The Effect of Lifestyle and Diet on Fertility: Focus on Diet and Specific Nutrients

part 2 of a series on fertility

By Susan T. Marcolina, MD, FACP. Dr. Marcolina is a board-certified internist and geriatrician in Issaquah, WA; she reports no financial relationship to this field of study.

The second part of this series reviews specific features of dietary intake that can influence fertility as well as overall general medical health.

Protein Intake and Ovulatory Infertility

An analysis of a subgroup of married female nurses from the Nurses' Health Study II examined the association between specific protein-rich foods and ovulatory infertility. After multivariate adjustment for age, parity, energy intake, smoking history, physical activity, and coffee, alcohol, and iron intake, women with the highest animal protein intake had a 39% increase in ovulatory infertility. Similarly, women in the highest quintile of total protein intake had a 41% greater risk of ovulatory infertility than women in the lowest quintile of intake.

Furthermore, this study examined the association of ovulatory infertility with the intake of specific protein-rich foods. The researchers found that the addition of one serving of meat to the diet isocalorically per day was associated with a 32% increased risk of ovulatory infertility (P = 0.01). The increased risk was primarily due to intake of chicken and turkey (the most common protein sources in this population), and to red meat, but to a lesser extent. Replacement of 5% of energy intake with animal protein instead of carbohydrates was associated with a 19% greater risk of ovulatory infertility (P = 0.03), whereas the replacement of 5% of total energy intake with vegetable protein in lieu of carbohydrates reduced the risk of ovulatory infertility by 43%. Finally, the consumption of vegetable protein instead of animal protein resulted in a 50% decrease in the risk of ovulatory infertility. This association between increased vegetable protein consumption and reduced ovulatory infertility was seen in women 32 years of age or older.1

Protein intake affects insulin and glucose sensitivity differently, depending upon the protein source. In diabetics, postprandial insulin response to vegetable (soy) protein and egg protein is lower than to red meat and turkey protein.2 Normal subjects respond similarly to vegetable protein with a lower insulin response than to animal protein.3 Thus, the differential effects of various protein sources on insulin sensitivity could be a mechanism that explains the effects of non-animal protein on fertility.

Adverse Effects

Vegetarian and vegans should make sure they're taking in sufficient vitamins and nutrients, specifically vitamin B12, which is readily available in a well-balanced diet as outlined in the Vegetarian Food Pyramid and Eating Guide.4 It takes wise meal planning together with proper supplementation or these diets are not going to be beneficial for general health or fertility. Vegans also need to focus on getting adequate amounts of vitamin D, zinc, iron, and calcium.

The Importance of Iron (Fe) in Fertility

Iron deficiency is common in women of childbearing age and is the most prevalent nutritional deficiency worldwide.5 Cook et al have shown that 21% of young women have depleted iron stores, defined as ferritin levels below 12 ng/mL.6 Given that it may be associated with adverse pregnancy and perinatal outcomes, women planning a pregnancy should have their baseline iron stores checked and consider taking supplements to restore and maintain adequate iron stores in view of the known increased requirements during pregnancy.7,8

Meloni et al found indirect evidence of the effect of iron deficiency on fertility.9 They diagnosed celiac disease (a malabsorptive condition caused by injury to the small intestinal absorptive surface due to an immune response to gluten contained in the common grains wheat, barley, and rye) more frequently among women with unexplained fertility than fertile controls. Some of these infertile women had iron-deficiency anemia and low ferritin levels as well as other nutrient deficiencies. Thus, it is possible that iron and other nutrient deficiencies may contribute to subclinical ovulatory disorders that result in infertility and cannot be diagnostically pinpointed readily.9 Sher et al found that women with celiac disease often have other disorders of reproductive function that include delayed menarche and early menopause in addition to infertility, which suggests that this disease affects ovulatory function.10

Chavarro et al, in a prospective cohort study of a population of married female nurses (ages 24-42) from the Nurses' Health Study II, used a semiquantitative food-frequency questionnaire to estimate dietary intake of both heme (derived from animal meat) and non-heme iron (derived from plant sources and supplements) and its effects on incident ovulatory fertility over eight years of follow-up.11 After adjustment for age, BMI, parity, smoking history, vitamin C, alcohol, multivitamin use, caffeine, and previous exposure to oral contraceptives (OCs), the use of iron supplements (the most common form of non-heme iron ingestion) was associated with half the risk of developing infertility compared to non-supplement users (P < 0.001). Furthermore, among the supplement users, consumption of supplements with a high iron content (> 51 mg/d) was associated with a 70% lower risk of ovulatory infertility (P = 0.003). There was a strong inverse association between non-heme iron intake and ovulatory infertility among women in the lowest half of heme iron intake (< 1 mg/d) but not among women with higher heme iron intake (> 1 mg/d). Common food sources of non-heme iron are listed in Table 1.12

Dosages

Most multivitamin tablets contain 18 mg iron and 400 mg folate per pill, while prenatal vitamins contain between 27-65 mg iron and 0.8-1 mg folate.13 In the Nurses' Health Study II, the intake of heme iron equivalent to consuming just one serving (2-3 ounces) of cooked lean meat, poultry, or fish daily did not affect ovulatory fertility.11

Fats and Fertility: Have We Reached the (Un)Saturation Point?

