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Dietary Supplement Information for Physicians
with Naturokinetics®
Flush-Free Niacin
Product Code: P0498
Categories: Vascular Support
TECHNICAL SUMMARY
Chemical Name: Inositol niacinate (1,2,3,5/4,6 Cyclohexanehexol
hexanicotinate)
Structural formula:
Molecular Formula: C42H30N6O12
−1
Molecular Weight: 810.72 g mol
Product Composition: Inositol Hexanicotinate, Cellulose (capsule),
Stearic Acid (vegetable source), Magnesium Stearate (vegetable source),
Rice Flour, Silica.
Delivery Form: Vegetable capsules
ROLE AS A NUTRIENT
Essentiality: Niacin, or nicotinic acid, is designated as Vitamin B3.
1
However, it can also be synthesized from the amino acid tryptophan.
Dietary Sources: The main dietary sources of niacin are meat, fish, poultry and whole grain cereals. Eggs and milk contain significant
1,2
amounts of tryptophan, a precursor to niacin formation in the body.
Typical Consumption: Recommended daily intakes of niacin range from 14 mg to 17 mg in adults. In the U.S., women and men aged 191
50 years old consume an average of 17 mg and 21 mg of niacin equivalents, respectively.
2
Prevalence of Nutrient Deficiency: Niacin deficiency, known as pellagra, is rare in developed countries.
Factors Affecting Nutrient Status: Alcoholism and consumption of incomplete diets low in niacin and tryptophan can lead to B3
deficiency. Also, individuals with Hartnup syndrome, an autosomal recessive disorder linked to vitamin transport, may suffer from vitamin
1,2
B3 deficiency.
Methods of Evaluation: Niacin status is assessed by 24-hour urinary output of its metabolite, N-methylnicotinamide (normal level ≥ 2
1,2
mg/g of creatinine).
Structural and Functional Role: Niacin is a direct precursor of nicotinamide adenine nucleotide (NAD) and nicotinamide adenine
nucleotide phosphate (NADP), which function as coenzymes in oxidation and reduction central to energy production throughout the
1,2
body. Other notable reactions include amino acid synthesis, DNA repair, and production of steroid hormones. Niacin inhibits adipocyte
lipolysis accompanied by a drop in plasma levels of fatty acids, thus reducing substrate supply for synthesis of TGs and VLDLs by the liver.
As a result, catabolism of HDL and accumulation of cholesterol esters in LDL particles are reduced. Additionally, niacin directly inhibits the
uptake and catabolism of ApoA1-containing HDL particles, thus acting to further increase plasma levels of HDL. Finally, two types of niacin
1
receptors closely related to its vasodilatatory effect, known as niacin flush, are present in some tissues.
RECOMMENDED USE
Flush-Free Niacin Supplementation: Free-form niacin supplementation is often accompanied by flushing (and pruritus) that can be
3
observed following doses as low as 100 mg. Flushing can be severe and can negatively affect compliance. Unlike niacin, inositol
4
hexanicotinate was not associated with flushing in clinical trials, even when it was used in dosages as high as 4 grams daily.
Vascular Support: A double blind, randomized, placebo-controlled trial was conducted to evaluate the effectiveness of inositol
hexanicotinate in relieving peripheral vasospastic symptoms associated with Raynaud's disease. A total of 23 patients with primary
Raynaud's disease were supplemented with either 4 grams/day of inositol hexanicotinate or placebo during cold weather months.
5
Patients in the intervention group had demonstrably shorter and fewer attacks of vasospasm during the trial period.
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Dietary Supplement Information for Physicians
with Naturokinetics®
NATUROKINETICS®
Liberation: Dissolution data is not available. Flush-free Niacin P0498 passes the standard disintegration test (< 60 minutes).
4
Absorption: Pharmacokinetic studies indicate the molecule is, at least in part, absorbed intact.
Distribution: Tissue distribution of inositol hexanicotinate is believed to be proportional to the rate of organ perfusion. Its metabolite,
niacin (see metabolism section below) has been shown to have an affinity to adipose tissue, skeletal and smooth muscle tissue and
3
vascular epithelium.
Metabolism: Inositol hexanicotinate is slowly hydrolyzed, with release of free niacin reaching maximum serum levels approximately 10
4
hours after ingestion (Tmax ≈ 10 hours). The hydrolysis of inositol hexanicotinate into niacin by human plasma has also been
6
demonstrated in vitro. Niacin is metabolized through two pathways: first to nicotinuric acid through nicotinyl–CoA by glycine
conjugation, and the second to niacinamide, which is utilized in NAD synthesis. Niacinamide is further transformed to Nmethylnicotinamide (typically assessed in urine to diagnose niacin deficiency) and 3 other metabolites through methylation and/or
7
oxidation.
1,2
Excretion: Niacin and its metabolites are excreted in urine.
SAFETY INFORMATION
1
Tolerable Upper Limit: In adults, the tolerable daily upper intake level for niacin is 35 mg.
Contraindications: Symptoms of kidney, liver, gall bladder, and peptic ulcer disease, as well as gout, hypotension, and certain allergies,
8,9
may be exacerbated by niacin supplementation. Diabetes can be difficult to control when niacin and anti-diabetic therapies are
9
combined.
Warning: High doses of niacin may cause gastric and hepatotoxic effects. High levels of niacin may also induce insulin resistance and
10
increase homocysteine levels.
INTERACTIONS
1
Drug Interaction: Large doses of niacin (1-3 grams/day) may counteract the effect of uricosuric drugs such as allopurinol, probenecid,
11
12
and sulfinpyrazone. Metabolism of primidone and carbamazepine may be reduced, and individuals taking clonodine may experience
13
orthostatic hypotension when taking niacin. Furthermore, bile sequestrants such as Colestipol and cholestyramine may decrease
14
absorption of niacin.
Supplement Interaction: Antioxidants such as vitamin C, vitamin E, beta-carotene and selenium may counteract the benefits of niacin by
15
hindering the rise of cardioprotective HDL/HDL-2. Zinc and hepatotoxic herbs such as borage leaf, red yeast rice, and comfrey may
16-17
increase the risk of liver damage when taken with pharmacologic doses of niacin (1-3 grams/day).
Additionally, niacin used in
18
combination with chromium may cause hypoglycemia.
Interaction with Lab Tests: Niacin supplementation may cause false positives in tests for urinary glucose (which rely on cupric sulfate
8
solution) and urinary catecholamines. Also, doses of 1-3 grams/day of niacin may increase homocysteine levels in individuals,
19
independent of cardiovascular disease.
Stability & Storage: Store in a cool dry place.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
Shils ME, Shike M, Ross AC, Caballera B, Cousins RJ (eds.) (2006). Niacin in Mondern Nutrition in Health and Disease, Tenth
Edition. Lipincott Williams & Wilkins, Philadelphia.
Depeint F, Bruce WR, Shangari N, Mehta R, O'Brien PJ. Mitochondrial function and toxicity: role of the B vitamin family on
mitochondrial energy metabolism. Chem Biol Interact. 2006 Oct 27; 163 (1-2): 94-112. Epub 2006 May 1.
Vosper H. Niacin: a re-emerging pharmaceutical for the treatment of dyslipidaemia. Br J Pharmacol. Sep 2009; 158 (2): 429-441.
Inositol hexaniacinate. Altern Med Rev. Jun 1998; 3 (3): 222-223.
Sunderland GT, Belch JJ, Sturrock RD, Forbes CD, McKay AJ. A double blind randomised placebo controlled trial of hexopal in
primary Raynaud's disease. Clin Rheumatol. Mar 1988; 7 (1): 46-49.
Harthon L, Brattsand R. Enzymatic hydrolysis of pentaerythritoltetranicotinate and meso-inositolhexanicotinate in blood and
tissues. Arzneimittelforschung. 1979; 29 (12): 1859-1862.
Inamadugu JK, Damaramadugu R, Mullangi R, Ponneri V. Simultaneous determination of niacin and its metabolites-nicotinamide, nicotinuric acid and N-methyl-2-pyridone-5-carboxamide--in human plasma by LC-MS/MS and its application to a
human pharmacokinetic study. Biomed Chromatogr. Oct 2010; 24 (10): 1059-1074.
McKevoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004; 164: 697-705.
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Dietary Supplement Information for Physicians
with Naturokinetics®
10. 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.
11. Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987; 2: 10-32.
12. Bourgeois BF, Dodson WE, Ferrendelli JA. Interactions between primidone, carbamazepine, and nicotinamide. Neurology 1982;
32: 1122-6.
13. Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998; 19: 355-71.
14. Product information: Niaspan. Kos Pharmaceuticals. Cranbury, NJ. 2005. Available at
www.niaspan.com/professional/content/pdfs/productinfo.pdf. (Accessed 3 March 2006).
15. Brown BG, Zhao XQ, Chait A. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary
disease. N Engl J Med 2001; 345: 1583-93.
16. Vannucchi H, Moreno FS. Interaction of niacin and zinc metabolism in patients with alcoholic pellagra. Am J Clin Nutr 1989; 50:
364-9.
17. Niacin and Niacinamide (vitamin B3) Monograph. Natural Comprehensive Database. Available at
http://naturaldatabase.therapeuticresearch.com/nd/Search.aspx?cs=&s=ND&pt=100&id=924&ds=interherb. Accessed April 7,
2011.
18. Urberg M, Zemel MB. Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in
elderly humans. Metabolism 1987; 36: 896-9.
19. Garg R, Malinow M, Pettinger M. Niacin treatment increases plasma homocyst(e)ine levels. Am Heart J 1999; 138: 1082-7.
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