Niacin deficiency causes pellagra, the symptoms of which include dermatitis, diarrhoea and dementia. Investigating the mechanism underlying these phenotypes has been challenging due to the lack of an appropriate animal model. Here, we report a mouse model of pellagra-related nausea induced by feeding mice a low-niacin diet and administering isoniazid (INH), which is thought to induce pellagra. Mice fed a normal or low-niacin diet received INH (0·3 or 1·0 mg/mg per animal, twice daily, 5 d), and nausea was evaluated based on pica behaviour, which considered the rodent equivalent of the emetic reflex. Furthermore, the effect of therapeutic niacin administration on nausea was evaluated in this model. Urinary and hepatic metabolite levels were analysed by LC coupled with MS. INH-induced pica was observed in mice fed a low-niacin diet but not in those fed a normal diet. Levels of urinary metabolites, such as 1-methyl-2-pyridone-5-carboxamide, kynurenic acid and xanthurenic acid, were significantly reduced in the mice treated with INH compared with those that did not receive INH. Furthermore, niacin supplementation prevented pica and restored the levels of some metabolites in this mouse model. Our findings suggest that INH-related nausea is pellagra-like. We also believe that our newly established method for quantifying pica is a useful tool for investigating the mechanisms of pellagra-related nausea.

Several studies have been conducted to investigate the relation between 25-hydroxyvitamin D [25(OH)D] level and diabetic neuropathy (DN). However, there is still no clear conclusion due to differences in study design and cut-off values used in the published work, in addition to the absence of a comprehensive meta-analysis (MA) on the topic. The present systematic review and MA therefore aims at clarifying the association between vitamin D level and peripheral DN in patients with type 2 diabetes mellitus. Primary research studies that explored the association between 25(OH)D level and diabetic peripheral neuropathy in type 2 diabetes were located from Medline, EMBASE, Web of Science, Cochrane Library, CINHAL and Google Scholar. Twenty-six studies met the inclusion criteria with 6277 participants where 2218 were diabetic with DN, 2959 were diabetic without DN and 406 were healthy. Diabetic patients with DN showed significantly lower serum 25(OH)D compared with patients without DN (standardised mean difference (SMD) of −0·92 (95 % CI −1·18, −0·65, I2 = 93·3 %, P < 0·0001). The pooled OR value of vitamin D deficiency was higher in patients with DN, 1·84 (95 % CI 1·46, 2·33, P < 0·0001) and 2·87 (95 % CI 1·10, 7·52, P = 0·03) when using fixed-effects and random-effects models, respectively. Vitamin D deficiency has been found to be highly prevalent among diabetic patients with neuropathy. Since 25(OH)D has been implicated in glucose haemostasis and showed benefit in reducing neuropathy symptoms, its supplementation is warranted for this population of patients.

A negative association between blood Pb level (BPbL) and vitamin D metabolites in occupationally exposed populations has been reported, but data from the general population are scarce. Furthermore, the association between BPbL and vitamin D binding protein (DBP) and free 25-hydroxyvitamin D (25(OH)D) has not been reported. We investigated the association of BPbL with DBP, total and free 25(OH)D in healthy adolescents (n 1347; age range 11–16 years) cross-sectionally selected from all Governorates of Kuwait, utilising multi-stage cluster random sampling. Pb in whole blood was analysed by inductively coupled plasma MS, and DBP with ELISA. Plasma 25(OH)D was analysed by LC-MS/MS, and free 25(OH)D was calculated utilising the levels and binding affinities of DBP and albumin for 25(OH)D. DBP was positively associated with BPbL (β = 0·81; 95 % CI 0·14, 0·22; P < 0·001). A negative association between BPbL and total 25(OH)D was non-significant (P = 0·24) when BPbL was used as a continuous variable but was significant when used as quartiles (P = 0·02). The negative association between BPbL and free 25(OH)D was significant whether BPbL was used as continuous, as quartiles or as cut-off point of <5 µg/dl (0·24 µmol/l). In multinomial logistic regression, the odds of vitamin D insufficiency and deficiency were more than two-fold higher in the upper quartiles of BPbL compared with the lowest quartile. The negative correlation of BPbL with free 25(OH)D was more robust than its correlation with total 25(OH)D. Future studies must consider the levels of DBP when assessing the association between Pb and vitamin D metabolites.

