Vitamin B3, also called niacin, is one of eight water-soluble B vitamins. All B vitamins help the body to convert carbohydrates into glucose (sugar), which is "burned" to produce energy. These B vitamins, often referred to as B complex vitamins, are essential in the breakdown of fats and protein. B complex vitamins also play an important role in maintaining muscle tone along the digestive tract and promoting the health of the nervous system, skin, hair, eyes, mouth, and liver.
Niacin plays an important role in ridding the body of toxic and harmful chemicals. It also helps the body make various sex and stress-related hormones in the adrenal glands and other parts of the body. Niacin is effective in improving circulation and reducing cholesterol levels in the blood. Niacin needs can be partially met by eating foods containing protein because the human body is able to convert tryptophan, an amino acid, into niacin.
Dietary deficiency of niacin tends to only occur in areas of the world where people eat corn as a staple and don't use lime in fertilization. Corn is the only grain that is low in niacin. Lime releases tryptophan which, again, can be converted to niacin in the body. Symptoms of mild deficiency include indigestion, fatigue, canker sores, vomiting, and depression. Severe deficiency of both niacin and tryptophan can cause a condition known as pellagra. Pellagra is characterized by cracked, scaly skin, dementia, and diarrhea. It is generally treated with a nutritionally balanced diet and niacin supplements. Niacin deficiency also results in burning in the mouth and a swollen, bright red tongue. In the United States alcoholism is the prime cause of Vitamin B3 deficiency.
Extremely high doses of niacin (available by prescription) have been shown to prevent and/or improve symptoms of the following conditions. Because of risk of toxicity people should always consult a knowledgeable health care provider before starting high doses of niacin.
Niacin is commonly used to lower elevated LDL ("bad") cholesterol and triglyceride (fat) levels in the blood and is more effective in increasing HDL ("good") levels than other cholesterol-lowering medications. However. High doses of niacin produce the side effects of flushing of the skin (which can be reduced by taking aspirin 30 minutes before the niacin), stomach upset (which usually subsides in a few weeks), headache, dizziness, blurred vision, and liver damage. Although the time-release form of niacin reduces flushing, long-term use is associated with liver damage.
High doses of niacin medications are used to prevent development of atherosclerosis (plaque along the blood vessels that can cause blockage) and to reduce recurrent complications such as heart attack and peripheral vascular disease (atherosclerosis of the blood vessels in the legs that can cause pain with walking, called intermittent claudication) in those with the condition. According to a review of major clinical trials, the use of niacin for prevention and treatment of atherosclerosis and related conditions is "based on strong and consistent evidence" and appears to be as effective as certain medications for heart disease. Studies also suggest that high dose niacin may help relieve the symptoms of claudication - namely diminish the pain experienced with walking.
A recent study also found that the combination of niacin and a cholesterol-lowering drug called simvastatin (which belongs to a class known as HmG CoA reductase inhibitors or statins) may dramatically slow the progression of heart disease, reducing risk of heart attack, and even death.
Because diabetes is often associated with atherosclerosis and heart disease, people with diabetes may benefit from nutrients that help manage elevated cholesterol levels and high blood pressure. Although niacin has been shown to boost HDL cholesterol and decrease triglyceride and LDL levels, there has been some concern that it may also raise blood sugar levels. In a recent study of 125 people with diabetes and 343 people without the condition, high doses of niacin (roughly 3000 mg/day), increased blood sugar in both groups, but hemoglobin A1C (considered a better measure of blood sugar over time) actually decreased in the diabetes group over a 60-week follow-up period. For this reason, if you have diabetes, niacin should only be used under the close monitoring of a qualified health care provider.
Some preliminary studies suggest that vitamin B3, as niacinamide, may improve arthritis symptoms, including increasing joint mobility and reducing the amount of anti-inflammatory medications needed. Researchers speculate that niacinamide may aid cartilage repair (damage to joint cartilage causes arthritis) and suggest that it may be used safely along with NSAIDs (non-steroidal anti-inflammatory medications) to reduce inflammation. Further research is needed to fully understand how vitamin B3 benefits people with OA and to determine whether the results apply to large numbers of people with the condition. It does appear, however, that niacinamide must be used for at least 3 weeks before the benefits described are seen. Experts also suggest that long-term use (1 to 3 years) may slow the progression of the disease.
Dietary vitamin B3, along with other nutrients is important for normal vision and prevention of cataracts (damage to the lens of the eye which can lead to cloudy vision.) One study including 2900 people living in Australia found that people who consumed the most protein, vitamin A, and vitamins B1 (thiamine), B2, and B3 (niacin) in their diets were significantly less likely to develop cataracts. A follow-up study also found that many supplemental B complex vitamins (including B12, B9, B3, B2, and B1) exert a protective effect against cataracts.
