Discussion: Use of Herbal/Supplement Niacin

Niacin

Natural Standard Professional Monograph, Copyright © 2015 (www.naturalstandard.com).

Synonyms/Common Names/Related Substances

· 2-Pyridone, 3-pyridine carboxamide, acipomox, Acipimox®, acipimox (5-methylpyrazinecarboxylic acid 4-oxide), antiblacktongue factor, antipellagra factor, B vitamin, B-complex vitamin, benicot, B-vitamin, chromium polynicotinate (niacin-bound chromium), coenzyme beta-nicotinamide adenine dinucleotide (NAD(+)), crystalline niacin, dihydropyridines, Efacin®, Endur-Acin® (sustained-release niacin (nicotinic acid)), Enduramide®, ER niacin, ER niacin monotherapy, ER niacin therapy, esters of niacin, extended-release niacin, extended-release niacin monotherapy, extended-release niacin therapy, Hexopal®, immediate-release niacin, immediate-release niacin, inositol hexaniacinate, inositol hexanicotinate, inositol nicotinate, kynurenine (KYN), low-dose sustained-release nicotinic acid (Tri-B3), meso-inositol hexanicotinate, methyl niacinamide, Nature’s Bounty® Flush Free Niacin Inositol Hexanicotinate 500mg Dietary Supplement, NIAC®, niacin, niacin, niacin equivalents, niacin ER, niacinamide, niacinamide adenine dinucleotide (NAD), niacinamide adenine dinucleotide phosphate (NADP), niacin-colestipol therapy, niacine, Niacor®, Niaspan® (prolonged-release nicotinic acid), Niaspan® (sustained-release nicotinic acid), Nicalex®, nicamid, Nicamin®, Nicangin®, Niceritrol, Nico-400®, Nicobid® (sustained-released niacin), Nicobid® (time-release niacin), Nicolar® (unmodified niacin), nicosedine, Nico-Span®, nicotinamide, nicotinate, Nicotinex®, nicotinic acid, nicotinic acid adenine, nicotinic acid adenine dinucleotide phosphate (NAADP), nicotinic acid amide, nicotinic acid analog (low plasma free fatty acid trial, LFA), nicotinic acid analogue, nicotinic amide, nicotinuric acid, nicotylamidum, nutrient supplements, Papulex®, pellagra-preventing factor, pentaerythritoltetranicotinate, perycit, PR nicotinic acid, prolonged-release nicotinic acid (niacine), pyridine-3-carboxylic acid, Slo-Niacin® (sustained-release niacin), sustained-release nicotinic acid (Nico-Span®), Tega-Span®, time-release niacin, Tri-B3®, trigonelline, tryptophan, vitamin B-3, vitamin B3, vitamin B3 derivative, vitamin B complex (vit-B), Wampocap®, wax-matrix sustained-release niacin (Endur-Acin®). Discussion: Use of Herbal/Supplement Niacin

· Combination product examples: ADVICOR® (niacin extended-release/lovastatin tablets), CordaptiveTM (niacin/laropiprant).

Clinical Bottom Line/Effectiveness

Brief Background

· Vitamin B3 is composed of niacin (nicotinic acid) and its amide, niacinamide, and may be found in many foods, including yeast, meat, fish, milk, eggs, green vegetables, and cereal grains. Dietary tryptophan, found in protein-containing foods such as red meat, poultry, eggs, and dairy products, is also converted to niacin after ingestion. Vitamin B3 is frequently found in combination with other B vitamins, including thiamine, riboflavin, pantothenic acid, pyridoxine, cyanocobalamin, and folic acid. Discussion: Use of Herbal/Supplement Niacin