Few studies have been conducted to investigate the association of kidney function decline with the trajectories of homocysteine (Hcy) over time, using repeated measurements. We aimed to investigate the association of kidney function with changes in plasma Hcy levels over time. Data were collected from the Rugao Longevity and Ageing Study. In detail, plasma Hcy and creatinine levels were measured in both waves (waves 2, 3 and 4) during the 3·5-year follow-up (n 1135). Wave 2 was regarded as the baseline survey. The estimated glomerular filtration rate (eGFR) was calculated based on creatinine. Subjects were categorised into four groups according to quartiles of eGFR at baseline. Linear mixed-effect models were used to investigate the association of eGFR with subsequent plasma Hcy levels. The mean eGFR at baseline was 90·84 (sd 11·42) ml/min per 1·73 m2. The mean plasma Hcy level was 14·09 (sd 6·82) at baseline and increased to 16·28 (sd 8·27) and 17·36 (sd 10·39) μmol/l during follow-ups. In the crude model, the interaction between time and eGFR at baseline was significant (β = −0·02, 95 % CI −0·02, −0·01, P = 0·002). After adjusting for confounding factors, a significant relationship remained (β = −0·02, 95 % CI −0·02, −0·01, P = 0·003), suggesting that kidney function decline at baseline was associated with a faster increase in Hcy levels. Kidney function decline is associated with a more pronounced increase in plasma Hcy levels. Further studies with longer follow-up periods and larger sample sizes are needed to validate our findings.

The objective was to investigate associations between life-course adiposity and sex hormone concentrations: trajectory of adiposity from age 5 to 40 (premenopausal)/60 (postmenopausal women and men) in relation to levels of oestrone (E1), oestradiol (E2), sex hormone-binding globulins (SHBG), testosterone in 4801 premenopausal and 6019 postmenopausal women in the Nurses’ Health Study (NHS) and NHS II, and 2431 men in the Health Professionals Follow-up Study. We used group-based trajectory models to identify groups within each cohort based on recalled somatotypes and reported BMI. Multivariate linear regression models were used to compare sex hormone concentration across different trajectory groups. The mean age at blood draw was 64·1 ± 8·1 years for men, 59·4 ± 6·0 for postmenopausal and 44·1 ± 4·6 for premenopausal women. In men, compared with the medium-stable group, lean-marked increase and medium increase groups had lower levels of SHBG (percentage difference: −17 and −9 %) and testosterone (−15 and −13 %). In postmenopausal women, compared with the medium-stable group, lean-marked increase and medium increase groups had higher levels of E1 (21 and 34 %) and E2 (45 and 68 %) but lower level of SHBG (–29 and −35 %). In premenopausal women, compared with the lean-moderate increase group, medium-stable/increase and heavy-stable/increase groups had lower levels of SHBG (–6 and −28 %). Attained adulthood adiposity and middle-life weight gain were associated with lower SHBG and testosterone in men, higher E1 and E2 and lower SHBG in postmenopausal women, and lower SHBG in premenopausal women. The study indicates the importance of maintaining a healthy body weight throughout life course for homoeostasis of sex hormones.

Fe deficiency has negative effects on voluntary physical activity (PA); however, the impact of consuming Fe-biofortified staple foods on voluntary PA remains unclear. This study compared the effects of consuming Fe-biofortified pearl millet or a conventional pearl millet on measures of voluntary PA in Indian schoolchildren (ages 12–16 years) during a 6-month randomised controlled feeding trial. PA data were collected from 130 children using Actigraph GT3X accelerometers for 6 d at baseline and endline. Minutes spent in light and in moderate-to-vigorous PA were calculated from accelerometer counts using Crouter’s refined two-regression model for children. Mixed regression models adjusting for covariates were used to assess relationships between intervention treatment or change in Fe status and PA. Children who consumed Fe-biofortified pearl millet performed 22·3 (95 % CI 1·8, 42·8, P = 0·034) more minutes of light PA each day compared with conventional pearl millet. There was no effect of treatment on moderate-to-vigorous PA. The amount of Fe consumed from pearl millet was related to minutes spent in light PA (estimate 3·4 min/mg Fe (95 % CI 0·3, 6·5, P = 0·031)) and inversely related to daily sedentary minutes (estimate −5·4 min/mg Fe (95 % CI –9·9, −0·9, P = 0·020)). Consuming Fe-biofortified pearl millet increased light PA and decreased sedentary time in Indian schoolchildren in a dose-dependent manner.