It is especially important for people who have sustained serious burns to obtain adequate amounts of nutrients in their daily diet. When skin is burned, a substantial percentage of micronutrients may be lost. This increases the risk for infection, slows the healing process, prolongs the hospital stay, and even increases the risk of death. Although it is unclear which micronutrients are most beneficial for people with burns, many studies suggest that a multivitamin including the B complex vitamins may aid in the recovery process.
An interesting area of research currently underway is the use of niacin skin care products as anti-aging agents, for treatment of acne, and, possibly, for prevention of skin cancer. Dermatologists expect that there will be information emerging about topical forms of niacin for these purposes over the next few years.
The best dietary sources of vitamin B3 are found in beets, brewer's yeast, beef liver, beef kidney, pork, turkey, chicken, veal, fish, salmon, swordfish, tuna, sunflower seeds, and peanuts.
Pharmacologic doses of nicotinic acid, but not nicotinamide, have been known to reduce serum cholesterol since 1955. Only one randomized placebo-controlled multicenter trial examined the effect of nicotinic acid therapy alone (3 grams daily) on outcomes of cardiovascular disease. The Coronary Drug Project (CDP) followed over 8,000 men with a previous myocardial infarction (heart attack) for 6 years. In the group that took 3 grams of nicotinic acid daily, total blood cholesterol decreased by an average of 10%, triglycerides decreased by 26%, recurrent nonfatal myocardial infarction decreased by 27%, and cerebrovascular events (stroke + transient ischemic attacks) decreased by 26% compared to the placebo group. Though nicotinic acid therapy did not decrease total deaths or deaths from cardiovascular disease during the 6-year study period, post-trial follow up 9 years later revealed a 10% reduction in total deaths. Four out of five major cardiovascular outcome trials found nicotinic acid in combination with other therapies to be of statistically significant benefit in men and women.
Nicotinic acid therapy has been found to result in markedly increased HDL- cholesterol levels, as well as decreased serum Lp(a) lipoprotein concentrations, and a shift from small dense LDL particles to large, buoyant LDL particles, all of which are considered cardioprotective changes in blood lipid profiles. Because of the adverse side effects associated with high doses of nicotinic acid, it has most recently been used in combination with other lipid-lowering medications in slightly lower doses. A recent randomized controlled trial found that a combination of nicotinic acid (2 to 3 grams/day) and a cholesterol-lowering drug (simvastatin) resulted in greater benefits on serum HDL levels and cardiovascular events, such as heart attack and stroke, than placebo in patients with coronary artery disease and low HDL levels. However, an antioxidant combination (vitamin E, vitamin C, selenium, and b-carotene) appeared to blunt the beneficial effects of niacin plus simvastatin.
Although it is a nutrient, at the pharmacologic dose required for cholesterol- lowering effects, the use of nicotinic acid should be approached as if it were a drug. Individuals should only undertake cholesterol-lowering therapy with nicotinic acid under the supervision of a qualified health care provider, so that the potential for adverse effects may be minimized and treatment benefit maximized.
It has been hypothesized that infection with human immunodeficiency virus (HIV), the virus that causes acquired immmunodeficiency syndrome (AIDS), increases the risk of niacin deficiency. Interferon-gamma (IF-g) is a cytokine produced by cells of the immune system in response to infection. IF-g levels are elevated in individuals infected with HIV, and higher IF-g levels have been associated with poorer prognosis. By stimulating the enzyme, indoleamine 2,3 dioxygenase (IDO), IF-g is known to increase the breakdown of tryptophan, a niacin precursor, supporting the idea that infection with HIV increases the risk of niacin deficiency. In a very small, uncontrolled study, treatment of four HIV positive individuals with 1,000 to 1,500 mg/day of nicotinamide for 2 months resulted in 40% increases in plasma tryptophan levels. An observational study of 281 HIV-positive men found that higher levels of niacin intake were associated with decreased progression rate to AIDS and improved survival.
Studies of cultured cells in vitro provide evidence that NAD content influences the cellular response to DNA damage, an important risk factor for cancer. Cellular NAD is consumed in the synthesis of ADP-ribose polymers, which play a role in DNA repair, and cyclic ADP-ribose may mediate cell-signaling pathways important in the prevention of cancer. Additionally, cellular NAD content has been found to influence levels of the tumor suppressor protein, p53, in human breast, skin, and lung cells. Neither the cellular NAD content nor the dietary intake of NAD precursors (niacin and tryptophan) necessary for optimizing protective responses following DNA damage has been determined, but they are likely to be higher than required for the prevention of pellagra. Niacin deficiency was found to decrease bone marrow NAD and poly-ADP-ribose levels and increase the risk of chemically induced leukemia, and niacin supplementation decreased the risk of ultraviolet light-induced skin cancers in mice. However, little is known regarding cellular NAD levels and the prevention of DNA damage or cancer in humans. Elevation of NAD levels in blood lymphocytes after supplementation of two healthy individuals with 100 mg/day of nicotinic acid for eight weeks reduced DNA strand breaks in lymphocytes exposed to free radicals in a test tube assay compared to those of non-supplemented individuals. More recently, nicotinic acid supplementation of up to 100 mg/day in 21 healthy smokers failed to provide any evidence of a decrease in cigarette smoke-induced genetic damage in blood lymphocytes compared to placebo.