· According to numerous clinical trials, niacin (not niacinamide) appears to be a relatively safe, inexpensive, and effective treatment for hyperlipidemia. Niacin supplementation is a lipid-modifying therapy that specifically addresses the triglyceride/high-density lipoprotein cholesterol axis (1). Niacin is also a widely used lipid-regulating agent in dyslipidemic patients (2;3;4;5). Niacin elicits significant increases in HDL, up to 20-30% at doses of 1-2g daily, with greater effects than other drugs (including 3-hydroxy 3-methylglutarylCoA; HMG-CoA reductase inhibitors/statins) (6;7;8;9). Niacin also causes mild reductions (~5-20%) in low-density lipoproteins (LDL), with stronger effects occurring at higher doses (3-4.5g daily) (10;11;12;13;14). Additional decreases in LDL levels may be achieved by combining niacin with an HMG-CoA reductase inhibitor or bile acid sequestrant (9). Preliminary evidence suggests that niacin therapy may reduce the incidence of atherosclerosis and secondary cardiovascular events (15). Niacin decreases lipoprotein (a) and fibrinogen levels; both have been associated with a decreased risk of coronary artery disease (16;17;18;4). Niacin may also decrease the carotid intima-media thickness (4;9). However, niacin therapy has also been found to increase plasma homocysteine levels by up to 55% (19;20), possibly negating any positive effects on serum lipids and increasing the risk of adverse cardiac events. Due to the adverse effects associated with niacin use, it is not often used in the treatment of pediatric dyslipidemia (21). Discussion: Use of Herbal/Supplement Niacin

· Niacin therapy has a high incidence of initial minor adverse events, including cutaneous flushing, pruritus, and gastrointestinal upset (22;23;24;25;26;27;28;29;30;31;32;33;34;35;36). Concomitant NSAIDs or aspirin are often recommended during the first 1-2 weeks to reduce flushing (likely prostaglandin mediated); aspirin (325mg), ibuprofen (200mg), naproxen, indomethacin, and laropiprant have been shown to significantly reduce the incidence of flushing experienced after niacin administration (37;38;39;40;41;42;43;44;45;46;47;48;49;50;51;52;3;53). Use of an antihistamine 15 minutes prior to a niacin dose may also suppress cutaneous flushing (54;55). The flushing response often spontaneously diminishes after 1-2 weeks of therapy. Numerous case reports have been published concerning the development of hepatotoxicity following niacin therapy, ranging from elevated aminotransferase levels to jaundice, ascites, and hepatitis (56;57;58;39;59;60;61;62;63;64;65;66;67;68;69;70;71;72;31;73;74;75;76;77;78;79;80;81). Concomitant use of niacin or niacinamide and other agents that elevate transaminases or elicit hepatotoxicity may have additive hepatotoxic effects. Both niacin and HMG-CoA reductase inhibitors may elevate liver function tests or result in hepatotoxicity, and transaminase levels should be monitored. Immediate-release nicotinic acid may pose less risk of hepatotoxicity than extended-release formulations. Niacin, particularly in large doses, may cause insulin resistance, hyperglycemia, and hyperinsulinemia (82;56;58;24;25;83;60;84;85;28;86;29;87;88;89;90;12;91;32;92;93;94;95;96;97;98;99).

· Niacinamide (not niacin) has been investigated for the prevention and delay of type 1 diabetes mellitus, possibly mediated through the protection and preservation of pancreatic beta-islet cell function. Initial human research has been equivocal. Preliminary evidence suggests potential for niacinamide as a treatment for osteoarthritis. Discussion: Use of Herbal/Supplement Niacin

· In preliminary studies, inositol hexanicotinate, an ester of niacin and inositol, has also been shown to share some beneficial effects with niacin without causing the adverse effects associated with niacin administration (100;101).

· Nicotinic analog hypolipidemic medications, such as 5-methylpyrazine carboxylic acid 4-oxide (Acipimox®), have been developed for lipid modification in individuals with hyperlipoproteinemia and cardiovascular disease (102;103;104;105;106). Acipimox® is not available in the United States. Skin rash, headache, transient low blood pressure, altered thyroid hormone levels, and elevated blood levels of uric acid have also been noted with nicotinic acid therapy.

· Niacin consumption for treatment of a condition should be monitored by a healthcare professional (107).

Scientific evidence for Common/Studied Uses

Indication	Grade
Hyperlipidemia	A
Pellagra	A
Atherosclerosis (as adjunct therapy; niacin)	B
Cardiovascular disease (niacin)	B
Age-related macular degeneration	C
Alzheimer’s disease/ cognitive decline	C
Erectile dysfunction	C
Headaches	C
Hepatitis C	C
High blood phosphorous level	C
Osteoarthritis (niacinamide)	C
Skin conditions (topical)	C
Type 1 diabetes mellitus: preservation of beta-islet cell function (niacinamide)	C
Type 2 diabetes	C
Type 1 diabetes mellitus prevention (niacinamide)	D

