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Sperm DNA methylation changes after short-term nut supplementation in healthy men consuming a Western-style diet.

Salas-Huetos, A., E.R. James, J. Salas-Salvadó, M. Bulló, K.I. Aston, D.T. Carrell, T.G. Jenkins, 2021. Sperm DNA methylation changes after short-term nut supplementation in healthy men consuming a Western-style diet. Andrology. 9(1):260-268.

Background: Many environmental and lifestyle factors have been implicated in the decline of sperm quality, with diet being one of the most plausible factors identified in recent years. Moreover, several studies have reported a close association between the alteration of specific sperm DNA methylation signatures and semen quality. Objectives: To evaluate the effect of tree nut consumption on sperm DNA methylation patterns in healthy individuals reporting eating a Western-style diet. Material and methods: This is a post hoc analysis conducted in a subset of participants (healthy, non-smoking, and young) from the FERTINUTS 14-wk randomized-controlled, parallel trial, recruited between December 2015 and February 2017. The participants included in the current study (n = 72) were randomly selected in a proportion 2:1 from the original FERTINUTS trial between the 98 participants that completed the entire dietary intervention (nut group, n = 48; control group, n = 24). Sperm DNA methylation patterns were examined at baseline and after 14 weeks in 48 individuals consuming 60 g/d of mixed nuts (nut group) and in 24 individuals following the usual Western-style diet avoiding consumption of nuts (control group). Results: Over the course of the trial, no significant changes in global methylation were observed between groups. However, in the nut group, we identified 36 genomic regions that were significantly differentially methylated between the baseline and the end of the trial and 97.2% of the regions displayed hypermethylation. We identified no such change in the control group over the same period of time. We also utilized the recently developed germ line age calculator to determine if nut consumption resulted in alterations to the epigenetic age of cells and no significant differences were found. Discussion and conclusion: Adding nuts to a regular Western-style diet subtly impacts sperm DNA methylation in specific regions, demonstrating that there are some sperm epigenome regions that could respond to diet.

The effect of almond consumption on postprandial metabolic and satiety response in high-risk pregnant women.

Lesser, M.N.R., K. Mauldin, L. Sawrey-Kubicek, V. Gildengorin, J.C. King, 2019. The effect of almond consumption on postprandial metabolic and satiety response in high-risk pregnant women. Nutrients. 11, 490; doi:10.3390/nu11030490.

Almonds provide a satiating, healthy source of fat and fiber. The postprandial metabolic and satiety response to 2 ounces of nuts or dairy was assessed in 18 overweight/obese women during late pregnancy. Serum glucose, triglycerides, insulin, c-peptide, leptin, ghrelin, and lipoprotein particles were measured prior to and during a 5-h postprandial period following the consumption of an isocaloric breakfast meal with equivalent amounts of fat from either nuts or dairy on two separate mornings. Satiety was assessed by visual analogue scale (VAS) questionnaires and ad libitum food intake at the end of the study. At 33 weeks gestation, the women had gained an average of 7.0±4.4 kg during gestation. Body fat averaged 41.9±5.5% and hemoglobin A1c levels were elevated, (7.2±0.6%). Fasting glucose levels were normal, but hyperinsulinemia was evident. The two test meals did not affect the postprandial metabolic response, but glucose, triglyceride, and ghrelin concentrations changed with time during the postprandial period (p < 0.001, p = 0.0008, p = 0.006). Satiety measures did not differ between the two test meals. Consuming an isocaloric breakfast meal with equivalent amounts of fat from nuts or dairy did not alter postprandial levels of blood lipids, glucose, hormones, or measures of satiety in overweight/obese, pregnant women.

Acute effect of pistachio intake on postprandial glycemic and gut hormone responses in women with gestational diabetes or gestational impaired glucose tolerance: A randomized, controlled, crossover study.

Feng, X., H. Liu, Z. Li, A. Carughi, S. Ge, 2019. Acute effect of pistachio intake on postprandial glycemic and gut hormone responses in women with gestational diabetes or gestational impaired glucose tolerance: A randomized, controlled, crossover study. Front Nutr. 17;6:186.  doi: 10.3389/fnut.2019.00186.

