Shi-Sheng Zhou

B-vitamin consumption and the prevalence of diabetes and obesity among the US adults: population based ecological study.

BackgroundThe global increased prevalence of obesity and diabetes occurred after the worldwide spread of B-vitamins fortification, in which whether long-term exposure to high level of B vitamins plays a role is unknown. Our aim was to examine the relationships between B-vitamins consumption and the obesity and diabetes prevalence.MethodsThis population based ecological study was conducted to examine possible associations between the consumption of the B vitamins and macronutrients and the obesity and diabetes prevalence in the US population using the per capita consumption data from the US Economic Research Service and the prevalence data from the US Centers for Disease Control and Prevention.ResultsThe prevalences of diabetes and adult obesity were highly correlated with per capita consumption of niacin, thiamin and riboflavin with a 26-and 10-year lag, respectively (R2 = 0.952, 0.917 and 0.83 for diabetes, respectively, and R2 = 0.964, 0.975 and 0.935 for obesity, respectively). The diabetes prevalence increased with the obesity prevalence with a 16-year lag (R2 = 0.975). The relationships between the diabetes or obesity prevalence and per capita niacin consumption were similar both in different age groups and in male and female populations. The prevalence of adult obesity and diabetes was highly correlated with the grain contribution to niacin (R2 = 0.925 and 0.901, respectively), with a 10-and 26-year lag, respectively. The prevalence of obesity in US adults during 1971-2004 increased in parallel with the increase in carbohydrate consumption with a 10-year lag. The per capita energy and protein consumptions positively correlated with the obesity prevalence with a one-year lag. Moreover, there was an 11-year lag relationship between per capita energy and protein consumption and the consumption of niacin, thiamin and riboflavin (R2 = 0.932, 0.923 and 0.849 for energy, respectively, and R2 = 0.922, 0.878 and 0.787 for protein, respectively).ConclusionsLong-term exposure to high level of the B vitamins may be involved in the increased prevalence of obesity and diabetes in the US in the past 50 years. The possible roles of B-vitamins fortification and excess niacin consumption in the increased prevalence of obesity and diabetes were discussed.

Excess vitamin intake: An unrecognized risk factor for obesity

Over the past few decades, food fortification and infant formula supplementation with high levels of vitamins have led to a sharp increase in vitamin intake among infants, children and adults. This is followed by a sharp increase in the prevalence of obesity and related diseases, with significant disparities among countries and different groups within a country. It has long been known that B vitamins at doses below their toxicity threshold strongly promote body fat gain. Studies have demonstrated that formulas, which have very high levels of vitamins, significantly promote infant weight gain, especially fat mass gain, a known risk factor for children developing obesity. Furthermore, ecological studies have shown that increased B vitamin consumption is strongly correlated with the prevalence of obesity and diabetes. We therefore hypothesize that excess vitamins may play a causal role in the increased prevalence of obesity. This review will discuss: (1) the causes of increased vitamin intake; (2) the non-monotonic effect of excess vitamin intake on weight and fat gain; and (3) the role of vitamin fortification in obesity disparities among countries and different groups within a country.

Dietary methyl-consuming compounds and metabolic syndrome

The metabolic syndrome, a major risk factor for type 2 diabetes and cardiovascular disease, is a cluster of metabolic abnormalities including obesity, insulin resistance, hypertension and dyslipidemia. Although systemic oxidative stress and aberrant methylation status are known to have important roles in the development of metabolic syndrome, how they occur remains unclear. The metabolism of methyl-consuming compounds generates reactive oxygen species and consumes labile methyl groups; therefore, a chronic increase in the levels of methyl-consuming compounds in the body can induce not only oxidative stress and subsequent tissue injury, but also methyl-group pool depletion and subsequent aberrant methylation status. In the past few decades, the intake amount of methyl-consuming compounds has substantially increased primarily due to pollution, food additives, niacin fortification and high meat consumption. Thus, increased methyl consumers might have a causal role in the development and prevalence of metabolic syndrome and its related diseases. Moreover, factors that decrease the elimination/metabolism of methyl-consuming compounds and other xenobiotics (for example, sweat gland inactivity and decreased liver function) or increase the generation of endogenous methyl-consuming compounds (for example, mental stress-induced increase in catecholamine release) may accelerate the progression of metabolic syndrome. Based on current nutrition knowledge and the available evidence from epidemiological, ecological, clinical and laboratory studies on metabolic syndrome and its related diseases, this review outlines the relationship between methyl supply-consumption imbalance and metabolic syndrome, and proposes a novel mechanism for the pathogenesis and prevalence of metabolic syndrome and its related diseases.

