Migraines are a common disease with limited treatment options and some dietary factors are recognized to trigger headaches. Although migraine pathogenesis is not completely known, aberrant DNA methylation has been reported to be associated with its occurrence. Folate, an essential micronutrient involved in one-carbon metabolism and DNA methylation, was shown to have beneficial effects on migraines. Moreover, the variability of the methylenetetrahydrofolate reductase gene, important in both folate metabolism and migraine pathogenesis, modulates the beneficial effects of folate for migraines. Therefore, migraine could be targeted by a folate-rich, DNA methylation-directed diet, but there are no data showing that beneficial effects of folate consumption result from its epigenetic action. Furthermore, contrary to epigenetic drugs, epigenetic diets contain many compounds, some yet unidentified, with poorly known or completely unknown potential to interfere with the epigenetic action of the main dietary components. The application of epigenetic diets for migraines and other diseases requires its personalization to the epigenetic profile of a patient, which is largely unknown. Results obtained so far do not warrant the recommendation of any epigenetic diet as effective in migraine prevention and therapy. Further studies including a folate-rich diet fortified with valproic acid, another modifier of epigenetic profile effective in migraine prophylaxis, may help to clarify this issue. Full article

The effectiveness of Lactobacillus reuteri DSM 17938 (L. reuteri) for the management of acute gastroenteritis (AGE) has been recently questioned. We performed a systematic review to update evidence on L. reuteri for treating AGE in children. We searched MEDLINE, EMBASE, the Cochrane Library databases, and additional data sources from January 2016 (end of search for our 2016 systematic review) to August 2019. The primary outcomes were stool volume and duration of diarrhea. Four RCTs were included. None of them evaluated stool volume. Compared with placebo or no treatment, L. reuteri reduced diarrhea duration (four RCTs, n = 347, mean difference, MD −0.87 days, 95% CI [−1.43, −0.31]). L. reuteri use was also associated with a reduced duration of hospitalization (three RCTs, n = 284, MD −0.54 days, 95% CI [−1.09, 0.0]). The small effect sizes of limited clinical relevance and methodological limitations of the included trials should be noted when interpreting these findings. Full article

Background: The renin-angiotensin system (RAS) in the brain plays a crucial role in maintaining blood pressure as well as neuroprotection. This study compared the effects of curcumin, quercetin, and saponin on blood pressure, the brain RAS, and cholinergic system using perindopril, an angiotensin converting enzyme inhibitor (ACEI), as a positive control. Methods: Five-week-old male mice were stabilized and randomly assigned into a control group (n = 8), three phytochemical-treated groups (curcumin (n = 8), quercetin (n = 8), and saponin (n = 8)), and a positive control group (n = 8). The groups treated with the phytochemical were orally administered daily at a dose of 50 mg/kg body weight of phytochemicals. During the experiments, the weight and dietary intakes were measured regularly. After experiments, the brain tissue was homogenized and centrifuged for an additional assay. The concentrations of ACE, angiotensin II (AngII), and aldosterone levels were measured, and the mRNA expressions of renin and ACE were measured. As biomarkers of neuroprotection, the concentrations of acetylcholine (ACh) as well as the concentration and activity of acetylcholine esterase (AChE) were measured. Results: After 4 weeks of treatment, the perindopril group showed the lowest blood pressure. Among the groups treated with the phytochemicals, treatment with curcumin and saponin significantly reduced blood pressure, although such effect was not as high as that of perindopril. Among phytochemicals, curcumin treatment significantly inhibited the concentration and activity of ACE, concentration of AngII, and mRNA expression of ACE. All phytochemical treatments significantly increased the concentration of ACh. The levels of AChE activity in groups exposed to curcumin or saponin (not quercetin) were significantly inhibited, Conclusion: Curcumin administration in rats reduced blood pressure by blocking the brain RAS components and protected the cholinergic system in brain by inhibiting the activity of AChE. Full article

