Nicotinamide benefit and dosage information
September 12 2016 by
Ray Sahelian, M.D.

Nicotinamide is an amide of vitamin B3. Enrichment of diet with this nutrient in the West was introduced in the 1940s to prevent the dietary deficiency disorder Pellagra. Pellagra was caused by a particular form of poor vegetarian diet leading to Nicotinamide and Tryptophan deficiency. Nicotinamide is available in two supplements, MultiVit Rx, a potent daily multivitamin, and Vitamin-B-Coenzyme.

Atheroscler Suppl. 2013 . Nicotinic acid as a lipid-modifying drug--a review. Nicotinic acid has complex effects on lipoprotein metabolism; it increases HDL cholesterol, decreases triglycerides and LDL cholesterol. It also reduces lipoprotein(a) levels by about 25% and exerts certain effects that may be antiatherogenic. Studies performed in the pre-statin era demonstrated a good effectiveness of nicotinic acid on the development of atherosclerotic lesions and on the morbidity and mortality due to cardiovascular diseases. Because of its HDL cholesterol raising properties, nicotinic acid appears to be an ideal companion to statins since low HDL cholesterol concentration has been shown to negatively influence statin-treated patients even when ideal LDL cholesterol concentrations have been reached.

Nicotinamide and aging
Since the beginning of the last century, seminal discoveries have identified pyridine nucleotides as the major redox carriers in all organisms. Recent research has unravelled an unexpectedly wide array of signalling pathways that involve nicotinamide adenine dinucleotide (NAD) and its phosphorylated form, NADP. NAD serves as substrate for protein modification including protein deacetylation, and mono- and poly-ADP-ribosylation. Both NAD and NADP represent precursors of intracellular calcium-mobilizing molecules. It is now beyond doubt that NAD(P)-mediated signal transduction does not merely regulate metabolic pathways, but might hold a key position in the control of fundamental cellular processes.

Alcohol
Nicotinamide protects the developing mouse brain from some of the deleterious effects of ethanol. Researchers investigated whether the nutrient nicotinamide could prevent the neurotoxic effects of ethanol exposure in the postnatal brain of mice and analyzed whether inhibition of ethanol-induced apoptotic neuronal death could prevent behavioral impairment in adult mice. The brain-growth spurt that occurs in the 7-day postnatal period in mice correlates with neural development that takes place in the third trimester in humans. Seven-day-old mice injected with ethanol showed a 15- to 20-fold increase of cleaved caspase-3 and widespread apoptotic neural cell death in the forebrain. However, administration of nicotinamide significantly reduced caspase-3 activation. Nicotinamide treatment 0, 2, 4, or 8 hours after ethanol administration prevented activation of caspase-3, with the strongest effect observed when nicotinamide was administered between 0 and 2 hours after ethanol exposure. PLoS Medicine, 2006.

Dialysis
Pharmacotherapy. 2013. Nicotinic acid and nicotinamide: a review of their use for hyperphosphatemia in dialysis patients.

Melanoma, skin cancer
Researchers had older, high-risk patients with at least two non-melanoma skin cancers during the previous five years take 500 mg nicotinamide twice daily for a year. By the end of the one-year study period, new non-melanoma skin cancer rates were down 23 percent in the nicotinamide group compared to the placebo group. The vitamin supplement also appeared to reduce the numbers of thick, scaly patches of skin that can become cancer. When people stopped taking their tablets after 12 months, the benefit was no longer seen.
   N Engl J Med. 2015. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months.  Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients.

Nicotinamide and Multiple Sclerosis
Boosting concentrations in the nervous system of a vital compound called NAD, by giving its chemical precursor, nicotinamide has shown considerable therapeutic potential in a mouse model of multiple sclerosis (MS). In mice with the MS-like disease EAE, nicotinamide treatment profoundly prevents the degeneration of axons already showing signs of degeneration. Daily under-the-skin injections of nicotinamide in the EAE mouse also prevents inflammation of the axons and loss of myelin -- the underlying problem in MS -- and delays the onset and severity of disability.
Nicotinamide had beneficial effects even when treatment was delayed until 10 days after the induction MS-like disease, when most of the animals had clear signs of neurologic disability, hinting that it may have an impact at later stages of MS. The Journal of Neuroscience, September 20, 2006.

Skin cancer, melanoma
Exp Dermatol. 2014. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes.

Nicotinamide adenine dinucleotide phosphate
The increased expression and activity of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex has emerged as a major common factor in the cause of many forms of cardiovascular diseases since the upregulation of intravascular NADPH oxidase results in the formation of superoxide (O(2)(-)), which in turn promotes vascular damage. An ever-increasing number of drugs commonly used in cardiovascular medicine have been shown to influence NADPH oxidase expression and activity. These include nitric oxide donors, nitroaspirin, eicosanoids, phosphodiesterase inhibitors, corticosteroids, antioxidants, and specific inhibitors.

N Engl J Med. 2015. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. We randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months.  Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients.

Too much of a good vitamin?
The present study suggests that long-term high nicotinamide intake (e.g. induced by niacin fortification) may be a risk factor for methylation- and insulin resistance-related metabolic abnormalities. Br J Nutr. 2013. Nicotinamide supplementation induces detrimental metabolic and epigenetic changes in developing rats.

Emails
Q. I saw some info on the supplement Nicotinamide Riboside, it is claimed to have weight loss, energy enhancement and anti-aging properties. Is this just a new fad supplement, or a possible missing link as far as supplementation goes.
   A. I have not seen human studies to confirm these claims.