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Review
Can Nutrition Help in the Treatment of Infertility?
Faculty of Nursing and Health Sciences, Notre Dame University-Louaize, Zouk Mosbeh 72, Lebanon
Correspondence to:This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Prev Nutr Food Sci 2021; 26(2): 109-120
Published June 30, 2021 https://doi.org/10.3746/pnf.2021.26.2.109
Copyright © The Korean Society of Food Science and Nutrition.
Abstract
Keywords
INTRODUCTION
Infertility is defined as “the inability to conceive after 12 months of unprotected intercourse or six months for women aged 35 years or older” (American Society for Reproductive Medicine, 2014). According to a study published by the World Health Organization (WHO) which compiled data from 277 national surveys in 190 countries, worldwide rates of infertility between 1990 and 2010 have remained relatively constant (Mascarenhas et al., 2012; WHO, 2019). Thus, the WHO estimated that in 2010, 48.5 million couples worldwide were unable to conceive. The physical, emotional, psychological, and financial statuses of infertile couples are tremendously affected especially after undergoing diagnostic-curative treatments [e.g.,
Following a nutritious/well-balanced diet and being physically active are two bases of a healthy lifestyle whereby they can help maintain a healthy weight and reduce the risk of chronic diseases (WHO, 2020). It is well-known that nutrition can play an important role in altering fertility-related outcomes in both men and women. In a large prospective cohort of 17,544 women in Nurses’ Health Study (NHS)-II, after controlling for certain confounders [age, body mass index (BMI), alcohol intake, coffee intake, smoking, and oral contraceptive use], women with the highest intake of a fertility diet [comprised of full-fat dairy foods, iron (Fe), monounsaturated fats, and plant protein] during the preconception period, were found to have a 66% lower risk of infertility related to ovulatory disorders and a 27% lower risk of infertility due to other causes compared to women with the lowest intake of this type of diet (Chavarro et al., 2007). While there is growing evidence that nutrition may be associated with reproductive outcomes in both sex, there is still no official guidelines for reproductive-aged couples (Rossi et al., 2016). This review aims to summarize the latest data on dietary factors (e.g., specific food groups, nutrients, and nutritional supplements) that have a major impact on both female and male sexual and reproductive functions.
MATERIALS AND METHODS
Our study was undertaken in the PubMed and the Google Scholar databases in November 2020, using the descriptor medical subject headings, without limitation as to the publication period (with emphasis on the most recent papers). Studies involving animals were not included. The following keyword combinations were used: “infertility” and “diet” (43 articles), “infertility” and “dietary supplements” (42 articles), “infertility” and “antioxidants” (6 articles), and “infertility” and “beverages” (15 articles). Eight articles were in common between the different combinations. Out of the total 104 articles, 24 were literature reviews, 68 were original studies, and 12 were reports from web pages of agencies and organizations. The above steps are shown in Fig. 1.
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Figure 1. Stages of study selection and inclusion of articles.
RESULTS AND DISCUSSION
Our review findings were reported in terms of pregnancy outcomes and semen variables where most of the studies reported improvement in no less than one of these outcome measures in the experimental group. Some studies that investigated the effect of dietary intake reported a positive correlation between specific macronutrient(s) or micronutrient(s) and the risk of infertility, while others reported conflicting results. The impact of various nutritional factors on male and female fertility are summarized in Table 1 and Table 2, respectively.
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Table 1 . Summary of literature on the association between diet and male fertility
Nutritional factors Findings References Dietary patterns Healthy eating patterns positively affect semen quality and improve fecundity, while unhealthy diets had the opposite relationship. Cutillas-Tolín et al. (2015); Eslamian et al. (2017); Karayiannis et al. (2017); Danielewicz et al. (2018) Proteins High intake of dairy products might affect semen quality and fertility. Limited evidence is available from human studies on the effect of soy on fertility; however, most of them showed no harmful effect. Jacobsen et al. (2014); Mínguez-Alarcón et al. (2015); Vanegas et al. (2015); Gaskins et al. (2018); Nassan et al. (2018); Wise et al. (2018) Dietary fats TFAs are related to reduced fertility, whereas ω-3FAs are protective against SDF, TT, and testicular volume. Mínguez-Alarcón et al. (2017); Salas-Huetos et al. (2018) Carbohydrates Diets with low-glycemic load that contain high amounts of whole grains might have positive impact on fertility. Liu et al. (2015) Antioxidants Antioxidant supplementation improves semen quality and may increase the probability of clinical pregnancy and live birth. Ahmadi et al. (2016); Majzoub and Agarwal (2018); Alahmar (2019); Li et al. (2019); Henkel et al. (2019) Vit B12 supplement Vit B12 may be protective against fertility by increasing sperm count, motility and minimizing sperm DNA damage. Banihani (2017) Vit D supplement Vit D may positively affect semen quality and sperm motility but not sperm concentration. Zhu et al. (2016); Abbasihormozi et al. (2017); de Angelis et al. (2017); Bosdou et al. (2019) Zn supplements Zn may elevate sperm quality in infertile males. Colagar et al. (2009); Zheng et al. (2012); Shi et al. (2014); Zhao et al. (2016); Lee (2018) Fa and Zn supplement Fa and Zn may impose a greater influence only on sperm concentration, morphology, and serum folate level. da Silva et al. (2013); Irani et al. (2017); Schisterman et al. (2020) Iron Iron may be inversely related to sperm concentration and motility. Adoamnei et al. (2019) CoQ10 supplement No significant correlation between CoQ10 and TT levels. Banihani (2018) DHA supplement DHA may increase ω-3FAs and DHA concentration in seminal plasma, TAC, and decrease SDF. Martínez-Soto et al. (2016) Beverages Occasional/moderate intake of alcohol and caffeine does not affect semen quality, while high intake of these beverages or SSBs negatively affects semen quality. Liu et al. (2015); Wesselink et al. (2016); Karmon et al. (2017); Ricci et al. (2017); Ricci et al. (2018); Ghosh et al. (2019) TFA, trans fatty acid; ω-3FA, omega-3 fatty acid; SDF, sperm DNA fragmentation; TT, testosterone; DHA, docosahexaenoic acid; Vit B12, vitamin B12; Vit D, vitamin D; CoQ10, coenzyme Q10; TAC, total antioxidant capacity; Zn, zinc; Fa, folic acid; SSB, sugar-sweetened beverage.