Historical or Theoretical Uses That Lack Sufficient Evidence

· Alcohol dependence (108), anemia (109;110), angina (105), anti-aging (111;112;113;114), antioxidant (115;116), anxiety, arthritis (117;118;119), Bell’s palsy (120), bone marrow suppression, breast cancer (121;122), bursitis, cancer prevention (123;114), cataract prevention (124;125), central nervous system disorders, chemotherapy-induced bone marrow suppression (126), choleric diarrhea (127;128;129), chronic diarrhea/hypokalemia (related to pancreatic islet cell dysplasia) (130), circulation improvement, coronary artery disease (131;132;133;134;135;136;137;138;139;140;141;142;143;15;26), cosmetic uses (144), dementia (confusion) (145;139), depression (146), dermatitis (101;147;148), diabetes mellitus (type 1) treatment (149;150;151;152;153;154;155;156;157;114;158;94), diabetic complications (lipid abnormalities) (159;160;14;161;162;138;163;164), diarrhea, digestion improvement, dizziness, drug-induced hallucinations, dysmenorrhea (165), edema (166), encephalopathy, erythema induratum, glossitis (167), growth (168), hearing loss (169), heart attack prevention (170;171;172), helminthic infections (173), hepatic encephalopathy (174), human immunodeficiency virus (175;176;177;178;179;180), hyperactivity, hyperkinesis, hypertension (181;14;182), insomnia, intermittent claudication (183;184;185;186;187), ischemia-reperfusion injury prevention (188;189;190;114;137), leprosy, liver disease (179;67;189), liver cancer (191), lupus (lipid abnormalities) (192), memory enhancement (193), Meniere’s syndrome (endolymphatic hydrops) (194;195;196), menstrual pain, metabolic syndrome (197;160;198), migraine headache (199;200;201), motion sickness, multiple sclerosis (202), nutrition supplementation (110), obesity (14;203), pain (sympathicolysis) (204), pancreatitis (205), Parkinson’s disease (114), peripheral vascular disease, photoprotection, platelet aggregation inhibition (206), polymorphous light eruption (207), pregnancy (208), premenstrual syndrome (209), prostate cancer (210), pruritus (chloroquine-induced) (211), psoriasis (101), psychosis, Raynaud’s phenomenon (212;213;214;101;215;216;217;218;219;220;221;222;223;224;225;226), schizophrenia (diagnostic) (215;216;217;218;219;220;221;222;223;224;225;47;227;228;229;230;231;232;233;234), scleroderma, sedative, seizure disorder (235), sexual arousal (orgasm improvement), sleep quality (235), smoking cessation, stroke (139), tardive dyskinesia, taste disturbances (236), thyroid disorders, tinnitus (237), tuberculosis, ulcers (238), vascular spasm (blood vessels) (239), vasculitis (erythema diutinum), vertigo, wound healing (240). Discussion: Use of Herbal/Supplement Niacin

Expert Opinion & Historic/Folkloric Precedent

· The dietary reference intake established by the Food and Nutrition Board for niacin (in the form of niacin equivalents, 1mg of niacin=60mg of tryptophan) is 14-18mg daily for adults (males and females), with an upper intake level set at 35mg daily (241).

· Data from dietary surveys in adults conducted in Germany, the United States, the Netherlands, and the United Kingdom report that suboptimal intake of vitamins, including niacin, still exist in affluent countries despite intake recommendations and access to diverse foods. However, inadequate intake of niacin is not considered to be critical (242). Women in resource-poor settings were shown in a systematic review of 52 studies from 1988-2008, were reported to have and intake of niacin that was 34% lower than the estimated average requirement (243). Several authors have evaluated the validity of food frequency questionnaires in different settings (244;245;246;247).

· The U.S. Food and Drug Administration (FDA) has approved niacin for use in treating vitamin B3 deficiency (pellagra), which may be characterized by dermatitis, dementia, and diarrhea. Niacin and niacinamide are generally considered as safe (GRAS) and may be added to certain foods, including cereal flours, macaroni and noodle products, and enriched bread, according to the FDA.

· Niacin has been studied in combination with oxycodone to help deter abuse. Pain reduction was superior when compared to placebo for bunionectomy surgery (248). However, the FDA did not approve the combination drug Acurox® in 2010.

· There are strong clinical data to support the safety and efficacy of niacin, alone or in combination with other medications, for the treatment of hypercholesterolemia and possibly the prevention of cardiovascular events and disease. Its use in the treatment of schizophrenia and osteoarthritis has also been explored, with few positive results.