Since fats and oils comprise 33% or more of the daily caloric intake of the American diet, they represent a potentially important point of dietary modification, which can affect overall health as well as fertility.14

Specific dietary unsaturated fatty acids can bind and activate the peroxisome proliferator-activated receptor-gamma (PPAR-G) receptors in a similar fashion to the synthetic PPAR-G ligands such as the TZDs. Nichols et al, using in vitro binding assays, found that of all the nuclear receptor isoforms, PPAR-Gs had the most restricted affinity profile for dietary fatty acids, binding most efficiently with long-chain polyunsaturated fatty acids (PUFAs), the n-6 (omega-6) fatty acids, such as gamma-linolenic acid, and the n-3 (omega-3) fatty acids, such as eicosapentaenoic acid, and weakly with mono-unsaturated fatty acids (MUFAs).

Saturated fatty acids of any chain length failed to bind efficiently with PPAR-G receptors.15 Binding affinities for the unsaturated fatty acids differed, however, for cis and trans stereoisomers.16 Kasim-Karakas et al found that a higher intake of cis unsaturated fatty acids (found in non-hydrogenated vegetable oils and salad dressings) was associated with improved metabolic and endocrine characteristics in women with polycystic ovarian syndrome that resulted in a decreased risk of type 2 diabetes.17 On the other hand, consumption of trans unsaturated fatty acids has been associated with insulin resistance18 and higher risk of type 2 diabetes.19

Berger reviewed the experimental evidence from in vitro and in vivo animal and clinical studies which showed that PPAR-G agonists mediate increases in insulin sensitivity in adipose tissue and a broad range of other tissues because they:

1. increase the uptake of fatty acids and decrease lipolysis by adipocytes;

2. increase the production of plasma levels of adipose-derived factors, such as Adipocyte-related complement protein (Acrp)30, which increase insulin sensitivity; and

3. downregulate production and/or the action of TNF-alpha, a pro-inflammatory mediator, which increases insulin resistance.

Thus, PPAR-G receptors link dietary fatty acid concentrations to glucose, lipid, and immune homeostasis, which has important ramifications for fertility.16

In addition to functioning as PPAR-G agonists, omega-3 and omega-6 PUFAs provide the precursors for prostaglandin synthesis, modulate key enzymatic processes involved in steroid metabolism, and are essential components of all cell membranes, especially the membranes of the sperm and oocyte.20 PUFA intake also has important effects on parturition and Olsen et al have shown in a prospective cohort study that women with higher intakes of omega-3 fatty acids (equivalent to daily consumption of at least 15 g of fish or 0.15 g of omega-3 fatty acids) during pregnancy have lower risks of preterm labor and low birth weight.21 Table 2 lists excellent dietary sources of omega-3 fatty acids.12

Dietary Ratios of Omega-6 and Omega-3 Fatty Acids

Clinical studies have addressed the fact that the ratio of dietary intake of omega-6 to omega-3 fatty acids is very important to regulation of metabolic and immune processes in the body. While modern Western dietary trends have increased this ratio from 10:1 to 25:1, it has been advocated that a return to the ratio of a more primitive human diet of 4:1 would reduce the production of inflammatory mediators and the incidence of cardiovascular disease, autoimmune diseases, and perhaps both male and female infertility.22 Since the American Diabetes Association recommends that daily intake of fat consist of 30% of total daily calories, the portion representing omega-3 PUFA intake should increase.23

Chavarro et al examined the effects of consumption of different types of fat on ovulatory infertility in a group of women aged 24-42 years of age from the Nurses Health study II, a cohort of female U.S. nurses followed prospectively for eight years. After controlling for multiple variables including age, parity, BMI, menstrual cycle length, former use of OCs, smoking, and the presence of clinical stigmata of androgen excess, intake of trans fatty acids (TFAs) versus carbohydrates, MUFA, or omega-6 PUFAs was associated with a significantly greater risk of ovulatory infertility (P = 0.02).24 This finding is consistent with the fact that dietary TFA intake has been associated with greater insulin resistance, risk of type 2 diabetes, and concentration of inflammatory markers such as TNF-alpha, which may adversely affect ovarian function. It is clear that minimization of dietary intake of TFAs improves both fertility and general cardiovascular health. The current recommendation from the American Heart Association for TFA intake is less than 1% of total daily calories.25

Conclusion

Infertility due to ovulatory dysfunction, specific nutritional deficiencies, and other causes can be affected by lifestyle and dietary factors such as body weight and physical activity, as well as specific nutrient intake and the types of fat and protein in the diet. These lifestyle and dietary factors influence insulin sensitivity, which is linked to their effects on the activity of PPAR-G on glucose, lipid, and immune system regulation.

