Niacin increased

Rare genetic disorders, including Tangier disease and LCAT (lecithin cholesterol acyltransferase) deficiency, are associated with extremely low levels of HDL. Familial hypoalphalipoproteinemia is a more common disorder with levels of HDL cholesterol usually below 35 mg/dL in men and 45 mg/dL in women. These patients tend to have premature atherosclerosis, and the low HDL may be the only identified risk factor. Management should include special attention to avoidance or treatment of other risk factors. Niacin increases HDL in many of these patients. Reductase inhibitors and fibric acid derivatives exert lesser effects. 

Niacin increases the clearance of VLDL, and increases levels of high-density lipoproteins (HDL). It also decreases the synthesis of VLDL, which in turn results in lower levels of LDL. 

Drugs Drug therapy can reduce fat absorption from the intestine (resins), modify hepatic cholesterol synthesis (HMG-CoA reductase inhibitors), decrease secretion of lipoproteins (niacin), increase peripheral clearance of lipoproteins (fibrates). and can perhaps exert other effects. These drugs are all given orally (Figure 35-1). 

Boyonoski AC, Spronck JC, Jacobs RM et al. Pharmacological intakes of niacin increase bone marrow poly(ADP-ribose) and the latency of ethyinitrosourea-induced carcinogenesis in rats. J Nutr 2002 132(1) 115-120. 

In a study assessing its effect on hepatocytes, niacin increased apo B intracellular degradation and decreased its subsequent secretion, but did not seem to alter the steady state expression of apo B or uptake of LDL into hepatocytes. The study also showed that niacin had no effect on MTP activity and therefore no effect on triglyceride transfer in hepatocytes (Ganji et at. 2003). 

Furthermore, Ganji et al. (2009) showed that in cultured human aortic endothelial cells, niacin increased nicotinamide adenine dinucleotide phosphate [NAD(P)H] levels by 54% and reduced glutathione (GSH) by 98%. Niacin inhibited ... 

Interestingly, Poynten et al. (2003) have shown that niacin-induced insulin resistance is largely mediated through increased availability of circulating fatty acids to muscle rather than with increased muscle lipid content, while Green-baum et al. (1996) showed that niacin increased insulin secretion per se whether this may subsequently deplete the reserve of p pancreatic cells is not yet clear. 

Inhibition by niacin of inflammatory and oxidative pathways may exert anti-atherosclerotic effects. In cultured human aortic endothelial cells, niacin increased cellular levels of nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) and glutathione, regulators of redox reactions, and reduced production of reactive oxygen species. Niacin inhibited monocyte adhesion through the inhibition of tumour necrosis factor-alpha (TNF-a) induced expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) (Ganji et al. 2009). Persistent increases in plasma adiponectin, an adipokine with anti-inflammatory properties, were found after 6 months of niacin treatment in humans (Linke et al. 2009). 

Along with increasing evidence of health benefits from consumption of vitamins at levels much higher than RE) A recommendations comes concern over potential toxicity. This topic has been reviewed (19). Like all chemical substances, a toxic level does exist for each vitarnin. Traditionally it has been assumed that all water-soluble vitamins are safe at any level of intake and all fat-soluble vitamins are toxic, especially at intakes more than 10 times the recommended allowances. These assumptions are now known to be incorrect. Very high doses of some water-soluble vitamins, especially niacin and vitamin B, are associated with adverse effects. In contrast, evidence indicates that some fat-soluble micronutrients, especially vitamin E, are safe at doses many times higher than recommended levels of intake. Chronic intakes above the RDA for vitamins A and D especially are to be avoided, however. 

The HMG-CoA reductase inhibitors have an additive effect when used with the bile acid sequestrants, which may provide an added benefit in treating hypercholesterolemia that does not respond to a single-drug regimen. There is an increased risk of myopathy (disorders of the striated muscle) when the HMG-CoA reductase inhibitors are administered with erythromycin, niacin, or cyclosporin a When the HMG-CoA reductase inhibitors are administered with oral anticoagulants, there is an increased anticoagulant effect. 

