Safety of high-dose nicotinamide: a review

Knip, Mikael; Douek, I. F.; Moore, W.; Gillmor, Hilary A; McLean, A. E. M.; Bingley, P. J.; Gale, E.A.M.

doi:10.1007/s001250051536

Cited by 361 publications

(258 citation statements)

References 40 publications

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“…47 In contrast, nicotinamide is rarely excreted into the urine in its original form due to a high rate of tubular reabsorption. 48 Thus, equivalent doses of nicotinamide may consume more methyl groups than nicotinic acid.…”

Section: Arsenicmentioning

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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Section: Arsenicmentioning

confidence: 99%

Dietary methyl-consuming compounds and metabolic syndrome

Zhou

et al. 2011

Hypertens Res

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“…The present study data and published data raise no safety concerns for clinical use. [47][48][49] Furthermore, niacinamide has been used systemically as a perfusion enhancer for palliative care in patients with breast cancer due to its relaxant effects on vascular smooth muscle cells. The results of this study suggest that cytostatic cutaneous symptoms among other health problems have a negative impact on quality of life for the patients.…”

Section: Discussionmentioning

confidence: 99%

Barrier protective use of skin care to prevent chemotherapy-induced cutaneous symptoms and to maintain quality of life in patients with breast cancer

2016

Journal of the American Academy of Dermatology

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Section: Discussionmentioning

confidence: 99%

“…At high doses, such as those used in ENDIT, peak levels of nicotinamide of 0.3-1.0 mmol/l are seen in the circulation; the 50% inhibition concentration of nicotinamide for PARP is about 0.1 mmol/l [29]. The safety profile of high dose nicotinamide has been reviewed, and the ratio of risk to benefit would be highly favourable if efficacy can be shown [30].First-degree relatives of a child with Type 1 diabetes are at increased risk of progression to the disease, and are highly motivated to participate in such studies; it is therefore logical to offer intervention to people in this category. Although now largely superseded by measurement of other autoantibodies, ICA for many years formed the basis of diabetes prediction, and were used to identify high risk of progression in ENDIT, as in current US studies of intervention in pre-type 1 diabetes [3].…”

mentioning

confidence: 99%

Intervening before the onset of Type 1 diabetes: baseline data from the European Nicotinamide Diabetes Intervention Trial (ENDIT)

Gale

Inte²

2003

Diabetologia

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Aims/hypothesis To set up a clinical trial to establish whether nicotinamide can prevent or delay clinical onset of Type 1 diabetes.Method The European Nicotinamide Diabetes Intervention Trial is a randomised, double-blind, placebo-controlled intervention trial undertaken in 18 European countries, Canada and the USA.Entry criteria were a first-degree family history of Type 1 diabetes, age 3-40 years, confirmed islet cell antibody (ICA) levels greater than or equal to 20 JDF units, and a non-diabetic OGTT; the study group was further characterised by intravenous glucose tolerance testing, measurement of antibodies to GAD, IA-2 and insulin and HLA class II genotyping.Results ICA screening was carried out in approximately 30,000 first-degree relatives. A total of 1004 individuals fulfilled ICA criteria for eligibility, and 552 (288 male) were randomised to treatment. Of these, 331 were aged less than 20 years (87% siblings and 13% offspring of the proband with diabetes) and 221 were 20 years of age or more (76% parents, 21% siblings and 3% offspring). Oral glucose tolerance was normal in 500 and impaired in 52 (9.4%), and first phase 1 insulin response in the IVGTT was below the 10 th centile in 34%. Additional islet autoantibodies were identified in 354 trial entrants. Diabetes-associated HLA class II haplotypes were found in 84% of the younger age group and 80% of the older group. The protective haplotype HLA-DQA1*0102-DQB1*0602 was found in 10% overall.Conclusions/interpretation ENDIT has shown that a trial of an intervention designed to halt or delay progression to Type 1 diabetes can be carried out on a multinational collaborative basis, as and when potentially safe and effective forms of intervention become available. Primary screening with biochemically defined autoantibodies will substantially reduce the number of lower risk individuals to be included in future intervention trials Europe includes countries with the highest incidence of Type 1 (insulin-dependent) diabetes mellitus in the world. These rates continue to rise rapidly, and the EURODIAB TIGER Concerted Action has shown an annual 3 to 4% increase in the incidence of childhood diabetes across our continent [1]. In Finland, it is estimated that childhood diabetes is now four times as common as 2 it was in the 1950s [2]. There is currently no means of preventing or curing this disorder. Type 1 diabetes can, however, be predicted by screening for islet autoantibodies, and both animal and human pilot studies suggest that prevention is possible. The US Diabetes Prevention Trial-Type 1 (DPT-1) has recently reported experience with parenteral insulin therapy in high risk relatives of an individual with Type 1 diabetes [3]. Here we show baseline data from a trial of high-dose oral nicotinamide, and demonstrate that a candidate preventive measure can be tested successfully on a multinational collaborative basis. MethodsStudy Design ENDIT is a randomised, double-blind, placebo controlled trial designed to test whether daily oral administration of hi...

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Safety of high-dose nicotinamide: a review

Cited by 361 publications

References 40 publications

Dietary methyl-consuming compounds and metabolic syndrome

Dietary methyl-consuming compounds and metabolic syndrome

Barrier protective use of skin care to prevent chemotherapy-induced cutaneous symptoms and to maintain quality of life in patients with breast cancer

Intervening before the onset of Type 1 diabetes: baseline data from the European Nicotinamide Diabetes Intervention Trial (ENDIT)

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