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Table 2 . Summary of literature on the association between diet and female fertility
Nutritional factors Findings References Dietary patterns Healthy dietary patterns (MedDiet and PD) have been shown to improve the chance of pregnancy and ART outcomes. Unhealthy diets (WestDiet) had the opposite relationship. Toledo et al. (2011); Karayiannis et al. (2018); Garruti et al. (2019); Gaskins et al. (2019) Proteins High-fat dairy products may increase risk of infertility whereas non-dairy protein (fish and white meat) have an important influence on female fertility. Braga et al. (2015); Kim et al. (2017); Souter et al. (2017); Wise et al. (2018) Dietary fats TFAs may increase risk of metabolic disorders that negatively affect ovarian functions; however, ω-3FAs improve fecundability. Fontana and Della Torre (2016); Gaskins et al. (2018); Wise et al. (2018) Carbohydrates Current evidence, though limited, suggest that diets with low-GL that contain high amounts of whole grains may benefit fecundity. Liese et al. (2003); Blomhoff (2005); Gaskins et al. (2016); Chiu et al. (2018) Antioxidants Antioxidants might provide benefit for subfertile women. Showell et al. (2020) Vit D supplement Vit D may be beneficial only for women with disorders like PCOS, insulin resistance, or low anti-Mullerian hormone levels. Jukic et al. (2015); Somigliana et al. (2016); Muscogiuri et al. (2017); Arslan and Akdevelioğlu (2018); Mumford et al. (2018) Fa and Zn supplement Fa and Zn may decrease the risk of ovulatory infertility, sporadic anovulation, and TTP. Cueto et al. (2016); Chiu et al. (2018) Zn and Se supplement Zn and Se may reduce TTP and risk of subfertility. Grieger et al. (2019); Maeda et al. (2019) Cu Cu does not have an important influence on female infertility. Bawa and Tyagi (2017) Hg Intake of fish with high levels of Hg may be of concern to women planning pregnancy or pregnant women. Maeda et al. (2019); Zhu et al. (2020) Fe Heme-Fe was much more associated with fecundability than non-heme Fe. Hahn et al. (2019) LC supplement LC may improve PCOS, amenorrhea disorders, sex hormone levels, oocyte health, as well as TAC and lipid peroxidation. Genazzani et al. (2011); Samimi et al. (2016); life’sDHA (2020) Beverages High intake of beverages (alcohol, caffeine, and SSBs) increases the risk of infertility. Schliep et al. (2015); Mikkelsen et al. (2016); Lyngsø et al. (2017); Machtinger et al. (2017); Arvizu Boy et al. (2018); Hatch et al. (2018) MedDiet, Mediterranean diet; PD, Prudent diet; ART, assisted reproductive technology; WestDiet, Western diet; TFA, trans fatty acid; ω-3FA, omega-3 fatty acid; GL, glycemic load; Vit D, vitamin D; PCOS, polycystic ovary syndrome; Fa, folic acid; Zn, zinc; TTP, time to pregnancy; Se, selenium; Cu, copper; Hg, mercury; LC, L-carnitine; TAC, total antioxidant capacity; SSB, sugar-sweetened beverage.
Dietary patterns
Protein
As for protein intake from non-dairy sources and its effect on fertility, Souter et al. (2017) showed that ovarian AFC was not affected by animal protein intake from non-dairy sources among women attending a fertility clinic. On the other hand, a large prospective study by Braga et al. (2015) found that consumption of red meat and poultry was inversely associated with the risk of infertility among women undergoing fertility treatment.
Regarding fish intake and the risk of infertility, Wise et al. (2018) and Gaskins et al. (2018) found that fish intake by both men and women was associated with shorter time to pregnancy (TTP). Another prospective cohort consisting of 351 women, showed that fish intake was positively associated with fertility; however, fish oil supplement use was not associated with live birth (Nassan et al., 2018). A common concern about recommending women who are pregnant or may become pregnant to consume fish is that seafood is the primary source of exposure to environmental contaminants [e.g., mercury (Hg)] (Nassan et al., 2018). This concern resulted in guidance from the Food and Drug Administration and the Environmental Protection Agency recommending pregnant women or those who may become pregnant to eat no more than 3 servings of seafood per week (US Food and Drug Administration, 2017). Most studies of fish intake and fertility showed that the benefits of fish consumption may outweigh the risk of environmental contaminants that might be carried by fish. However, certain factors such as the type or the amount of fish consumed might influence those benefits.
Only data from animal studies suggest that certain phytoestrogens may affect endocrine processes by influencing estrogen-dependent pathways and hypothesized that consumption of soy might affect fertility (Wocławek-Potocka et al., 2013; Amir et al., 2018). In a prospective study conducted among 184 men, soy intake was unrelated to the probability of live birth in couples undergoing infertility treatment (Mínguez-Alarcón et al., 2015).
Another prospective study done among 315 women, dietary soy intake was positively associated with the probability of having a live birth during infertility treatment with ART (Vanegas et al., 2015). Even though available data suggest no harmful effect, the present studies are not very recent and with small sample sizes (Jacobsen et al., 2014; Mínguez-Alarcón et al., 2015; Vanegas et al., 2015). Therefore, the association between soy protein intake and fertility remains inconclusive.
Fats
Fats, which comprise 30% to 40% of daily energy intake in Western countries, are important components of cell membranes. They modify the expression of enzymes involved in prostaglandin and steroid hormone metabolism both vital for reproduction (Wise et al., 2018).