The vitamin B group, including riboflavin, plays paramount roles in one-carbon metabolism (OCM), and disorders related to this pathway have been linked to cancer development. The variants of genes encoding OCM enzymes and the insufficiency of B vitamins could contribute to carcinogenesis. Very few observational studies have revealed a relationship between riboflavin and gastric cancer (GC), especially under conditions of modified genetic factors. We carried out a study examining the association of riboflavin intake and its interaction with MTRR (rs1532268) genetic variants with GC risk among 756 controls and 377 cases. The OR and 95 % CI were evaluated using unconditional logistic regression models. We observed protective effects of riboflavin intake against GC, particularly in the female subgroup (OR = 0·52, 95 % CI 0·28, 0·97, Ptrend = 0·031). In the MTRR (rs1532268) genotypes analysis, the dominant model showed that the effects of riboflavin differed between the CC and CT + TT genotypes. Compared with CC carriers, low riboflavin intake in T+ carriers was significantly associated with a 93 % higher GC risk (OR = 1·93, 95 % CI 1·09, 3·42, Pinteraction = 0·037). In general, higher riboflavin intake might help reduce the risk of GC in both CC and TC + TT carriers, particularly the T+ carriers, with marginal significance (OR = 0·54, 95 % CI 0·28, 1·02, Pinteraction = 0·037). Our study indicates a protective effect of riboflavin intake against GC. Those who carry at least one minor allele and have low riboflavin intake could modify this association to increase GC risk in the Korean population.

We investigated the associations between dietary patterns and chronic disease mortality in Switzerland using an ecological design and explored their spatial dependence, i.e. the tendency of near locations to present more similar and distant locations to present more different values than randomly expected. Data of the National Nutrition Survey menuCH (n 2057) were used to compute hypothesis- (Alternate Healthy Eating Index (AHEI)) and data-driven dietary patterns. District-level standardised mortality ratios (SMR) were calculated using the Swiss Federal Statistical Office mortality data and linked to dietary data geographically. Quasipoisson regression models were fitted to investigate the associations between dietary patterns and chronic disease mortality; Moran’s I statistics were used to explore spatial dependence. Compared with the first, the fifth AHEI quintile (highest diet quality) was associated with district-level SMR of 0·95 (95 % CI 0·93, 0·97) for CVD, 0·91 (95 % CI 0·88, 0·95) for ischaemic heart disease (IHD), 0·97 (95 % CI 0·95, 0·99) for stroke, 0·99 (95 % CI 0·98, 1·00) for all-cancer, 0·98 (95 % CI 0·96, 0·99) for colorectal cancer and 0·93 (95 % CI 0·89, 0·96) for diabetes. The Swiss traditional and Western-like patterns were associated with significantly higher district-level SMR for CVD, IHD, stroke and diabetes (ranging from 1·02 to 1·08) compared with the Prudent pattern. Significant global and local spatial dependence was identified, with similar results across hypothesis- and data-driven dietary patterns. Our study suggests that dietary patterns partly contribute to the explanation of geographic disparities in chronic disease mortality in Switzerland. Further analyses including spatial components in regression models would allow identifying regions where nutritional interventions are particularly needed.

