Efficacy of a low-FODMAP diet in adult irritable bowel syndrome: a systematic review and meta-analysis.

PURPOSE: This review provides an updated overview of observational and intervention studies investigating the effect of a low-FODMAP (fermentable oligo-, di- and monosaccharides, and polyols) diet (LFD) on gastrointestinal (GI) symptoms, quality of life (QoL), nutritional adequacy, and gut microbiome in irritable bowel syndrome (IBS) patients. METHODS: We systematically searched available literature until October 2020 for studies that investigated the effect of LFDs on GI symptoms, QoL, nutritional adequacy, and the gut microbiome in IBS patients. The data were represented as standardized mean differences (SMD) for IBS severity, and as mean differences (MD) for IBS-QoL. Meta-analyses were performed for the quantitative analyses using random effects models with inverse variance weighing. RESULTS: Twelve papers (nine parallel trials, three crossover studies) were included for the meta-analysis. The LFD reduced IBS severity by a moderate-to-large extent as compared to a control diet (SMD - 0.66, 95% CI - 0.88, - 0.44, I2 = 54%). When analyzing only studies that used the validated IBS-SSS questionnaire, a mean reduction of 45 points (95% CI - 77, - 14; I2 = 89%) was observed. Subgroup analyses on adherence, age, intervention duration, IBS subtype, outcome measure, and risk of bias revealed no significantly different results. The LFD also increased IBS-QoL scores, when compared with a control diet (MD 4.93; 95% CI 1.77, 8.08; I2 = 42%). CONCLUSIONS: The low-FODMAP diet reduces GI symptoms and improves quality of life in IBS subjects as compared to control diets. Future work is required to obtain definitive answers regarding potential long-term effects of such diets on nutritional adequacy and the gut microbiome. PROSPERO REGISTRATION NUMBER: CRD42020175157.

Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials.

BACKGROUND: The effect of folic acid on endothelial function, a prognostic factor for cardiovascular diseases, is not well established. We calculated this effect in a meta-analysis of randomized, double-blind, placebo-controlled trials in humans. OBJECTIVE: The objective of the study was to quantify the effect of folic acid on endothelial function, as measured with the use of flow-mediated dilatation (FMD). DESIGN: We conducted a meta-analysis of randomized, double-blind, placebo-controlled folic acid trials evaluating endothelial function. Trials were identified through MEDLINE (1966-15 Sept 2005), by hand-searching of references, and by contact with investigators for unpublished results. Two of us (AdB and RD) independently extracted trial data. A pooled estimate was calculated by using random-effects meta-analysis. Previously defined stratified analyses were conducted to explore the influence of study characteristics. RESULTS: Of 163 identified studies, 14 met inclusion criteria and provided data on 732 persons. Evidence for publication bias was not obvious. In the overall pooled estimate, folic acid improved FMD by 1.08 (95% CI: 0.57,1.59; P = 0.0005) percentage points over placebo. Of the study characteristics, only folic acid dose significantly influenced the outcome. Post hoc analysis, which should be interpreted with caution, seemed to indicate a dose-response effect: the change in FMD was -0.07 (95% CI: -0.37, 0.22) percentage points at doses between 400 and 800 microg/d, 1.37 (95% CI: 1.12, 1.54) percentage points at doses of 5000 microg/d, and 2.04 (95% CI: 1.43, 2.65) percentage points at doses of 10,000 microg/d. CONCLUSION: This study indicates that high doses of folic acid improve endothelial function, which could potentially reduce the risk of cardiovascular disease.

Consumption of antioxidant-rich beverages and risk for breast cancer in French women.

PURPOSE: The objective of the study is to evaluate the relation between antioxidant-rich beverages and the incidence of breast cancer. METHODS: This prospective study consisted of 4396 women without a history of cancer who were participants in the French Supplémentation en Vitamines et Minéraux Antioxydants Study. Beverage consumption was estimated by using three nonconsecutive 24-hour recalls. Incident cancer cases were identified through clinical examinations performed every other year, including, e.g., a screening mammogram, and through a monthly health questionnaire. RESULTS: During the median 6.6 years of follow-up, 95 breast cancers were diagnosed. In a multivariate model, an inverse association between herbal tea consumption and risk for breast cancer was observed (compared with nondrinkers, drinking 1 to 149 mL/d; relative risk [RR], 0.93; 95% confidence interval [CI], 0.48-1.80, and for > or =150 mL/d; RR, 0.43; 95% CI, 0.20-0.94; p for trend = 0.04). Consumption of coffee, tea, fruit juices, or wine was not associated with risk for breast cancer. CONCLUSION: Results of this study suggest that consumption of herbal tea may have a role in the prevention of breast cancer.

Homocysteine is not associated with arterial thickness and stiffness in healthy middle-aged French volunteers.

