Assessing the influence of preconception diet on male fertility: a systematic scoping review.

BACKGROUND: The last decade has seen increased research on the relationship between diet and male fertility, but there are no clearly defined nutritional recommendations for men in the preconception period to support clinical fertility outcomes. OBJECTIVE AND RATIONALE: The purpose of this scoping review is to examine the extent and range of research undertaken to evaluate the effect(s) of diet in the preconception period on male clinical fertility and reproductive outcomes. SEARCH METHODS: Four electronic databases (MEDLINE and EMBASE via Ovid, CAB Direct, and CINAHL via EBSCO) were searched from inception to July 2023 for randomized controlled trials (RCTs) and observational studies (prospective/retrospective, case-control, and cross-sectional). Intervention studies in male participants or couples aiming to achieve dietary or nutritional change, or non-intervention studies examining dietary or nutritional components (whole diets, dietary patterns, food groups or individual foods) in the preconception period were included. Controls were defined as any comparison group for RCTs, and any/no comparison for observational studies. Primary outcomes of interest included the effect(s) of male preconception diet on clinical outcomes such as conception (natural or via ART), pregnancy rates and live birth rates. Secondary outcomes included time to conception and sperm parameters. OUTCOMES: A total of 37 studies were eligible, including one RCT and 36 observational studies (prospective, cross-sectional, and case-control studies; four studies in non-ART populations) published between 2008 and 2023. Eight reported clinical outcomes, 26 reported on secondary outcomes, and three reported on both. The RCT did not assess clinical outcomes but found that tomato juice may benefit sperm motility. In observational studies, some evidence suggested that increasing fish or reducing sugar-sweetened beverages, processed meat or total fat may improve fecundability. Evidence for other clinical outcomes, such as pregnancy rates or live birth rates, showed no relationship with cereals, soy and dairy, and inconsistent relationships with consuming red meat or a 'healthy diet' pattern. For improved sperm parameters, limited evidence supported increasing fish, fats/fatty acids, carbohydrates and dairy, and reducing processed meat, while the evidence for fruits, vegetables, cereals, legumes, eggs, red meat and protein was inconsistent. Healthy diet patterns in general were shown to improve sperm health. WIDER IMPLICATIONS: Specific dietary recommendations for improving male fertility are precluded by the lack of reporting on clinical pregnancy outcomes, heterogeneity of the available literature and the paucity of RCTs to determine causation or to rule out reverse causation. There may be some benefit from increasing fish, adopting a healthy dietary pattern, and reducing consumption of sugar-sweetened beverages and processed meat, but it is unclear whether these benefits extend beyond sperm parameters to improve clinical fertility. More studies exploring whole diets rather than singular foods or nutritional components in the context of male fertility are encouraged, particularly by means of RCTs where feasible. Further assessment of core fertility outcomes is warranted and requires careful planning in high-quality prospective studies and RCTs. These studies can lay the groundwork for targeted dietary guidelines and enhance the prospects of successful fertility outcomes for men in the preconception period. Systematic search of preconception diet suggests that increasing fish and reducing sugary drinks, processed meats and total fat may improve male fertility, while consuming healthy diets, fish, fats/fatty acids, carbohydrates and dairy and reducing processed meat can improve sperm health.

Assessing the influence of preconception diet on female fertility: a systematic scoping review of observational studies.

BACKGROUND: Preconception diet is a proposed modifiable risk factor for infertility. However, there is no official guidance for women in the preconception period as to which dietary approaches may improve fertility. OBJECTIVE AND RATIONALE: A comprehensive synthesis of the relevant evidence is key to determine the potentially effective dietary patterns and components as well as evidence gaps, and to provide information for nutritional recommendations for couples planning a pregnancy. SEARCH METHODS: In this systematic scoping review, four electronic databases (Medline and EMBASE via Ovid processing, CAB Direct, and CINAHL via EBSCO) were searched for observational studies (prospective and retrospective cohort, cross-sectional, and case-control studies) from inception to 27 September 2021. Eligible studies included women of reproductive age during the preconception period, and evaluated exposures related to preconception diet and outcomes related to fertility. Results were synthesized using a descriptive approach. OUTCOMES: A total of 36 studies were eligible for inclusion (31 prospective, 3 cross-sectional, and 2 case-control studies) and were published between 2007 and 2022. Of the assessed dietary exposures, increased adherence to the Mediterranean diet displayed the strongest and most consistent association with improved clinical pregnancy rates. Reducing trans fatty acids (TFAs), saturated fatty acids, and discretionary food intake (fast food and sugar-sweetened beverages) were associated with improvements in live birth, clinical pregnancy rates, and related ART outcomes. The dietary components of seafood, dairy, and soy demonstrated inconsistent findings across the few included studies. WIDER IMPLICATIONS: Due to heterogeneity and the limited available literature on most exposures, there is insufficient evidence to support any specific dietary approach for improving fertility. However, following some of the dietary approaches outlined in this review (anti-inflammatory diets, reducing TFA, and discretionary food intake) are consistent with broad healthy eating guidelines, have little to no associated risk, and offer a plausible set of possible benefits. This warrants further exploration in randomized controlled trials.

