with GnRH analogs, danocrine, and estradiol implants or patches with progestin are effective. Oral contraceptive pills prevent ovulation and may be effective for the treatment of PMS/PMDD, but limited evidence does not support efficacy for oral contraceptive agents containing progestins derived from 19-nortestosterone. A new oral contraceptive pill containing low-dose estrogen and the progestin drospirenone may reduce symptoms of water retention and other side effects related to estrogen excess and may be effective in the treatment of PMDD.

Rapkin A. A review of treatment of premenstrual syndrome and premenstrual dysphoric disorder. Psychoneuroendocrinology. 2003 Aug;28 Suppl 3:39-53. doi: 10.1016/s0306-4530(03)00096-9. PMID: 12892989

Jurczewska J, Szostak-Węgierek D. The Influence of Diet on Ovulation Disorders in Women-A Narrative Review. Nutrients. 2022 Apr 8;14(8):1556. doi: 10.3390/nu14081556. PMID: 35458118; PMCID: PMC9029579

Female infertility is often due to ovulation disorders, which can be influenced by factors such as age, smoking, stress, and diet. A diet rich in low glycemic index carbohydrates, plant protein, monounsaturated and polyunsaturated fatty acids, folic acid, vitamin D, antioxidants, and iron, such as the Mediterranean diet, can have a positive effect on ovulation. Conversely, a diet high in animal protein, saturated and trans fatty acids, and high glycemic index carbohydrates can have a negative effect. More research is needed to establish a direct link between nutrition and anovulatory infertility.

Jurczewska J, Szostak-Węgierek D. The Influence of Diet on Ovulation Disorders in Women-A Narrative Review. Nutrients. 2022 Apr 8;14(8):1556. doi: 10.3390/nu14081556. PMID: 35458118; PMCID: PMC9029579

Gaskins AJ, Chavarro JE. Diet and fertility: a review. Am J Obstet Gynecol. 2018 Apr;218(4):379-389. doi: 10.1016/j.ajog.2017.08.010. Epub 2017 Aug 24. PMID: 28844822; PMCID: PMC5826784

Studies show that supplemental folic acid intake is related to lower frequency of infertility, lower risk of pregnancy loss, and greater success in infertility treatment. Antioxidant supplementation does not offer benefits to women undergoing infertility treatment, but it appears to be beneficial when the male partner is supplemented. Long chain omega 3 fatty acids improve female fertility, and adherence to healthy diets favoring seafood, poultry, whole grains, fruits, and vegetables are related to better fertility in women and better semen quality in men. Dairy, soy, moderate alcohol, and caffeine intake have not been consistently related to poor fertility. Further research is needed to jointly consider female and male diets and test consistent findings in randomized trials.

Gaskins AJ, Chavarro JE. Diet and fertility: a review. Am J Obstet Gynecol. 2018 Apr;218(4):379-389. doi: 10.1016/j.ajog.2017.08.010. Epub 2017 Aug 24. PMID: 28844822; PMCID: PMC5826784

Kohil A, Chouliaras S, Alabduljabbar S, Lakshmanan AP, Ahmed SH, Awwad J, Terranegra A. Female infertility and diet, is there a role for a personalized nutritional approach in assisted reproductive technologies? A Narrative Review. Front Nutr. 2022 Jul 22;9:927972. doi: 10.3389/fnut.2022.927972. PMID: 35938101; PMCID: PMC9353397

Female infertility is a global challenge, and nutrition and environmental factors can impact reproductive health and the outcome of assisted reproductive technologies. Dietary factors, such as polyunsaturated fatty acids, fiber, and the Mediterranean diet, have beneficial effects on female reproductive outcomes. The mechanisms linking diet to fertility are not fully understood, but genomic, epigenomic, and microbial pathways may be involved.

Kohil A, Chouliaras S, Alabduljabbar S, Lakshmanan AP, Ahmed SH, Awwad J, Terranegra A. Female infertility and diet, is there a role for a personalized nutritional approach in assisted reproductive technologies? A Narrative Review. Front Nutr. 2022 Jul 22;9:927972. doi: 10.3389/fnut.2022.927972. PMID: 35938101; PMCID: PMC9353397