We aim to examine the relation of several folate forms (5-methyltetrahydrofolate (5-mTHF), unmetabolised folic acid (UMFA) and MeFox) with kidney function and albuminuria, which remained uncertain. The cross-sectional study was conducted in 18 757 participants from National Health and Nutrition Examination Survey 2011–2018. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) (<60 ml/min/1·73 m2), microalbuminuria (albumin:creatinine ratio (ACR) of 30–299 mg/g) and macroalbuminuria (ACR ≥ 300 mg/g). Overall, there were significant inverse associations between serum 5-mTHF and kidney outcomes with significant lower prevalence of reduced eGFR (OR, 0·71; 95 % CI: 0·57, 0·87) and macroalbuminuria (OR, 0·65; 95 % CI: 0·46, 0·91) in participants in quartiles 3–4 (v. quartiles 1–2; both Pfor trend across quartiles <0·05). In contrast, there were significant positive relationship between serum UMFA and kidney outcomes with significant higher prevalence of reduced eGFR in participants in quartiles 2–4 (v. quartile 1; OR, 2·12; 95 % CI: 1·45, 3·12; Pfor trend <0·001) and higher prevalence of macroalbuminuria in participants in quartile 4 (v. quartiles 1–3; OR, 1·46; 95 % CI: 1·06, 2·01; Pfor trend <0·001). However, there was no significant associations of 5-mTHF and UMFA with microalbuminuria. In addition, there were significant positive relationships of serum MeFox with reduced eGFR, microalbuminuria and macroalbuminuria (all Pfor trend <0·01). In conclusion, higher 5-mTHF level, along with lower UMFA and MeFox level, was associated with lower prevalence of kidney outcomes, which may help counsel future clinical trials and nutritional guidelines regarding the folate supplement.

From health and sustainability perspectives, reduction in the consumption of animal-based foods, especially red meat, is a key strategy. The present study examined the prevalence, sociodemographic and lifestyle factors, food consumption and food choice motives of vegetarians and consumers of low and high amounts of red and processed meat (RPM) among Finnish adults. We applied the data from three national health studies: FINRISK 2007 (n 4874), FINRISK 2012 (n 4812) and FinHealth 2017 (n 4442). Participants addressed their food consumption with a FFQ and answered other questionnaires about sociodemographic and lifestyle factors, as well as food choice motives. The prevalence of vegetarianism increased from 0·7 % in 2012 to 1·8 % in 2017, and median daily RPM consumption decreased from 128 g in 2007 to 119 g in 2012 and to 96 g in 2017. Vegetarians and members of the low-RPM group were more often women, younger and more highly educated than the high-RPM group, both in 2007 and 2017. Still, the importance of sex for the probability of a vegetarian diet decreased, while its importance for high-RPM consumption increased. Vegetarians consumed more fruit, vegetables, legumes, nuts and seeds than either the low- or high-RPM groups. The high-RPM group had the lowest scores in several aspects of healthy and sustainable diet, healthy food choice motives and healthy lifestyle. Vegetarians and groups differing in their RPM consumption levels might benefit from differing interventions and nutrition information taking into account their other dietary habits, food choice motives and lifestyle factors.

Using data from a nationally generalisable birth cohort, we aimed to: (i) describe the cohort’s adherence to national evidence-based dietary guidelines using an Infant Feeding Index (IFI) and (ii) assess the IFI’s convergent construct validity, by exploring associations with antenatal maternal socio-demographic and health behaviours and with child overweight/obesity and central adiposity at age 54 months. Data were from the Growing Up in New Zealand cohort (n 6343). The IFI scores ranged from zero to twelve points, with twelve representing full adherence to the guidelines. Overweight/obesity was defined by BMI-for-age (based on the WHO Growth Standards). Central adiposity was defined as waist-to-height ratio > 90th percentile. Associations were tested using multiple linear regression and Poisson regression with robust variance (risk ratios, 95 % CI). Mean IFI score was 8·2 (sd 2·1). Maternal characteristics explained 29·1 % of variation in the IFI score. Maternal age, education and smoking had the strongest independent relationships with IFI scores. Compared with children in the highest IFI tertile, girls in the lowest and middle tertiles were more likely to be overweight/obese (1·46, 1·03, 2·06 and 1·56, 1·09, 2·23, respectively) and boys in the lowest tertile were more likely to have central adiposity (1·53, 1·02, 2·30) at age 54 months. Most infants fell short of meeting national Infant Feeding Guidelines. The associations between IFI score and maternal characteristics, and children’s overweight/obesity/central adiposity, were in the expected directions and confirm the IFI’s convergent construct validity.

