Niacin is a member of the B vitamin family. This term is used for nicotinic acid and nicotinamide (also called niacinamide). These two compounds have identical vitamin activities but are different in their pharmacological activities.
Niacin is water-soluble, stable under acidic and alkali conditions, and resistant to light and oxidation.
Nicotinic acid in pharmacological doses is used as a cholesterol lowering agent in drugs such as Niacor®, Nicolar®, and Niaspan® or in combination drugs such as Advicor® and Simcor® (containing Lovastatin and Simvastatin, respectively).
In more than 200 redox and non-redox enzyme reactions, niacin is active as nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).
Both nicotinic acid and nicotinamide are efficiently absorbed from the stomach and small intestine with almost complete absorption of doses up to 4 g.
Tryptophan can be converted to niacin; it is estimated that 60 mg of tryptophan can be converted to 1 mg of niacin.
Niacin coenzymes are involved in a variety of biological processes:
NAD+ and the reduced form (NADH) transfer electrons through the electron transport chain, ultimately producing ATP.
NADP+ and the reduced form (NADPH) act as a reducing agent in biosynthetic pathways including synthesis of fatty acids, cholesterol, and steroids. NADPH also maintains glutathione in its reduced form.
NAD+ and NADP+ are both involved in the biosyntheses of signaling molecules.
Male 9 to 13 years 14 to 18 years 19+ years Female 13 to 19 years 14 to 18 years 19+ years
12 16 16
12 14 14
20 30 35
20 30 35
Pregnancy <= 18 years 19 to 50 years
18 18
30 35
Lactation <= 18 years 19 to 50 years
17 17
30 35
* Values are Adequate Intakes (AI), others are RDA. DRI for niacin based on niacin equivalents (NE); 1 mg niacin = 60 mg tryptophan; 0 - 6 months based on preformed niacin and not NE. ND: Not determinable due to lack of data of adverse effects
in this age group and concern with regard to lack of ability to handle excess
amounts.
The UL is based on the amount known to elicit a vasodilatory effect, i.e., flushing of the skin on the face, neck, arms and chest.
A niacin deficiency can occur if a person consumes a low protein diet.
A severe deficiency of niacin can result in pellagra which is characterized by dermatitis, diarrhea, and dementia. Pellagra, if not treated, can result in death.
Pellagra related dermatitis is characterized by skin lesions located primarily on sun exposed areas of the face, hands, arms, and feet.
Pellagra is rare in the U.S. and other industrialized countries due to the enrichment of refined flours with niacin, started in the 1930s.
Temporary flushing will affect some people at doses as low as 50 mg. In addition to reddening of skin, symptoms can include tingling, a burning sensation, sweating, chills, and itching.
In addition to its role as a vitamin, niacin is a prescription drug used to raise HDL-cholesterol and lower LDL-cholesterol and triglycerides. Prescription doses range from 500 to 3,000 mg/day.
Symptoms such as headache, diarrhea, dyspepsia, vomiting, and abdominal pain occur in 2% to 10% of patients in the dose range of 500 to 3,000 mg/day. Rarer symptoms include migraine headache, fast/irregular heartbeat, and vision problems.
Hepatotoxic effects occur at daily doses in the range of 3 to 9 g/day, with consequences including jaundice and elevated liver enzymes.
Extended-release prescription niacin (Niaspan®) is thought less likely to cause flushing but more likely to cause liver and gastrointestinal adverse effects compared to immediate-release niacin (Niacor®). Patients switching from prescription immediate release niacin to prescription extended-release niacin are advised to drop down to the lowest dose for extended-release, and then increase under the supervision of a healthcare professional.
Niacin and its precursors are found naturally in meat, poultry, fish, legumes, and yeast. The voluntary fortification of flour started in the late 1930s was superseded by required fortification starting in 1945. As a result, the combination of breads and cereals provide more than 20% of total niacin intake.1
Nicotinic acid is effective in raising HDL cholesterol, lowering LDL cholesterol, and lowering triacylglycerols. It has been found to significantly decrease cardiovascular and cerebrovascular events in those with coronary heart disease.
Patients taking HMG-CoA reductase inhibitors, such as lovastatin and simvastatin, to treat hypercholesterolemia, and more than 1 g daily of niacin, increase the risk of developing myopathy and rhabdomyolysis. However, patients who take extended-release niacin with various HMG-CoA reduction inhibitors, have less risk of rhabdomyolysis. Patients should consult their physician before taking niacin supplements with these medications.
Niacin is reported to potentiate the hypotensive effects of ganglionic blocking drugs. It is advisable to avoid concomitant administration of the drug and niacin.
The long-term use of isoniazid, an antimycobacterial agent, may interfere with the conversion of dietary tryptophan to niacin. This may increase the required dose of niacin.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
Extended-release niacin or ezetimibe and carotid intima-media thickness.
A randomized, double-blind clinical trial investigated the effects of extended-release niacin versus ezetimibe in combination with long-term statin therapy. Men and women with coronary heart disease who were on long-term statin therapy were enrolled in the study; the study was ended after 208 participants completed the trial, on the basis of efficacy. Participants were randomly assigned to receive extended-release niacin (2,000 mg/day) or ezetimibe (10 mg/day) for the duration of the 14 month trial. Mean HDL cholesterol increased by 18.4% in the niacin group (P<0.001); LDL cholesterol and triglycerides were significantly reduced in the niacin group. Mean LDL cholesterol decreased by 19.2% in the ezetimibe group (P<0.001); HDL cholesterol and triglyceride levels were reduced in the ezetimibe group. Niacin produced a greater change in mean carotid intima-media thickness than ezetimibe (P=0.003), producing a significant reduction of mean (P=0.001) and maximal carotid intima-media thickness (P6
Lipid-altering efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in patients with type IIa or type IIb hyperlipidemia.
