Niacin (Vitamin B3, Nicotinic acid), Niacinamide
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| Niacin, Niacinamide |
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- Vitamin B3 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 B3 is often found in combination with other B vitamins including thiamine, riboflavin, pantothenic acid, pyridoxine, cyanocobalamin, and folic acid.
- 3-Pyridine carboxamide, anti-blacktongue factor, antipellagra factor, B-complex vitamin, benicot, Efacin®, ENDUR-ACIN®, Enduramide®, Hexopal®, 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®.
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 evidence | Grade* |
| 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. Patients should check with a physician and pharmacist before starting niacin.
| A |
| Pellagra (niacin)
Niacin (vitamin B3) and niacinamide are U.S. Food and Drug Administration (FDA)-approved for the treatment of niacin deficiency. Pellagra is a nutritional disease that develops due to insufficient dietary amounts of vitamin B3 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 the risk of 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, for 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 |
| Age-related macular degeneration (AMD)
Niacin may benefit the choroidal blood vessels, which underlie the region of the retina called the macula. Age-related macular degeneration (AMD) may result from disrupted blood flow in the choroidal vessels. Studies suggest that niacin may be used to treat AMD, but more well-designed studies are needed.
| C |
| Alzheimer's disease/ cognitive decline
Dementia can be caused by severe niacin insufficiency, but it is unclear whether variation in intake of niacin in the usual diet is linked to neurodegenerative decline or Alzheimer's disease (AD). Further research is needed before a conclusion can be drawn.
| C |
| Diabetes (Type 1/Type 2)
Niacinamide may prevent diabetes or delay the need for insulin. More research is needed to determine if niacinamide delays or prevents the onset of insulin dependence in individuals with type 1 diabetes.Niacin has been used to treat dyslipidemia associated with type 2 diabetes. However, this treatment has been controversial because it may worsen glycemic control. Patients should seek medical advice before starting niacin.
| C |
| Headaches
There is not enough information about the treatment or prevention of headaches with niacin. More research is needed.
| C |
| High blood phosphorous level (hyperphosphatemia)
Niacinamide may reduce the high serum phosphate levels in hyperphosphatemia. However, more research is needed before niacinamide can be used to treat hyperphosphatemia.
| C |
| Liver cancer
A large, five-year study examined the effect of niacin supplementation on liver cancer. Although niacin did not appear to prevent liver cancer, deaths due to liver cancer were decreased in those who took supplements containing niacin. The ability of niacin to prevent liver cancer deaths should be further examined.
| 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 |
| Skin conditions
Niacinamide has been used in skin care products, including moisturizers, anti-aging products, and rosacea treatments. The benefits of niacinamide in skin care needs to be further studied before recommendations are 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;
F: Strong scientific evidence against this use.
Grading rationale
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, arrhythmia, Bell's palsy, blood circulation improvement, bone marrow damage from chemotherapy, brain damage, cancer prevention, cataract prevention, central nervous system disorders, cholera, chronic diarrhea, confusion, coronary heart disease (CHD), deafness, depression, diagnostic test for schizophrenia, diarrhea, digestion improvement, dizziness, drug-induced hallucinations, edema, hearing loss, high blood pressure, HIV prevention, hyperactivity, hypothyroidism (reduced thyroid function), insomnia, ischemia-reperfusion injury prevention, leprosy, liver disease, low blood sugar, memory loss, Ménière's syndrome, motion sickness, multiple sclerosis, orgasm improvement, painful menstruation, peripheral vascular disease / claudication, photosensitivity, pregnancy problems, premenstrual headache prevention, premenstrual syndrome, prostate cancer, psoriasis, psychosis, Raynaud's phenomenon, schizophrenia, scleroderma, sedative, seizure, smoking cessation, stomach ulcer, tardive dyskinesia, taste disturbances (diminished/distorted sense of taste), thyroid disease, tinnitus (ringing in the ears), tuberculosis, tumor detection, ulcers, vascular spasm, vertigo.
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 (over 18 years old)
- Taking niacin with food may reduce stomach upset and the risk of stomach ulcers. Doses usually start low and are 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 one to two 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 one to two 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.
- 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. 50 milligrams to 6 grams has been taken in divided doses for other conditions based on physician and pharmacist recommendations.
- 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). For skin conditions, 2-5% niacinamide cream has been used.
- Niacin dosing may vary according to the condition it is being used to treat. In clinical studies, doses have included 500 milligrams (single dose) for age-related macular degeneration, 375 milligrams (single dose) for hyperphosphatemia, up to 1 gram daily for pellagra, up to 3 grams daily for diabetes, up to 3 grams daily for osteoarthritis, and up to 4.3 grams daily (either along or combined with other agents) for cardiovascular disease.