In another prospective cohort study, seafood intake (canned tuna fish, fish, crab, shrimp, or other shellfish caught in an unknown location or in local water) was collected daily from 501 couples planning for pregnancy, and they were followed for 1 year or until pregnancy was detected. Couples with male and female partners who consumed eight or more seafood servings per cycle had 47% and 60% greater fecundity respectively than couples with male and female partners who consumed one or less seafood serving per cycle. However, the results might not be generalizable to all women of reproductive age since all couples were given fertility monitors to help time intercourse and ovulation. Moreover, there was no control for dietary confounders such as dietary supplements since the dietary assessment was not practical, and data on different types and sources of seafood was not collected during follow-up (Gaskins et al., 2018).
Carbohydrates (CHO)
Quantity and quality of dietary CHO influence glucose homeostasis and insulin sensitivity (Chiu et al., 2018), which may influence ovarian function. A common indicator of CHO quality is glycemic index (GI, a measure of the relative impact of carbohydrate-containing foods on blood glucose) whereas glycemic load (GL, product of the GI value of food and its CHO content) is an indicator of CHO quality, quantity, and amount of dietary fiber; related to the extent to which CHO has been refined (whole or refined grains).
Antioxidants
Antioxidants [vitamin E, vitamin C, β-carotene, L-carnitine (LC), N-acetyl cysteine, co-enzyme Q10 (CoQ10), zinc (Zn), selenium (Se), folic acid (Fa), and lycopene] are substances that inhibit the oxidation of cells by scavenging existing free radicals. Free radicals are highly reactive molecules that contain one or more unpaired electrons and cause damage to the cells.
Vitamin B12
Vitamin B12 or cobalamin is a water-soluble vitamin that acts as a co-factor in DNA synthesis and in both fatty acid and amino acid metabolism (Office of Dietary Supplements, 2020d). Over the past 20 years, study findings showed that vitamin B12 affects semen quality positively by increasing sperm count, motility, and minimizing sperm DNA damage (Banihani, 2017).
Vitamin D
Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis. Vitamin D helps regulate calcium and phosphate in the body to keep bones, teeth, and muscles healthy (Office of Dietary Supplements, 2020e).
In a large cohort of premenopausal women aged 30 to 49 years (n=1,430), vitamin D was inversely related to urinary FSH and for every increase of 10 ng/mL of 25(OH)D serum levels, urinary FSH decreased by 14%, consequently decreasing fertility rate (Jukic et al., 2015; Muscogiuri et al., 2017). Another case-control study compared early pregnancy levels of vitamin D between women who took 12∼24 months to get pregnant with age-matched women conceiving in less than 1 year and found no association (Somigliana et al., 2016). Similarly, no association between baseline serum vitamin D levels or vitamin D deficiency (<20 ng/mL) and fecundability was found among a large cohort of women (Mumford et al., 2018).
In the case of vitamin D deficiency during infertility treatment, vitamin D supplementation can be recommended for women with disorders like polycystic ovary syndrome, insulin resistance, or low anti-Mullerian hormone levels; considering possible toxic effects of very high doses of vitamin D (Arslan and Akdevelioğlu, 2018).
Most human studies suggest that vitamin D deficiency independently affects female and male fertility. However, there is still no strong and conclusive evidence from interventional studies; most studies were of small sample sizes with major heterogeneity with respect to the best vitamin D dose and duration.
Zn
Zn is an essential mineral that is naturally present in foods, added to others, and available as a dietary supplement. It plays an important role in protein and DNA synthesis, immune function, and cell division (Office of Dietary Supplements, 2020f). Zn also acts as an antioxidant by scavenging superoxide anions, but it can turn into a prooxidant causing mitochondrial oxidative stress when supplemented in high amounts (Lee, 2018). Some studies showed that the Zn level in the seminal plasma of infertile males was extensively lower than that of normal males (Colagar et al., 2009; Zheng et al., 2012; Shi et al., 2014; Zhao et al., 2016). Also, Zn supplementation was shown to drastically elevate sperm quality of infertile males. This may be due to the importance of this mineral in the synthesis of DNA in sperm. However, these studies had small sample sizes and the association was not clear if the change in seminal plasma Zn concentration was caused by male infertility or vice versa.
Fa and Zn
Fa is the fully oxidized form of the folate water-soluble vitamin (B9) that is used in most dietary supplements. Fa acts as a co-enzyme in the synthesis of DNA and ribonucleic acid (RNA) and metabolism of amino acids (Office of Dietary Supplements, 2020b).
Zn, copper (Cu), and Se
Cu is an essential mineral naturally present in foods and dietary supplements. It is a cofactor for numerous enzymes involved mechanisms of the body such as energy production and Fe metabolism (Office of Dietary Supplements, 2020a).
Se is a trace element that is naturally present in foods and dietary supplements. Se is a constituent of selenoproteins with antioxidant properties important for reproduction and DNA synthesis (Office of Dietary Supplements, 2020c).
Hg and Se
Hg, a naturally found element and introduced contaminant, tends to affect the nervous system. The primary source of organic Hg in humans is the consumption of fish contaminated with methylmercury (Kimáková et al., 2018). Overall, larger- and longer-lived fish (e.g., king mackerel, marlin, orange roughy, shark, etc.) tend to have high levels of Hg.
A case-control study of 98 infertile women receiving fertility treatment and 43 fertile females provided blood samples and filled a questionnaire on lifestyle and dietary habits (Maeda et al., 2019). After adjusting for potential confounders (other metals), significant associations of infertility with increased Hg and decreased Se levels were established. However, the nature of this study helps establish an association but not causation between fish intake (exposure) and fertility (outcome); adding to that, it may be prone to selection and recall bias. Furthermore, a positive, insignificant, and non-linear association between Hg and infertility was found in a cross-sectional study of 1,796 participants from the National Health and Nutrition Examination Survey (2013∼2016) (Zhu et al., 2020). Analyses identified an inflection point of 5.278 μg/L, when blood Hg>5.278 μg/L, a 1 unit increase in Hg (log2) was associated with 157% greater adjusted odds of infertility. Even if few people showed a total blood Hg>5.278 μg/L, yet, it is notable that even small increments of Hg exposure could drastically affect fertility rates. Therefore, women who are infertile should take into consideration the potentially toxic effect of Hg.