A multicenter, randomized, double-blind trial investigated the efficacy of extended-release niacin for people with hyperlipidemia. The study enrolled 1,220 people with type IIa or IIb hyperlipidemia for the 24 week trial. Participants were randomly assigned to receive ezetimibe/simvastatin (E/S, 10 mg/20 mg daily), extended-release niacin (N, titrated to 2 g daily), or E/S plus niacin (E/S+N). Compared with E/S or N alone, the combination (E/S+N) produced significantly greater reductions in LDL-C, non-high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipid/lipoprotein ratios (p<0.001). E/S+N increased levels of apolipoprotein A-I and high-density lipoprotein cholesterol significantly more than E/S (p<0.001). High-sensitivity C-reactive protein levels were increased significantly by E/S+N compared to N alone (p=0.005). The results of this study suggest that addition of extended-release niacin to ezetimibe/simvastatin treatment may improve hyperlipidemia.7
Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study.
A randomized, placebo-controlled, double-blind study investigated the effects of addition of extended-release niacin to statin therapy for progression of atheroschlerosis. One-hundred-sixty-seven people (mean age 67 years) with coronary heart disease and low HDL cholesterol levels participated in the one year study. Participants were randomly assigned to receive 1 g extended-release niacin or a placebo daily in addition to their ongoing statin therapy. One-hundred-forty-nine participants completed the study. In the niacin supplemented group, HDL cholesterol increased 21% (39 to 47 mg/dL). Mean carotid intima-media thickness (CIMT) increased significantly in the placebo group (0.044+/-0.100 mm; P<0.001). CIMT remained unchanged in the niacin group (0.014+/-0.104 mm; P=0.23); niacin significantly reduced the rate of IMT progression in subjects without insulin resistance (P=0.026). Clinical cardiovascular events occurred in 3 patients treated with niacin (3.8%) and 7 patients treated with placebo (9.6%; P=0.20). The results of this study indicate that extended-release niacin may improve HDL cholesterol profiles and positively influence CIMT for people with atherosclerosis who are already on statin therapy.8
The effects of extended-release niacin on carotid intimal media thickness, endothelial function and inflammatory markers in patients with the metabolic syndrome.
A randomized, double-blind, placebo-controlled study investigated the effects of extended-release niacin on markers of endothelial function and inflammation in people with metabolic syndrome. Participants (n=50) were randomly assigned to receive either extended-release niacin (N, 1,000 mg) or a placebo daily for 52 weeks. After 52 weeks of treatment, there was an increase in carotid intimal media thickness (IMT) of +0.009 mm in the placebo group and a decrease of -0.005 mm in the niacin group (p=0.021 between groups). The niacin group demonstrated in amprovement of endothelial function (22%; p<0.001) but no changes were seen in the placebo group. High sensitivity C-reactive protein decreased by 20% in the group treated with niacin for 52 weeks (p=0.013). HDL-C was increased in the niacin group (p<0.001) and low-density lipoprotein cholesterol and triglycerides were decreased in the niacin group (p<0.001). These results suggest that extended-release niacin may improve intimal media thickness, endothelial function, and inflammatory markers for people with metabolic syndrome.9
Many dietary supplement companies sell inositol hexanicotinate (IHN) as a non-prescription, “flush-free” niacin for maintaining healthy lipid levels. The evidence is not consistent. Three older clinical trials claim a benefit. Three subsequent trials and a case study have reported no benefit. IHN consists of six nicotinic acid molecules esterified to an inositol molecule in the center. The molecule is absorbed intact and then hydrolyzed, releasing free nicotinic acid and inositol. Hydrolysis of the inositol molecule is a slow process, not reaching maximum serum concentrations of the constituent parts until approximately 10 hours after ingestion.10
The three clinical trials cited as evidence for efficacy date from 1961 11,12 (Dorner, Welsh) and 1983 13 (El-Enein). The three efficacy studies described as in support of inositol hexanicotinate as being more effective than nicotinic acid, and effective at 1,200 to 1,600 mg/day (divided over 3-4 doses per day)10-13. Details are not provided. Another clinical trial reported treating patients with clofibrate with or without 1,200 mg/day of inositol hexanicotinate and seeing similar cholesterol and triglyceride lowering with both treatment regimens. 14
In contast, a recent review by the European Food Safety Authority provided a description of a 1977 trial of IHN equivalent to 1,326 mg/day of nicotinic acid. In 59 subjects there was no improvement to total cholesterol and a trend for lower HDL-C. 15 In a case report of a patient who substituted 2,000 mg/day of a “flush free” niacin supplement for prescribed niacin, there was no change to HDL-C at 6 months. However, after returning to his extended release prescription niacin, his HDL-C increased from 29 to 35 mg/dl by the end of 3 months. 16 In a 3 month, placebo-control, trial of 22 men with baseline HDL-C less than 1.04 mmol/L (40 mg/dl), the group recieving 1,500 mg/day of IHN (n=11) had an increase of HDL-C from 0.89 to 0.94 mmol/L while the control group (n=11) had an increase from 0.88 to 0.91 mmol/L (IHN effect not significantly different from placebo). Changes to total cholesterol, LDL-C and triglycerides were also not significant for either group. 17
The dietary supplement information contained on this site has been compiled from published sources thought to be reliable, but it cannot be guaranteed. Efforts have been made to assure this information is accurate and current. However, some of this information may be purported or outdated due to ongoing research or discoveries. The authors, editors and publishers cannot accept responsibility for errors or omissions or for any consequences from applications of the information in this site and make no warranty, expressed or implied, with respect to the contents herein.
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