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Niacin (Vitamin-B3, Nicotinic acid), Niacinamide, and Inositol hexanicotinate


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Niacin (Vitamin-B3, Nicotinic acid), Niacinamide, and Inositol hexanicotinate

Background

Vitamin B-3 is made up of niacin (nicotinic acid) and its amide, niacinamide, and can be found in many foods, including yeast, meat, fish, milk, eggs, green vegetables, and cereal grains. Dietary tryptophan is also converted to niacin in the body. Vitamin B-3 is often found in combination with other B vitamins including thiamine, riboflavin, pantothenic acid, pyridoxine, cyanocobalamin, and folic acid.

Synonyms

3-Pyridine carboxamide, anti-blacktongue factor, antipellagra factor, B-complex vitamin, benicot, Efacin®, ENDUR-ACIN®, Enduramide®, Hexopal®, inositol hexaniacinate, NIAC®, Niacor®, Niaspan®, Nicalex®, nicamid, Nicamin®, Nico-400®, Nicobid®, Nicolar®, Nicotinex®, nicosedine, Nico-Span®, nicotinamide, nicotinic acid amide, nicotinic amide, nicotylamidum, Papulex®, pellagra preventing factor, Slo-Niacin®, Tega-Span®, Tri-B3®, Wampocap®.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*High cholesterol (niacin)
Niacin is a well-accepted treatment for high cholesterol. Multiple studies show that niacin (not niacinamide) has significant benefits on levels of high-density cholesterol (HDL or "good cholesterol"), with better results than prescription drugs such as "statins" like atorvastatin (Lipitor®). There are also benefits on levels of low-density cholesterol (LDL or "bad cholesterol"), although these effects are less dramatic. Adding niacin to a second drug such as a statin may increase the effects on low-density lipoproteins. The use of niacin for the treatment of dyslipidemia associated with type 2 diabetes has been controversial because of the possibility of worsening glycemic control. However, a recent randomized controlled multicenter trial reports that of 148 patients, only 4 discontinued niacin because of inadequate glucose control. Doses of 1000-1500 mg per day (in a controlled release formulation) were reported as a potential treatment option for type 2 diabetics with dyslipidemia by these researchers. Patients should check with a physician and pharmacist before starting niacin.

A

Pellagra (niacin)
Niacin (vitamin B-3) and niacinamide are FDA approved for the treatment of niacin deficiency. Pellagra is a nutritional disease that develops due to insufficient dietary amounts of vitamin B-3 or the chemical it is made from, tryptophan. Symptoms of pellagra include skin disease, diarrhea, dementia and depression.

A

Atherosclerosis (niacin)
Niacin decreases blood levels of cholesterol and lipoprotein (a), which may reduce atherosclerosis ("hardening" of the arteries). However, niacin also can increase homocysteine levels, which may have the opposite effect. Overall, the scientific evidence supports the use of niacin in combination with other drugs (but not alone) to decrease cholesterol and slow the process of atherosclerosis. More research is needed in this area before a firm conclusion can be drawn.

B

Prevention of a second heart attack (niacin)
Niacin decreases levels of cholesterol, lipoprotein (a), and fibrinogen, which can reduce the risk of heart disease. However, niacin also increases homocysteine levels, which can increase this risk. Numerous studies have looked at the effects of niacin, alone and in combination with other drugs, on the prevention of heart disease and fatal heart attacks. Overall, this research suggests benefits of niacin, especially when combined with other cholesterol-lowering drugs.

B

Type 1 Diabetes mellitus prevention (niacinamide)
Animal research reports that niacinamide (not niacin) has a protective effect on insulin-producing cells of the pancreas and may delay the development of type 1 diabetes mellitus. Preliminary human research suggests that niacinamide lowers blood sugar, increases C-peptide levels, and allows people to reduce their insulin dosages. However, these studies have been poorly designed with mixed results. More research is necessary before firm conclusions can be drawn.

C

Osteoarthritis (niacinamide)
Preliminary human studies suggest that niacinamide may be useful in the treatment of osteoarthritis. Further research is needed before a recommendation can be made.

