Effect of Pb-exposure and B vitamin deficiencies on δ-aminolevulinic acid dehydratase activity among workers from Pb recycling plants.

Previous studies reported that Pb exposure causes a negative association with delta-aminolevulinic acid dehydratase activity (δ-ALAD), but the impact of Pb exposure (dose and time), B vitamin deficiencies, and lifestyle factors needs to be explored. In this study, the impact of Pb exposure, B vitamin deficiencies, and lifestyle factors on δ-ALAD activity among workers exposed to Pb from the Pb-recycling process was evaluated. Blood lead levels (BLLs), B vitamins (B6, B9, and B12), hematological factors (Hb% and HCT), lifestyle factors, and δ-ALAD activity was assessed in 170 male Pb-exposed workers engaged in the Pb recycling process. BLLs are estimated using the ICP-OES method. B vitamins in serum samples from workers were determined using the ELISA method. The δ-ALAD activity in whole blood samples was determined using the spectrophotometer method. The lifestyle factors were collected using a standard questionnaire. The δ-ALAD activity was significantly decreased in workers with the habits of alcohol use, tobacco consumption, hematocrit < 41%, mild and moderate categories of anemia, vitamin B6 and B12 deficiency, and BLL categories of 10-30, 30-50, and > 50 µg/dL. Multiple regression analysis revealed that the independent variables of alcohol consumption (ß = - 0.170; P = 0.025), BLLs (ß = - 0.589; P = 0.001) and Hb% (ß = 0.183; P = 0.001) significantly influenced the δ-ALAD activity with 44.2% (R2 = 0.442). Among the workers exposed to Pb from the Pb recycling plant, δ-ALAD activity was considerably reduced by Pb exposure, B vitamin deficiency, hematological parameters, and lifestyle factors.

B vitamins and bone health: a meta-analysis with trial sequential analysis of randomized controlled trials.

Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions. PURPOSE: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs). METHODS: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses. RESULTS: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 - 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias. CONCLUSIONS: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs. TRIAL REGISTRATION: PROSPERO registration number: CRD42023427508.

Transsulfuration and folate pathways in rheumatoid arthritis: A systematic review and meta-analysis.

BACKGROUND: Metabolomic assessment of the transsulfuration and folic acid biochemical pathways could lead to the identification of promising biomarkers of nitric oxide dysregulation and oxidative stress in rheumatoid arthritis (RA). METHODS: We conducted a systematic review and meta-analysis of transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6 , and vitamin B12 ) metabolites in RA patients in remission and healthy controls. Electronic databases were searched from inception to 15 July 2023 for relevant articles. We assessed the risk of bias using the JBI checklist and the certainty of evidence using GRADE. RESULTS: In 28 eligible studies, compared to controls, RA patients had significantly higher concentrations of homocysteine (standardized mean difference, SMD = 0.74, 95% CI 0.54-0.93, p < 0.001; low certainty of evidence) and methionine (SMD = 1.00, 95% CI 0.57-1.44, p < 0.001; low certainty) and lower concentrations of vitamin B6 (SMD = -6.62, 95% CI -9.65 to -3.60, p < 0.001; low certainty). By contrast, there were non-significant between-group differences in vitamin B12 and folic acid. In meta-regression and subgroup analysis, there were no associations between the effect size and several study and patient characteristics except for homocysteine (year of publication, C-reactive protein, triglycerides, and analytical method) and folic acid (biological matrix). CONCLUSIONS: The results of our study suggest that homocysteine, methionine, and vitamin B6 are promising biomarkers to assess nitric oxide dysregulation and oxidative stress in RA. (PROSPERO registration number: CRD42023461081).

Higher dietary methyl donor micronutrient consumption is associated with higher muscle strength in adults: a cross-sectional study.

