Nicotinamide, also known as niacinamide and nicotinic acid amide, is the amide of nicotinic acid (vitamin B3 / niacin).

Nicotinamide is a water-soluble vitamin and is part of the vitamin B group. Nicotinic acid, also known as niacin, is converted to nicotinamide ', and, though the two are identical in their vitamin functions, nicotinamide does not have the same pharmacologic and toxic effects of niacin, which occur incidental to niacin's conversion. Thus nicotinamide does not reduce cholesterol or cause flushing,[1] although nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.[

Safety Study of Nicotinamide to Treat Alzheimer's Disease

http://clinicaltrials.gov/ct2/show/NCT00580931 Detailed Description: The goal of this proposal is to show that, nicotinamide (NA), a B3 vitamin, is safe and effective for the treatment of patients with mild to moderate Alzheimer's disease (AD). NA is known to block the ability of certain proteins to regulate other proteins by removing their acetyl groups. Recent evidence has demonstrated that inhibitors such as NA prevent nerve cell degeneration in models of Huntington's disease (HD), Parkinson's disease and Lou Gehrig's disease (or ALS). Despite these beneficial effects in many different animal models, there have been no studies to date using these inhibitors in AD. In some of our recent studies we found that the potent inhibitor, NA, significantly improves learning and memory in transgenic mice that develop AD. NA treatment also resulted in striking changes in tau, a protein that abnormally accumulates in AD. NA has been extensively used in clinical studies over the last 40 years and is generally safe and well-tolerated. As NA is a safe and readily available vitamin supplement, our recent results provide a strong argument for a study of NA in patients with AD. We therefore propose to treat 50 patients with mild to moderate AD with either NA (1500 milligrams twice a day) or an identical but inactive drug (placebo) for 24 weeks. At 6 week intervals we will assess functions such as learning and memory, and ability to carry out daily activities as well as caregiver reports using standardized tests. We will also perform spinal taps at the beginning and end of the study to measure the level of abnormal tau protein in the cerebrospinal fluid. Blood tests will periodically be done to assess liver function and complete blood counts. The results of this study may provide the basis for a more extensive study of NA for the treatment of mild to moderate AD. 1: Experimental Subjects will receive experimental drug in a blinded fashion. Intervention: Drug: Nicotinamide Drug: Nicotinamide 1500 mg twice a day for 6 months Other Name: Enduramide

In pharmacological doses, niacin has been proven to reverse atherosclerosis by reducing total cholesterol, triglycerides, very-lowdensity lipoprotein (VLDL), and low-density lipoprotein (LDL), and increasing high-density lipoprotein (HDL). It has been proposed that niacin has the ability to lower lipoprotein(a), which is beneficial at reducing thrombotic tendency.[15] Niacin, prescribed in doses between 1000 and 2000 mg, two to three times daily,[16] blocks the breakdown of fats in adipose tissue. These fats are used to build very-low-density lipoproteins (VLDL) in the liver, which are precursors of low-density lipoprotein (LDL) or "bad" cholesterol. Because niacin blocks the breakdown of fats, it causes a decrease in free fatty acids in the blood and, as a consequence, decreases the secretion of VLDL and cholesterol by the liver.[17] By lowering VLDL levels, niacin also increases the level of high-density lipoprotein (HDL) or "good" cholesterol in blood, and therefore it is sometimes prescribed for patients with low HDL, who are also at high risk of a heart attack.[18][19] The ARBITER 6-HALTS study, reported at the 2009 annual meeting of the American Heart Association and in the New England Journal of Medicine[20] concluded that, when added to statins, 2000 mg/day of slow-release niacin was more effective than ezetimibe (Zetia) in reducing carotid intima-media thickness, a marker of atherosclerosis.[21] As of August 2008, a combination of niacin with laropiprant is being tested in a clinical trial. Laropiprant reduces facial flushes induced by niacin. [22] Pharmacological doses of niacin (1.5 - 6 g per day) often lead to side effects that can include dermatological conditions such as skin flushing and itching, dry skin, and skin rashes including eczema exacerbation and acanthosis nigricans. Gastrointestinal complaints, such as dyspepsia (indigestion), nausea and liver toxicity fulminant hepatic failure, have also been reported. Side effects of hyperglycemia, cardiac arrhythmias and "birth defects in experimental animals" have also been reported.[23] The flush lasts for about 15

to 30 minutes, and is sometimes accompanied by a prickly or itching sensation, in particular, in areas covered by clothing. This effect is mediated by prostaglandin and can be blocked by taking 300 mg of aspirin half an hour before taking niacin, or by taking one tablet of ibuprofen per day. Taking the niacin with meals also helps reduce this side effect. After several weeks of a consistent dose, most patients no longer flush.[24] Slow- or "sustained"-release forms of niacin have been developed to lessen these side effects.[17][25] One study showed the incidence of flushing was significantly lower with a sustained release formulation[26] though doses above 2 g per day have been associated with liver damage, in particular, with slow-release formulations.[23] Flushing is often thought to involve histamine, but histamine has been shown not to be involved in the reaction.[27] Prostaglandin (PGD2) is the primary cause of the flushing reaction, with serotonin appearing to have a secondary role in this reaction.[27]

Niacin in cholesterol lowering doses (5002000 mg per day) causes facial flushes by stimulating biosynthesis of prostaglandin D2, especially in the skin. PG D2 acts as a vasodilator via DP1 receptors, increasing blood flow and thus leading to flushes.[4][5] Laropiprant acts as a DP1 antagonist, reducing the vasodilation.[4] Taking 650 mg of aspirin 2030 minutes prior to taking niacin has also been proven to prevent flushing in 90% of patients, presumably by suppressing prostaglandin synthesis,[6] but this medication also increases the risk of gastrointestinal bleeding,[7] though the increased risk is less than 1 percent.[8]