BACKGROUND: To study the association between the total plasma homocysteine (tHcy) concentration and the carotid artery intima-medial wall thickness (IMT), pulse wave velocity (PWV) and the presence of arterial plaques in a French population. METHODS: Cross-sectional analysis of data from 556 male and 559 female middle-aged participants (mean (+/-SD) age 59.6+/-4.7 years) provided by an ongoing intervention trial. RESULTS: Mean geometric tHcy concentration was higher for men than for women (10.6 vs. 8.5 micromol/L, p<0.001) and was associated in the expected direction with known determinants. The mean IMT was 0.71+/-0.1 mm for men and 0.69+/-0.1 mm for women (p<0.001), the mean PWV was, respectively, 12.0+/-2.8 and 10.9+/-2.2 m/sec (p<0.001), and the percentages of subjects with plaques were, respectively, 40.8% and 22.7% (p<0.001). In men only, the age-adjusted mean IMT and PWV increased with an increasing tHcy concentration: the IMT was 0.71 mm in the first tHcy-quartile and 0.73 mm in the fourth tHcy-quartile (p for linear trend=0.03), the PWV values were, respectively, 11.6 and 12.4 m/sec (p for linear trend=0.01). These associations disappeared after adjustment for conventional cardiovascular disease risk factors. CONCLUSION: In this population, the tHcy concentration was not associated with measures of arterial thickness and stiffness.

Consumption of foods rich in flavonoids is related to a decreased cardiovascular risk in apparently healthy French women.

A high consumption of flavonoids may lower cardiovascular risk through their antioxidant capacity. This study evaluated the relation between consumption of foods rich in flavonoids and estimated cardiovascular risk. A cross-sectional analysis was performed in 1286 women and 1005 men of the SU.VI.MAX Study (an 8-y trial evaluating the effect of antioxidant supplementation on the incidence of major chronic diseases). Dietary intakes were estimated using six 24-h dietary records collected during the year between the clinical measurement of blood pressure, weight and height and the biological measurement of total serum cholesterol and fasting plasma glucose. The relation between flavonoid rich food consumption and cardiovascular risk factors was evaluated with analyses of covariance and the effect on cardiovascular risk with logistic regression analyses. In women, flavonoid-rich food consumption was inversely related to systolic blood pressure (P = 0.005). No relation between risk factors and flavonoid-rich food consumption was seen in men. Women in the highest tertile of flavonoid-rich food consumption were at lower risk for cardiovascular disease [odds ratio (OR): 0.31; 95%CI: 0.14, 0.68], whereas a positive tendency was seen in men (OR: 1.38; 95%CI: 0.96, 2.00). These results indicate that in women, a high consumption of flavonoid-rich foods may prevent cardiovascular disease.

Effect of the methylenetetrahydrofolate reductase 677C-->T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate and homocysteine metabolism. The common MTHFR 677C-->T polymorphism decreases the enzyme's activity. OBJECTIVE: The objective of the study was to assess the effect of the polymorphism on the relations among folate intake, plasma folate concentration, and total plasma homocysteine (tHcy) concentration. DESIGN: The design was a cross-sectional analysis in a random sample (n = 2051) of a Dutch cohort (aged 20-65 y). RESULTS: At a low folate intake (166 micro g/d), folate concentrations differed significantly among the genotypes (7.1, 6.2, and 5.4 nmol/L for the CC, CT, and TT genotypes, respectively; P for all comparisons < 0.05). At a high folate intake (250 microg/d), folate concentrations in CT and CC subjects did not differ significantly (8.3 and 8.6 nmol/L, respectively, but were significantly higher (P = 0.2) than those in TT subjects (7.3 nmol/L; P = 0.04). At a low folate concentration (4.6 nmol/L), TT subjects had a significantly higher (P = 0.0001) tHcy concentration than did CC and CT subjects (20.3 compared with 15.0 and 14.1 micromol/L, respectively), whereas at a high folate concentration (11.9 nmol/L), the tHcy concentration did not differ significantly between genotypes (P > 0.2; <13.1 for all genotypes). The relation between folate intake and tHcy concentration had a pattern similar to that of the relation between plasma folate and tHcy concentrations. CONCLUSIONS: At any folate intake level, TT subjects have lower plasma folate concentrations than do CT and CC subjects. Yet, at high plasma folate concentrations, tHcy concentrations in TT subjects are as low as those in CT and CC subjects.

Coronary heart disease mortality, plasma homocysteine, and B-vitamins: a prospective study.