Methyl donor micronutrients might affect muscle strength via DNA methylation. We aimed to evaluate the combined relationship of dietary methyl donor micronutrients containing betaine, choline, methionine, vitamin B12, vitamin B6 and folate on muscle strength. This cross-sectional study was conducted on 267 subjects including 113 men and 154 women. Dietary intake of micronutrients was assessed utilising a validated 168-item semi-quantitative FFQ, and methyl donor micronutrient score (MDMS) was calculated. The muscle strength of the participants was measured using a digital handgrip dynamometer. The association was determined using linear regression analysis. The mean age of participants was 36·8 ± 13·2 years. After taking into account potential confounding variables, there was no significant association between dietary methyl donor micronutrient score (MDMS) and the mean left-hand muscle strength (ß: 0·07, se: 0·05, P = 0·07); however, the changes were significant in the mean right-hand muscle strength (ß: 0·09, se: 0·04, P = 0·03). There was also a significant positive relationship between mean muscle strength and methyl donors' intake after fully adjusting for potential confounders (ß: 0·08, se: 0·04, P = 0·04). In conclusion, our findings revealed that higher dietary methyl donor micronutrient consumption is associated with enhanced muscle strength. As a result, advice on a higher intake of methyl donor-rich foods including grains, nuts, dairy products and seafood might be recommended by dietitians as a general guideline to adhere to. Additional prospective studies are needed to confirm the findings.

Association between dietary macronutrient composition and plasma one-carbon metabolites and B-vitamin cofactors in patients with stable angina pectoris.

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analysed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (FFQ) and plasma one-carbon metabolites and related B-vitamin status markers (GC-MS/MS, LC-MS/MS or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol and total energy intake. Average (geometric mean (95 % prediction interval)) intake was forty-nine (38, 63) energy percent (E%) from carbohydrate, thirty-one (22, 45) E% from fat and seventeen (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e. with higher plasma pyridoxal 5'-phosphate (PLP) (% change (95 % CI) 3·1 (2·1, 4·1)), cobalamin (2·9 (2·1, 3·7)), riboflavin (2·4 (1·1, 3·7)) and folate (2·1 (1·2, 3·1)) and lower total homocysteine (tHcy) (-1·4 (-1·9, -0·9)) and methylmalonic acid (MMA) (-1·4 (-2·0, -0·8)). Substitution analyses replacing MUFA or PUFA with SFA demonstrated higher plasma concentrations of riboflavin (5·0 (0·9, 9·3) and 3·3 (1·1, 5·6)), tHcy (2·3 (0·7, 3·8) and 1·3 (0·5, 2·2)) and MMA (2·0 (0·2, 3·9) and 1·7 (0·7, 2·7)) and lower PLP (-2·5 (-5·3, 0·3) and -2·7 (-4·2, -1·2)). In conclusion, a higher protein intake and replacing saturated with MUFA and PUFA were associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk.

Characterisation of Indian gut microbiome for B-vitamin production and its comparison with Chinese cohort.

The human gut microbiota can biosynthesize essential micronutrients such as B-vitamins and is also known for its metabolic cooperative behaviour. The present study characterises such B-vitamin biosynthesizers, their biosynthetic pathways, explores their prevalence and abundance, examines how lifestyle or diet affects them in multiple Indian cohorts and compares it with the Chinese cohort. To achieve this, publicly available faecal metagenome data of healthy individuals from multiple Indian (two urban and three tribal populations) and a Chinese cohort were analysed. The distribution of prevalence and abundance of B-vitamin biosynthesizers showed similar profiles to that of the entire gut community of the Indian cohort, and there were 28 B-vitamin biosynthesizers that had modest or higher prevalence and abundance. The omnivorous diet affected only the prevalence of a few B-vitamin biosynthesizers; however, lifestyle and/or location affected both prevalence and abundance. A comparison with the Chinese cohort showed that fourteen B-vitamin biosynthesizers were significantly more prevalent and abundant in Chinese as compared with Indian samples (False Discovery Rate (FDR) <= 0·05). The metabolic potential of the entire gut community for B-vitamin production showed that within India, the tribal cohort has a higher abundance of B-vitamin biosynthesis pathways as compared with two urban cohorts namely, Bhopal and Kasargod, and comparison with the Chinese cohort revealed a higher abundance in the latter group. Potential metabolic cooperative behaviour of the Indian gut microbiome for biosynthesis of the B-vitamins showed multiple pairs of species showed theoretical complementarity for complete biosynthetic pathways genes of thiamine, riboflavin, niacin and pantothenate.