C

* Key to grades
A:
Strong scientific evidence for this use;
B:
Good scientific evidence for this use;
C:
Unclear scientific evidence for this use;
D:
Fair scientific evidence against this use (it may not work);
F:
Strong scientific evidence against this use (it likely does not work).

Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Acne, alcohol dependence, anti-aging, anxiety, arthritis, Bell's palsy, blood circulation improvement, blood vessel spasms, bone marrow damage from chemotherapy, cancer prevention, cataract prevention, central nervous system disorders, cholera diarrhea, chronic diarrhea, confusion, depression, diagnostic test for schizophrenia, digestion improvement, drug-induced hallucinations, ear ringing, edema, glucose intolerance, hearing loss, heart attack prevention, HIV prevention, high blood pressure, hypothyroidism (reduced thyroid function), insomnia, intermittent claudication (painful legs from clogged arteries), "ischemia-reperfusion injury" prevention, kava-related skin disorders, leprosy, liver disease, low blood sugar, memory loss, Meniere's syndrome, migraine headache, motion sickness, multiple sclerosis, orgasm improvement, painful menstruation, peripheral vascular disease, photosensitivity, pregnancy problems, premenstrual headache prevention, premenstrual syndrome, prostate cancer, psoriasis, psychosis, Raynaud's phenomenon, schizophrenia, scleroderma, sedative, seizure, skin disorders, smoking cessation, stomach ulcer, tardive dyskinesia, taste disturbances (diminished/distorted sense of taste), tuberculosis, tumor detection, vertigo.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

Note : Taking niacin with food may reduce stomach upset and the risk of stomach ulcer. Doses are usually started low and gradually increased to minimize the common side effect of skin flushing. Taking aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) at the same time during the first 1 to 2 weeks may reduce this flushing. Use of an antihistamine 15 minutes prior to a niacin dose may also be helpful. The flushing response may decrease on its own after 1 to 2 weeks of therapy. Extended release niacin products may cause less flushing than immediate release (crystalline) formulations, but may have a higher risk of stomach upset or liver irritation. In general, not all niacin products are equivalent. Patients switching from one product to another may have an increase or decrease in side effects.

Dietary intake : The dietary reference intake established by the Food and Nutrition Board for niacin (in the form of niacin equivalents, 1 milligram niacin = 60 milligrams tryptophan) ranges from 16 to 18 milligrams daily for adults, with a maximum intake of 35 milligrams daily.

High cholesterol : Clinical trials have most commonly studied immediate release (crystalline) niacin at doses of 500 to 3000 milligrams taken by mouth daily. Dosing may be started at 100 milligrams three times daily and increased gradually to an average of 1000 milligrams three times daily, as tolerated. Significant increases in high-density lipoproteins (HDL) by up to 30% may occur at doses ranging from 1 to 1.5 grams daily. Mild reductions in low-density lipoprotein (LDL) levels may occur at these doses, with stronger effects (up to 20%) occurring at higher doses (3 to 4.5 grams daily), or when used with a "statin" drug or bile acid sequestrant. The maximum recommended daily dose is 3 grams, although some studies have used 4.5 to 6 grams daily. Extended or sustained release niacin may be started at a dose of 500 milligrams daily (or nightly), and increased to 1 to 2 grams per day.

Pellagra (niacin deficiency) : Dosing in the range of 50 milligrams to 1 gram daily has been studied.

Atherosclerosis : Niacin in doses of 1 to 4 grams daily has been studied.

Cardiovascular disease : Niacin at a dose of 3 grams daily has been studied.

Diabetes mellitus (type 1), preservation of β-islet cell function : Niacinamide has been studied in the preservation of pancreas cell (β-islet) function in patients with newly diagnosed diabetes mellitus (type 1) in divided doses, up to 3 grams daily.

Children (younger than 18 years)

There is not enough scientific evidence to recommend the safe use of niacin or niacinamide in children. Niacinamide has been studied in children at daily doses of 150 to 300 milligrams per year of the child's age, or 25 milligrams per kilogram daily, for the prevention of type 1 diabetes mellitus in "high-risk" individuals. No serious side effects have been reported, although safety and effectiveness are not clear. Patients should speak with a qualified health care provider if considering this therapy.