Generally, relationships between dietary factors and cancer are established first in epidemiological studies and followed up by basic cancer research on the cellular level. In the case of niacin, research on biochemical and cellular aspects of DNA repair have stimulated an interest in the relationship between niacin intake and cancer risk in human populations. Recently, a large case-control study found increased consumption of niacin, along with antioxidant nutrients, to be associated with decreased incidence of oral (mouth), pharyngeal (throat), and esophageal cancers in northern Italy and Switzerland. An increase in niacin intake of 6.2 mg was associated with about a 40% decrease in cases of cancers of the mouth and throat, while a 5.2 mg increase in niacin intake was associated with a similar decrease in cases of cancer of the esophagus.
1. Walter Neary. Treatment Reduces Risk of Heart Attack by 60 to 90 Percent, Reverses Arterial Plaque Buildup; Antioxidant Vitamins Diminish Beneficial Effect. Health and Medicine, Nov. 28, 2001.
Treatment with a combination of statin and niacin can slash the risk of a fatal or non-fatal heart attack or hospitalization for chest pain by 70 percent among patients who are likely to suffer heart attacks and/or death from coronary heart disease, according to a study by University of Washington researchers in the Nov. 29 New England Journal of Medicine. Cardiovascular disease is the No. 1 killer in most industrialized countries. The study also found that a mixture of antioxidant vitamins had no beneficial effect on cardiovascular outcomes.
The treatment that cut the risk for cardiovascular events combines two well-known ways of improving cardiac health: the use of a statin drug to lower levels of the "bad" cholesterol, LDL, and the use of niacin to boost levels of the "good" cholesterol, HDL. The study found that use of this combined treatment, in people with low levels of "good" HDL and average levels of "bad" LDL, could even reverse plaque buildup in the arteries.
At the start of the study and again after three years of treatment, doctors performed angiograms of the patients' arteries. The angiograms, using computerized measurements, showed that in most of the patients who received the combination treatment, plaque buildup had actually decreased.
"This is the first demonstration of a striking clinical benefit from this form of combination drug therapy used in patients with a common type of coronary disease," said Dr. B. Greg Brown, lead author of the study, a cardiologist and UW professor of medicine.
The study was funded by the National Heart, Lung, and Blood Institute (NHLBI).
"This study shows that improving cholesterol levels in people with heart disease --especially lowering LDL "bad" cholesterol substantially, together with raising HDL "good" cholesterol -- greatly reduces the risk for a heart attack and heart disease complications and can actually reverse the buildup of cholesterol in the arteries of the heart," said Dr. Claude Lenfant, director of the National Heart, Lung, and Blood Institute. "The study also contributes to the evidence that antioxidant vitamins may not be beneficial in the treatment of heart disease."
The study found that a mixture of antioxidant vitamins blunted the expected rise in the "good" HDL cholesterol usually seen with the simvastatin and niacin combination. Scientists are not sure why this is so, since there has been laboratory evidence that suggests antioxidants should be helpful. However, Oxford University's recent Heart Protection Study from the United Kingdom confirmed the lack of benefit from the vitamin combination.
The study had included antioxidants because there has been considerable evidence that they should help protect against the basic mechanisms for cholesterol buildup. The antioxidants involved in this study include Vitamins C, E, beta carotene and selenium.
Brown was director of the first study in the late 1980s that showed that a member of the statin class, lovastatin, could cause improvement in arterial blockage and reduce the occurrence of major cardiovascular events. Giving statins to people with cardiovascular disease is now common, and has been proven to reduce cardiovascular risk by 25 to 35 percent over five years of treatment.
Brown and colleagues had surmised that combining simvastatin with niacin might more effectively prevent heart attacks and the need for procedures such as coronary bypass. The goal would be to reduce plaque buildup. That's important because the growth of cholesterol-rich plaque blocks blood flow and can lead to fatal complications.
"What is expected with statins is a slowing of the disease progression, but not a reversal. Arteries continue to get narrower, but not as fast," Brown said. "But when niacin is combined with a statin, the artery blockage actually improves a bit, on average."
The statins lower blood levels of LDL, which is called the "bad" cholesterol because it contributes to plaque growth and arterial blockage. HDL, on the other hand, helps protect against heart disease. Niacin, or Vitamin B3, is the best agent known to raise blood levels of HDL, which helps remove cholesterol deposits from the artery walls.