A systematic review on the impact of nutrition and possible supplementation on the deficiency of vitamin complexes, iron, omega-3-fatty acids, and lycopene in relation to increased morbidity in women after menopause.

A balanced and healthy diet during the menopausal transition and after menopause is crucial for women to reduce the risk for morbidities and chronic diseases due to deficiency of essential nutrients. PURPOSE: The objective of this study was to conduct a systematic review of studies that analyzed the impact of vitamin and nutrient deficiencies in postmenopausal women in relation to increased morbidities and chronic conditions. METHODS: Observational studies were searched in the databases PubMed, UpToDate, and Google Scholar. RESULTS: We searched 122 studies, of which 90 were included in our analysis. The meta-analysis of the data could not be performed because of the heterogeneity of the statistical methods in the included studies. In our study, we focused on the aspects of vitamin B6, vitamin B12, vitamin D, iron, omega-3-fatty acids, and lycopene, belonging to the family of carotenoids. Postmenopausal women with deficiencies of these nutrients are more vulnerable to comorbidities such as cardiovascular and cerebrovascular events, metabolic diseases, osteoporosis, obesity, cancer and neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, depression, cognitive decline, dementia, and stroke. We concluded that women after menopause tend to have a greater probability of suffering from deficiencies in various vitamins and nutrients, and consequently have an increased risk of developing morbidities and chronic diseases. CONCLUSION: In conclusion, maintaining optimum serum levels of nutrients and vitamins, either through a balanced and healthy diet consuming fresh fruits, vegetables, and fats or by taking appropriate supplementation, is essential in maintaining optimal health-related quality of life and reducing the risk for women during the menopausal transition and after menopause. Nevertheless, more recent studies need to be assessed to formulate adequate recommendations to achieve positive clinical outcomes.

Phentolamine and B vitamins for feeding intolerance in late preterm infants: a randomised trial.

BACKGROUND AND OBJECTIVES: Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications. METHODS AND STUDY DESIGN: We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment. RESULTS: The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05). CONCLUSIONS: Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.

Concurrent nutrient deficiencies are associated with dementia incidence.

INTRODUCTION: While observational research suggests a protective role for nutrition in brain aging, intervention studies remain inconclusive. This failing translation from observational to interventional research may result from overlooking nutrient interactions. METHODS: We developed a nutrient status index capturing the number of suboptimal statuses of omega-3 fatty acids, homocysteine, and vitamin D (range 0 to 3). We associated this index with dementia incidence in a subsample (age ≥ 50 years) of the Framingham Heart Study Offspring cohort. RESULTS: Among 968 participants, 79 developed dementia over 15.5 years (median follow-up). Each point increase in nutrient status index was associated with a 50% higher risk of dementia (hazard ratio [HR] = 1.50; 95% confidence interval [CI] = 1.16, 1.96). Participants with three high-risk statuses had a four-fold increased risk of dementia compared to participants without high-risk status (HR = 4.68; 95% CI = 1.69, 12.94). DISCUSSION: Concurrent nutrient deficiencies are associated with the risk of dementia. The potential of optimizing nutritional status to lower dementia risk warrants further study. HIGHLIGHTS: Nutrition and dementia research calls for multiple-nutrient approaches. We studied combined suboptimal statuses of omega-3 polyunsaturated fatty acids, homocysteine, and vitamin D. Suboptimal status of the three nutrients was associated with dementia risk. The risk estimate was larger than for other factors (ie, diabetes, apolipoprotein E Îµ4 carrier). Future studies should assess the effect of improving nutrient status on dementia risk.

Effect of dietary protein source and Saccharina latissima on nutritional and safety characteristics of milk.

