The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-informed advice to anyone with an interest in the role of nutrition in health. The BOND program provides ...information with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect, which will be especially useful for readers who want to assess nutrient status. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutritional status at the individual and population levels. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, folate, zinc, iron, vitamin A, and vitamin B-12. This review of vitamin A is the current article in this series. Although the vitamin was discovered >100 y ago, vitamin A status assessment is not trivial. Serum retinol concentrations are under homeostatic control due in part to vitamin A's use in the body for growth and cellular differentiation and because of its toxic properties at high concentrations. Furthermore, serum retinol concentrations are depressed during infection and inflammation because retinol-binding protein (RBP) is a negative acute-phase reactant, which makes status assessment challenging. Thus, this review describes the clinical and functional indicators related to eye health and biochemical biomarkers of vitamin A status (i.e., serum retinol, RBP, breast-milk retinol, dose-response tests, isotope dilution methodology, and serum retinyl esters). These biomarkers are then related to liver vitamin A concentrations, which are usually considered the gold standard for vitamin A status. With regard to biomarkers, future research questions and gaps in our current understanding as well as limitations of the methods are described.
Abstract
There is uncertainty regarding carotenoid intake recommendations, because positive and negative health effects have been found or are correlated with carotenoid intake and tissue levels ...(including blood, adipose tissue, and the macula), depending on the type of study (epidemiological vs intervention), the dose (physiological vs supraphysiological) and the matrix (foods vs supplements, isolated or used in combination). All these factors, combined with interindividual response variations (eg, depending on age, sex, disease state, genetic makeup), make the relationship between carotenoid intake and their blood/tissue concentrations often unclear and highly variable. Although blood total carotenoid concentrations <1000 nmol/L have been related to increased chronic disease risk, no dietary reference intakes (DRIs) exist. Although high total plasma/serum carotenoid concentrations of up to 7500 nmol/L are achievable after supplementation, a plateauing effect for higher doses and prolonged intake is apparent. In this review and position paper, the current knowledge on carotenoids in serum/plasma and tissues and their relationship to dietary intake and health status is summarized with the aim of proposing suggestions for a “normal,” safe, and desirable range of concentrations that presumably are beneficial for health. Existing recommendations are likewise evaluated and practical dietary suggestions are included.
The role of hepatic lipoprotein metabolism in diet-induced remission of type 2 diabetes is currently unclear. Here, we determined the contributions of hepatic VLDL1-triglyceride production rate and ...VLDL1-palmitic acid content to changes in intra-pancreatic fat and return of first phase insulin response in a subgroup of the Diabetes Remission Clinical Trial. Liver fat, VLDL1-triglyceride production, and intra-pancreatic fat decreased after weight loss and remained normalized after 24 months of remission. First-phase insulin response remained increased only in those maintaining diabetes remission. Compared with those in remission at 24 months, individuals who relapsed after initial remission had a greater rise in the content of VLDL1-triglyceride and VLDL1-palmitic acid, re-accumulated intra-pancreatic fat, and lost first-phase response by 24 months. Thus, we observed temporal relationships between VLDL1-triglyceride production, hepatic palmitic acid flux, intra-pancreatic fat, and β-cell function. Weight-related disordered fat metabolism appears to drive development and reversal of type 2 diabetes.
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•Remission of type 2 diabetes is associated with a major fall in liver fat export•Re-emergence is associated with increased liver-derived plasma triglycerides•These changes are reflected by intra-pancreatic fat content•Beta-cell dysfunction is related to raised intra-pancreatic fat
Al Mrabeh et al. show that remission of type 2 diabetes over 2 years is associated with decreased liver triglyceride export and intra-pancreatic fat. Weight gain and re-emergence of diabetes were associated with increase in liver-derived plasma triglyceride, re-accumulation of fat within the pancreas, and recurrence of beta cell dysfunction.