Note that there are concerns about the lack of evidence regarding treatment of childhood lipid disorders, including long-term psychological and metabolic effects. For many disorders, dietary alteration is considered acceptable as first line treatment, without the use of lipid-lowering drugs until adulthood is reached.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Rarely, anaphylactic shock (severe allergic reaction) has been described after intravenous or oral niacin therapy.

Side Effects and Warnings

Most people taking niacin experience skin flushing and a warm sensation, especially of the face, neck and ears, when they begin treatment or increase dose. This reaction is usually mild, but has been intolerable enough to cause up to half of participants in studies to stop therapy. Dry skin and itching is also commonly experienced. Taking aspirin or non-steroidal anti-inflammatory drugs such as ibuprofen (Advil®, Motrin®), naproxen (Naprosyn®), or indomethacin (Indocin®) can reduce the flushing. Use of an antihistamine 15 minutes prior to a niacin dose may also be helpful. Slow-release niacin products may have less skin flushing than regular release niacin preparations or may simply delay the appearance of flushing. The flushing response often decreases on its own after 1 to 2 weeks of therapy. Mild stomach upset, nausea, vomiting and diarrhea also may occur when beginning niacin therapy, and usually resolve with continued use.

More serious side effects include liver toxicity, worsening of stomach ulcers, and altered blood chemistry levels (increased blood sugar and uric acid concentrations). Numerous case reports describe liver toxicity, including increased liver enzyme levels in the blood, skin yellowing (jaundice), fluid in the abdomen (ascites), or liver failure. Monitoring of liver blood tests while using niacin is recommended. While slow-release niacin products may have less skin flushing than regular release niacin preparations, they may worsen stomach and liver side effects.

Niacin can cause significant alterations in blood sugar levels and insulin. This has been a potential concern in patients with diabetes, although a recent randomized controlled trial reports that of 148 patients, only 4 discontinued niacin because of inadequate glucose control (doses of 1000-1500 mg per day in a controlled release formulation were used). Nonetheless, caution is advised in patients with diabetes or hypoglycemia, and in those taking insulin, drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary. Although niacinamide is generally not associated with other side effects, it may affect insulin and blood sugar levels.

In theory, gout may occur during niacin treatment, due to increased blood uric acid levels. Lactic acidosis has been reported after taking sustained-release niacin. Niacin-induced muscle cell damage (myopathy) and increased blood levels of creatine kinase (a marker of muscle damage) have been reported in studies.

Abnormal heart rhythms and heart palpitations have occurred in niacin studies. Based on human research, taking niacin alone or with colestipol may increase blood homocysteine levels. High levels of homocysteine have been associated with an increased risk of heart disease.

Blood clotting problems have been reported during treatment with sustained-release niacin. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary. Low white blood cell number (leukopenia) and slightly increased blood eosinophils have also been reported.

Rarely reported side effects include headache, tooth or gum pain, dizziness, breathing difficulty, increased anxiety, panic attacks, and decreased thyroid function (hypothyroidism). There are published accounts of temporary side effects of the eye including macular swelling and blurred vision as well as toxic amblyopia ("lazy eye"). These side effects resolved when niacin was stopped.

Pregnancy and Breastfeeding

Use of niacin supplementation during pregnancy or breastfeeding is not recommended due to lack of sufficient research of safety and effectiveness.

References

1. Arcavi L, Shahar A. [Drug related taste disturbances: emphasis on the elderly] Harefuah. 2003 Jun;142(6):446-50, 485, 484. Review. Hebrew .

2. Ayyobi AF, Brunzell JD. Lipoprotein distribution in the metabolic syndrome, type 2 diabetes mellitus, and familial combined hyperlipidemia. Am J Cardiol. 2003 Aug 18;92 (4A) :27J-33J.