BACKGROUND: Wheat distillers' grains (WDG) and seaweeds are recommended as alternative protein sources and enteric methane mitigators in dairy cow diets, respectively, but little is known about their impact on milk quality and safety. In the present study, 16 cows in four 4 × 4 Latin squares were fed isonitrogenous diets (50:50 forage:concentrate ratio), with rapeseed meal (RSM)-based or WDG-based concentrate (230 and 205 g kg-1 dry matter) and supplemented with or without Saccharina latissima. RESULTS: Replacement of RSM with WDG enhanced milk nutritional profile by decreasing milk atherogenicity (P = 0.002) and thrombogenicity (P = 0.019) indices and the concentrations of the nutritionally undesirable saturated fatty acids - specifically, lauric (P = 0.045), myristic (P = 0.022) and palmitic (P = 0.007) acids. It also increased milk concentrations of the nutritionally beneficial vaccenic (P < 0.001), oleic (P = 0.030), linoleic (P < 0.001), rumenic (P < 0.001) and α-linolenic (P = 0.012) acids, and total monounsaturated (P = 0.044), polyunsaturated (P < 0.001) and n-6 (P < 0.001) fatty acids. Feeding Saccharina latissima at 35.7 g per cow per day did not affect the nutritionally relevant milk fatty acids or pose any risk on milk safety, as bromoform concentrations in milk were negligible and unaffected by the dietary treatments. However, it slightly reduced milk concentrations of pantothenate. CONCLUSION: Feeding WDG to dairy cows improved milk fatty acid profiles, by increasing the concentrations of nutritionally beneficial fatty acids and reducing the concentration of nutritionally undesirable saturated fatty acids, while feeding seaweed slightly reduced pantothenate concentrations. However, when considering the current average milk intakes in the population, the milk compositional differences between treatments in this study appear relatively small to have an effect on human health. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

[Determination of 11 nutrients in liquid milk by ultra-performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 11 nutritional components(thiamine, riboflavin, nicotinamide, nicotinic acid, pantothenic acid, pyridoxine, pyridoxal, pyridoxamine, biotin, choline, L-carnitine) in liquid milk. METHODS: Milk samples were shaken with 20 mmol/L ammonium formate solution and heated in a water bath at 100 ℃ for 30 min, then incubated with papain and acid phosphatase at 45 ℃ for 16 h, the lower liquid was collected after centrifugation for analysis. UPLC separation was performed on an ACQUITY~(TM) HSS T3(3.0 mm×150 mm, 1.8 µm) column, 2 mmol/L ammonium formate(containing 0.1% formic acid) solution and acetonitrile(containing 0.1% formic acid) were used as mobile phase. Quantitative detection was performed by internal standard method. RESULTS: 11 nutritional components can be effectively separated and detected in 12 min, and the linear correlation coefficients(R~2) were all above 0.995. The limits of detection(LODs) were between 0.05 and 0.50 µg/L, and the limits of quantification(LOQs) were between 0.20 and 1.25 µg/L. The recovery rates of three-level addition were 85.6%-119.3%, and the precision RSDs were between 3.68% and 7.82%(n=6). Based on the detection of 60 liquid milk samples from 5 different animals, it was found that the contents of 11 nutrients in liquid milk from different milk sources were significantly different, but pyridoxine could not be detected. CONCLUSION: The method can quantitatively detect 11 water-soluble nutrients, including free and bound forms, by effective enzymolysis. It is sensitive, reproducible and can meet the needs of quantitative detection.

[Influence of the rat diet enrichment with oat ß-gucans on the assimilation of B group vitamins, mineral elements and lipid metabolism].