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives

Nicotinamide and catecholamines are both degraded by S-adenosylmethionine-dependent methylation. Whether excess nicotinamide affects the degradation of catecholamines is unknown. The aim of this study was to investigate the effect of nicotinamide on the methylation status of the body and methylation-mediated catecholamine degradation in both normotensives and hypertensives. The study was conducted in 19 normotensives and 27 hypertensives, using a nicotinamide-loading test (100 mg orally). Plasma nicotinamide, N1-methylnicotinamide, homocysteine (Hcy), betaine, norepinephrine, epinephrine, normetanephrine and metanephrine levels before and 5 h after nicotinamide loading were measured. Compared with normotensives, hypertensives had higher baseline (fasting) levels of plasma nicotinamide, Hcy and norepinephrine, but lower levels of plasma normetanephrine, a methylated norepinephrine derivative. Nicotinamide loading induced a significant increase in the levels of plasma N1-methylnicotinamide and norepinephrine, and a significant decrease in the levels of O-methylated epinephrine (metanephrine) and betaine, a major methyl donor, in both hypertensives and normotensives. Moreover, nicotinamide-loading significantly increased plasma Hcy levels, but decreased plasma normetanephrine levels in normotensives. The baseline levels of plasma epinephrine in hypertensives were similar to those of normotensives, but the post-nicotinamide-loading levels of plasma epinephrine in hypertensives were higher than those of normotensives. This study demonstrated that excess nicotinamide might deplete the labile methyl pool, increase Hcy generation and inhibit catecholamine degradation. It also revealed that hypertensives had an abnormal methylation pattern, characterized by elevated fasting plasma levels of unmethylated substrates, nicotinamide, Hcy and norepinephrine. Therefore, it seems likely that high nicotinamide intake may be involved in the pathogenesis of Hcy-related cardiovascular disease.

The skin function: a factor of anti-metabolic syndrome

The body’s total antioxidant capacity represents a sum of the antioxidant capacity of various tissues/organs. A decrease in the body’s antioxidant capacity may induce oxidative stress and subsequent metabolic syndrome, a clustering of risk factors for type 2 diabetes and cardiovascular disease. The skin, the largest organ of the body, is one of the major components of the body’s total antioxidant defense system, primarily through its xenobiotic/drug biotransformation system, reactive oxygen species-scavenging system, and sweat glands- and sebaceous glands-mediated excretion system. Notably, unlike other contributors, the skin contribution is variable, depending on lifestyles and ambient temperature or seasonal variations. Emerging evidence suggests that decreased skin’s antioxidant and excretory functions (e.g., due to sedentary lifestyles and low ambient temperature) may increase the risk for metabolic syndrome. This review focuses on the relationship between the variability of skin-mediated detoxification and elimination of exogenous and endogenous toxic substances and the development of metabolic syndrome. The potential role of sebum secretion in lipid and cholesterol homeostasis and its impact on metabolic syndrome, and the association between skin disorders (acanthosis nigricans, acne, and burn) and metabolic syndrome are also discussed.

Vitamin paradox in obesity: Deficiency or excess?

Since synthetic vitamins were used to fortify food and as supplements in the late 1930s, vitamin intake has significantly increased. This has been accompanied by an increased prevalence of obesity, a condition associated with diabetes, hypertension, cardiovascular disease, asthma and cancer. Paradoxically, obesity is often associated with low levels of fasting serum vitamins, such as folate and vitamin D. Recent studies on folic acid fortification have revealed another paradoxical phenomenon: obesity exhibits low fasting serum but high erythrocyte folate concentrations, with high levels of serum folate oxidation products. High erythrocyte folate status is known to reflect long-term excess folic acid intake, while increased folate oxidation products suggest an increased folate degradation because obesity shows an increased activity of cytochrome P450 2E1, a monooxygenase enzyme that can use folic acid as a substrate. There is also evidence that obesity increases niacin degradation, manifested by increased activity/expression of niacin-degrading enzymes and high levels of niacin metabolites. Moreover, obesity most commonly occurs in those with a low excretory reserve capacity (e.g., due to low birth weight/preterm birth) and/or a low sweat gland activity (black race and physical inactivity). These lines of evidence raise the possibility that low fasting serum vitamin status in obesity may be a compensatory response to chronic excess vitamin intake, rather than vitamin deficiency, and that obesity could be one of the manifestations of chronic vitamin poisoning. In this article, we discuss vitamin paradox in obesity from the perspective of vitamin homeostasis.

Early Infant Exposure to Excess Multivitamin: A Risk Factor for Autism?

Autism, a neurodevelopmental disorder that affects boys more than girls, is often associated with altered levels of monoamines (serotonin and catecholamines), especially elevated serotonin levels. The monoamines act as both neurotransmitters and signaling molecules in the gastrointestinal and immune systems. The evidence related to monoamine metabolism may be summarized as follows: (i) monoamine neurotransmitters are enzymatically degraded/inactivated by three mechanisms: oxidative deamination, methylation, and sulfation. The latter two are limited by the supply of methyl groups and sulfate, respectively. (ii) A decrease in methylation- and sulfation-mediated monoamine inactivation can be compensated by an increase in the oxidative deamination catalyzed by monoamine oxidase, an X-linked enzyme exhibiting higher activity in females than in males. (iii) Vitamins can, on one hand, facilitate the synthesis of monoamine neurotransmitters and, on the other hand, inhibit their inactivation by competing for methylation and sulfation. Therefore, we postulate that excess multivitamin feeding in early infancy, which has become very popular over the past few decades, may be a potential risk factor for disturbed monoamine metabolism. In this paper, we will focus on the relationship between excess multivitamin exposure and the inactivation/degradation of monoamine neurotransmitters and its possible role in the development of autism.

