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Vitamin b3
Vitamin B-3 Vitamin
- Niacin


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®, 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®

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, age-related macular degeneration, 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, non-ST-segment elevation acute coronary syndromes, 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.

Interactions

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. Use of niacin with HMG-CoA reductase inhibitors or gemfibrozil may increase the risk of serious side effects such as liver or muscle damage. The bile acid sequestrants cholestyramine and colestipol may reduce niacin absorption into the body.

Based on human study, niacin may increase blood sugar levels, and may require dosing adjustments of insulin or prescription diabetes drugs. In research on children, use of niacinamide and insulin together has been shown to lead to a reduction in insulin dosage in patients with type 1 (insulin-dependent) diabetes mellitus. Caution is advised when using medications that may affect blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare provider. Medication adjustments may be necessary.

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, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve® ).

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 study, 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.

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. Examples include ackee, bee pollen, birch oil, blessed thistle, borage, bush tea, butterbur, chaparral, coltsfoot, comfrey, DHEA, Echinacea purpurea , Echium spp., germander, Heliotropium spp., horse chestnut, Jin-bu-huan (Lycopodium serratum), kava, lobelia, L-tetrahydropalmatine (THP), mate, Paraguay tea, periwinkle, Plantago lanceolata , pride of Madeira, rue, sassafras, scullcap, Senecio spp./groundsel, tansy ragwort, turmeric/curcumin, Tu-san-chi ( Gynura segetum ), uva ursi, valerian, and white chameleon.

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 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 guggal. 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 study with 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. Blood glucose levels may require monitoring, and doses may need adjustment. Possible examples of herbs that may lower blood sugar include: Aloe vera , American ginseng, bilberry, bitter melon, burdock,fenugreek, fish oil, gymnema, horse chestnut seed extract (HCSE), marshmallow, milk thistle, Panax ginseng, rosemary, Siberian ginseng, stinging nettle and white horehound. Agents that may raise blood sugar levels include: Arginine, cocoa, and ephedra (when combined with caffeine).

In theory, niacin therapy may increase 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. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases. Some examples include: alfalfa, American ginseng, angelica, anise, Arnica montana , asafetida, aspen bark, bilberry, birch, black cohosh, bladderwrack, bogbean, boldo, borage seed oil, bromelain, capsicum, cat's claw, celery, chamomile, chaparral, clove, coleus, cordyceps, danshen, devil's claw, dong quai, evening primrose, fenugreek, feverfew, flaxseed/flax powder (not a concern with flaxseed oil), ginger, grapefruit juice, grapeseed, green tea, guggul, gymnestra, horse chestnut, horseradish, licorice root, lovage root, male fern, meadowsweet, nordihydroguairetic acid (NDGA), onion, papain, Panax ginseng, parsley, passionflower, poplar, prickly Ash, propolis, quassia, red clover, reishi, Siberian ginseng, sweet clover, rue, sweet birch, sweet clover, turmeric , vitamin E, white willow, wild carrot, wild lettuce, willow, wintergreen, and yucca.

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). Examples of herbs with possible estrogen properties include alfalfa, black cohosh, bloodroot, burdock, hops, kudzu, licorice, pomegranate, red clover, soy, thyme, white horehound, and yucca.

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.

Interactions with Foods
Hot beverages, when taken with niacin, may worsen niacin-induced skin flushing.

Methodology

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, B.Sc.Phm, PhD (University of Toronto); Chi Dam, PharmD (Northeastern University); Ivo Foppa, MD, PhD (Harvard School of Public Health); Dana A. Hackman, BS (c) Northeastern University); Paul Hammerness, MD (Massachusetts General Hospital); Beth N. Kerbel, PharmD (Northeastern University); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Mamta Vora, PharmD (Northeastern University).


Other useful Vitamin information: Vitamin B-2 | Vitamin K | Inositol

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