The association between vitamin D [25(OH)D] and bone health has been widely studied in children. Given that 25(OH)D and bone health are associated with muscular fitness, this could be the cornerstone to understand this relationship. Hence, the purpose of this work was to examine if the relation between 25(OH)D and areal bone mineral density (aBMD) was mediated by muscular fitness in children with overweight/obesity. Eighty-one children (8-11 years, 53 boys) with overweight/obesity were included. Body composition was measured with dual energy X-ray Absorptiometry (DXA), 25(OH)D was measured in plasma samples and muscular fitness was assessed by handgrip and standing long jump tests (averaged z-scores were used to represent overall muscular fitness). Simple mediation analyses controlling for sex, years from peak height velocity, lean mass and season were carried out. Our results showed that muscular fitness z-score, handgrip strength and standing long jump acted as mediators in the relationship between 25(OH)D and aBMD outcomes (percentages of mediation ranged from 49.6% to 68.3%). In conclusion, muscular fitness mediates the association of 25(OH)D with aBMD in children with overweight/obesity. Therefore, 25(OH)D benefits to bone health could be dependent on muscular fitness in young ages. Full article

Brain gray (GM) and white matter (WM) are associated with resting energy expenditure (REE). The impact of weight loss on GM and WM masses, as well as on their associations with REE and the ratio between body and brain metabolism, i.e., encephalic measure (EM)), are unknown. Longitudinal data of 69 female Caucasian subjects (age range 19–69 years) with detailed information on fat mass (FM), fat free mas (FFM), GM, WM and REE. Mean weight loss was 14.5 ± 11.9 kg with changes in FM (−12.9 ± 9.8 kg), FFM (−1.7 ± 4.8 kg) and REE (−159 ± 191 kcal/24 h) (all p < 0.05). With weight loss, there were no changes in GM and WM. Before and after weight loss, FFM was the main determinant of REE (r² = 0.483 and 0.413; p < 0.05). After weight loss, GM added to the variances in REE (3.6%), REE_adjFFM (6.1%) and the REE on FFM residuals (6.6%). In addition, before and after weight loss GM explained 25.0% and 10.0% of the variances in EM (p < 0.05). Weight loss had no effect on volumes of GM and WM. After weight loss, both, GM added to the variances of REE, REE on FFM residuals and EM. Full article

Choline is a vitamin-like essential nutrient, important throughout one’s lifespan. Therefore, choline salts are added to infant formula, supplements and functional foods. However, if choline is present in a natural form, e.g. bound to phospholipids, it may be more efficiently absorbed. The study’s aim was to evaluate if choline uptake is improved after consumption of an egg yolk phospholipid drink, containing 3 g of phospholipid bound choline, compared to a control drink with 3 g of choline bitartrate. We performed a randomized, double blind, cross-over trial with 18 participants. Plasma choline, betaine and dimethylglycine concentrations were determined before and up to six hours after consumption of the drinks. The plasma choline response, as determined by the incremental area under the curve, was four times higher after consumption of the egg yolk phospholipid drink compared with the control drink (p < 0.01). Similar outcomes were also observed for choline’s main metabolites, betaine (p < 0.01) and dimethylglycine (p = 0.01). Consumption of natural choline from egg yolk phospholipids improved choline absorption compared to consumption of chemically produced choline bitartrate. This information is of relevance for the food industry, instead of adding choline-salts, adding choline from egg yolk phospholipids can improve choline uptake and positively impact health. Full article

This study aimed to observe the relationship between iodine nutrition status (dietary iodine intake and estimated iodine intake based on urinary iodine concentration (UIC)) and thyroid disease-related hormones. This study involved 6090 subjects >19 years old with valid UIC, assessed between 2013 and 2015 by the Korean National Health and Nutrition Examination Survey, using a stratified, multistage, clustered probability-sampling design. The estimated iodine intake in participants was measured using UIC and urine creatinine. To examine the effect of iodine intake on thyroid disease, the iodine intake was divided into Korean Dietary Reference Intakes groups, and logistic regression analysis was performed via the surveylogistic procedure to obtain odds ratios (ORs) and 95% confidence intervals (CIs). The estimated iodine intake showed a significant positive correlation with dietary iodine intake (r = 0.021, p < 0.001), UIC (r = 0.918, p < 0.001), and thyroid-stimulating hormone (TSH) (r = 0.043, p < 0.001), but a significant negative correlation with free thyroxine (FT4) (r = −0.037, p < 0.001). Additionally, as the estimated iodine intake increased, age, TSH, and UIC increased, but FT4 decreased (p for trend < 0.0001). The risk of thyroid disease was higher in the “≥tolerable upper intake level (UL ≥ 2400 µg/day)” group than in the “<estimated average requirement (EAR < 150 µg/day)” group in females (OR: 2.418; 95% CI: 1.010–5.787). Also, as iodine intake increased, the risk of thyroid disease increased (p for trend < 0.038). Full article