Despite the widespread use of oat ß-glucans as ingredient of foods and dietary supplements, there is insufficient data on their effect on the metabolism of vitamins and minerals. The purpose of the study was to evaluate the effect of including oat bran with a high content of ß-glucans (ß-glucan) in the diet on the absorption of micronutrients and lipid metabolism in growing rats deficient in vitamins D, group B and trace elements (iron, copper, zinc). Material and methods. After the development of micronutrient deficiency (for 23 days), in order to assess the effect of oat bran (5%) with a high content of ß-glucans on the correction of the micronutrient status of growing male Wistar rats (with initial body weight of 70.7±0.7 g), the missing micronutrients were introduced in the semi-synthetic diet deficient in vitamins D, group B, iron, copper and zinc within 7 days either along with ß-glucan (1.47%) or without its addition. Indicators of micronutrient sufficiency (riboflavin serum concentration, daily urinary excretion of thiamine, riboflavin and 4-pyridoxic acid, measured by fluorometric methods; serum concentration and urinary excretion of calcium, magnesium, iron, zinc, copper, phosphorus, measured by the atomic absorption method or using standard methods on a biochemical analyzer) and the biochemical parameters of blood serum were compared with the parameters of rats adequately provided with all micronutrients throughout the experiment. Results. Replenishment of missing micronutrients in the diet of rats with deficiency in vitamins D and group B, iron, copper and zinc for 7 days led to the elimination of deficiency of vitamins B1, B2 and B6, regardless of the presence of ß-glucans in the diet. At the same time, against the background of the presence of ß-glucans in the feed, an increase in the absorption of iron was observed, as evidenced by an increase by 1.73 times in iron blood plasma level (р<0.05) and a tendency towards its urinary excretion decrease by 1.60 fold (р<0.10) compared to animals from the control group. Adding oat bran with ß-glucans to the feed did not lead to a decrease in blood plasma level of total cholesterol and low-density lipoproteins cholesterol. The levels of high-density lipoprotein cholesterol and triglycerides in rats of all three groups did not have statistically significant differences. Conclusion. The presence of ß-glucans in the diet had virtually no effect on the absorption of B vitamins and improved the absorption of iron.

B vitamin supply in plants and humans: the importance of vitamer homeostasis.

B vitamins are a group of water-soluble micronutrients that are required in all life forms. With the lack of biosynthetic pathways, humans depend on dietary uptake of these compounds, either directly or indirectly, from plant sources. B vitamins are frequently given little consideration beyond their role as enzyme accessory factors and are assumed not to limit metabolism. However, it should be recognized that each individual B vitamin is a family of compounds (vitamers), the regulation of which has dedicated pathways. Moreover, it is becoming increasingly evident that individual family members have physiological relevance and should not be sidelined. Here, we elaborate on the known forms of vitamins B1 , B6 and B9 , their distinct functions and importance to metabolism, in both human and plant health, and highlight the relevance of vitamer homeostasis. Research on B vitamin metabolism over the past several years indicates that not only the total level of vitamins but also the oft-neglected homeostasis of the various vitamers of each B vitamin is essential to human and plant health. We briefly discuss the potential of plant biology studies in supporting human health regarding these B vitamins as essential micronutrients. Based on the findings of the past few years we conclude that research should focus on the significance of vitamer homeostasis - at the organ, tissue and subcellular levels - which could improve the health of not only humans but also plants, benefiting from cross-disciplinary approaches and novel technologies.

Study on the correlation between B vitamins and breast cancer.

BACKGROUND: Relevant studies suggest that serum vitamin level is related to the risk of breast cancer, and dietary pattern and drug supplementation can significantly affect the level of vitamin in the body. Therefore, intervention of vitamin level in the body is expected to be a potential strategy to reduce the risk of breast cancer. However, the current epidemiological findings of serum vitamin levels and breast cancer risk are inconsistent, and the relationship between serum vitamin and breast cancer is still controversial. In this study, we compared the serum vitamin expression levels of healthy people, benign breast patients, and breast cancer patients, and evaluated the relationship between B vitamin levels and breast cancer risk. METHODS: The study used liquid chromatography-tandem mass spectrometry to determine the serum vitamin levels of 520 people who attended Yunnan Cancer Hospital from September 2020 to December 2020. After screening by exclusion criteria, 38 patients with benign breast diseases, 87 patients with breast cancer and 91 healthy controls were finally included. The kruskal-wallis H test was used to compare the differences in serum vitamin levels of subjects. Χ2 test was used to evaluate the relationship between B vitamin level and age,BMI,TNM staging,Ki-67,Her-2,surgery and chemotherapy, and other baseline characteristics and through binary logistic regression analysis, calculating odds ratio and 95% confidence interval (CI) to evaluate the relationship between B vitamins and breast cancer risk. CONCLUSION: The levels of VitB1 and VitB5 in the serum of breast cancer patients and patients with benign breast diseases were higher than those in the healthy control group, while the expression levels of VitB3 in breast cancer patients were lower than those in the healthy control group and the breast benign disease groups. The level of VitB1 was positively correlated with breast cancer risk. The VitB3 level was negatively correlated with breast cancer risk. The VitB5 level is not significantly related to the risk of breast cancer.