· A sustained-release form of low-dose niacin may be suitable if a patient is using niacin for the first time (249). Changing niacin products may affect the dose needed.

Brief Safety Summary

· Likely Safe: When niacin is used orally in daily recommended intakes under the supervision of a qualified healthcare provider (58;24;250;61;63;64;66;67;68;251;87;70;90;71;46;74;76;77;78;79;96;80;81). Periodic monitoring of liver function tests is recommended (every three months initially) (58;24;250;61;63;64;66;67;68;251;87;70;90;71;46;74;76;77;78;79;96;80;81). Homocysteine levels should also be monitored. The adverse effects profile of niacin at therapeutic doses may limit patient compliance: most patients experience initial flushing, and concomitant NSAIDs or aspirin are often recommended to reduce flushing; antihistamines may also be effective. Taking with food or milk may also be suggested. Gastrointestinal distress may also occur, and taking niacin with food may decrease stomach upset and the risk of peptic ulcer. Immediate release of (crystalline) niacin is sometimes preferred to sustained-release formulations, due to reports of superior HDL effects and a lower incidence of hepatotoxicity and gastrointestinal side effects. Some sustained-release products, such as Niaspan®, may be associated with a lower incidence of flushing than immediate-release niacin. Discussion: Use of Herbal/Supplement Niacin

· Possibly Safe: When used in patients with diabetes, according to emerging clinical evidence in humans, despite original findings of increased glucose levels (252;143); monitoring of glucose levels is suggested. Extended-release niacin up to 2g daily for up to 44 weeks was found to be safe in patients with HIV infection (253).

· Possibly Unsafe: When used in higher-than-recommended doses without supervision of a qualified healthcare provider or when taken by subjects with diabetes mellitus who are not monitored by a qualified healthcare provider. Niacin has been shown to raise serum glucose levels and may interfere with glycemic control (58;24;25;83;254;255;86;29;87;90;12;93;256;257;96;98). Caution is also warranted in patients with gout. Niacin has been shown to increase plasma uric acid levels and may exacerbate gout symptoms (54;58;25;24;26;254;255;84;85;86;29;12;258;259;260;261;257;98;262). Concerns about the use of lipid-lowering agents in children have been raised, and close medical monitoring is merited in children with dyslipidemias. Due to the adverse effects associated with niacin use, it is not frequently used in the treatment of pediatric dyslipidemia (21). Caution is advised when used in patients with bleeding disorders or those taking anticoagulants (263). In addition, thrombocytopenia has been observed in clinical trials of niacin therapy (264;27;88).

· Likely Unsafe: When used in patients with known allergies or hypersensitivities to niacin, niacinamide, or any product containing one or both of these agents. When used in patients with hepatic disease or dysfunction. Niacin has been implicated as a cause of hepatotoxicity in humans (56;58;39;60;61;62;63;64;68;65;66;67;69;70;71;74;76;77;78;79;80;81). When used in patients with peptic ulcer disease, as it has been reported to induce or reactivate peptic ulcer disease at therapeutic doses (250;265). When used in patients with arterial bleeding, according to secondary sources.

Dosing/Toxicology

General

· Doses may be based on those most commonly used in available trials, or on historical practice. However, with natural products it is often not clear what the optimal doses are to balance efficacy and safety. Preparation of products may vary from manufacturer to manufacturer, and from batch to batch within one manufacturer. Because it is often not clear what the active component(s) of a product is, standardization may not be possible, and the clinical effects of different brands may not be comparable. Discussion: Use of Herbal/Supplement Niacin

· Notes on niacin dosing: Taking niacin with food may decrease stomach upset and the risk of peptic ulcer (39). Doses are usually started low and gradually increased to decrease the adverse effect of facial flushing (57;39;398;37;38;40;41;43;44;46;47;50;51;52;42;45;48;49). Concomitant NSAIDs or aspirin are often recommended during the first 1-2 weeks to reduce flushing (likely prostaglandin mediated); aspirin (325mg), ibuprofen (200mg), naproxen, indomethacin, and laropiprant have been shown to significantly reduce the incidence of flushing experienced after niacin administration (37;38;39;40;41;42;43;44;45;46;47;48;49;50;51;52;3;53). Use of an antihistamine 15 minutes prior to a niacin dose may also suppress cutaneous flushing (54;55). The flushing response often spontaneously diminishes after 1-2 weeks of therapy. A once-daily extended-release niacin formulation has been shown to significantly reduce flushing compared to immediate-release niacin (675), although extended-release niacin products may be associated with an increased incidence of gastrointestinal upset, transaminitis, and hepatitis (57;69;70;71;72;31;73;75;76;59). Not all niacin products are equivalent, and patients switching from one product to another have reported an increase in adverse effects (676). Combining niacin with other lipid-modifying medications may increase the risk of adverse events (677). Older individuals appear to be at no greater risk for adverse events from a wax-matrix sustained-release form of niacin (324). Patients advised to use niacin should be carefully screened and monitored (678).