Insulin resistance and associated factors in female adolescents from two capital cities in the north and south of Brazil.

BACKGROUND: It has been described that physiological changes in glucose metabolism, represented by insulin resistance (IR), are predicted during pubertal evolution, and obesity may be associated with its persistence even at the end of puberty. The aim of this study was to investigate the prevalence of IR in female adolescents with possible associated factors and evaluate the relationship of time since menarche (< 2 vs. ≥ 2 years) in the occurrence of IR in two Brazilian capital cities: Porto Velho (RO) and Porto Alegre (RS). METHODS: This is a cross-sectional school-based study, using information from the Study of Cardiovascular Risks (ERICA) database for adolescents aged 12-17 years, enrolled in public and private schools, in municipalities with more than 100,000 inhabitants in Brazil, between 2013 and 2014. The present study included 889 adolescents, 382 in Porto Velho (PVh) and 507 in Porto Alegre (PoA). The homeostasis model assessment for insulin resistance (HOMA-IR) ≥ 3.16 and fasting insulin ≥ 15 mU/L was used to determine the outcome variable of IR. Estimates of crude and adjusted prevalence ratios with confidence intervals of 95% were calculated using Poisson regression with robust variance. Sociodemographic, behavioral, reproductive and nutritional characteristics were considered as potential confounding factors in multivariable models based on a conceptual framework of IR determination. RESULTS: In the total sample, the prevalence of IR was 22.03% (95% CI 17.84-26.89). After adjusting the models, age 15-17 years and time since menarche ≥ 2 years were found to act as protective factors for IR; in contrast, the highest probability of IR was observed in black adolescents, with increased waist circumference (WC) and overweight/obesity (Ow/Ob). The protective effect of two or more years since menarche (post-menarche) was observed for both higher HOMA-IR and fasting insulin in PVh; in PoA, such protection was maintained only for fasting insulin ≥ 15 mU/L after adjustments in the multivariate models. CONCLUSIONS: IR is more prevalent during the peri-menarche period, especially in younger and black adolescents, compared to their white and post-menarche counterparts. The association between Ow/Ob and high WC with the occurrence of IR was independent of age and ethnicity variables.

Are vitamin D deficiency and VDR gene polymorphisms associated with high blood pressure as defined by the ACC/AHA 2017 criteria in postmenopausal women?

OBJECTIVES: To assess the vitamin D levels, prevalence of vitamin D deficiency and genotypes of Fok-I, Bsm-I, Apa-I and Taq-I polymorphisms in the VDR gene and to determine whether vitamin D deficiency and VDR gene variants are associated with blood pressure levels and systemic arterial hypertension as defined by the 2017 ACC/AHA criteria. STUDY DESIGN: A cross-sectional study of biobanked blood samples from 339 postmenopausal women. MAIN OUTCOME MEASURES: Blood pressure strata were defined according to the 2017 ACC/AHA cutoffs. Circulating 25(OH)D levels were considered deficient if <20 ng/mL. RESULTS: Mean serum total 25(OH)D levels were 22.99 ± 8.54 ng/mL, and 40.1% of participants were deficient in vitamin D. Overall, 7.7% had elevated blood pressure, 36.6% had stage 1 and 37.8% had stage 2 hypertension. Mean total (p = 0.014) and free 25(OH)D levels (p = 0.029) were lower in women with stage 2 hypertension than in those with normal blood pressure. A higher prevalence rate of stage 2 hypertension was associated with age (PR 1.058; 95%CI 1.033-1.083; p < 0.001), BMI (PR 1.046; 95%CI 1.025-1.068; p < 0.001), vitamin D deficiency (PR 1.333; 95%CI 1.016-1.749; p = 0.038) and Taq-I polymorphism (PR 1.764; 95%CI 1.030-3.019; p = 0.039). Women with vitamin D deficiency and the AA+AG genotype of Taq-I polymorphism were 33% and 76% more likely to have stage 2 hypertension, respectively, but these associations lost significance when adjusted for age and BMI. CONCLUSION: The results suggest that vitamin D deficiency and Taq-I polymorphism are associated with stage 2 hypertension, depending on age and BMI, in postmenopausal women.