Long-term consumption of pistachios could potentially improves glucose homeostasis. Impaired postprandial glucose, insulin, and glucagon-like peptide-1 (GLP-1) responses have been reported in gestational diabetes mellitus (GDM) patients. The objective of this study was to evaluate the acute effects of two isocaloric test meals, 42 g pistachios and 100 g whole-wheat bread (WWB) on postprandial glucose, insulin, and gut derived incretin levels in Chinese women with gestational impaired glucose tolerance (GIGT) or GDM. Expected glucose and insulin responses were observed after WWB consumption. Isocaloric pistachio intake had minimal effect on blood glucose or insulin. In both GIGT and GDM patients, significant higher GLP-1 levels were observed at 90 and 120 min after pistachio compared to WWB intake. Significant lower gastric inhibitory polypeptide (GIP) levels were observed at 30 and 60 min in GDM patients or 120 min in GIGT patients after pistachio compared to WWB intake. In summary, isocaloric pistachio intake induced significantly lower postprandial glucose, insulin and GIP but higher GLP-1 levels compared to WWB. Our data suggest pistachios are effective alternative to a low-fat, high-carbohydrate food to improve postprandial glucose, insulin, and GLP-1 response in women with GDM and GIGT.

Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial.

Al Wattar, B.H., J. Dodds, A. Placzek, L. Beresford, E. Spyreli, A. Moore, A. Moore, F.J. Gonzalez Carreras, F. Austin, N. Murugesu, T.J. Roseboom, M. Bes-Rastrollo, G.A. Hitman, R. Hooper, K.S. Khan, S. Thangaratinam, for the ESTEEM study group, 2019. Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial. PLoS Med 16(7): e1002857. https://doi.org/10.1371/journal. pmed.1002857

Background: Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in highrisk women. Methods and findings: We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, nonrefined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks’ gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3–10.6, p ≤ 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0–64.6, p ≤ 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56–1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58– 1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47–0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference −1.2 Kg, 95% CI −2.2 to −0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio [OR] 0.67, 95% CI 0.53–0.84, I2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study’s limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers. Conclusions: A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes.

A Mediterranean diet with an enhanced consumption of extra virgin olive oil and pistachios improves pregnancy outcomes in women without gestational diabetes mellitus: A sub-analysis of the St. Carlos Gestational Diabetes Mellitus Prevention Study.

Assaf-Balut, C., N. García de la Torre, A. Duran, M. Fuentes, E. Bordiú, L. Del Valle, C. Familiar, J. Valerio, I. Jiménez, M.A. Herraiz, N. Izquierdo, M.J. Torrejon, M.Á. Cuadrado, I. Ortega, F.J. Illana, I. Runkle, P. de Miguel, I. Moraga, C. Montañez, A. Barabash, M. Cuesta, M.A. Rubio, A.L. Calle-Pascual, 2019. A Mediterranean diet with an enhanced consumption of extra virgin olive oil and pistachios improves pregnancy outcomes in women without gestational diabetes mellitus: A sub-analysis of the St. Carlos Gestational Diabetes Mellitus Prevention Study. Ann Nutr Metab. 74(1):69-79.

AIMS: The aim of the study was to evaluate the effect of a Mediterranean diet (MedDiet), enhanced with extra virgin olive oil (EVOO) and nuts, on a composite of adverse maternofoetal outcomes of women with normoglycemia during pregnancy. METHODS: This was a sub-analysis of the St Carlos gestational diabetes mellitus Prevention Study. Only normoglycemic women were analysed (697). They were randomized (at 8-12th gestational weeks) to: standard-care control group (337), where fat consumption was limited to 30% of total caloric intake; or intervention group (360), where a MedDiet, enhanced with EVOO and pistachios (40-42% fats of total caloric intake) was recommended. The primary outcome was a composite of maternofoetal outcomes (CMFOs): at least having 1 event of emergency C-section, perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational-age and small-for gestational-age. RESULTS: Crude relative risk showed that the intervention was associated with a significant reduction in the risk of CMFOs (0.48 [0.37-0.63]; p = 0.0001), with a number-needed-to-treat = 5. Risk of urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age new-borns were also significantly reduced. CONCLUSION: A MedDiet, enhanced with EVOO and nuts, was associated with a risk reduction of CMFOs in over 50% in normoglycemic pregnant women. Therefore, it might be a potentially adequate diet for pregnant women.

Effect of nut consumption on semen quality and functionality in healthy men consuming a Western-style diet: a randomized controlled trial.

Salas-Huetos, A., R. Moraleda, S. Giardina, E. Anton, J. Blanco, J. Salas-Salvadó, M. Bulló, 2018. Effect of nut consumption on semen quality and functionality in healthy men consuming a Western-style diet: a randomized controlled trial. Am J Clin Nutr. 108:953–962.