Daily Folic Acid and/or Vitamin B12 Supplementation Between 6 and 30 Months of Age and Cardiometabolic Risk Markers After 6-7 Years: A Follow-Up of a Randomized Controlled Trial.

BACKGROUND: Deficiencies of vitamin B12 and folate are associated with elevated concentrations of metabolic markers related to CVDs. OBJECTIVES: We investigated the effect of supplementation of vitamin B12 with or without folic acid for 6 mo in early childhood on cardiometabolic risk markers after 6-7 y. METHODS: This is a follow-up study of a 2 × 2 factorial, double-blind, randomized controlled trial of vitamin B12 and/or folic acid supplementation in 6-30-mo-old children. The supplement contained 1.8 µg of vitamin B12, 150 µg of folic acid, or both, constituting >1 AI or recommended daily allowances for a period of 6 mo. Enrolled children were contacted again after 6 y (September 2016-November 2017), and plasma concentrations of tHcy, leptin, high molecular weight adiponectin, and total adiponectin were measured (N = 791). RESULTS: At baseline, 32% of children had a deficiency of either vitamin B12 (<200 pmol/L) or folate (<7.5 nmol/L). Combined supplementation of vitamin B12 and folic acid resulted in 1.19 µmol/L (95% CI: 0.09; 2.30 µmol/L) lower tHcy concentration 6 y later compared to placebo. We also found that vitamin B12 supplementation was associated with a lower leptin-adiponectin ratio in subgroups based on their nutritional status. CONCLUSIONS: Supplementation with vitamin B12 and folic acid in early childhood was associated with a decrease in plasma tHcy concentrations after 6 y. The results of our study provide some evidence of persistent beneficial metabolic effects of vitamin B12 and folic acid supplementation in impoverished populations. The original trial was registered at www. CLINICALTRIALS: gov as NCT00717730, and the follow-up study at www.ctri.nic.in as CTRI/2016/11/007494.

Long-Term Intake of Folate, Vitamin B6, and Vitamin B12 and the Incidence of Parkinson's Disease in a Sample of U.S. Women and Men.

BACKGROUND: Folate and vitamins B6 and B12 have been proposed as protective against the development of Parkinson's disease (PD). Two prior longitudinal studies were inconclusive. OBJECTIVE: The aim was to examine the association of long-term intake of folate, vitamin B6, and vitamin B12 with the incidence of PD. METHODS: The study population comprised 80,965 women (Nurses' Health Study, 1984-2016) and 48,837 men (Health Professionals Follow-up Study, 1986-2016) followed prospectively for the development of PD. Intake of B vitamins was measured at baseline and every 4 years thereafter using food frequency questionnaires. We estimated the hazard ratio (HR) and 95% confidence interval (CI) of PD based on quintiles of cumulative average intake adjusting for potential confounders. Secondary analyses considered different lagged exposure periods as well as baseline and recent intakes. RESULTS: In separate analyses of cumulative average intake, total folate, B6, and B12 were not associated with the risk of PD. Results from 8-, 12-, and 16-year lag analyses were consistent with these findings. Results for baseline intake of folate and B6 also pointed toward a null association. In contrast, a lower PD risk was observed among individuals with higher baseline total intake of B12 (pooled HR top vs. bottom quintile: 0.80; 95% CI: 0.67-0.95; P-trend = 0.01); results from 20-year lag analyses were consistent with this finding. CONCLUSIONS: Our results do not support the hypothesis that a higher intake of folate or vitamin B6 would reduce PD risk in this population. Our results provide moderate support for a possible protective effect of vitamin B12 on the development of PD. © 2023 International Parkinson and Movement Disorder Society.

High-dose folic acid and cancer risk; unjustified concerns by von Wrede and colleagues regarding our paper.