Children (under 18 years old)
- 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. There is a lack of reported serious side effects, and safety and effectiveness are not clear. Patients should speak with a qualified healthcare provider if considering this therapy.
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 one to two weeks of therapy. Mild stomach upset, nausea, vomiting, and diarrhea also may occur when beginning niacin therapy; these symptoms usually resolve with continued use.
- More serious side effects include liver toxicity, worsening of stomach ulcers, and altered blood sugar or insulin levels or 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. High doses of niacin may also cause low blood pressure.
- Lactic acidosis, 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. 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.
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. 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.
Interactions with Drugs
- In theory, there may be an increased risk of liver damage if niacin is taken with alcohol or drugs that are toxic to the liver. Niacin-induced flushing may be increased by simultaneous use of alcohol and nicotine.
- Based on human study, use of niacin with cholesterol-lowering drugs, such as "statins" (HMG-CoA reductase inhibitors) including lovastatin (Mevacor®) or atorvastatin (Lipitor®), bile acid sequestrants like cholestyramine, probucol, or anti-lipid agents like gemfibrozil may result in further reductions in cholesterol than caused by either agent alone. However, bile acid sequestrants cholestyramine and colestipol may reduce niacin absorption into the body. Use of niacin with HMG-CoA reductase inhibitors or gemfibrozil may increase the risk of serious side effects such as liver or muscle damage.
- Based on human study, niacin may increase blood sugar levels, and may require dosing adjustments of insulin or prescription diabetes drugs. Caution is advised when using medications that may affect blood sugar.
- Antibiotics can lead to decreased amounts of B vitamins in the body. Conversely, based on animal study, pyrazinamide may increase niacin levels. Use of niacin with neomycin may add to the cholesterol-lowering effects of niacin. Based on laboratory study, niacinamide may interact with the antifungal drug griseofulvin (increases its solubility), with possible effects on its activity.
- In theory, niacin therapy may increase the risk of bleeding. There are published case reports of patients who developed reversible abnormal blood clotting (coagulopathy) conditions while taking sustained-release niacin. In addition, low blood platelet number (thrombocytopenia) has been observed in studies of niacin therapy. Some examples of drugs that may increase the risk of bleeding if taken with niacin include aspirin and anticoagulants ("blood thinners") such as warfarin (Coumadin®).
- Based on animal research, use of niacinamide with seizure medications like diazepam (Valium®), carbamazepine (Tegretol®), or sodium valproate (Depakote®) may increase their anti-seizure action. In laboratory studies, niacinamide has interacted with diazepam (increases its solubility) with uncertain overall effects. If taken with blood pressure-lowering drugs, niacinamide may cause a greater lowering of blood pressure.
- Based on human study, niacin may alter thyroid hormones and require dosing adjustment of thyroid medications. Based on laboratory research, niacinamide may interact with testosterone, estrogen, or progesterone. Use of birth control pills may increase the amount of niacin produced in the body, thus lowering the doses of niacin needed for treatment.
- Because niacin may alter blood flow in age-related macular degeneration (AMD), patients using drugs or supplements to treat AMD should use niacin cautiously.
Interactions with Herbs and Dietary Supplements
- In theory, use of niacin or niacinamide with herbs or supplements that have potential to cause liver injury may cause greater risk of liver toxicity.
- Use of aspirin has been shown to reduce the tingling, itching, flushing, and warmth associated with oral niacin administration, an effect which may also result from the use of possible salicylate-containing herbs like black cohosh, meadowsweet, poplar, sweet birch, willow bark, and wintergreen. However, levels of salicylates in herbs may vary or be too low to have this desired effect.
- Niacin may add to the effects of herbs that may lower blood cholesterol levels, including fish oil, garlic, or guggul. Based on human study, taking such combinations as chromium polynicotinate (niacin-bound chromium) with grape seed proanthocyanidin, or niacin with β-sitosterol and dihydro-β-sitosterol, may result in greater improvements in cholesterol than either agent alone.
- Antioxidants may reduce niacin's beneficial effects on cholesterol levels and heart disease, possibly by interfering with niacin's effects on high-density cholesterol (HDL). Recent research suggests that the addition of antioxidants to a combination of niacin plus simvastatin (Zocor®) reduced the benefit of niacin on heart blood vessel plaques, suggesting possible interference by antioxidants. In other research, use of niacin with vitamin A and vitamin E had greater effects on cholesterol levels than niacin alone. Vitamin E in combination with colestipol and niacin has also been associated with greater benefits on heart blood vessel plaques. This remains an area of controversy.