Fe
In a cross-sectional study of 209 healthy male university students in Spain, a statistically significant inverse correlation between Fe intake from foods and sperm concentration and motility was observed. However, further studies in male populations consulting for infertility problems are needed (Adoamnei et al., 2019). Hahn et al. (2019) found that heme Fe intake was associated with fecundability whereas non-heme Fe intake and supplement use were inconsistent (heme Fe is more readily absorbed by the body than non-heme Fe) but have some indication of beneficial effects on fertility among women having a higher possibility of Fe deficiency.
CoQ10
LC
Docosahexaenoic acid (DHA)
Alcohol
Caffeine and caffeinated beverages
Coffee intake within moderation (3 to 4 cups a day) has a positive influence on a person’s health (Poole et al., 2017). However, in higher doses, it may influence fertility by affecting sperm quality, ovulation, or menstrual characteristics (Wesselink et al., 2016).
Sugar-sweetened beverages (SSBs)
In conclusion, the above compiled results show that despite the multifactorial etiology of reproductive dysfunction, dietary factors may affect reproduction in both males and females. To put it briefly, adherence to a healthy dietary pattern favoring healthy fats, fish, poultry, whole grains, fruits, and vegetables, is related to better fertility in both genders. Moreover, this review included some articles that only studied the effect of dietary patterns on couples undergoing ARTs, thus, future studies focusing on the effect of diet and couples not undergoing ARTs are needed. Because much of the above evidence came from observational studies of small sample sizes, future well-designed and larger RCTs are essential to validate these findings to provide solid practical recommendations for couples planning a pregnancy. To increase the awareness of these couples, it is highly recommended that counseling on nutritional habits for both genders be implemented in preconception care worldwide.
AUTHOR DISCLOSURE STATEMENT
The authors declare no conflict of interest.
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Article
Review
Prev Nutr Food Sci 2021; 26(2): 109-120
Published online June 30, 2021 https://doi.org/10.3746/pnf.2021.26.2.109
Copyright © The Korean Society of Food Science and Nutrition.
Can Nutrition Help in the Treatment of Infertility?
Antoine Aoun , Veronique El Khoury, Roubina Malakieh
Faculty of Nursing and Health Sciences, Notre Dame University-Louaize, Zouk Mosbeh 72, Lebanon
Correspondence to:Antoine Aoun, Tel: +961-9-218-950, E-mail: aaoun@ndu.edu.lb
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Infertility is defined as the inability to conceive after 12 months of unprotected intercourse or six months for women aged 35 years or older. The physical, emotional, psychological, and financial statuses of infertile couples are tremendously affected especially after undergoing diagnostic and/or curative treatments. Human fertility is influenced by multiple factors including female or male, and modifiable or non-modifiable factors. There is growing evidence that nutrition may play an important role in adjusting fertility-related outcomes in both men and women. The objective of our study was to summarize the latest data on nutritional factors (specific food groups, nutrients, and nutritional supplements) that have an impact on female or male sexual and reproductive function. PubMed and Google Scholar platforms were used to collect appropriate articles for the review using several combinations of keywords (infertility, diet, dietary supplements, antioxidants, and beverages). Adherence to a healthy dietary pattern favoring fish, poultry, whole grains, fruits, vegetables, and healthy fats, was related to better fertility in both genders. Despite the multifactorial etiology of sexual infertility, nutrition may affect the sexual/reproductive function in both women and men.
Keywords: antioxidants, beverages, diet, dietary supplements, infertility
INTRODUCTION
Infertility is defined as “the inability to conceive after 12 months of unprotected intercourse or six months for women aged 35 years or older” (American Society for Reproductive Medicine, 2014). According to a study published by the World Health Organization (WHO) which compiled data from 277 national surveys in 190 countries, worldwide rates of infertility between 1990 and 2010 have remained relatively constant (Mascarenhas et al., 2012; WHO, 2019). Thus, the WHO estimated that in 2010, 48.5 million couples worldwide were unable to conceive. The physical, emotional, psychological, and financial statuses of infertile couples are tremendously affected especially after undergoing diagnostic-curative treatments [e.g.,
Following a nutritious/well-balanced diet and being physically active are two bases of a healthy lifestyle whereby they can help maintain a healthy weight and reduce the risk of chronic diseases (WHO, 2020). It is well-known that nutrition can play an important role in altering fertility-related outcomes in both men and women. In a large prospective cohort of 17,544 women in Nurses’ Health Study (NHS)-II, after controlling for certain confounders [age, body mass index (BMI), alcohol intake, coffee intake, smoking, and oral contraceptive use], women with the highest intake of a fertility diet [comprised of full-fat dairy foods, iron (Fe), monounsaturated fats, and plant protein] during the preconception period, were found to have a 66% lower risk of infertility related to ovulatory disorders and a 27% lower risk of infertility due to other causes compared to women with the lowest intake of this type of diet (Chavarro et al., 2007). While there is growing evidence that nutrition may be associated with reproductive outcomes in both sex, there is still no official guidelines for reproductive-aged couples (Rossi et al., 2016). This review aims to summarize the latest data on dietary factors (e.g., specific food groups, nutrients, and nutritional supplements) that have a major impact on both female and male sexual and reproductive functions.
MATERIALS AND METHODS
Our study was undertaken in the PubMed and the Google Scholar databases in November 2020, using the descriptor medical subject headings, without limitation as to the publication period (with emphasis on the most recent papers). Studies involving animals were not included. The following keyword combinations were used: “infertility” and “diet” (43 articles), “infertility” and “dietary supplements” (42 articles), “infertility” and “antioxidants” (6 articles), and “infertility” and “beverages” (15 articles). Eight articles were in common between the different combinations. Out of the total 104 articles, 24 were literature reviews, 68 were original studies, and 12 were reports from web pages of agencies and organizations. The above steps are shown in Fig. 1.
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Figure 1. Stages of study selection and inclusion of articles.
RESULTS AND DISCUSSION
Our review findings were reported in terms of pregnancy outcomes and semen variables where most of the studies reported improvement in no less than one of these outcome measures in the experimental group. Some studies that investigated the effect of dietary intake reported a positive correlation between specific macronutrient(s) or micronutrient(s) and the risk of infertility, while others reported conflicting results. The impact of various nutritional factors on male and female fertility are summarized in Table 1 and Table 2, respectively.
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Table 1 . Summary of literature on the association between diet and male fertility.
Nutritional factors Findings References Dietary patterns Healthy eating patterns positively affect semen quality and improve fecundity, while unhealthy diets had the opposite relationship. Cutillas-Tolín et al. (2015); Eslamian et al. (2017); Karayiannis et al. (2017); Danielewicz et al. (2018) Proteins High intake of dairy products might affect semen quality and fertility. Limited evidence is available from human studies on the effect of soy on fertility; however, most of them showed no harmful effect. Jacobsen et al. (2014); Mínguez-Alarcón et al. (2015); Vanegas et al. (2015); Gaskins et al. (2018); Nassan et al. (2018); Wise et al. (2018) Dietary fats TFAs are related to reduced fertility, whereas ω-3FAs are protective against SDF, TT, and testicular volume. Mínguez-Alarcón et al. (2017); Salas-Huetos et al. (2018) Carbohydrates Diets with low-glycemic load that contain high amounts of whole grains might have positive impact on fertility. Liu et al. (2015) Antioxidants Antioxidant supplementation improves semen quality and may increase the probability of clinical pregnancy and live birth. Ahmadi et al. (2016); Majzoub and Agarwal (2018); Alahmar (2019); Li et al. (2019); Henkel et al. (2019) Vit B12 supplement Vit B12 may be protective against fertility by increasing sperm count, motility and minimizing sperm DNA damage. Banihani (2017) Vit D supplement Vit D may positively affect semen quality and sperm motility but not sperm concentration. Zhu et al. (2016); Abbasihormozi et al. (2017); de Angelis et al. (2017); Bosdou et al. (2019) Zn supplements Zn may elevate sperm quality in infertile males. Colagar et al. (2009); Zheng et al. (2012); Shi et al. (2014); Zhao et al. (2016); Lee (2018) Fa and Zn supplement Fa and Zn may impose a greater influence only on sperm concentration, morphology, and serum folate level. da Silva et al. (2013); Irani et al. (2017); Schisterman et al. (2020) Iron Iron may be inversely related to sperm concentration and motility. Adoamnei et al. (2019) CoQ10 supplement No significant correlation between CoQ10 and TT levels. Banihani (2018) DHA supplement DHA may increase ω-3FAs and DHA concentration in seminal plasma, TAC, and decrease SDF. Martínez-Soto et al. (2016) Beverages Occasional/moderate intake of alcohol and caffeine does not affect semen quality, while high intake of these beverages or SSBs negatively affects semen quality. Liu et al. (2015); Wesselink et al. (2016); Karmon et al. (2017); Ricci et al. (2017); Ricci et al. (2018); Ghosh et al. (2019) TFA, trans fatty acid; ω-3FA, omega-3 fatty acid; SDF, sperm DNA fragmentation; TT, testosterone; DHA, docosahexaenoic acid; Vit B12, vitamin B12; Vit D, vitamin D; CoQ10, coenzyme Q10; TAC, total antioxidant capacity; Zn, zinc; Fa, folic acid; SSB, sugar-sweetened beverage..
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Table 2 . Summary of literature on the association between diet and female fertility.
Nutritional factors Findings References Dietary patterns Healthy dietary patterns (MedDiet and PD) have been shown to improve the chance of pregnancy and ART outcomes. Unhealthy diets (WestDiet) had the opposite relationship. Toledo et al. (2011); Karayiannis et al. (2018); Garruti et al. (2019); Gaskins et al. (2019) Proteins High-fat dairy products may increase risk of infertility whereas non-dairy protein (fish and white meat) have an important influence on female fertility. Braga et al. (2015); Kim et al. (2017); Souter et al. (2017); Wise et al. (2018) Dietary fats TFAs may increase risk of metabolic disorders that negatively affect ovarian functions; however, ω-3FAs improve fecundability. Fontana and Della Torre (2016); Gaskins et al. (2018); Wise et al. (2018) Carbohydrates Current evidence, though limited, suggest that diets with low-GL that contain high amounts of whole grains may benefit fecundity. Liese et al. (2003); Blomhoff (2005); Gaskins et al. (2016); Chiu et al. (2018) Antioxidants Antioxidants might provide benefit for subfertile women. Showell et al. (2020) Vit D supplement Vit D may be beneficial only for women with disorders like PCOS, insulin resistance, or low anti-Mullerian hormone levels. Jukic et al. (2015); Somigliana et al. (2016); Muscogiuri et al. (2017); Arslan and Akdevelioğlu (2018); Mumford et al. (2018) Fa and Zn supplement Fa and Zn may decrease the risk of ovulatory infertility, sporadic anovulation, and TTP. Cueto et al. (2016); Chiu et al. (2018) Zn and Se supplement Zn and Se may reduce TTP and risk of subfertility. Grieger et al. (2019); Maeda et al. (2019) Cu Cu does not have an important influence on female infertility. Bawa and Tyagi (2017) Hg Intake of fish with high levels of Hg may be of concern to women planning pregnancy or pregnant women. Maeda et al. (2019); Zhu et al. (2020) Fe Heme-Fe was much more associated with fecundability than non-heme Fe. Hahn et al. (2019) LC supplement LC may improve PCOS, amenorrhea disorders, sex hormone levels, oocyte health, as well as TAC and lipid peroxidation. Genazzani et al. (2011); Samimi et al. (2016); life’sDHA (2020) Beverages High intake of beverages (alcohol, caffeine, and SSBs) increases the risk of infertility. Schliep et al. (2015); Mikkelsen et al. (2016); Lyngsø et al. (2017); Machtinger et al. (2017); Arvizu Boy et al. (2018); Hatch et al. (2018) MedDiet, Mediterranean diet; PD, Prudent diet; ART, assisted reproductive technology; WestDiet, Western diet; TFA, trans fatty acid; ω-3FA, omega-3 fatty acid; GL, glycemic load; Vit D, vitamin D; PCOS, polycystic ovary syndrome; Fa, folic acid; Zn, zinc; TTP, time to pregnancy; Se, selenium; Cu, copper; Hg, mercury; LC, L-carnitine; TAC, total antioxidant capacity; SSB, sugar-sweetened beverage..
Dietary patterns
Protein
As for protein intake from non-dairy sources and its effect on fertility, Souter et al. (2017) showed that ovarian AFC was not affected by animal protein intake from non-dairy sources among women attending a fertility clinic. On the other hand, a large prospective study by Braga et al. (2015) found that consumption of red meat and poultry was inversely associated with the risk of infertility among women undergoing fertility treatment.
Regarding fish intake and the risk of infertility, Wise et al. (2018) and Gaskins et al. (2018) found that fish intake by both men and women was associated with shorter time to pregnancy (TTP). Another prospective cohort consisting of 351 women, showed that fish intake was positively associated with fertility; however, fish oil supplement use was not associated with live birth (Nassan et al., 2018). A common concern about recommending women who are pregnant or may become pregnant to consume fish is that seafood is the primary source of exposure to environmental contaminants [e.g., mercury (Hg)] (Nassan et al., 2018). This concern resulted in guidance from the Food and Drug Administration and the Environmental Protection Agency recommending pregnant women or those who may become pregnant to eat no more than 3 servings of seafood per week (US Food and Drug Administration, 2017). Most studies of fish intake and fertility showed that the benefits of fish consumption may outweigh the risk of environmental contaminants that might be carried by fish. However, certain factors such as the type or the amount of fish consumed might influence those benefits.
Only data from animal studies suggest that certain phytoestrogens may affect endocrine processes by influencing estrogen-dependent pathways and hypothesized that consumption of soy might affect fertility (Wocławek-Potocka et al., 2013; Amir et al., 2018). In a prospective study conducted among 184 men, soy intake was unrelated to the probability of live birth in couples undergoing infertility treatment (Mínguez-Alarcón et al., 2015).
Another prospective study done among 315 women, dietary soy intake was positively associated with the probability of having a live birth during infertility treatment with ART (Vanegas et al., 2015). Even though available data suggest no harmful effect, the present studies are not very recent and with small sample sizes (Jacobsen et al., 2014; Mínguez-Alarcón et al., 2015; Vanegas et al., 2015). Therefore, the association between soy protein intake and fertility remains inconclusive.
Fats
Fats, which comprise 30% to 40% of daily energy intake in Western countries, are important components of cell membranes. They modify the expression of enzymes involved in prostaglandin and steroid hormone metabolism both vital for reproduction (Wise et al., 2018).
In another prospective cohort study, seafood intake (canned tuna fish, fish, crab, shrimp, or other shellfish caught in an unknown location or in local water) was collected daily from 501 couples planning for pregnancy, and they were followed for 1 year or until pregnancy was detected. Couples with male and female partners who consumed eight or more seafood servings per cycle had 47% and 60% greater fecundity respectively than couples with male and female partners who consumed one or less seafood serving per cycle. However, the results might not be generalizable to all women of reproductive age since all couples were given fertility monitors to help time intercourse and ovulation. Moreover, there was no control for dietary confounders such as dietary supplements since the dietary assessment was not practical, and data on different types and sources of seafood was not collected during follow-up (Gaskins et al., 2018).
Carbohydrates (CHO)
Quantity and quality of dietary CHO influence glucose homeostasis and insulin sensitivity (Chiu et al., 2018), which may influence ovarian function. A common indicator of CHO quality is glycemic index (GI, a measure of the relative impact of carbohydrate-containing foods on blood glucose) whereas glycemic load (GL, product of the GI value of food and its CHO content) is an indicator of CHO quality, quantity, and amount of dietary fiber; related to the extent to which CHO has been refined (whole or refined grains).
Antioxidants
Antioxidants [vitamin E, vitamin C, β-carotene, L-carnitine (LC), N-acetyl cysteine, co-enzyme Q10 (CoQ10), zinc (Zn), selenium (Se), folic acid (Fa), and lycopene] are substances that inhibit the oxidation of cells by scavenging existing free radicals. Free radicals are highly reactive molecules that contain one or more unpaired electrons and cause damage to the cells.
Vitamin B12
Vitamin B12 or cobalamin is a water-soluble vitamin that acts as a co-factor in DNA synthesis and in both fatty acid and amino acid metabolism (Office of Dietary Supplements, 2020d). Over the past 20 years, study findings showed that vitamin B12 affects semen quality positively by increasing sperm count, motility, and minimizing sperm DNA damage (Banihani, 2017).
Vitamin D
Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis. Vitamin D helps regulate calcium and phosphate in the body to keep bones, teeth, and muscles healthy (Office of Dietary Supplements, 2020e).