Background: Human semen quality has declined in industrialized countries. Pollution, smoking, and the consumption of a Western style diet are all hypothesized as potential causes. Objective: We evaluated the effect of chronic consumption of nuts on changes in conventional semen parameters and the potential mechanisms implicated. Design: The FERTINUTS study was a 14-wk randomized, controlled, parallel trial. A total of 119 healthy men, aged 18–35 y, were allocated to 1 of 2 intervention groups: one group was fed the usual Western-style diet enriched with 60 g of a mixture of nuts/d (nut group), and the other was fed the usual Western-style diet avoiding nuts (control group). Semen and blood samples were collected at baseline and at the end of the intervention. Dietary information was recorded throughout the trial. Changes in conventional semen parameters (pH, volume, sperm count and concentration, motility, and morphology) were determined as primary outcomes. The effect of nut consumption on sperm DNA fragmentation (SDF), reactive oxygen species (ROS) production, chromosome anomalies (X, Y, and 18), total DNA methylation, and microRNA expression were measured in sperm samples as potential causes of the changes in the seminogram. Results: Compared with the control group, improvements in total sperm count (P = 0.002) and vitality (P = 0.003), total motility (P = 0.006), progressive motility (P = 0.036), and morphology of sperm (P = 0.008) were observed in the nut group. Participants in the nut group showed an increase in the consumption of total fat, monounsaturated fatty acids, polyunsaturated fatty acids, magnesium, vitamin E, α-linolenic acid, total omega-3 (n–3) and ω-3: ω-6 ratio intake during the intervention. Participants in the nut group showed a significant reduction in SDF (P < 0.001) and in the expression of hsa-miR-34b-3p (P = 0.036). No significant changes in ROS, sperm chromosome anomalies, or DNA methylation were observed between groups. Conclusions: The inclusion of nuts in a Western-style diet significantly improves the total sperm count and the vitality, motility, and morphology of the sperm. These findings could be partly explained by a reduction in the sperm DNA fragmentation. This trial was registered at ISRCTN as ISRCTN12857940.

Effectiveness of a walnut-enriched diet on murine sperm: involvement of reduced peroxidative damage.

Coffua, L.S., P.A. Martin-Deleon, 2017. Effectiveness of a walnut-enriched diet on murine sperm: involvement of reduced peroxidative damage. Heliyon. 2017 Feb 20;3(2):e00250. doi: 10.1016/j.heliyon.2017.e00250.

Abstract: A walnut supplement for a Western-style diet in men was shown to improve sperm motility, vitality, and morphology. To gain further insights into factors underlying this improvement, we administered a parallel walnut-enriched diet to mice [including those with a defect in sperm motility due to deletion of Plasma Membrane Ca2+-ATPase 4 (Pmca4−/−)] to determine if there is a similar improvement that is accompanied by reduced sperm membrane peroxidative damage. Although sperm vitality and acrosome reaction rate were unaffected, the diet led to a significant improvement in motility (P < 0.05) and morphology (P < 0.04) in wild-type sperm and in morphology (P < 0.01) in Pmca4−/−, confirming the diet’s efficacy, which appeared to be more modest in mice than in humans. In both strains of mice, the diet resulted in a significant decrease in sperm lipid peroxidation (oxidative stress) levels, but did not rescue the significantly increased apoptotic levels seen in the testis and epididymis of Pmca4 nulls. Our findings support the effectiveness of walnuts on sperm quality, associated with reduced peroxidative damage; and suggest that oxidative stress is involved in the mechanism(s) underlying male reproductive defects in Pmca4−/−.

Effect of simple, targeted diet in pregnant women with metabolic risk factors on maternal and fetal outcomes (ESTEEM): study protocol for a pragmatic multicentre randomised trial.

Al Wattar, B.H., J. Dodds, A. Placzek, E. Spyreli, A. Moore, R. Hooper, L. Beresford, T.J. Roseboom, M. Bes-Rastrollo, G. Hitman, K.S. Khan, S. Thangaratinam; ESTEEM study group, 2016. Effect of simple, targeted diet in pregnant women with metabolic risk factors on maternal and fetal outcomes (ESTEEM): study protocol for a pragmatic multicentre randomised trial. BMJ Open. 2016;6:e013495. doi:10.1136/bmjopen-2016013495.

Introduction: Women with metabolic risk factors are at higher risk of adverse pregnancy outcomes. Mediterranean-based dietary interventions have the potential to minimise these risks. We aim to evaluate the effectiveness of a simple, targeted intervention modelled on Mediterranean diet in preventing maternal and fetal complications in pregnant women with metabolic risk factors. Methods and Analysis: Pregnant women with a singleton pregnancy <18 weeks gestation, and without pre-existing diabetes, chronic renal disease and autoimmune diseases will be recruited. Women with metabolic risk factors will be randomised to receive a dietary intervention based on a Mediterranean pattern, supplemented with extra virgin olive oil and mixed nuts until delivery. The intervention will be delivered through a series of one to one and group sessions. The primary outcome is a composite maternal outcome of pre-eclampsia or gestational diabetes and a composite fetal outcome of stillbirth, small for gestational age fetus or admission to the neonatal intensive care unit. Secondary outcomes include maternal, fetal, dietary and laboratory outcomes. We aim to randomise 1230 eligible women with metabolic risk factors. We will also compare the outcomes in women with and without these risk factors. The sample size will provide us with 80% power at 5% significance, assuming a 20% loss to follow-up to detect a 30% reduction in maternal and fetal complications. Ethics and Dissemination: The ESTEEM trial is designed to provide a definitive estimate of the effects of Mediterranean dietary pattern in pregnancy on maternal and fetal outcomes. The pragmatic nature of ESTEEM ensures the applicability of its findings into clinical practice. The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings and congresses.