The 160 patients involved in the study had low levels of HDL cholesterol (a level of 35 mg/dl or less). At least four out of every 10 people with coronary artery disease fit this profile.
Some patients in this study received simvastatin and niacin, while others received antioxidants. A third group received all these treatments, while a control group received placebos. All patients received exercise training, as well as anti-smoking and dietary counseling.
The results for those receiving statin and niacin were startlingly different from control patients. The average level of HDL increased from 31 to 39, or 26 percent, while the average LDL dropped from 125 to 76 (down 43 percent) -- that is considered an extremely good level of the bad cholesterol. Angiograms showed that most of these people had no additional plaque buildup over the years. In many of them, the amount of plaque actually decreased.
"What we saw was a reversal of the disease," Brown said. The patients' arteries, on average, had stopped narrowing and begun to improve somewhat. Those receiving this lipid therapy combination had 60 to 90 percent fewer major cardiovascular events than the control group.
For the patients receiving antioxidants, the progressive narrowing of the arteries and frequency of major cardiovascular events did not differ from the control patients. And those receiving lipid therapy and antioxidants had less favorable outcomes than the group that had simvastatin and niacin alone. This was due to the observed blunting of the HDL response. The study concludes that niacin adds substantially to the already proven simvastatin benefit, and that the use of antioxidant vitamins to prevent heart disease should be questioned.
The study involved use of niacin at moderately high and carefully supervised levels. Brown said that patients should only take niacin under a doctor's supervision, because in some patients, the doctor may wish to monitor the patient's liver function. Rarely, the unsupervised use of niacin can cause severe liver problems, including liver failure.
2. Guyton JR. Effect of Niacin on Atherosclerotic Cardiovascular Disease. Am J Cardiol. 1998 Dec 17;82(12A):18U-23U; discussion 39U-41U.
Niacin has been studied in 6 major clinical trials with cardiovascular endpoints. The Coronary Drug Project (CDP) was the largest of these trials and the only one to use niacin monotherapy affecting cardiovascular outcomes: recurrent myocardial infarction and cerebrovascular events were significantly decreased. After long-term (15 years) follow-up, total mortality was also found to be decreased. The other 5 trials used varying combinations of niacin with other pharmacologic agents, examining coronary and total mortality, coronary events, and angiographic progression/regression. Significant benefit was found in all trials except for one in patients with normal cholesterol levels at entry. Thus, the use of niacin to prevent or treat atherosclerotic cardiovascular disease is based on strong and consistent evidence from clinical trials.
3. Niacin as a Potential Aids Preventive Factor. Med Hypotheses. 1999 Nov;53 (5):375-9.
A pentad of findings consistent with niacin depletion have been described in patients with AIDS. There are also clinical and laboratory data to support the potential benefit of niacin in HIV infection. In this paper, it is hypothesized that HIV infection induces niacin depletion, and that therapeutic niacin will act as an AIDS preventive factor. While viral inhibition is incontrovertibly the primary 'AIDS preventive factor', costly antiretroviral medications are simply out of reach for the majority of the world's HIV-infected people. Along with antiviral research, investigation must go forward to look at strategies to overcome the massive metabolic disruption caused by the production of approximately one billion virus particles per day. Niacin, the same B complex vitamin found in the early part of this century to be the 'pellagra preventive factor', is proposed here as a secondary 'AIDS preventive factor' in HIV-infected persons.
4. Niacin and Carcinogenesis. Nutr Cancer. 2003;46(2):110-8.
The dietary status of niacin (vitamin B3) has the potential to influence DNA repair, genomic stability, and the immune system, eventually having an impact on cancer risk, as well as the side effects of chemotherapy in the cancer patient. In addition to its well-known redox functions in energy metabolism, niacin, in the form of NAD, participates in a wide variety of ADP-ribosylation reactions. Poly(ADP-ribose) is a negatively charged polymer synthesized, predominantly on nuclear proteins, by at least seven different enzymes. Poly(ADP-ribose) polymerase-1 (PARP-1) is responsible for the majority of polymer synthesis and plays important roles in DNA damage responses, including repair, maintenance of genomic stability, and signaling events for stress responses such as apoptosis. NAD is also used in the synthesis of mono(ADP -ribose), often on G proteins, with poorly understood roles in signal transduction. Last, NAD and NADP are required for the synthesis of cyclic ADP-ribose and nicotinic acid adenine dinucleotide (NAADP), two mediators of intracellular calcium signaling pathways. Disruption of any of these processes has the potential to impair genomic stability and deregulate cell division, leading to enhanced cancer risk. There are various sources of evidence that niacin status does have an impact on cancer risk, including animal models of leukemogenesis and skin cancer, as well as epidemiological data from human populations.
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