Standardization

· Niacinamide (nicotinamide) and niacin (nicotinic acid) are used in cosmetics as hair and skin conditioning agents (144). Niacinamide and niacin may be found in cosmetic formulations such as shampoos, hair tonics, skin moisturizers, and cleansing formulations. The concentration of niacinamide varies from a low of 0.0001% in night preparations to a high of 3% in body and hand creams, lotions, powders, and sprays. Niacin concentrations range from 0.01% in body and hand creams, lotions, powders, and sprays to 0.1% in paste masks (mud packs).

Adults (age ≥ 18)

Oral:

· Dietary intake: The dietary reference intake established by the Food and Nutrition Board for niacin (in the form of niacin equivalents, 1mg of niacin=60mg of tryptophan) is 14-18mg daily for adults, with an upper intake level set at 35mg daily (241).

· Age-related macular degeneration: A single dose of 500mg of immediate-release niacin has been used (266).

· Atherosclerosis: In a meta-analysis of 14 trials, niacin doses were 3,000-4,000mg daily alone or in combination with any statin, ezetimibe plus simvastatin, gemfibrozil plus cholestyramine, colestipol, clofibrate, or colestipol for 0.5-6.2 years (267).

· 1,000mg of extended-release niacin has been used (15). In trials in which niacin is combined with other agents, up to 4.2g of niacin has been used, for up to 2.5 years, in combination with colestipol (10g three times daily) and/or lovastatin (20mg two times daily) (59;26;268;269;270;271;272;19;273;274). 0.25-4g of niacin has been used daily for an unknown duration (275).

· Cardiovascular disease: In meta-analysis and systematic reviews, niacin was administered at doses of 0.125-12g daily for up to three years (275;276;277).

· 1,000mg of extended-release niacin in addition to statin therapy has been used (15). 4g of immediate-release niacin has been used daily for five years (96). Dosages of up to 3g daily have been evaluated in the treatment of patients with cardiovascular disease (278;172;279;268). At 3g daily, niacin has been used in combination with clofibrate, gemfibrozil, and cholestyramine, as well as pravastatin, gemfibrozil, and cholestyramine, for up to five years (269;280;281;282;172). Discussion: Use of Herbal/Supplement Niacin

· Erectile dysfunction: An initial dose of 500mg of Niaspan® (Abbott Laboratories, Abbott Park, IL) has been used nightly, with a dose escalation of 500mg every two weeks until a maximum of 1,500mg was reached. The tolerable dose was administered for a total trial duration of 12 weeks (283).

· Hyperlipidemia: In a systematic review of four trials using wax-matrix niacin, dosages were 1,000-2,000mg of niacin daily (in divided doses) for 20-44 weeks (284). In a systematic review of five trials, participants in the included studies were administered 750-4,500mg of niacin daily; however, the duration was unclear (285). Clinical trials have most commonly administered immediate-release (crystalline) niacin at doses of 500-3,000mg daily (286;27;250;287;288;254;88;289;290;31;258;291;292;293;294;295;296;297;298;299). Dosing may be initiated at 100mg three times daily and increased gradually to an average of 1,000mg three times daily, as tolerated (286;27;250;287;288;254;88;289;290;31;258;291;292;293;294;295;296;297;298). Significant increases in high-density lipoproteins (HDL), up to 30%, may occur at doses of 1-2g daily (300;301;292;302;10;262;11;12;303;304;305;75;31;306). Mild reductions in low-density lipoprotein (LDL) levels may occur at these doses, with stronger effects (up to 20%) occurring at higher doses (3-4.5g daily) (307;300;10;11;12;305;304;308;75;31;306), or when used in combination with an HMG-CoA reductase inhibitor or bile acid sequestrant. Plasma concentrations of lipoprotein (a) and apolipoproteins are also affected by niacin administration. At a dose of 4g daily for six weeks, niacin significantly decreased lipoprotein (a) levels (18). Doses of 4-12g daily of nicotinic acid have been used for reduction of apolipoproteins C-I, C-II, C-III, and E, which correlated to a reduction of very-low-density lipoprotein triglyceride levels (309;310). 0.25-4g of niacin has been used daily for an unknown duration (275).