Niacin 50 to 750 mg tabs or caps, i m med i ate- re I ease 250 to 750 mg sustained-release 1 -5 g/day in three or more divided doses 1-2 g/day (never exceed 2 g/day due to increased risk of hepatotoxicity) hyperuricemia. 

Niacin (vitamin B3) has broad applications in the treatment of lipid disorders when used at higher doses than those used as a nutritional supplement. Niacin inhibits fatty acid release from adipose tissue and inhibits fatty acid and triglyceride production in liver cells. This results in an increased intracellular degradation of apolipoprotein B, and in turn, a reduction in the number of VLDL particles secreted (Fig. 9-4). The lower VLDL levels and the lower triglyceride content in these particles leads to an overall reduction in LDL cholesterol as well as a decrease in the number of small, dense LDL particles. Niacin also reduces the uptake of HDL-apolipoprotein A1 particles and increases uptake of cholesterol esters by the liver, thus improving the efficiency of reverse cholesterol transport between HDL particles and vascular tissue (Fig. 9-4). Niacin is indicated for patients with elevated triglycerides, low HDL cholesterol, and elevated LDL cholesterol.3... 

In general, niacin reduces LDL cholesterol from 5% to 25%, reduces triglycerides by 20% to 50%, and increases HDL cholesterol by 15% to 35% (Table 9-8). Niacin has been shown to reduce CHD events and total mortality31 as well as the progression of atherosclerosis when combined with a statin.31... 

The predominant effects of fibrates are a decrease in triglyceride levels by 20% to 50% and an increase in HDL cholesterol levels by 9% to 30% (Table 9-8). The effect on LDL cholesterol is less predictable. In patients with high triglycerides, however, LDL cholesterol may increase. Fibrates increase the size and reduce the density of LDL particles much like niacin. 

Niacin can be combined with a fibrate in patients with high elevations in serum triglycerides. The combination may increase the risk of myopathy compared to either agent alone. 

Milk is an excellent source of calcium, phosphorus, riboflavin (vitamin B2), thiamine (vitamin Bl) and vitamin B12, and a valuable source of folate, niacin, magnesium and zinc (Food Standards Agency, 2002). In particular, dairy products are an important source of calcium, which is vital for maintaining optimal bone health in humans (Prentice, 2004). The vitamins and minerals it provides are all bioavailable (i.e. available for absorption and use by the body) and thus milk consumption in humans increases the chances of achieving nutritional recommendations for daily vitamins and mineral intake (Bellew et al., 2000). 

Niacin (nicotinic acid) reduces the hepatic synthesis of VLDL, which in turn leads to a reduction in the synthesis of LDL. Niacin also increases HDL by reducing its catabolism. 

Gemfibrozil reduces the synthesis of VLDL and, to a lesser extent, apolipoprotein B with a concurrent increase in the rate of removal of triglyceride-rich lipoproteins from plasma. Clofibrate is less effective than gemfibrozil or niacin in reducing VLDL production. 

Regimens intended to increase HDL levels should include either gemfibrozil or niacin, bearing in mind that statins combined with either of these drugs may result in a greater incidence of hepatotoxicity or myositis. 

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. 

Concomitant lipid-lowering therapy- Simvastatin is effective alone or when used concomitantly with bile acid sequestrants. The combined use of simvastatin with gemfibrozil, other fibrates, or lipid-lowering doses (1 g/day or more) of niacin should be avoided unless the benefit of further alteration in lipid levels is likely to outweigh the increased risk of this drug combination. 

The usual recommended starting dose for extended-release niacin tablets is 500 mg at bedtime. Niacin extended-release tablets must be titrated and the dose should not be increased by more than 500 mg every 4 weeks up to a maximum dose of 2000 mg/day, to reduce the incidence and severity of side effects. Patients already receiving a stable dose of niacin extended-release tablets may be switched directly to a niacin-eguivalent dose of niacin extended-release/lovastatin tablets. 

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