C-reactive protein gene rs1205 polymorphism is associated with low-grade chronic inflammation in postmenopausal women.

BACKGROUND: Cardiovascular disease is the leading cause of death in postmenopausal women, and inflammation is a key mechanism involved in the pathogenesis of atherosclerosis. High-sensitivity C-reactive protein (hs-CRP) has been used as a biomarker of inflammation. Considering that CRP gene rs1205 polymorphism has been associated with hs-CRP circulating levels, we evaluated whether rs1205 genotypes influence the presence of low-grade chronic inflammation, acting as a marker of cardiovascular risk. METHODS: We performed a cross-sectional study with biobanked blood samples from 327 postmenopausal women with no evidence of clinical disease. Genotyping for rs1205 C > T SNP of the CRP gene was done by real-time polymerase chain reaction with allelic discrimination assays. RESULTS: Mean age was 55.6 ± 5.6 years. Mean body mass index (BMI) was 27.3 ± 4.7. Participants were divided according to hs-CRP levels: ≥3 mg/l (low-grade chronic inflammation) or < 3 mg/l. The frequency of allele C at rs1205 was 74.2% in the hs-CRP ≥ 3 mg/l group vs. 59% in the hs-CRP < 3 mg/l. In a multivariable model, higher prevalence of hs-CRP ≥ 3 mg/l was associated with CC genotype (PR 1.53; 95%CI 1.07-2.18; p = 0.018) and waist circumference ≥ 88 cm (PR 2.45; 95%CI 1.66-3.60; p < 0.001). CONCLUSIONS: CRP rs1205 CC homozygotes may be at higher risk of a low-grade chronic inflammatory status compared to individuals carrying the T allele.

Prevalence of vitamin D deficiency in women from southern Brazil and association with vitamin D-binding protein levels and GC-DBP gene polymorphisms.

Vitamin D deficiency is highly prevalent worldwide, and vitamin D-binding protein (DBP) a major regulator of serum vitamin D levels. The rs4588 and rs7041 polymorphisms of the GC gene constitute the genetic basis of the three major isoforms of circulating DBP (GC1s, GC1f, and GC2), while the rs2282679 variant is located in an important regulatory region of the GC gene. The aim of this study was to assess the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency and to ascertain whether it is associated with DBP levels and with GC gene variants. Biorepository samples of 443 women aged 20 to 72 years, with no evidence of clinical disease, were analyzed. Circulating levels of 25(OH)D were considered sufficient if ≥20 ng/mL and deficient if <20 ng/mL. Genotype analysis was performed by RT-PCR. Mean age was 53.4±9.4 years; mean BMI was 27.8±5.8 kg/m2. The overall sample had mean 25(OH)D levels of 22.8±8.3 ng/mL; 39.7% of participants had deficient circulating 25(OH)D levels. Higher prevalence ratios (PR) of 25(OH)D deficiency were found for the CC genotype of rs2282679 (PR 1.74; 95%CI 1.30 to 2.24; p<0.001), GC2 isoform (PR 1.66; 95%CI 1.17 to 2.38; p = 0.005), time since menopause (PR 1.02; 95%CI 1.003 to 1.03, p = 0.016), and HOMA-IR (PR 1.02; 95%CI 1.01 to 1.03, p = 0.004). DBP levels (per 30 µg/mL increase in DBP) were associated with lower PR for 25(OH)D deficiency (PR 0.89; 95%CI 0.80;0.99; p = 0.027). Except for HOMA-IR, these prevalence ratios remained significant after adjustment for age and BMI. In conclusion, the rs2282679 polymorphism and the GC2 isoform of DBP were associated with lower serum DBP levels and with susceptibility to 25(OH)D deficiency in Brazilian women with no evidence of clinical disease.