3. Ballantyne CM, Corsini A, Davidson MH, Holdaas H, Jacobson TA, Leitersdorf E, Marz W, Reckless JP, Stein EA. Risk for myopathy with statin therapy in high-risk patients. Comment in: Arch Intern Med. 2003 Jul 14;163(13):1615-6; author reply 1616. Arch Intern Med. 2003 Mar 10;163(5):553-64.

4. Bays HE, Dujovne CA, McGovern ME, White TE, Kashyap ML, Hutcheson AG, Crouse JR; ADvicor Versus Other Cholesterol-Modulating Agents Trial Evaluation. Comparison of once-daily, niacin extended-release/lovastatin with standard doses of atorvastatin and simvastatin (the ADvicor Versus Other Cholesterol-Modulating Agents Trial Evaluation [ADVOCATE]). Am J Cardiol. 2003 Mar 15;91(6):667-72.

5. Bhatnagar D. Should pediatric patients with hyperlipidemia receive drug therapy? Paediatr Drugs. 2002;4(4):223-30. Review.

6. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345(22):1583-1592.

7. Bucher HC, Griffith LE, Guyatt GH. Systematic review on the risk and benefit of different cholesterol-lowering interventions. Arterioscler Thromb Vasc Biol 1999;19(2):187-195.

8. Capuzzi DM, Morgan JM, Weiss RJ, Chitra RR, Hutchinson HG, Cressman MD. Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels. Am J Cardiol. 2003 Jun 1;91(11):1304-10.

9. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21(8):1320-1326.

10. Elam MB, Hunninghake DB, Davis KB, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. Arterial Disease Multiple Intervention Trial. JAMA 2000;284(10):1263-1270.

11. Freedman JE. Antioxidant versus lipid-altering therapy: some answers, more questions. N Engl J Med 2001;345(22):1636-1637.

12. Goldberg A, Alagona P Jr., Capuzzi DM, et al. Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol 2000;85(9):1100-1105.

13. Grundy SM, Vega GL, McGovern ME, Tulloch BR, Kendall DM, Fitz-Patrick D, Ganda OP, Rosenson RS, Buse JB, Robertson DD, Sheehan JP; Diabetes Multicenter Research Group. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial. Arch Intern Med. 2002 Jul 22;162(14):1568-76.

14. Guyton JR, Capuzzi DM. Treatment of hyperlipidemia with combined niacin-statin regimens. Am J Cardiol 1998;82(12A):82U-84U.

15. Guyton JR, Goldberg AC, Kreisberg RA, et al. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol 1998;82(6):737-743.

16. Guyton JR, Blazing MA, Hagar J, et al. Extended-release niacin vs. gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol: Niaspan-Gemfibrozil Study Group. Arch Intern Med 2000;160(8):1177-1184.

17. Hannan F, Davoren P. Use of nicotinic acid in the management of recurrent hypoglycemic episodes in diabetes. Diabetes Care 2001;24(7):1301.

18. Kashyap ML, McGovern ME, Berra K, et al. Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. Am J Cardiol 2002;89(6):672-678.

19. McKenney JM, McCormick LS, Schaefer EJ, et al. Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia. Am J Cardiol 2001;88(3):270-274.

20. Pozzilli P, Browne PD, Kolb H. Meta-analysis of nicotinamide treatment in patients with recent-onset IDDM: The Nicotinamide Trialists. Diabetes Care 1996;19(12):1357-1363.

21. Schectman G, Hiatt J. Dose-response characteristics of cholesterol-lowering drug therapies: implications for treatment. Ann Intern Med 1996;125(12):990-1000.

22. Sprecher DL. Raising high-density lipoprotein cholesterol with niacin and fibrates: a comparative review. Am J Cardiol 2000;86(12A):46L-50L.

23. Wink J, Giacoppe G, King J. Effect of very-low-dose niacin on high-density lipoprotein in patients undergoing long-term statin therapy. Am Heart J 2002;143(3):514-518.

24. Wolfe ML, Vartanian SF, Ross JL, et al. Safety and effectiveness of Niaspan when added sequentially to a statin for treatment of dyslipidemia. Am J Cardiol 2001;87(4):476-9, A7.

January 01, 2004

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