The results of prospective studies on the relations between the plasma concentration of total homocysteine (tHcy) and B-vitamins, on the one hand, and coronary heart disease (CHD) mortality, on the other hand, are inconclusive and scarce considering the relation with B-vitamins. We prospectively determined these relations in a case-cohort study. The full-cohort existed in approximately 36,000 Dutch adults aged 20-59 years at baseline. The statistical analyses were done with a random sample from the cohort (n=630) complemented with all subjects who died of CHD (n=102) during a mean follow-up of 10.3 years. All subjects reported the absence of cardiovascular diseases (CVDs) at baseline. The plasma concentrations of tHcy, folate, PLP, and vitamin B12 were determined in samples obtained at baseline. Men with a tHcy concentration in the highest tertile (T3) compared with men in the lowest tertile (T1) had a relative risk (RR) of 1.14 for CHD (95% confidence interval (CI): 0.50, 2.61) after adjusting for age, study center, hypertension, HDL and total cholesterol, smoking, and creatinine. For women, this RR was 2.04 (95% CI: 0.48, 8.62). For each 5 micromol/l increase in tHcy, the RR of CHD was 1.03 (95% CI: 0.83-1.29) for men and women combined. In women only, high folate levels were associated with a statistically significant protection of fatal CHD (T3 versus T1; RR: 0.22, 95% CI: 0.06, 0.87). Plasma PLP (B6) and vitamin B12 concentrations were not associated with CHD risk. We conclude that elevated tHcy concentrations do not seem to be a risk factor for CHD mortality in these relatively young healthy Dutch subjects free of baseline CVD. Higher folate concentrations may be protective of CHD, but this needs confirmation.

Homocysteine determinants and the evidence to what extent homocysteine determines the risk of coronary heart disease.

Cardiovascular diseases (CVD), especially coronary heart disease (CHD), are the most important causes of death in industrialized countries. Increased concentrations of total plasma homocysteine (tHcy) have been associated with an increased risk of CHD. Assuming that this relation is causal, a lower tHcy concentration will reduce the occurrence and recurrence of CHD. Therefore, it is important to know which factors determine the tHcy concentration. In the general population, the most important modifiable determinants of tHcy are folate intake and coffee consumption. Smoking and alcohol consumption are also associated with the tHcy concentration, but more research is necessary to elucidate whether these relations are not originating from residual confounding due to other lifestyle factors. The most important nonmodifiable determinant is the 677 C>T polymorphism in the gene that encodes methylenetetrahydrofolate reductase (MTHFR), a regulating enzyme in homocysteine metabolism. Especially subjects with the homozygous form of this polymorphism (i.e., 677TT genotype) and a low folate status have elevated tHcy concentrations. Specific clinical conditions like the use of antiepileptic drugs or methotrexate, renal failure, cancer, rheumatoid arthritis, and hypothyroidism may lead to elevated tHcy concentrations. The available epidemiological evidence indicates that an increased tHcy concentration is not an important risk factor for CHD in healthy subjects. However, prospective studies, which included subjects at high risk of CHD, and secondary prevention trials with intermediary endpoints consistently show that elevations in the tHcy concentration may be an important risk factor in these subjects for a (recurrent) CHD event. The induction of vascular endothelial dysfunction by homocysteine may underlie this increased risk. Ongoing intervention trials will indicate whether homocysteine-lowering through vitamin supplementation, prevents CHD in the treatment groups.

Dietary monoglutamate and polyglutamate folate are associated with plasma folate concentrations in Dutch men and women aged 20-65 years.

Dietary folate consists of monoglutamate and polyglutamate folate species. In the small intestine, folate polyglutamate is deconjugated to the monoglutamate form before absorption takes place. This enzymatic deconjugation might limit the bioavailability of polyglutamate folate. Until now, no data have been available on dietary intake of both folate forms and their associations with folate status. Therefore, we estimated the intake of monoglutamate and polyglutamate folate in the Dutch population and studied whether the association with plasma folate is different for these two folate forms. Dietary intake of monoglutamate and polyglutamate folate from nonfortified foods was estimated for 2435 subjects (1275 men; 1160 women) aged 20-65 y. The intake of monoglutamate folate was about one third of total folate intake, derived mainly from bread (approximately 20%) and meat (approximately 18%), whereas two thirds consisted of polyglutamates, derived mainly from vegetables (approximately 25%). The predictive power of the regression model with total folate intake as the independent variable adjusted for age, smoking and alcohol intake, did not increase when including the ratio of monoglutamate to polyglutamate folate intake. In addition, linear regression models showed that both monoglutamate and polyglutamate folate intake were associated positively with plasma folate levels. However, in men, the monoglutamate folate form appeared to be a threefold stronger determinant of plasma folate levels than polyglutamate folate, whereas in women, both folate forms were equally strong determinants. This might be explained by different food intake patterns of men and women, including alcohol intake. At present, it does not seem necessary to distinguish between food folate forms in advising an increase in folate intake from nonfortified foods.