Niacin significance

Studies have shown that niacin significantly reduces ICAM-1, VCAM-1, PECAM and E-selectin levels. It also reduced the tumour necrosis (actor-alpha (TNF-a) induced rise in ICAM (it does this by reducing mRNA-induced expression of ICAM). It also decreased the production of ICAM through its reduction in interferon-y (IFN-y) and interleukin-1 (IL-l). Through these mechanisms, niacin induces a reduction of monocyte adhesion in endothelial cells This may possibly lead to decreased leucocyte adhesion to endothelium, which is an important early event in atherosclerosis (Tavintharan et al. 2009). 

Observational studies In 71 subjects with low HDL cholesterol, 12 months of treatment with niacin significantly reduced carotid plaque wall area [63 ]. 

A fibrate derivative or niacin should be considered in select patients with a low high-density lipoprotein (HDL) cholesterol less than 40 mg/dL (1.04 mmol/L) and/or a high triglyceride level greater than 200 mg/dL (2.26 mmol/L). In a large randomized trial in men with established CAD and low levels of HDL cholesterol, the use of gemfibrozil (600 mg twice daily) significantly decreased the risk of non-fatal myocardial infarction or death from coronary causes.78... 

Thus GPR109A mediates the niacin-induced antilipolysis effect in adipocytes and vasodilation effect in skin. This discovery represents significant progress in understanding the mechanism of action for niacin, but also poses a challenge to develop a therapeutic agent to separate the lipid and vasodilation effects. 

Prior to the discovery of niacin receptors, medicinal chemistry efforts were mainly directed toward small heterocyclic carboxylic acids that are structurally similar to niacin. Systematic study of nitrogen-containing five- and six-membered heterocyclic carboxylic acids revealed that activity at GPR109A was significantly reduced for any of the variants of niacin shown in general structures (A and B) [45,46]. These heterocycles include pyrazole, isoxazole, thiazole, pyrazine, and pyrimidine. 

In clinical trials, the combination of niacin with lovastatin (14) afforded significant HDL elevation (30%) and reduced LDL-C (47%) and TG (41%) after 16 weeks of treatment [19]. At 52 weeks of treatment, HDL increased by 41% with this combination therapy [19]. 

Niacin, riboflavin, pantothenic acid and vitamin B6 contents are greatly increased in tempeh during fermentation, whereas thiamin exhibits no significant change. H. oligosporus appears to have a great synthetic capacity for niacin, riboflavin, pantothenic acid, and vitamin B, but not for thiamin. 

Increase in vitamins, such as niacin, riboflavin pantothenic acid, Vitamin Be and Vitamin B12, is of great nutritional significance, especially where fortifying foods with synthetic vitamins is not practiced. 

Crestor Astra-Zeneca) and lovastatin + niacin (Advicor Kos Pharmaceutical) — that can also cause rhabdomyolysis remain on the market. Although scientists agree that the other statins "seem to have essentially identical safety profiles and benefif-risk rafios," FDA said the ADRs associated with Baycol "have been reported significantly more frequently than for other approved statins." ... 

Niacin (but not niacinamide) decreases VLDL and LDL levels, and Lp(a) in most patients. It often increases HDL levels significantly. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

Yeast protein is easily digested (87%) and provides amino acids essential to human nutrition. Most commercial yeasts show the following pattern of amino acids, among others, as percent of protein 8.2% lysine 5.5% valine 7.9% leucine 2.5% methionine 4.5% phenylalanine 1.2% tryptophan 1.6% cystine 4% histidine 5% tyrosine and 5% arginine. The usual therapeutic dose of dried yeast is 40 grams/day, which supplies significant daily needs of thiamine, riboflavin, niacin, pyridoxine, and general protein. 

The desugaring of cane juice concentrates the heat- and alkali-stable vitamins in the final molasses. Even after this accumulation, only myo-inositol may have reached the level of minimum dietary requirements.109 Niacin, pantothenic acid and riboflavin are also present in significant quantities109 the thiamine, pyridoxin, pantothenic acid, biotin and folic acid contents of molasses have been estimated by bioassay.110 111 The biotin content of Hawaiian and Cuban molasses was 2.1 and 1.7 gammas per gram, respectively.119 The antistiffness factor (closely related to stigmasterol) has been found in cane molasses.88 89 The distillery slop from the yeast fermentation of molasses is marketed as a vitamin concentrate this product also contains vitamins originating in the yeast. 

A number of nutrients of lesser dietary significance are present in orange juice and other citrus juices. Measurable levels of Vitamin A, riboflavin (Vitamin B2), niacin, pyridoxine (Vitamin B5) and pantothenic acid have been reported in orange juice. The levels of these nutrients are generally in the range of 2-3% of their respective U.S. RDA s. For a more extensive review of these nutrients, one should consult Ting (23) and Araujo (33). 

This combination effectively controls VLDL levels during resin therapy of familial combined hyperlipoproteinemia or other disorders involving both increased VLDL and LDL levels. When VLDL and LDL levels are both initially increased, doses of niacin as low as 1-3 g/d may be sufficient in combination with a resin. The niacin-resin combination is effective for treating heterozygous familial hypercholesterolemia. Niacin also significantly elevates levels of HDL cholesterol and frequently decreases levels of Lp(a). 

In a small (81 patients) retrospective analysis, patients on lipidlowering medication (statins, fibrates, or niacin derivatives) at the time of PCI had a significantly lower incidence of adverse events during the procedure, such as emboli and dissections, as compared to those not taking such agents (57). A high-total cholesterol, low-density lipoprotein, or ratio of low to high-density lipoprotein were also associated with increased adverse events,... 

Niacin is unusual among the vitamins in that it was discovered as a chemical compound, nicotinic acid produced by the oxidation of nicotine, in 1867 -long before there was any suspicion that it might have a role in nutrition. Its metabolic function as part of what was then called coenzyme II [nicotinamide adenine dinucleotide phosphate (NADP)] was discovered in 1935, again before its nutritional significance was known. 

Cats, which have some 30- to 50-fold higher activity of picolinate carboxylase than other species, are entirely reliant on a dietary source of preformed niacin, and are not capable of any significant synthesis of NAD from tryptophan. 

In view of the central role of the nicotinamide nucleotides in energy-yielding metabolism, and the fact that, at least in theory, the nicotinamide released by ADP-ribosyltransferase (Section 8.4.2) and poly(ADP-ribose) polymerase (Section 8.4.3) is available to be reutilized for nucleotide synthesis (although this may not occur when these enzymes are significantly activated), niacin requirements are conventionally calculated on the basis of energy expenditure. 

---