· Combination HMG-CoA reductase inhibitor or bile acid sequestrant: In a systematic review of 28 trials, participants were administered 500-2,000mg of extended-release niacin plus 20-40mg of lovastatin or 10-40mg of simvastatin (NER/S) daily for a mean treatment duration of 8-16 weeks (311). In a meta-analysis of 14 trials, niacin doses were 3,000-4,000mg daily alone or in combination with any statin, ezetimibe plus simvastatin, gemfibrozil plus cholestyramine, colestipol, clofibrate, or colestipol for 0.5-6.2 years (267). In a systematic review, doses used in the included studies were 1-4g of niacin daily in combination with statin treatment for 1-3 years (312). 500-2,000mg of niacin twice daily for up to 28 weeks in combination with an HMG-CoA reductase inhibitor (pravastatin, lovastatin, rosuvastatin) was more effective than niacin alone (313;314;315;316;317;318). The U.S. Food and Drug Administration (FDA) has approved a combination tablet (Advicor®) containing lovastatin (10mg) and niacin (500mg) for the treatment of hypercholesterolemia, based on the results of an open-label study that found the combination tablet to be effective at decreasing LDL, triglyceride, and lipoprotein (a) levels, and at increasing HDL levels, with few adverse effects (319). Discussion: Use of Herbal/Supplement Niacin

· Extended-release: Extended- or sustained-release niacin may be initiated at a dose of 500mg daily (or nightly) and titrated up to 3g daily. Up to 3g of extended-release niacin daily for up to 26 weeks has been used (29;86;320;321;322;323;324;325;326;327;99). The duration of the above-noted studies has been up to 60 weeks.

· Maximum dose: The maximum recommended daily dose is 3g, although a number of clinical trials have used 4.5-12g daily (286;23;24;255;98;276). Multiple trials have found that niacin (not niacinamide) administration causes significant decreases in serum cholesterol (328;329;330;24;250;331;332;92;333;334;257;335;336;10).

· Hyperlipidemia (in HIV-infected patients) : Up to 2,000mg of extended-release niacin has been taken daily for up to 44 weeks (253). Patients received 500mg (Niaspan; Abbott Laboratories, Abbott Park, IL) at bedtime for two weeks, increasing by 500mg biweekly to a maximum of 2g for two years(337).

· High blood phosphorus level: A single 375mg dose of extended-release nicotinic acid has been used (338).

· Osteoarthritis (niacinamide): 3g of niacinamide daily for 12 weeks has been used (339).

· Pellagra: The available evidence regarding dosing of niacin in the treatment of pellagra specifies dosing in the range of 50mg to 1g daily (340;341;342). Supplementation during pregnancy is not required; the catabolism of tryptophan is accelerated during pregnancy, resulting in increased niacin production (343).

· Type 1 diabetes mellitus prevention (niacinamide): Niacinamide has been used for the preservation of beta-islet cell function in patients with newly diagnosed diabetes mellitus (type 1), at doses of 200mg and up to 3g daily for up to one year (344;152;345;346;347;348;349;350;351). Not all studies show evidence of benefit. For instance, 20-40mg/kg daily for up to one year has not shown evidence of benefit (352;353;354;355;356).

· Type 2 diabetes: 0.5g of nicotinamide three times daily for six months has been used (357).

Topical:

· General: According to various websites, niacinamide (nicotinamide) and niacin (nicotinic acid) are used in cosmetics, as well as hair and skin conditioning agents. The concentration of niacinamide varies from a low of 0.0001% in night preparations to a high of 3% in body and hand creams, lotions, powders, and sprays. Niacin concentrations range from 0.01% in body and hand creams, lotions, powders, and sprays to 0.1% in paste masks (mud packs).

· Skin conditions: 2-5% of niacinamide cream for up to 12 weeks has been used (358;113).

Parenteral (Intravenous/Intramuscular):

· Hyperlipidemia: Continuous intravenous infusion of 2g of niacin over 11 hours at night resulted in significant decreases in plasma triglyceride levels not seen when the same infusion was administered during the day (359).

Children (age < 18)