Niacin adverse effects

Along with increasing evidence of health benefits from consumption of vitamins at levels much higher than RE) A recommendations comes concern over potential toxicity. This topic has been reviewed (19). Like all chemical substances, a toxic level does exist for each vitarnin. Traditionally it has been assumed that all water-soluble vitamins are safe at any level of intake and all fat-soluble vitamins are toxic, especially at intakes more than 10 times the recommended allowances. These assumptions are now known to be incorrect. Very high doses of some water-soluble vitamins, especially niacin and vitamin B, are associated with adverse effects. In contrast, evidence indicates that some fat-soluble micronutrients, especially vitamin E, are safe at doses many times higher than recommended levels of intake. Chronic intakes above the RDA for vitamins A and D especially are to be avoided, however. 

The major adverse effect of niacin treatment is intense cutaneous flushing (vasodilation), which manifests as an uncomfortable burning sensation and itchiness of the face and upper body, thereby limiting patient compliance to therapy [13]. Moreover, a short half-life, dyspepsia, hyperuricemia, and modest hyperglycemia were also reported [14-16]. 

Type III hyperlipoproteinemia may be treated with fibrates or niacin. Although fibrates have been suggested as the drugs of choice, niacin is a reasonable alternative because of the lack of data supporting a cardiovascular mortality benefit from fibrates and because of their potentially serious adverse effects. Fish oil supplementation may be an alternative therapy. 

Action HMG-CoA reductase inhibitor Dose 5-40 mg PO daily max 5 mg/d w/cyclosporine, 10 mg/d w/gemfibrozil or CrCl <30 mL/rain (avoid Al-/Mg-based antacids for 2 h after) Caution [X, /-] Contra Active liver Dz, unexplained T LFT Disp Tabs SE Myalgia, constipation, asthenia, abd pain, N, myopathy, rarely rhabdomyolysis Interactions T Effects OF warfarin T risk of myopathy W/ cyclosporine, fibrates, niacin, statins EMS T Effects of warfarin concurrent EtOH use can T risk of liver tox Asian pts have an T risk of adverse effects OD Unlikely to cause life-threatening Sxs... 

The beneficial and adverse effects of nicotinic acid (niacin) have been reviewed (12). Standard nicotinic acid from an immediate-release formulation is metabolized primarily by conjugation, which results in a high frequency of flushing. Long-acting nicotinic acid is metabolized through the nicotinamide pathway, which results in less flushing but increases the risk of hepatotoxicity. Modified-release nicotinic acid, on the other hand, has a more balanced metabolism and causes fewer of both types of adverse effects. 

Quantitative evidence of reversal of coronary disease was demonstrated with this regimen in three major clinical trials. Effects on lipoprotein levels are sustained, and no additional adverse effects have developed other than those encountered when the drugs are used singly. The drugs may be taken together, because niacin does not bind to the resins. LDL levels in patients with heterozygous familial hypercholesterolemia are usually normalized with daily doses of up to 6.5 g of niacin with 24-30 g of resin. 

Adverse effects The most common side effects of niacin therapy are an intense cutaneous flush (accompanied by an UnCOmfOrt-... 

Pieper JA (2003) Overview of niacin formulations differences in pharmacokinetics, efficacy, and safety. Am J Health Syst Pharm 60(Suppl 2) S9-14. Knodel LC, Talbert RL (1987) Adverse effects of hypolipidaemic drugs. Med Toxicol 2 10-32. 

Capuzzi DM, Morgan JM, Brusco OA Jr., and Intenzo CM (2000) Niacin dosing relationship to benefits and adverse effects. Current Atherosclerosis Report 2, 64-71. 

Pellagra-associated encephalopathy has been suspected as an adverse effect of isoniazid administration in several patients with tuberculosis. Deficiency of niacin (nicotinic acid) is characterized by dermatitis, diarrhea, and dementia. Other symptoms can occur, such as seizures, hallucinations, spasticity, and glossitis. Pellagra induced by isoniazid is promoted by malnutrition or a vegetarian diet with low intake of the nicotinamide precursors tryptophan and nicotinic acid. Specific supplementation is essential (10). 

Allergic skin reactions (17) and other adverse effects, including dermatological problems and neurological symptoms, have been described in individuals using such formulations. Heavy chronic consumption of kava-kava can lead to a pellagroid dermopathy that appears to be unrelated to niacin deficiency (18). 

Adverse effects of niacin are most commonly seen when this vitamin is used at pharmacological doses above I g/day in the treatment of dyslipidemia. Notable adverse effects include flushing due to vasodilatation dermatological effects including dry skin pruritus and hyperkeratosis gastrointestinal effects including peptic ulcer,. stomach pain, nausea. and diarrhea elevations in serum uric acid and glucose and hepatotoxicity. ... 

Nicotinic acid or niacin (vitamin B2) Many adverse effects... 

In a long-term follow-up of the Coronary Drug Project, Canner et al. (54) found in 8,341 men with established CHD that treatment with niacin resulted in an 11% relative risk reduction for mortality compared with placebo. Interestingly, despite beneficial effects on HDL cholesterol levels, treatment with estrogen was halted early in this trial for an increase in adverse effects and outcomes (55). 

The two primary adverse effects of the HMG-CoA reductase inhibitors are hepatotoxicity and myopathy. Patients taking these drugs should have liver function tests performed before starting therapy and then at regular intervals during therapy. Serum concentrations of alanine and aspartate aminotransferase are used as markers of hepatocellular toxicity. The answer is (B). The major recognized effect of niacin is reduction of VLDL secretion by the Uver (Figure 35-2). The answer is (C). 

Cardiovascular event reductions occurred in randomized trials using twice-daily mealtime niacin, but not in a recent trial of niacin administered at bedtime with minimal or no food intake. This raises the possibility that niacin s effect of blocking the normal fuel supply of fatty acids released from adipocytes might have adverse consequences that restrict the ability of bedtime niacin to reduce cardiovascular events. 

Niacin has also been trialled in combination with a statin and its safety compared with a statin alone [64 ]. Flushing occurred in 67% of patients and was the most common treatment-related adverse effect 21% of patients stopped taking niacin for a variety of symptoms and the incidence of adverse effects apart from flushing was 85%. There were three cases of chest pain, which were regarded as serious adverse events. Gastrointestinal discomfort was not uncommon. Fasting blood glucose concentrations rose by 7.7% over the 12 weeks of the study. In contrast in another study there was improved whole-body insulin sensitivity in an open study over 6 months [65 ]. 

Uses Type 2 DM Action a-Glucosidase inhibitor delays digestion of carbohydrates Dose Initial 25 mg PO rid maint 50-100 mg rid (w/ 1st bite of each meal) Caution [B, —] Contra DKA, obst/inflammatory GI disorders SCr >2 mg/dL Disp Tabs SE Flatulence, D, abd pain Interactions T Effects W/ celery, coriander, juniper berries, ginseng, garlic X- effects W/ENH, niacin, intestinal absorbents, amylase, pancreatin X- effects OF digoxin, propranolol, ranitidine EMS Can X- digoxin level-monitor ECG in pts on digoxin therapy OD May cause severe adverse GI Sxs symptomatic and supportive... 

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