Women using antiseizure medication in pregnancy are often advised to use high doses of folic acid supplements (1mg to 5 mg) to reduce the risk of teratogenicity. Recently, we published a report showing an association between maternal prescription fill of high dose folic acid in relation to pregnancy and childhood cancer in the offspring. The report has sparked a debate about which dose of folic acid that should be recommended in pregnancy in women in need of antiseizure medication. In this Commentary, we explain our findings and the method used in our report, and answer recent questions that have emerged.

The effects of multi-nutrient formulas containing a combination of n-3 PUFA and B vitamins on cognition in the older adult: a systematic review and meta-analysis.

There is now evidence to suggest that there may be an interaction between B vitamins and n-3 PUFA, with suggestions that increasing intake of both nutrients simultaneously may benefit cognition in older adults. The aim of this systematic review was to investigate whether supplementation with a combination of n-3 PUFA and B vitamins can prevent cognitive decline in older adults. Randomised controlled trials conducted in older adults that measured cognitive function were retrieved. The included trials provided a combination of n-3 PUFA and B vitamins alone, or in combination with other nutrients. Trials that provided n-3 PUFA alone and also measured B vitamin status or provided B vitamin supplementation alone and measured n-3 PUFA status were also included. The databases searched were The Cochrane Library, EMBASE, CINAHL, Scopus and MEDLINE. A total of 14 papers were included in the analysis (n 4913; age: 60-70 years; follow-up 24 weeks to 4 years). The meta-analysis results found a significant benefit of nutrient formulas, which included both n-3 PUFA and B vitamins alongside other nutrients, v. placebo on global cognition assessed using composite scores from a neuropsychological test battery (G = 0·23, P = 0·002), global cognition using single measures of cognition (G = 0·28, P = 0·004) and episodic memory (G = 0·32, P = 0·001). The results indicate that providing a combination of n-3 PUFA and B vitamins as part of a multi-nutrient formula benefits cognition in older adults v. a placebo, and the potential for an interaction between these key nutrients should be considered in future experimental work.

The acute postprandial response of homocysteine to multivitamin and mineral supplementation with a standard meal is not impaired in older compared to younger adults.

PURPOSE: B vitamins are required for the complex regulation of homocysteine and one-carbon (1C) metabolism. Nutritional supplements are frequently used by older adults to counter nutritional inadequacies. However, the postprandial use of B vitamins from supplements in 1C metabolism may be altered with age owing to impaired nutrient absorption and metabolic regulation. Despite implications for health and nutritional status, postprandial 1C metabolite responses have not been characterised in older adults. METHODS: Healthy older (n = 20, 65-76 years) and younger (n = 20, 19-30 years) participants were recruited through online and printed advertisements in Auckland, New Zealand. Participants consumed a multivitamin and mineral supplement with a standard breakfast meal. Blood samples were collected at baseline and hourly for 4 h following ingestion. Plasma 1C metabolites (betaine, choline, cysteine, dimethylglycine, glycine, methionine, serine) were quantified using liquid chromatography coupled with mass spectrometry. Serum homocysteine, folate and vitamin B12 were quantified on a Cobas e411 autoanalyzer. RESULTS: Older adults had higher fasting homocysteine concentrations (older: 14.0 ± 2.9 µmol/L; younger: 12.2 ± 2.5 µmol/L; p = 0.036) despite higher folate (older: 36.7 ± 17.4 nmol/L; younger: 21.6 ± 7.6 nmol/L; p < 0.001) and similar vitamin B12 concentrations (p = 0.143) to younger adults. However, a similar postprandial decline in homocysteine was found in older and younger subjects in response to the combined meal and supplement. Except for a faster decline of cystathionine in older adults (p = 0.003), the postprandial response of other 1C metabolites was similar between young and older adults. CONCLUSION: Healthy older adults appear to maintain postprandial responsiveness of 1C metabolism to younger adults, supported by a similar postprandial decline in homocysteine concentrations.

Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial.

PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 µg folic acid, 8 mg vitamin B6, 6.4 µg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (ß = -1.680, P = 0.004) and betaine (ß = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .