Nicotinamide overload may play a role in the developmentof type 2 diabetes

Zhou, Shi-Sheng; Li, Da; Sun, Wuping; Guo, Mengping; Lun, Yongzhi; Zhou, Yiming; Xiao, Fucheng; Li-xin, Jing; Sun, Shuhan; Zhang, Libin; Luo, Nancy; Bian, Fu-Ning; Zou, Wei; L, Dong; Zhao, Zhenjuan; Li, Sheng-Fan; Gong, Xia; Zhang, Yu; Sun, Chang-Bin; Zheng, Cuifang; Jiang, Dong-Ju; Li, Zhengning

doi:10.3748/wjg.15.5674

Cited by 73 publications

(81 citation statements)

References 50 publications

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“…1,3,18 Recently, our studies found that excess nicotinamide may induce oxidative stress, and suggested that obesity and type 2 diabetes, two major risk factors for CVD, may involve increased niacin consumption. 8,13,19 The present study further demonstrated that excess nicotinamide may contribute to increased circulating catecholamines, as well as increasing plasma Hcy levels.…”

Section: Discussionsupporting

confidence: 74%

“…8 The latter two factors may contribute to chronic nicotinamide overload (i.e. nicotinamide toxicosis) and subsequent methyl depletion, oxidative stress, insulin resistance and liver injury.…”

Section: Discussionmentioning

confidence: 99%

“…Nicotinamide and N 1 -methylnicotinamide were analyzed as previously described. 8 HPLC analysis of plasma Hcy was performed according to Pfeiffer et al 9 A mixture of 50 ml of plasma, 25 ml of internal standard (10 mmol l À1 cystamine) and 25 ml of phosphate-buffered saline (pH 7.4) was incubated with 10 ml of 100 g l À1 tris (2-carboxyethyl) phosphine hydrochloride for 30 min at room temperature, to reduce and release protein-bound thiols, after which 90 ml of 100 g l À1 trichloroacetic acid containing 1 mmol l À1 EDTA was added for deproteinization. Then, after centrifugation (13 000 g for 10 min), 50 ml of the supernatant was transferred to another Eppendorf tube, containing 10 ml of 1.55 mol l À1 NaOH, 125 ml of 0.125 mol l À1 borate buffer containing 4 mmol l À1 EDTA (pH9.5) and 25 ml of 1 g l À1 4-fluoro-7-sulfobenzofurazan ammonium salt in the borate buffer.…”

Section: Determination Of Nicotinamide N 1 -Methylnicotinamide Hcy mentioning

confidence: 99%

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

Sun

Lun

et al. 2011

Hypertens Res

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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, N 1 -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 N 1 -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-nicotinamideloading 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.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Determination Of Nicotinamide N 1 -Methylnicotinamide Hcy mentioning

confidence: 99%

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

Sun

Lun

et al. 2011

Hypertens Res

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“…Our recent study demonstrated that excessive nicotinamide might increase the generation of hydrogen peroxide, a highly ROS, and have a role in the development of insulin resistance. 35,60 It is interesting to know whether niacin fortification may have adverse effects. Although niacin fortification has been implemented to prevent niacin deficiency (that is, pellagra) for more than half a century, there are virtually no studies that document and track the long-term changes of the levels of plasma niacin and labile methyl donors, or the changes in the redox status.…”

Section: Arsenicmentioning

confidence: 99%

“…They involve the xenobiotic-metabolizing enzymes 80 and the sweat glands. 81 Most importantly, some toxic compounds (for example, nicotinamide 60 ) cannot be effectively excreted through urine in its natural form, but can be eliminated through sweat. Therefore, sweating can prevent oxidative stress and also avoid methyl depletion.…”

Section: Proposed Mechanism For the Effects Of Methyl Consumersmentioning

confidence: 99%

Dietary methyl-consuming compounds and metabolic syndrome

Zhou

et al. 2011

Hypertens Res

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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.

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Homocysteine and Related B Vitamins in Pre-diabetes and Diabetes Mellitus

Mutavdzin

Djuric

2020

Biochemistry of Cardiovascular Dysfunction in Obesity

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Nicotinamide overload may play a role in the developmentof type 2 diabetes

Cited by 73 publications

References 50 publications

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

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

Dietary methyl-consuming compounds and metabolic syndrome

Homocysteine and Related B Vitamins in Pre-diabetes and Diabetes Mellitus

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