Micronutrient Powder (MNP) is beneficial to control anemia, but some iron-related side-effects are common. A high level of iron in the groundwater used for drinking may exacerbate the side-effects among MNP users. We conducted a randomized controlled trial examining the effect of a low-dose iron MNP compared with the standard MNP in children aged 2–5 years residing in a high-groundwater-iron area in rural Bangladesh. We randomized 327 children, who were drinking from the “high-iron” wells (≥2 mg/L), to receive either standard (12.5 mg iron) or low-dose iron (5.0 mg iron) MNP, one sachet per day for two months. Iron parameters were measured both at baseline and end-point. The children were monitored weekly for morbidities. A generalized linear model was used to determine the treatment effect of the low-dose iron MNP. Poisson regressions were used to determine the incidence rate ratios of the morbidities. The trial was registered at ISRCTN60058115. Changes in the prevalence of anemia (defined as a hemoglobin level < 11.0 g/dL) were 5.4% (baseline) to 1.0% (end-point) in the standard MNP; and 5.8% (baseline) to 2.5% (end-point) in the low-dose iron MNP groups. The low-dose iron MNP was non-inferior to the standard MNP on hemoglobin outcome (β = −0.14, 95% CI: −0.30, 0.013; p = 0.07). It resulted in a lower incidence of diarrhea (IRR = 0.29, p = 0.01, 95% CI: 0.11–0.77), nausea (IRR = 0.24, p = 0.002, 95% CI: 0.09–0.59) and fever (IRR = 0.26, p < 0.001, 95% CI: 0.15–0.43) compared to the standard MNP. Low-dose iron MNP was non-inferior to the standard MNP in preventing anemia yet demonstrated an added advantage of lowering the key side-effects. Full article

Chronic cerebral hypoperfusion (CCH) causes cognitive impairment and neurogenic inflammation by reducing blood flow. We previously showed that Fructus mume (F. mume) improves cognitive impairment and inhibits neuroinflammation in a CCH rat model. One of the components of F. mume, Mumefural (MF), is known to improve blood flow and inhibit platelet aggregation. Whether MF affects cerebral and cognitive function remains unclear. We investigated the effects of MF on cognitive impairment and neurological function-related protein expression in the rat CCH model, established by bilateral common carotid arterial occlusion (BCCAo). Three weeks after BCCAo, MF (20, 40, or 80 mg/kg) was orally administrated once a day for 42 days. Using Morris water maze assessment, MF treatment significantly improved cognitive impairment. MF treatment also inhibited cholinergic system dysfunction, attenuated choline acetyltransferase-positive cholinergic neuron loss, and regulated cholinergic system-related protein expressions in the basal forebrain and hippocampus. MF also inhibited myelin basic protein degradation and increased the hippocampal expression of synaptic markers and cognition-related proteins. Moreover, MF reduced neuroinflammation, inhibited gliosis, and attenuated the activation of P2X7 receptor, TLR4/MyD88, NLRP3, and NF-κB. This study indicates that MF ameliorates cognitive impairment in BCCAo rats by enhancing neurological function and inhibiting neuroinflammation. Full article