A number of epidemiological studies have suggested that diets rich in whole grains are linked to lower cardiovascular disease (CVD) risk and mortality. Quinoa, a pseudo-cereal, is included in the ..."whole grain" category but the effects of quinoa consumption in humans is not widely studied. Our aim was to undertake a dietary intervention study to investigate the effects of daily consumption of quinoa-enriched bread (providing 20 g quinoa flour) on CVD risk markers compared with a 100% refined wheat bread control. Thirty-seven healthy overweight men (35⁻70 years, body mass index >25 kg/m²) completed a 4-week cross-over intervention, separated by a 4-week washout period. Fasting blood samples were collected at the beginning and end of each intervention period. Continuous glucose monitoring was undertaken at the end of each intervention period. After 4 weeks of intervention, blood glucose and low density lipoprotein (LDL) cholesterol were significantly lower than baseline in both groups but there was no difference between quinoa and control. Anthropometric measures and other blood metabolites were not different between the two treatments. The cumulative area under the blood glucose curve for the last 4 days of the quinoa intervention tended to be lower than the first 4 days of wash-out (
= 0.054), and was significantly lower than the corresponding period of the wheat treatment (
= 0.039). In conclusion, daily consumption of quinoa in this short-term intervention appears to modify glucose response, but has minimal effects on other CVD risk biomarkers.
BACKGROUND: The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses, modulate nitric oxide synthesis, and promote ...vasodilation, which thereby improves blood flow. Resveratrol may therefore modulate aspects of brain function in humans. OBJECTIVE: The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults. DESIGN: In this randomized, double-blind, placebo-controlled, crossover study, 22 healthy adults received placebo and 2 doses (250 and 500 mg) of trans-resveratrol in counterbalanced order on separate days. After a 45-min resting absorption period, the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min. Cerebral blood flow and hemodynamics, as indexed by concentration changes in oxygenated and deoxygenated hemoglobin, were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy. The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort (n = 9). RESULTS: Resveratrol administration resulted in dose-dependent increases in cerebral blood flow during task performance, as indexed by total concentrations of hemoglobin. There was also an increase in deoxyhemoglobin after both doses of resveratrol, which suggested enhanced oxygen extraction, that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance. Cognitive function was not affected. Resveratrol metabolites were present in plasma throughout the cognitive task period. CONCLUSION: These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables.
The effects of buckwheat intake on cardiovascular diseases (CVDs) have not been systematically investigated. The aim of the present study was to comprehensively summarize studies in humans and ...animals, evaluating the impact of buckwheat consumption on CVD risk markers and to conduct a meta-analysis of relevant data. Thirteen randomized, controlled human studies, two cross-sectional human studies and twenty-one animal studies were identified. Using random-effects models, the weighted mean difference of post-intervention concentrations of blood glucose, total cholesterol and triglycerides were significantly decreased following buckwheat intervention compared with controls differences in blood glucose: -0.85 mmol/L (95% CI: -1.31, -0.39), total cholesterol: 0.50 mmol/L (95% CI: -0.80, -0.20) and triglycerides: 0.25 mmol/L (95% CI: -0.49, -0.02). Responses of a similar magnitude were seen in two cross-sectional studies. For animal studies, nineteen of twenty-one studies showed a significant reduction in total cholesterol of between 12% and 54%, and fourteen of twenty studies showed a significant reduction in triglycerides of between 2% and 74%. All exhibited high unexplained heterogeneity. There was inconsistency in HDL cholesterol outcomes in both human and animal studies. It remains unclear whether increased buckwheat intake significantly benefits other markers of CVD risk, such as weight, blood pressure, insulin, and LDL-cholesterol, and underlying mechanisms responsible for any effects are unclear.
