There is a 20 mg per day recommended Daily Value (DV) of niacin from any source and in any form. The Tolerable Upper Intake Level (UL) for niacin is set at 35 mg per day, which is primarily based on one form of vitamin B₃ (niacin itself, also called nicotinic acid) potentially causing an uncomfortable “niacin flush”. ¹  However, all forms of niacin are lumped together under this arbitrary upper limit, with no real scientific justification given for their inclusion. ²  Federal regulations also require that all forms of niacin be lumped together and primarily labeled as “Niacin”, with the exact form(s) secondarily listed in parentheses. This understandably leads to a lot of confusion about the use and potential side effects of various forms of niacin.

 

It is well documented that niacinamide (nicotinamide) does not cause a niacin flush. ^2,3 Nor does inositol hexanicotinate ⁴, sold commonly as “Flush Free Niacin” and utilized by many physicians as part of their cholesterol management programs.  This means that these forms should probably not be (but are) included in the UL for niacin (nicotinic acid).  

 

In many NOW products, including multivitamins and B-complex vitamins, only the flush-free forms niacinamide (nicotinamide) and inositol hexanicotinate are actually included in the formulas.  A few  formulas contain the co-enzyme form of niacin, called NAD - an analog of NAD(H) - in small amounts, and this form is also considered to be safe (it doesn’t cause a niacin flush).

 

ChromeMate® is a unique, patented form of biologically active niacin-bound chromium called chromium nicotinate or polynicotinate that dramatically increases the effectiveness of chromium. ^{22, 23}  NOW uses this form of chromium in several products, and it has a proven safety record. ^{24, 25}  A serving of ChromeMate® provides 200 mcg of elemental chromium and 1.1 mg of niacin, a relatively low level supplying only 5.5% of the Daily Value.

 

Based on the references, it does not appear that the forms and amounts of niacin present in NOW supplements would normally cause any significant adverse effects when used as directed on the labels, even when taking niacin in potencies above the UL, such as B-50 caps or Adam. Higher amounts than recommended on a product label should only be used as directed by a health professional, who should monitor the person for symptoms of toxicity that could occur at much higher levels.  Adverse effects (other than the niacin flush) have occurred at relatively high doses of 1,500 mg/day for niacin and 3,000 mg/day for niacinamide, far above the 35 mg/day UL set for all forms of niacin. ⁵

 

The niacin flush consists of skin reddening, itching and/or burning starting 10–20 min after oral ingestion of the nutrient and lasting about 60–90 min. ^3,6  Although most patients experience tolerance to the flush within a week ^3,7, as many as 40% of patients started on nicotinic acid eventually discontinue therapy, even when started on sustained release formulations ^3,8.  The niacin flush can also be largely avoided by taking aspirin at least 30 minutes before the niacin, so those who take aspirin daily may be largely protected from this uncomfortable side effect even when taking niacin. ³ There is some evidence that the risk of developing liver toxicity from very high doses of niacin could possibly be lowered by supplementing with a methyl donor, such as TMG (betaine), to prevent depletion of SAM (SAM-e). ²⁶ 

 

All forms of niacin are not created equal from a scientific viewpoint, even though government scientists have apparently decreed otherwise. It is important for the needs of individual biochemistry and health that various forms of niacin are available in potencies above the UL, which was set largely for people to avoid the niacin flush, along with information on their safe use. ^9-21

 

REFERENCES:

 

1  From the NIH Institute of Medicine (IOM) website: "The Tolerable Upper Intake Level (UL) for niacin for adults is 35 mg/day, which was based on flushing as the critical adverse effect." http://books.nap.edu/openbook.php?record_id=6015&page=123

 

2  Although nicotinamide appears not to be associated with flushing effects, a UL for nicotinic acid that is based on flushing is considered protective against potential adverse effects of nicotinamide. http://books.nap.edu/openbook.php?record_id=6015&page=142

 

3  "Nicotinic acid is a safe, broad-spectrum lipid agent shown to prevent cardiovascular disease, yet its widespread use is limited by the prostaglandin D(2) (PGD(2)) mediated niacin flush...The PGD(2) secretion was dependent on the concentration of nicotinic acid and the time of exposure. Nicotinuric acid, but not nicotinamide, also induced PGD(2) secretion.  Meyers CD, Liu P, Kamanna VS, Kashyap ML. Nicotinic acid induces secretion of prostaglandin D(2) in human macrophages: An in vitro model of the niacin flush. Atherosclerosis. 2006 Aug 29; [Epub ahead of print] PMID: 16945375

 

4  Bolzano K, Krempler F, Haslauer F. [Treatment of various types of hyperlipoproteinaemia with a combination of Mg-chlorophenoxy-isobutyrate and mesoinositol-hexanicotinate (author's transl)]. Arzneimittelforschung. 1979;29(10):1621-4. German. PMID: 583231

 

5  The Tolerable Upper Intake Level (UL) developed here applies to all forms of niacin added to foods or taken as supplements (e.g., immediaterelease, slow or sustained-release nicotinic acid, and niacinamide [nicotinamide]). Adverse effects such as nausea, vomiting, and signs and symptoms of liver toxicity have been observed at nicotinamide intakes of 3,000 mg/day (Rader et al., 1992) compared with intakes of nicotinic acid of 1,500 mg/day (McKenney et al., 1994). http://books.nap.edu/openbook.php?record_id=6015&page=140

 

6  Meyers CD, Carr MC, Park S, Brunzell JD. Varying cost and free nicotinic acid content in over-the-counter niacin preparations for dyslipidemia. Ann Intern Med 2003;139:996–1002.

 

7  Stern RH, Spence JD, Freeman DJ, Parbtani A. Tolerance to nicotinic acid flushing. Clin Pharmacol Ther 1991;50:66–70.

 

8  Gray DR, Morgan T, Chretien SD, Kashyap ML. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med 1994;121:252–8.

 

9  Ring EFJ, Porto LO, Bacon PA. Quantitative thermal imaging to assess inositol nicotinate treatment for Raynaud's syndrome. J Int Med Res. 1981;9:393-400.

 

10  O'Hara J, Jolly PN, Nicol CG. The therapeutic efficacy of inositol hexanicotinate (Hexopal®) in intermittent claudication: A controlled trial. Br J Clin Pract. 1988;42:377-383.

 

11  Murphy R. The effect of inositol hexanicotinate (Hexopal) in patients with Raynaud's syndrome. Clin Trials J. 1985;22:521-529.

 

12  Kiff RS. Does inositol hexanicotinate (Hexopal) influence intermittent claudication? Br J Clin Pract. 1988;42:141-145

 

13  Head A. Treatment of intermittent claudication with inositol nicotinate. Practitioner. 1986;230:49-54

 

14  Eur J Clin Pharmacol. 1979 Aug;16(1):11-5. Nocturnal inhibition of lipolysis in man by nicotinic acid and derivatives. Kruse W, Kruse W, Raetzer H, Heuck CC, Oster P, Schellenberg B, Schlierf G. PMID: 499296 [PubMed - indexed for MEDLINE]

 

15  Welsh AL, Ede M. Inositol hexanicotinate for improved nicotinic acid therapy. Int Record Med. 1961;174:9-15

 

16  Hammerl H, Kraenzyl CH, Sudlar M. Metabolic studies for determination of the action mechanism of a ß-sympathometic. Wein Klin Woschenschr. 1968;80:269

 

17  Sommer H. Nicotinic acid levels in the blood and fibrinolysis under the influence of the hexanicotinic ester of m-inositol. Arzneim Forsch. 1975;15:1337

 

18  Dorner VG, Fischer FW. The influence of m-inositol hexanicotinate ester on the serum lipids and lipoproteins. Arzneim Forsch. 1961;11:110-113

 

19  El-Eneim AMA, Hafez YS, Salem H, Abdel M. The role of nicotinic acid and inositol hexanicotinate as anticholesterolemic and antilipemic agents. Nutr Reports Int. 1983;28:899-911

 

20  Mercier J, Gavend MR, Dessaigne S. Effect of inositol and its derivatives on hypercholesterolemic rabbits. Cong Union Therap Intern (Brussels). 1963;8:11

 

21  Kruse W, Kruse W, Raetzer H, et al. Nocturnal inhibition of lipolysis in man by nicotinic acid and derivatives. Eur J Clin Pharmacol. 1979;16:11-15

 

22  Chromate: http://www.interhealthusa.com/research/research.aspx

 

23  Preuss HG, Grojec PL, Lieberman S and Anderson RA, Effects of Different Chromium Compounds on Blood Pressure and Lipid Peroxidation in Spontaneously Hypertensive Rats, Clinical Nephrology, 47:325-330, 1997

 

24  T. Yasmin, M.A., Shara, D. Bagchi, A. Kincaid, A. Limpach, R. Sandstrom, and M. Bagchi, Long-Term Safety Evaluation of a Novel Oxygen-Coordinated Niacin-bound Chromium (III) Complex, Annual Meeting of the American College of Nutrition, Reno, Nevada, Abs. 95, Pg. 465, Vol. 25, No. 5, October 5-8, 2006

 

25  M. Shara, T. Yasmin, A.E. Kincaid, A.L. Limpach, J. Bartz, K.A. Brenneman, A.Chatterjee, M. Bagchi, S.J. Stohs and D. Bagchi. Safety and toxicological evaluation of a novel niacin-bound chromium (III) complex. Journal of Inorganic Biochemistry 99: 2161-2183 (2005)

 

26  McCarty MF. Co-administration of equimolar doses of betaine may alleviate the hepatotoxic risk associated with niacin therapy. Med Hypotheses. 2000 Sep;55(3):189-94. PMID: 10985907