Effects of monocarboxylic acid-derived Cl- channel blockers on depolarization-activated potassium currents in rat ventricular myocytes.

The effects of monocarboxylic acid‐derived Cl− channel blockers on cardiac depolarization‐activated K+ currents were investigated. Membrane currents in rat ventricular myocytes were recorded using the whole‐cell configuration of the patch‐clamp technique. 5‐Nitro‐2‐(3‐phenylpropylamino)‐benzoic acid (NPPB) and niflumic acid (NFA) induced an outward current at 0 mV. Both NPPB and NFA failed to induce any current when used intracellularly or after K+ in the bath and pipette solutions was replaced by equimolar Cs+. Voltage pulse protocols revealed that NPPB and NFA enhanced the steady‐state K+ current but inhibited the transient outward K+ current. Genistein, a tyrosine kinase (PTK) inhibitor, inhibited NPPB‐ and NFA‐induced outward current. Another PTK inhibitor, lavendustin A, produced a comparable effect. In contrast, the inactive analogue of genistein, daidzein, was ineffective. Orthovanadate, a tyrosine phosphatase inhibitor, markedly slowed the deactivation of the outward current induced by NPPB and NFA. The protein kinase A (PKA) inhibitor H‐89 inhibited NPPB‐induced outward current at 0 mV. In contrast, the protein kinase C (PKC) inhibitor H‐7 was without significant effect on the action of NPPB. Pretreatment of the myocytes with genistein or H‐89 prevented the enhancing effect of NPPB. Increasing intracellular Cl− from 22 to 132 mm slightly reduced NPPB‐induced outward current at 0 mV. These results demonstrate that the monocarboxylic acid‐derived Cl− channel blockers NPPB and NFA enhance cardiac steady‐state K+ current, and suggest that the enhancing effect of the Cl− channel blockers is mediated by stimulation of PKA and PTK signalling pathways.

Maternal nicotinamide supplementation causes global DNA hypomethylation, uracil hypo-incorporation and gene expression changes in fetal rats

Recent evidence shows that excess nicotinamide can cause epigenetic changes in developing rats. The aim of the present study was to investigate the effects of maternal nicotinamide supplementation on the fetus. Female rats were randomised into four groups fed a standard chow diet (control group) or diets supplemented with 1 g/kg of nicotinamide (low-dose group), 4 g/kg of nicotinamide (high-dose group) or 4 g/kg of nicotinamide plus 2 g/kg of betaine (betaine group) for 14-16 d before mating and throughout the study. Fetal tissue samples were collected on the 20th day of pregnancy. Compared with the control group, the high-dose group had a higher fetal death rate, and the average fetal body weight was higher in the low-dose group but lower in the high-dose group. Nicotinamide supplementation led to a decrease in placental and fetal hepatic genomic DNA methylation and genomic uracil contents (a factor modifying DNA for diversity) in the placenta and fetal liver and brain, which could be completely or partially prevented by betaine. Moreover, nicotinamide supplementation induced tissue-specific alterations in the mRNA expression of the genes encoding nicotinamide N-methyltransferase, DNA methyltransferase 1, catalase and tumour protein p53 in the placenta and fetal liver. High-dose nicotinamide supplementation increased fetal hepatic α-fetoprotein mRNA level, which was prevented by betaine supplementation. It is concluded that maternal nicotinamide supplementation can induce changes in fetal epigenetic modification and DNA base composition. The present study raises the concern that maternal nicotinamide supplementation may play a role in the development of epigenetic-related diseases in the offspring.

Preeclampsia and future cardiovascular risk: A point of view from the clearance of plasma vasoactive amines.

ABSTRACT Objective: To summarize the reported evidence on the relationship between vasoactive amines and preeclampsia. Methods: A literature search was conducted in MEDLINE/PubMed and EMBASE. Results: The summarized results are as follows: (1) Menstruation can effectively eliminate vasoactive amines norepinephrine, serotonin and histamine. (2) Pregnancy increases norepinephrine production due to fetal brain development and decreases vasoactive-amine elimination due to amenorrhea. (3) Preeclampsia is associated with a low renal and/or sweating capacity, or in rare cases, with increased norepinephrine production due to maternal pheochromocytoma and fetal neuroblastoma. Conclusion: Preeclampsia is mainly due to decreased excretion of norepinephrine and other vasoactive amines.