Sedentary Lifestyle and High-Carbohydrate Intake are Associated with Low-Grade Chronic Inflammation in Post-Menopause: A Cross-sectional Study.

Introduction Cardiovascular disease (CVD) is the leading cause of death in post menopausal women, and inflammation is involved in the atherosclerosis process. Purpose to assess whether dietary pattern, metabolic profile, body composition and physical activity are associated with low-grade chronic inflammation according to high-sensitivity C-reactive protein (hs-CRP) levels in postmenopausal women. Methods ninety-five postmenopausal participants, with no evidence of clinical disease, underwent anthropometric, metabolic and hormonal assessments. Usual dietary intake was assessed with a validated food frequency questionnaire, habitual physical activity was measured with a digital pedometer, and body composition was estimated by bioelectrical impedance analysis. Patients with hs-CRP ≥10 mg/L or using hormone therapy in the last three months before the study were excluded from the analysis. Participants were stratified according to hs-CRP lower or ≥3 mg/L. Sedentary lifestyle was defined as walking fewer than 6 thousand steps a day. Two-tailed Student's t-test, Wilcoxon-Mann-Whitney U or Chi-square (χ(2)) test were used to compare differences between groups. A logistic regression model was used to estimate the odds ratio of variables for high hs-CRP. Results participants with hs-CRP ≥3 mg/L had higher body mass index (BMI), body fat percentage, waist circumference (WC), triglycerides, glucose, and homeostasis model assessment of insulin resistance (HOMA-IR) (p = 0.01 for all variables) than women with hs-CRP <3 mg/L. Also, women with hs-CRP ≥3 mg/L had a higher glycemic load diet and lower protein intake. Prevalence of sedentary lifestyle (p < 0.01) and metabolic syndrome (p < 0.01) was higher in women with hs-CRP ≥3 mg/L. After adjustment for age and time since menopause, the odds ratio for hs-CRP ≥3 mg/L was higher for sedentary lifestyle (4.7, 95% confidence interval [95%CI] 1.4-15.5) and carbohydrate intake (2.9, 95%CI 1.1-7.7). Conclusions sedentary lifestyle and high-carbohydrate intake were associated with low-grade chronic inflammation and cardiovascular risk in postmenopause.

Subclinical cardiovascular disease in postmenopausal women with low/medium cardiovascular risk by the Framingham risk score.

OBJECTIVES: To evaluate the prevalence of subclinical cardiovascular disease (CVD) and its association with clinical and hormone variables in postmenopausal women from Southern Brazil. STUDY DESIGN: Cross-sectional study. MAIN OUTCOME MEASURES: Coronary artery calcification (CAC) assessed by electron-beam computed tomography. Carotid intima-media thickness (IMT) and atheromatous plaques assessed using B-mode ultrasound. IMT was measured at three segments. Subclinical CVD was defined as the presence of plaque and/or IMT >0.9 mm. RESULTS: Ninety-seven postmenopausal women (mean age 55 ± 5 years, median duration of menopause 5.8 [3-10] years) were studied. A low/medium Framingham risk score (FRS) was present in 97.9% of participants; 35.1% had subclinical CVD on carotid ultrasound, and 24.7% had the presence of plaque. Seven women had a CAC score ≥ 100, and two had a score ≥ 200. CAC score (p<0.001) and FRS (p=0.013) were higher in patients with subclinical atherosclerosis. Positive correlations were found between IMT and age (rs=0.293 p=0.004), duration of menopause (rs=0.237, p=0.020), and CAC score (rs=0.468, p<0.001). Common carotid IMT (IMT-CC) was negatively associated with estradiol levels (ß=-0.237, p=0.018) and positively with age (ß=0.210, p=0.033), and BMI (ß=0.260, p=0.010). However, correlations with estradiol and age did not remain significant when adjusted for systolic blood pressure and LDL-cholesterol levels. CONCLUSION: A high prevalence of subclinical atherosclerosis was detected in this sample of postmenopausal women with low/medium CV risk by the FRS. The association between IMT-CC and age or endogenous estrogen levels was dependent of blood pressure and LDL-cholesterol in these postmenopausal women from Southern Brazil.