Lietz discusses the study of Sowa et al which aimed to test the effect of vitamin A (VA) program overlap by simulating the exposure of Zambian children to provitamin A biofortified foods and ...preformed VA food fortification using an animal model. Although it is not surprising that combined consumption of preformed VA with biofortified maize increased liver VA stores more effectively than either approach alone, their statement that this overlap resulted in "excessive" liver VA stores, despite downregulation of provitamin A conversion, potentially increases the concern about the safety of overlapping VA interventions. The study by raises an important question as to whether provitamin A carotenoid intake needs to be more carefully evaluated. However, because of the current uncertainty regarding the liver VA cutoff value for "hypervitaminosis A," more research is urgently needed to establish a well-defined cutoff value for evaluating the safety of VA interventions and programs.
Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its ...widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana.
This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only. Each participant's household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin among WRA and children and milk micronutrient concentrations among lactating women. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development.
Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa.
The trial was registered on ClinicalTrials.gov (NCT05178407) and the Pan-African Clinical Trial Registry (PACTR202206868437931). This manuscript reflects protocol version 4 (August 29, 2022).
Diets rich in whole grains are associated with improved health and a lower risk of non-communicable diseases, but the mechanisms through which these health benefits are conveyed are uncertain. One ...mechanism may be improvements in the gut environment by the delivery of fermentable substrates and associated phytochemicals to the lower gut and modification of the gut microbiome. Quinoa is included in the whole-grain category because of its structural similarities to cereals but the effects of its consumption on the gut microbiome have not been investigated to date. Our aim was to examine the impact of daily quinoa consumption on the gut microbiome in a 4-week randomised cross-over intervention separated by a 4-week wash-out period involving 28 adult males. Participants consumed either a quinoa-enriched wheat-bread roll providing 20 g quinoa flour each day, or a control wheat-only bread roll. Stool samples were collected in sterile collection tubes immediately before and at the end of each intervention period. DNA was then extracted, and the 16S rRNA V4 region of extracted DNA was amplified and sequenced. For both the control and quinoa bread periods, there were no changes at the phyla or genus level between baseline and week 4 (all p > 0.05). Diversity in the microbiome profile was not different from baseline after either intervention arms. The results show that small changes in the type of cereal consumed—substituting 20 g of refined wheat flour with whole-grain quinoa flour—was not able to significantly modulate the gut microbiome. Further studies with higher levels of quinoa or longer exposure periods are needed to ascertain if there is a dose−response effect of quinoa, and if these effects are able to translate into clinical outcomes.
Evidence from cell culture studies indicates that β-carotene-(BC)-derived apocarotenoid signaling molecules can modulate the activities of nuclear receptors that regulate many aspects of adipocyte ...physiology. Two BC metabolizing enzymes, the BC-15,15'-oxygenase (Bcmo1) and the BC-9',10'-oxygenase (Bcdo2) are expressed in adipocytes. Bcmo1 catalyzes the conversion of BC into retinaldehyde and Bcdo2 into β-10'-apocarotenal and β-ionone. Here we analyzed the impact of BC on body adiposity of mice. To genetically dissect the roles of Bcmo1 and Bcdo2 in this process, we used wild-type and Bcmo1(-/-) mice for this study. In wild-type mice, BC was converted into retinoids. In contrast, Bcmo1(-/-) mice showed increased expression of Bcdo2 in adipocytes and β-10'-apocarotenol accumulated as the major BC derivative. In wild-type mice, BC significantly reduced body adiposity (by 28%), leptinemia and adipocyte size. Genome wide microarray analysis of inguinal white adipose tissue revealed a generalized decrease of mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) target genes. Consistently, the expression of this key transcription factor for lipogenesis was significantly reduced both on the mRNA and protein levels. Despite β-10'-apocarotenoid production, this effect of BC was absent in Bcmo1(-/-) mice, demonstrating that it was dependent on the Bcmo1-mediated production of retinoids. Our study evidences an important role of BC for the control of body adiposity in mice and identifies Bcmo1 as critical molecular player for the regulation of PPARγ activity in adipocytes.
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