In a large cohort of premenopausal women aged 30 to 49 years (n=1,430), vitamin D was inversely related to urinary FSH and for every increase of 10 ng/mL of 25(OH)D serum levels, urinary FSH decreased by 14%, consequently decreasing fertility rate (Jukic et al., 2015; Muscogiuri et al., 2017). Another case-control study compared early pregnancy levels of vitamin D between women who took 12∼24 months to get pregnant with age-matched women conceiving in less than 1 year and found no association (Somigliana et al., 2016). Similarly, no association between baseline serum vitamin D levels or vitamin D deficiency (<20 ng/mL) and fecundability was found among a large cohort of women (Mumford et al., 2018).
In the case of vitamin D deficiency during infertility treatment, vitamin D supplementation can be recommended for women with disorders like polycystic ovary syndrome, insulin resistance, or low anti-Mullerian hormone levels; considering possible toxic effects of very high doses of vitamin D (Arslan and Akdevelioğlu, 2018).
Most human studies suggest that vitamin D deficiency independently affects female and male fertility. However, there is still no strong and conclusive evidence from interventional studies; most studies were of small sample sizes with major heterogeneity with respect to the best vitamin D dose and duration.
Zn
Zn is an essential mineral that is naturally present in foods, added to others, and available as a dietary supplement. It plays an important role in protein and DNA synthesis, immune function, and cell division (Office of Dietary Supplements, 2020f). Zn also acts as an antioxidant by scavenging superoxide anions, but it can turn into a prooxidant causing mitochondrial oxidative stress when supplemented in high amounts (Lee, 2018). Some studies showed that the Zn level in the seminal plasma of infertile males was extensively lower than that of normal males (Colagar et al., 2009; Zheng et al., 2012; Shi et al., 2014; Zhao et al., 2016). Also, Zn supplementation was shown to drastically elevate sperm quality of infertile males. This may be due to the importance of this mineral in the synthesis of DNA in sperm. However, these studies had small sample sizes and the association was not clear if the change in seminal plasma Zn concentration was caused by male infertility or vice versa.
Fa and Zn
Fa is the fully oxidized form of the folate water-soluble vitamin (B9) that is used in most dietary supplements. Fa acts as a co-enzyme in the synthesis of DNA and ribonucleic acid (RNA) and metabolism of amino acids (Office of Dietary Supplements, 2020b).
Zn, copper (Cu), and Se
Cu is an essential mineral naturally present in foods and dietary supplements. It is a cofactor for numerous enzymes involved mechanisms of the body such as energy production and Fe metabolism (Office of Dietary Supplements, 2020a).
Se is a trace element that is naturally present in foods and dietary supplements. Se is a constituent of selenoproteins with antioxidant properties important for reproduction and DNA synthesis (Office of Dietary Supplements, 2020c).
Hg and Se
Hg, a naturally found element and introduced contaminant, tends to affect the nervous system. The primary source of organic Hg in humans is the consumption of fish contaminated with methylmercury (Kimáková et al., 2018). Overall, larger- and longer-lived fish (e.g., king mackerel, marlin, orange roughy, shark, etc.) tend to have high levels of Hg.
A case-control study of 98 infertile women receiving fertility treatment and 43 fertile females provided blood samples and filled a questionnaire on lifestyle and dietary habits (Maeda et al., 2019). After adjusting for potential confounders (other metals), significant associations of infertility with increased Hg and decreased Se levels were established. However, the nature of this study helps establish an association but not causation between fish intake (exposure) and fertility (outcome); adding to that, it may be prone to selection and recall bias. Furthermore, a positive, insignificant, and non-linear association between Hg and infertility was found in a cross-sectional study of 1,796 participants from the National Health and Nutrition Examination Survey (2013∼2016) (Zhu et al., 2020). Analyses identified an inflection point of 5.278 μg/L, when blood Hg>5.278 μg/L, a 1 unit increase in Hg (log2) was associated with 157% greater adjusted odds of infertility. Even if few people showed a total blood Hg>5.278 μg/L, yet, it is notable that even small increments of Hg exposure could drastically affect fertility rates. Therefore, women who are infertile should take into consideration the potentially toxic effect of Hg.
Fe
In a cross-sectional study of 209 healthy male university students in Spain, a statistically significant inverse correlation between Fe intake from foods and sperm concentration and motility was observed. However, further studies in male populations consulting for infertility problems are needed (Adoamnei et al., 2019). Hahn et al. (2019) found that heme Fe intake was associated with fecundability whereas non-heme Fe intake and supplement use were inconsistent (heme Fe is more readily absorbed by the body than non-heme Fe) but have some indication of beneficial effects on fertility among women having a higher possibility of Fe deficiency.
CoQ10
LC
Docosahexaenoic acid (DHA)
Alcohol
Caffeine and caffeinated beverages
Coffee intake within moderation (3 to 4 cups a day) has a positive influence on a person’s health (Poole et al., 2017). However, in higher doses, it may influence fertility by affecting sperm quality, ovulation, or menstrual characteristics (Wesselink et al., 2016).
Sugar-sweetened beverages (SSBs)
In conclusion, the above compiled results show that despite the multifactorial etiology of reproductive dysfunction, dietary factors may affect reproduction in both males and females. To put it briefly, adherence to a healthy dietary pattern favoring healthy fats, fish, poultry, whole grains, fruits, and vegetables, is related to better fertility in both genders. Moreover, this review included some articles that only studied the effect of dietary patterns on couples undergoing ARTs, thus, future studies focusing on the effect of diet and couples not undergoing ARTs are needed. Because much of the above evidence came from observational studies of small sample sizes, future well-designed and larger RCTs are essential to validate these findings to provide solid practical recommendations for couples planning a pregnancy. To increase the awareness of these couples, it is highly recommended that counseling on nutritional habits for both genders be implemented in preconception care worldwide.
AUTHOR DISCLOSURE STATEMENT
The authors declare no conflict of interest.
Fig 1.