Intermittent fasting improves metabolic and cardiac health. However, increased hunger towards the end of the fasting period may affect compliance and limit its application. Our aim was to determine the effect of anorexigenic agent co-therapy on subjective ratings of appetite during the 16–24 h period of a day-long water-only intermittent fast. Thirty adult men were recruited and required to fast for 24 h from 18:00 h to 18:00 h on the same day of the week for three subsequent weeks. Treatments of either a placebo or one of two doses (high dose; HD: 250 mg or low dose; LD: 100 mg) of a bitter hops-based appetite suppressant (Amarasate®) were given twice per day at 16 and 20 h into the fast. From 18–24 h of the 24 h fast, both the HD and LD treatment groups exhibited a statistically significant (p < 0.05) > 10% reduction in hunger. Additionally, the expected lunchtime increase in hunger that was present in the placebo group (12:00 h) was absent in both the HD and LD groups. These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during intermittent fasting, and show that bitter compounds may regulate appetite independently of meal timing. Full article

Mexico is facing the double burden of malnutrition, and adolescents are not an exception. Diet plays an important role, both in causing overweight and undernutrition. This study aimed to describe the dietary patterns (DPs) of Mexican adolescents and to examine its association with nutritional status using data from adolescents aged 12–19 years (n = 7380) from the National Survey of Health and Nutrition (ENSANUT-2006). Principal component analysis was used to derivate the DPs. Associations between DP and nutritional status were determined by prevalence ratio (PR). Four DPs were identified: nontraditional and breakfast-type, Western, plant-based, and protein-rich. The prevalence of overweight and obesity was higher in adolescents who scored high on the Western pattern (PR: 1.15, 95% CI: 1.08–1.21) or on the plant-based pattern (PR: 1.09, 95% CI: 1.03–1.17). The Western pattern was positively associated with anemia in girls (PR: 1.18, 95% CI: 1.03–1.35), while the nontraditional and breakfast-type pattern was inversely associated with anemia in adolescents aged 12–15 years (PR: 0.87, 95% CI: 0.76–0.99) and in girls (PR: 0.84, 95% CI: 0.75–0.97). The Western and plant-based patterns were simultaneously associated with overweight–obesity and at least one indicator of undernutrition. In the context of the double burden of malnutrition, dietary advice must consider malnutrition in all its forms. Full article

Little is known about the impact of less healthy snack foods on weight trajectories during infancy. This secondary analysis of data from the Nurture cohort explored prospective associations of less healthy snack foods with infant weight trajectories. Pregnant women were recruited and, upon delivery of a single live infant, 666 mothers agreed to participate. Mothers completed sociodemographic and infant feeding questionnaires, and infant anthropometrics were collected during home visits at 3, 6, 9, and 12 months. Less healthy snack food consumption was assessed by asking how frequently baby snacks and sweets were consumed each day during the previous three months. Multilevel growth curve models explored associations of baby snacks and sweets with infant weight-for-length (WFL) z-scores. On average, mothers were 27 years old, 71.5% were non-Hispanic Black, and 55.4% had household incomes of ≤$20,000/year. Consumption of less healthy snack foods increased during infancy with a median intake of 3.0 baby snacks/day and 0.7 sweets/day between 10 and 12 months. Growth curve models showed that infants who consumed sweets >2 times/day had significantly higher WFL z-scores during the second half of infancy compared to infants who never consumed sweets. Less healthy snacks may contribute to the risk of obesity during infancy and promoting healthy snack food choices during this critical time is important. Full article