Recommendation

For patients who are planning a pregnancy, physicians should emphasize fertility-promoting behaviors.

These lifestyle and dietary modifications improve overall general health as well as pregnancy and perinatal outcomes. They may also improve the chances of successful artificial reproductive technology outcomes should they be necessary to achieve pregnancy.

References

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2. Gannon MC, et al. An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes. Am J Clin Nutr 2003;78:734-741.

3. Hubbard R, et al. Effect of dietary protein on serum insulin and glucagon levels in hyper-and normocholesterolemic men. Atherosclerosis 1989;76:55-61.

4. MayoClinic.com. Food and Nutrition. Vegetarian diet: How to get the best nutrition. Available at: www.mayoclinic.com/health/vegetarian-diet/HQ01596. Accessed Sept. 1, 2008.

5. Centers for Disease Control and Prevention. Iron Deficiency—United States, 1999-2000. MMWR Morb Mortal Wkly Rep 2002;51:897-899.

6. Cook JD, et al. Estimates of iron sufficiency in the US population. Blood 1986;68:726-731.

7. Verstraelen H, et al. Subclinical iron deficiency is a strong predictor of bacterial vaginosis in early pregnancy. BMC Infect Dis 2005;5:55.

8. Rasmussen K. Is there a causal relationship between iron deficiency or iron-deficiency anemia and weight at birth, length of gestation and perinatal mortality? J Nutr 2001; 131:590S-601S.

9. Meloni GF, et al. The presence of coeliac disease in infertility. Hum Reprod 1999;14:2759-2761.

10. Sher KS, Mayberry JF. Female fertility, obstetric and gynaecological history in celiac disease: A case-control study. Acta Paediatr Suppl 1996;412:76-77.

11. Chavarro JE, et al. Iron intake and risk of ovulatory infertility. Obstet Gynecol 2006;108:1145-1152.

12. Mateljan G. The World's Healthiest Foods. The Best Sources of Iron. Honolulu, HI: The George Mateljan Foundation; 2007:762.

13. E-Medicine. Prenatal Vitamins. Available at: www.emedicine.com/med/images/large/32783278prenatal_vitamins_ table.pdf. Accessed Sept. 2, 2008.

14. Bialostosky K, et al. Dietary intake of macronutrients, micronutrients, and other dietary constituents: United States 1988-94. Vital Health Stat 11 2002;(245):1-158.

15. Nichols JS, et al. Development of a scintillation proximity assay for peroxisome proliferator-activated receptor gamma ligand binding domain. Anal Biochem 1998;257:112-119.

16. Berger J, Moller DE. The mechanism of action of PPARs. Annu Rev Med 2002;53:409-435.

17. Kasim-Karakas SE, et al. Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome. J Clin Endocrinol Metab 2004;89:615-620.

18. Lefevre M, et al. Comparison of the acute response to meals enriched with cis- or trans-fatty acids on glucose and lipids in overweight individuals with differing FABP2 genotypes. Metabolism 2005;54:1652-1658.

19. Salmeron J, et al. Dietary fat intake and risk of type 2 diabetes in women. Am J Clin Nutr 2001;73:1019-1026.

20. Wathes DC, et al. polyunsaturated fatty acids in male and female reproduction. Biol Reprod 2007;77:190-201.

21. Olsen SF, Secher NJ. Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: Prospective cohort study. BMJ 2002;324:447.

22. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002;21:495-505.

23. Nutrition Recommendations and Interventions for Diabetes—2006. A position statement of the American Diabetes Association. Available at: http://care.diabetesjournals.org/cgi/content/full/29/9/2140. Accessed Sept. 5, 2008.

24. Chavarro JE, et al. Dietary fatty acid intakes and the risk of ovulatory infertility. Am J Clin Nutr 2007;85:231-237.

25. American Heart Association Nutrition Committee, et al. Diet and lifestyle recommendations revision 2006: A scientific statement from the American Heart Association Nutrition Committee. Circulation 2006;114:82-96.