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Table 1 . Summary of literature on the association between diet and male fertility
Nutritional factors Findings References Dietary patterns Healthy eating patterns positively affect semen quality and improve fecundity, while unhealthy diets had the opposite relationship. Cutillas-Tolín et al. (2015); Eslamian et al. (2017); Karayiannis et al. (2017); Danielewicz et al. (2018) Proteins High intake of dairy products might affect semen quality and fertility. Limited evidence is available from human studies on the effect of soy on fertility; however, most of them showed no harmful effect. Jacobsen et al. (2014); Mínguez-Alarcón et al. (2015); Vanegas et al. (2015); Gaskins et al. (2018); Nassan et al. (2018); Wise et al. (2018) Dietary fats TFAs are related to reduced fertility, whereas ω-3FAs are protective against SDF, TT, and testicular volume. Mínguez-Alarcón et al. (2017); Salas-Huetos et al. (2018) Carbohydrates Diets with low-glycemic load that contain high amounts of whole grains might have positive impact on fertility. Liu et al. (2015) Antioxidants Antioxidant supplementation improves semen quality and may increase the probability of clinical pregnancy and live birth. Ahmadi et al. (2016); Majzoub and Agarwal (2018); Alahmar (2019); Li et al. (2019); Henkel et al. (2019) Vit B12 supplement Vit B12 may be protective against fertility by increasing sperm count, motility and minimizing sperm DNA damage. Banihani (2017) Vit D supplement Vit D may positively affect semen quality and sperm motility but not sperm concentration. Zhu et al. (2016); Abbasihormozi et al. (2017); de Angelis et al. (2017); Bosdou et al. (2019) Zn supplements Zn may elevate sperm quality in infertile males. Colagar et al. (2009); Zheng et al. (2012); Shi et al. (2014); Zhao et al. (2016); Lee (2018) Fa and Zn supplement Fa and Zn may impose a greater influence only on sperm concentration, morphology, and serum folate level. da Silva et al. (2013); Irani et al. (2017); Schisterman et al. (2020) Iron Iron may be inversely related to sperm concentration and motility. Adoamnei et al. (2019) CoQ10 supplement No significant correlation between CoQ10 and TT levels. Banihani (2018) DHA supplement DHA may increase ω-3FAs and DHA concentration in seminal plasma, TAC, and decrease SDF. Martínez-Soto et al. (2016) Beverages Occasional/moderate intake of alcohol and caffeine does not affect semen quality, while high intake of these beverages or SSBs negatively affects semen quality. Liu et al. (2015); Wesselink et al. (2016); Karmon et al. (2017); Ricci et al. (2017); Ricci et al. (2018); Ghosh et al. (2019) TFA, trans fatty acid; ω-3FA, omega-3 fatty acid; SDF, sperm DNA fragmentation; TT, testosterone; DHA, docosahexaenoic acid; Vit B12, vitamin B12; Vit D, vitamin D; CoQ10, coenzyme Q10; TAC, total antioxidant capacity; Zn, zinc; Fa, folic acid; SSB, sugar-sweetened beverage.
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Table 2 . Summary of literature on the association between diet and female fertility
Nutritional factors Findings References Dietary patterns Healthy dietary patterns (MedDiet and PD) have been shown to improve the chance of pregnancy and ART outcomes. Unhealthy diets (WestDiet) had the opposite relationship. Toledo et al. (2011); Karayiannis et al. (2018); Garruti et al. (2019); Gaskins et al. (2019) Proteins High-fat dairy products may increase risk of infertility whereas non-dairy protein (fish and white meat) have an important influence on female fertility. Braga et al. (2015); Kim et al. (2017); Souter et al. (2017); Wise et al. (2018) Dietary fats TFAs may increase risk of metabolic disorders that negatively affect ovarian functions; however, ω-3FAs improve fecundability. Fontana and Della Torre (2016); Gaskins et al. (2018); Wise et al. (2018) Carbohydrates Current evidence, though limited, suggest that diets with low-GL that contain high amounts of whole grains may benefit fecundity. Liese et al. (2003); Blomhoff (2005); Gaskins et al. (2016); Chiu et al. (2018) Antioxidants Antioxidants might provide benefit for subfertile women. Showell et al. (2020) Vit D supplement Vit D may be beneficial only for women with disorders like PCOS, insulin resistance, or low anti-Mullerian hormone levels. Jukic et al. (2015); Somigliana et al. (2016); Muscogiuri et al. (2017); Arslan and Akdevelioğlu (2018); Mumford et al. (2018) Fa and Zn supplement Fa and Zn may decrease the risk of ovulatory infertility, sporadic anovulation, and TTP. Cueto et al. (2016); Chiu et al. (2018) Zn and Se supplement Zn and Se may reduce TTP and risk of subfertility. Grieger et al. (2019); Maeda et al. (2019) Cu Cu does not have an important influence on female infertility. Bawa and Tyagi (2017) Hg Intake of fish with high levels of Hg may be of concern to women planning pregnancy or pregnant women. Maeda et al. (2019); Zhu et al. (2020) Fe Heme-Fe was much more associated with fecundability than non-heme Fe. Hahn et al. (2019) LC supplement LC may improve PCOS, amenorrhea disorders, sex hormone levels, oocyte health, as well as TAC and lipid peroxidation. Genazzani et al. (2011); Samimi et al. (2016); life’sDHA (2020) Beverages High intake of beverages (alcohol, caffeine, and SSBs) increases the risk of infertility. Schliep et al. (2015); Mikkelsen et al. (2016); Lyngsø et al. (2017); Machtinger et al. (2017); Arvizu Boy et al. (2018); Hatch et al. (2018) MedDiet, Mediterranean diet; PD, Prudent diet; ART, assisted reproductive technology; WestDiet, Western diet; TFA, trans fatty acid; ω-3FA, omega-3 fatty acid; GL, glycemic load; Vit D, vitamin D; PCOS, polycystic ovary syndrome; Fa, folic acid; Zn, zinc; TTP, time to pregnancy; Se, selenium; Cu, copper; Hg, mercury; LC, L-carnitine; TAC, total antioxidant capacity; SSB, sugar-sweetened beverage.
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