Sedentary Lifestyle and High-Carbohydrate Intake are Associated with Low-Grade Chronic Inflammation in Post-Menopause: A Cross-sectional Study / Sedentarismo e alto consumo de carboidratos associados à inflamação crônica de baixo grau na pós-menopausa: um estudo transversal

Abstract Introduction Cardiovascular disease (CVD) is the leading cause of death in post menopausal women, and inflammation is involved in the atherosclerosis process. Purpose to assess whether dietary pattern, metabolic profile, body composition and physical activity are associated with low-grade chronic inflammation according to highsensitivity C-reactive protein (hs-CRP) levels in postmenopausal women. Methods ninety-five postmenopausal participants, with no evidence of clinical disease, underwent anthropometric, metabolic and hormonal assessments. Usual dietary intake was assessed with a validated food frequency questionnaire, habitual physical activity was measured with a digital pedometer, and body composition was estimated by bioelectrical impedance analysis. Patients with hs-CRP ≥ 10 mg/L or using hormone therapy in the last three months before the study were excluded from the analysis. Participants were stratified according to hs-CRP lower or ≥3 mg/L. Sedentary lifestyle was defined as walking fewer than 6 thousand steps a day. Two-tailed Student's t-test, Wilcoxon-Mann-Whitney U or Chi-square (x 2) test were used to compare differences between groups. A logistic regression model was used to estimate the odds ratio of variables for high hs-CRP. Results participants with hs-CRP ≥ 3 mg/L had higher body mass index (BMI), body fat percentage, waist circumference (WC), triglycerides, glucose, and homeostasis model assessment of insulin resistance (HOMA-IR) (p = 0.01 for all variables) than women with hs-CRP <3 mg/L. Also, women with hs-CRP ≥3 mg/L had a higher glycemic load diet and lower protein intake. Prevalence of sedentary lifestyle (p < 0.01) and metabolic syndrome (p < 0.01) was higher in women with hs-CRP ≥3 mg/L. After adjustment for age and time since menopause, the odds ratio for hs- CRP ≥3 mg/L was higher for sedentary lifestyle (4.7, 95% confidence interval [95%CI] 1.4-15.5) and carbohydrate intake (2.9, 95%CI 1.1-7.7). Conclusions sedentary lifestyle and high-carbohydrate intake were associated with low-grade chronic inflammation and cardiovascular risk in postmenopause.

Resumo Introdução A doença cardiovascular é a principal causa de morte em mulheres na pós-menpausa e inflamação está envolvida com o processo de aterosclerose. Objetivo avaliar se o padrão alimentar, o perfilmetabólico, a composição corporal e a atividade física estão associados à inflamação crônica de baixo grau, de acordo com os níveis de proteína C-reativa (PCR-us), em mulheres na pós-menopausa. Métodos noventa e cinco participantes pós-menopáusicas foram submetidas a avaliações antropométrica, metabólica e hormonal. A ingestão alimentar foi avaliada por meio de questionário de frequência alimentar, a atividade física habitual, com pedômetro digital, e a composição corporal, por bioimpedância elétrica. Pacientes com PCR-us ≥10 mg/L ou em uso de terapia hormonal nos últimos três meses antes do estudo foram excluídas. As participantes foram estratificadas de acordo PCR-us inferior ou ≥3 mg/L. Pacientes com menos de 6 mil passos/dia foram consideradas sedentárias. Para análise estatística foram utilizados teste t de Student, Wilcoxon-Mann- Whitney U ou Qui-quadrado (x 2), além de modelo de regressão logística para estimar a razão de chances para PCR-us elevada. Resultados participantes com PCR-us ≥3 mg/L apresentaram maior índice de massa corporal (IMC), percentual de gordura corporal, circunferência da cintura, triglicerídeos, glicose e índice de insulino-resistência (HOMA-IR) (p = 0,01) comparadas às mulheres com PCR-us <3 mg/L. O grupo PCR-us ≥3 mg/L apresentou uma dieta com maior carga glicêmica e menor ingestão de proteínas. A prevalência de sedentarismo e síndrome metabólica foi maior em mulheres com PCR-us ≥3 mg/L (p < 0,01). Após ajuste para idade e tempo de menopausa, a razão de chances para PCR-us ≥3mg/L foi maior nas sedentárias (4,7, intervalo de confiança de 95% [95%CI] 1,4-15,5) e com maior ingestão de carboidratos (2,9, 95%CI 1.1-7,7). Conclusões Sedentarismo e alta ingestão de carboidratos foram associados com inflamação crônica de baixo grau e risco cardiovascular em mulheres na pósmenopausa.