Leptin is a hormone crucial in the regulation of food intake and body-weight maintenance. However, the genes and gene variants that influence its plasma levels are still not well known. Results of studies investigating polymorphisms in candidate genes have been inconsistent, and, in addition, very few genome-wide association studies (GWAS) have been undertaken. Our aim was to investigate the genes and gene variants most associated with plasma leptin concentrations in a high-cardiovascular-risk Mediterranean population. We measured plasma leptin in 1011 men and women, and analyzed the genetic factors associated using three approaches: (1) Analyzing the single nucleotide polymorphisms (SNPs) reported in a GWAS meta-analysis in other populations (including an SNP in/near each of these LEP, SLC32A1, GCKR, CCNL, COBLL1, and FTO genes); (2) Investigating additional SNPs in/near those genes, also including the RLEP gene; and (3) Undertaking a GWAS to discover new genes. We did not find any statistically significant associations between the previously published SNPs and plasma leptin (Ln) in the whole population adjusting for sex and age. However, on undertaking an extensive screening of other gene variants in those genes to capture a more complete set of SNPs, we found more associations. Outstanding among the findings was the heterogeneity per sex. We detected several statistically significant interaction terms with sex for these SNPs in the candidate genes. The gene most associated with plasma leptin levels was the FTO gene in men (specifically the rs1075440 SNP) and the LEPR in women (specifically the rs12145690 SNP). In the GWAS on the whole population, we found several new associations at the p < 1 × 10⁻⁵ level, among them with the rs245908-CHN2 SNP (p = 1.6 × 10⁻⁶). We also detected a SNP*sex interaction at the GWAS significance level (p < 5 × 10⁻⁸), involving the SLIT3 gene, a gene regulated by estrogens. In conclusion, our study shows that the SNPs selected as relevant for plasma leptin levels in other populations, are not good markers for this Mediterranean population, so supporting those studies claiming a bias when generalizing GWAS results to different populations. These population-specific differences may include not only genetic characteristics, but also age, health status, and the influence of other environmental variables. In addition, we have detected several sex-specific effects. These results suggest that genomic analyses, involving leptin, should be estimated by sex and consider population-specificity for more precise estimations. Full article

Bone is a major storage site as well as an endogenous source of lead in the human body. Dietary sodium and potassium intake may play a role in the mobilization of lead from bone to the circulation. We examined whether association between bone lead and urinary lead, a marker of mobilized lead in plasma, was modified by dietary intake of sodium and potassium among 318 men, aged 48–93 years, in the Veterans Affairs (VA) Normative Aging Study. Dietary sodium and potassium were assessed by flame photometry using 24-h urine samples, and a sodium-to-potassium ratio was calculated from the resulting measures. Patella and tibia bone lead concentrations were measured by K-shell-x-ray fluorescence. Urinary lead was measured by inductively coupled plasma mass spectroscopy in 24-h urine samples. Linear regression models were used to regress creatinine clearance-corrected urinary lead on bone lead, testing multiplicative interactions with tertiles of sodium, potassium, and sodium-to-potassium ratio, separately. After adjustment for age, body mass index, smoking, vitamin C intake, calcium, and total energy intake, participants in the highest tertile of sodium-to-potassium ratio showed 28.1% (95% CI: 12.5%, 45.9%) greater urinary lead per doubling increase in patella lead, whereas those in the second and lowest tertiles had 13.8% (95% CI: −1.7%, 31.7%) and 5.5% (95% CI: −8.0%, 21.0%) greater urinary lead, respectively (p-for-interaction = 0.04). No statistically significant effect modification by either sodium or potassium intake alone was observed. These findings suggest that relatively high intake of sodium relative to potassium may play an important role in the mobilization of lead from bone into the circulation. Full article

In the 1940s, the diet-heart hypothesis proposed that high dietary saturated fat and cholesterol intake promoted coronary heart disease in “at-risk” individuals. This hypothesis prompted federal recommendations for a low-fat diet for “high risk” patients and as a preventive health measure for everyone except infants. The low carbohydrate diet, first used to treat type 1 diabetes, became a popular obesity therapy with the Atkins diet in the 1970s. Its predicted effectiveness was based largely on the hypothesis that insulin is the causa prima of weight gain and regain via hyperphagia and hypometabolism during and after weight reduction, and therefore reduced carbohydrate intake would promote and sustain weight loss. Based on literature reviews, there are insufficient randomized controlled inpatient studies examining the physiological significance of the mechanisms proposed to support one over the other. Outpatient studies can be confounded by poor diet compliance such that the quality and quantity of the energy intake cannot be ascertained. Many studies also fail to separate macronutrient quantity from quality. Overall, there is no conclusive evidence that the degree of weight loss or the duration of reduced weight maintenance are significantly affected by dietary macronutrient quantity beyond effects attributable to caloric intake. Further work is needed. Full article