- Based on human study, niacin may increase blood sugar levels and may require dosing adjustments of hypoglycemic agents. In children, use of niacinamide and insulin together has been shown to lead to a reduction in insulin dosage in patients with type 1 diabetes mellitus. Caution is advised when using herbs or supplements that may affect blood sugar.
- In theory, niacin therapy may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. There are published case reports of patients who developed reversible abnormal blood clotting (coagulopathy) conditions while taking sustained-release niacin. In addition, low blood platelet number (thrombocytopenia) has been observed in studies of niacin therapy. Multiple cases of bleeding have been reported with the use of Ginkgo biloba , and fewer cases with garlic or saw palmetto.
- Based on laboratory study, niacinamide may interact with herbs or supplements with estrogen-like properties, and theoretically may increase the amount of niacin produced in the body (thus lowering the doses of niacin needed for treatment).
- Based on human study, niacin may interact with thyroid-active herbs or supplements such as bladderwrack, and alter thyroid hormone blood tests. Preliminary human research reports that zinc sulfate increases the amount of niacin breakdown products in the urine, suggesting a possible interaction between the two agents.
- Because niacin may alter blood flow in age-related macular degeneration (AMD), patients using herbs or supplements to treat AMD should use niacin cautiously.
- This information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Ethan Basch, MD (Memorial Sloan-Kettering Cancer Center); Samuel Basch, MD (Mt. Sinai School of Medicine, NY); Steve Bent, MD (University of California, San Francisco); Heather Boon, BScPhm, PhD (University of Toronto); Wendy Chao, PhD (Natural Standard Research Collaboration); Dawn Costa, BA, BS (Natural Standard Research Collaboration); Chi Dam, PharmD (Northeastern University); Ivo Foppa, MD, PhD (Harvard School of Public Health); Dana A. Hackman, BS Northeastern University); Paul Hammerness, MD (Massachusetts General Hospital); Beth N. Kerbel, PharmD (Northeastern University); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Mamta Vora, PharmD (Northeastern University); Wendy Weissner, BA (Natural Standard Research Collaboration).
Methodology details
- Birjmohun RS, Hutten BA, Kastelein JJ, et al. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials. J Am Coll Cardiol 2005;45(2):185-197.
- Bissett DL, Oblong JE, Berge CA. Niacinamide: A B vitamin that improves aging facial skin appearance. Dermatol Surg 2005 Jul;31(7 Pt 2):860-5; discussion 865.
- 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.
- Gerber MT, Mondy KE, Yarasheski KE, et al. Niacin in HIV-infected individuals with hyperlipidemia receiving potent antiretroviral therapy. Clin Infect Dis 2004;39(3):419-425.
- Grundy SM, Vega GL, McGovern ME, et al. 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;162(14):1568-1576.
- 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.
- Metelitsina TI, Grunwald JE, DuPont JC, et al. Effect of niacin on the choroidal circulation of patients with age related macular degeneration. Br J Ophthalmol 2004;88(12):1568-1572.
- Qu CX, Kamangar F, Fan JH, et al. Chemoprevention of primary liver cancer: a randomized, double-blind trial in Linxian, China. J Natl Cancer Inst 2007 Aug 15;99(16):1240-7.
- Rubenfire M. Safety and compliance with once-daily niacin extended-release/lovastatin as initial therapy in the Impact of Medical Subspecialty on Patient Compliance to Treatment (IMPACT) study. Am J Cardiol 2004;94(3):306-311.
- Studer M, Briel M, Leimenstoll B, et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med 2005;165(7):725-730.
- Toth PP, Davidson MH. Therapeutic interventions targeted at the augmentation of reverse cholesterol transport. Curr Opin Cardiol 2004;19(4):374-379.
- Veverka A, Jolly JL. Recent advances in the secondary prevention of coronary heart disease. Expert Rev Cardiovasc Ther 2004;2(6):877-889.
- Villamor E, Saathoff E, Bosch RJ, et al. Vitamin supplementation of HIV-infected women improves postnatal child growth. Am J Clin Nutr 2005;81(4):880-888.
- Whitney EJ, Krasuski RA, Personius BE, et al. A randomized trial of a strategy for increasing high-density lipoprotein cholesterol levels: effects on progression of coronary heart disease and clinical events. Ann Intern Med 2005;142(2):95-104.
- 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.
March 01, 2008.
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This evidence-based monograph was prepared by the Natural Standard Research Collaboration. The information provided should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. Talk to your health care provider before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Copyright© 2008 Natural Standard (www.naturalstandard.com). All Rights Reserved.
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