Urinary Na excretion is a potential risk factor for CVD. However, the underlying biological mechanisms and effects of salt sensitivity are unclear. The purpose of this study was to characterise the relative contribution of biological factors to the Na–CVD association. A total of 2112 participants were enrolled in this study. Structured questionnaires and blood and urine samples were obtained. Twenty-four-hour Na excretion was estimated using a single overnight urine sample. Hypertension, the metabolic syndrome and overweight status were considered to indicate salt sensitivity. Cox proportional hazard models were used to investigate the effects of salt sensitivity on urinary Na excretion and CVD risk. The traditional mediation approach was used to calculate the proportion of mediation. The mean age (sd) of the 2112 participants was 54·5 (sd 12·2) years, and they were followed up for a mean of 14·1 (sd 8·1) years. Compared with those in the lowest quartile, the highest baseline urinary Na excretion (>4·2 g/24 h) was associated with a 43 % higher CVD risk (hazard ratio, 1·43; 95 % CI 1·02, 1·99). Participants with high urinary Na excretion, hypertension or the metabolic syndrome had a significantly high risk of CVD. The carotid intima-media thickness had the largest mediating effect (accounting for 35 % of the Na–CVD association), followed by systolic blood pressure (BP) (33 %), left ventricular mass (28 %) and diastolic BP (14 %). Higher urinary Na excretion increased the risk of CVD, which was explained largely by carotid media-thickness and systolic BP.

Se is a trace mineral that has antioxidant and anti-inflammatory properties. This study aimed to investigate the association between Se intake, diabetes, all-cause and cause-specific mortality in a representative sample of US adults. Data from 18 932 adults who attended the 2003–2014 National Health and Nutrition Examination Survey were analysed. Information on mortality was obtained from the US mortality registry updated to 2015. Multivariable logistic regression and Cox regression were used. Cross-sectionally, Se intake was positively associated with diabetes. When comparing the extreme quartiles of Se intake, the OR for diabetes was 1·44 (95 % CI 1·09, 1·89). During a mean of 6·6 years follow-up, there were 1627 deaths (312 CVD, 386 cancer). High intake of Se was associated with a lower risk of all-cause mortality. When comparing the highest with the lowest quartiles of Se intake, the hazard ratios for all-cause, CVD mortality, cancer mortality and other mortality were 0·77 (95 % CI 0·59, 1·01), 0·62 (95 % CI 0·35, 1·13), 1·42 (95 % CI 0·78, 2·58) and 0·60 (95 % CI 0·40, 0·80), respectively. The inverse association between Se intake and all-cause mortality was only found among white participants. In conclusion, Se intake was positively associated with diabetes but inversely associated with all-cause mortality. There was no interaction between Se intake and diabetes in relation to all-cause mortality.

What a mother thinks about her child’s weight status might influence what and how she feeds her child. We examined the association between maternal perception, concern and dissatisfaction with child weight alongside feeding practices. Participants were from the Generation XXI birth cohort (n = 3233). A validated version of the Child Feeding Questionnaire and the Overt/Covert Control scale were used. Associations were evaluated by linear regression models (β coefficients and 95 % confidence intervals (95 % CI) with Bonferroni correction). Perceived underweight was associated with practices promoting food intake, such as higher pressure to eat at ages 4 and 7 years (β = 0·229; 95 % CI: 0·059, 0·398 and β = 0·190; 95 % CI:0·005, 0·376, respectively) and lower restriction at age 4 (β = –0·175; 95 % CI: –0·0310, –0·039). At age 7, perceived overweight was associated with higher covert control (β = 0·203; 95 % CI: 0·029, 0·376). Mothers who were concerned about child weight reported higher restriction (β = 0·226; 95 % CI: 0·142, 0·310 at 4 years and β = 0·261; 95 % CI: 0·169, 0·353 at 7 years) and covert control (β = 0·183; 95 % CI: 0·083, 0·282 at 4 years and β = 0·171; 95 % CI: 0·073, 0·269 at 7 years). Maternal desire for a heavier child was associated with higher pressure to eat at both ages (β = 0·285; 95 % CI: 0·163, 0·406 and β = 0·393; 95 % CI: 0·266, 0·520), while the desire for a thinner child was related to higher covert control at 7 years of age (β = 0·158; 95 % CI: 0·001, 0·316). Maternal perceptions and concern for child weight status are associated with feeding practices independently of actual weight status.