Walnuts improve semen quality in men consuming a western-style diet: randomized control dietary intervention trial.

Robbins, W.A., L. Xun, L.Z. FitzGerald, S. Esguerra, S.M. Henning, C.L. Carpenter, 2012. Walnuts improve semen quality in men consuming a western-style diet: randomized control dietary intervention trial. Biol Reprod. doi:10.1095/biolreprod.112.101634

Purpose: We tested the hypothesis that 75 gm of whole-shelled walnuts/day added to a Westernstyle diet of healthy young men would beneficially affect semen quality. Methods: A randomized, parallel two-group, dietary intervention trial with single-blind masking of outcome assessors, was conducted with 117 healthy men, age 21 – 35 years, who routinely consumed a Western-style diet. Primary outcome evaluated was improvement from baseline to 12 weeks in conventional semen parameters and sperm aneuploidy. Secondary endpoints included blood serum and sperm fatty acid (FA) profiles, sex hormones, and serum folate. Conclusions: The group consuming walnuts (n=59) experienced improvement in sperm vitality, motility, and morphology and the group continuing their usual diet but avoiding tree nuts (n=58) saw no change. Comparing differences from baseline between the groups, significance was found for vitality p=0.003, motility p=0.009, and morphology (normal forms) p=0.04. Serum FA profiles improved in the walnut group with increases in omega-6 (p=0.0004) and omega-3 p=0.0007) but not the control group. Only the plant source of omega-3, α-linolenic acid (ALA), increased (p=0.0001). Sperm aneuploidy was inversely correlated with sperm ALA, particularly sex chromosome nullisomy (-0.41, p=0.002). Findings demonstrated that walnuts added to a Western-style diet improved sperm vitality, motility and morphology.

Peanut and tree nut consumption during pregnancy and allergic disease in children—should mothers decrease their intake? Longitudinal evidence from the Danish National Birth Cohort.

Maslova, E., C. Granstrőm, S. Hansen, S.B. Petersen, M. Strøm, W.C. Willett, S.F. Olsen, 2012.  Peanut and tree nut consumption during pregnancy and allergic disease in children—should mothers decrease their intake? Longitudinal evidence from the Danish National Birth Cohort. J Allergy Clin Immunol. 130:724-32.

Background: The relation between maternal peanut intake during pregnancy and allergic disease development in children has been controversial. Objective: We used data from the Danish National Birth Cohort to examine associations between maternal peanut and tree nut intake during pregnancy and allergic outcomes in children at 18 months and 7 years of age. Methods: We estimated maternal peanut and tree nut intake (n 5 61,908) using a validated midpregnancy food frequency questionnaire. At 18 months, we used parental report of childhood asthma diagnosis, wheeze symptoms, and recurrent wheeze (>3 episodes). We defined current asthma at 7 years as doctor-diagnosed asthma plus wheeze in the past 12 months and allergic rhinitis as a self-reported doctor’s diagnosis. We also used alternative classifications based on registry-based International Classification of Diseases, Tenth Revision, codes and drug dispensary data. We report here odds ratios (ORs) comparing intake of 1 or more times per week versus no intake. Results: We found that maternal intake of peanuts (OR, 0.79; 95% CI, 0.65-0.97) and tree nuts (OR, 0.75; 95% CI, 0.67-0.84) was inversely associated with asthma in children at 18 months of age. Compared with mothers consuming no peanuts, children whose mothers reported eating peanuts 1 or more times per week were 0.66 (95% CI, 0.44-0.98) and 0.83 (95% CI, 0.70-1.00) times as likely to have a registry-based and medication related asthma diagnosis, respectively. Higher tree nut intake was inversely associated with a medication-related asthma diagnosis (OR, 0.81; 95% CI, 0.73-0.90) and self-reported allergic rhinitis (OR, 0.80; 95% CI, 0.64-1.01). Conclusions: Our results do not suggest that women should decrease peanut and tree nut intake during pregnancy; instead, consumption of peanuts and tree nuts during pregnancy might even decrease the risk of allergic disease development in children.