GI Absorption of Niacin in Humans

Bechgaard, Helle; Jespersen, Sune Nørhøj

doi:10.1002/jps.2600660635

Cited by 53 publications

(23 citation statements)

References 7 publications

(1 reference statement)

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“…1,11 The present results showed that the plasma nicotinamide levels had virtually returned to baseline (fasting) 5 h after an oral 100-mg nicotinamide load in both normotensives and hypertensives (Figure 2a), whereas N 1 -methylnicotinamide remained at very high levels (about six times higher than the baseline values in both groups; Figure 2b). The mean plasma N 1 -methylnicotinamide levels either before or 5 h after nicotinamide loading in hypertensives were slightly higher than that of normotensives (143.1±9.8 vs.…”

Section: Patterns Of Nicotinamide Metabolism In Normotensives and Hypsupporting

confidence: 49%

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives

Sun

Lun

et al. 2011

Hypertens Res

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Nicotinamide and catecholamines are both degraded by S-adenosylmethionine-dependent methylation. Whether excess nicotinamide affects the degradation of catecholamines is unknown. The aim of this study was to investigate the effect of nicotinamide on the methylation status of the body and methylation-mediated catecholamine degradation in both normotensives and hypertensives. The study was conducted in 19 normotensives and 27 hypertensives, using a nicotinamide-loading test (100 mg orally). Plasma nicotinamide, N 1 -methylnicotinamide, homocysteine (Hcy), betaine, norepinephrine, epinephrine, normetanephrine and metanephrine levels before and 5 h after nicotinamide loading were measured. Compared with normotensives, hypertensives had higher baseline (fasting) levels of plasma nicotinamide, Hcy and norepinephrine, but lower levels of plasma normetanephrine, a methylated norepinephrine derivative. Nicotinamide loading induced a significant increase in the levels of plasma N 1 -methylnicotinamide and norepinephrine, and a significant decrease in the levels of O-methylated epinephrine (metanephrine) and betaine, a major methyl donor, in both hypertensives and normotensives. Moreover, nicotinamide-loading significantly increased plasma Hcy levels, but decreased plasma normetanephrine levels in normotensives. The baseline levels of plasma epinephrine in hypertensives were similar to those of normotensives, but the post-nicotinamideloading levels of plasma epinephrine in hypertensives were higher than those of normotensives. This study demonstrated that excess nicotinamide might deplete the labile methyl pool, increase Hcy generation and inhibit catecholamine degradation. It also revealed that hypertensives had an abnormal methylation pattern, characterized by elevated fasting plasma levels of unmethylated substrates, nicotinamide, Hcy and norepinephrine. Therefore, it seems likely that high nicotinamide intake may be involved in the pathogenesis of Hcy-related cardiovascular disease.

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Section: Patterns Of Nicotinamide Metabolism In Normotensives and Hypsupporting

confidence: 49%

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives

Sun

Lun

et al. 2011

Hypertens Res

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“…Humans obtain nicotinic acid from two sources: an exogenous source where the vitamin is obtained from the diet via intestinal absorption and an endogenous source where the vitamin is produced (when the exogenous supply of the vitamin is low) via the metabolic conversion of tryptophan (1,14). Nicotinic acid is distributed to different body tissues via the circulation, where the vitamin exists in plasma at levels of 0.1-1 M (9, 29).…”

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confidence: 99%

Mechanism of nicotinic acid transport in human liver cells: experiments with HepG2 cells and primary hepatocytes

Said¹,

Nabokina²,

Balamurugan³

et al. 2007

American Journal of Physiology-Cell Physiology

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This study reports on the functional expression of a specific, high-affinity carrier-mediated mechanism for the transport of niacin (nicotinic acid) in human liver cells. Both human-derived liver HepG2 cells and human primary hepatocytes were used as models in these investigations. The initial rate of transport of nicotinic acid into HepG2 cells was found to be acidic pH, temperature, and energy dependent; it was, however, Na(+) independent in nature. Evidence for the existence of a carrier-mediated system that is specific for [(3)H]nicotinic acid transport was found and included the following: 1) saturability as a function of concentration with an apparent K(m) of 0.73 +/- 0.16 microM and V(max) of 25.02 +/- 1.45 pmol.mg protein(-1).3 min(-1), 2) cis-inhibition by unlabeled nicotinic acid and nicotinamide but not by unrelated organic anions (lactate, acetate, butyrate, succinate, citrate, and valproate), and 3) trans-stimulation of [(3)H]nicotinic acid efflux by unlabeled nicotinic acid. Transport of the vitamin into human primary hepatocytes occurs similarly via an acidic pH-dependent and specific carrier-mediated process. Inhibitors of the Ca(2+)-calmodulin-mediated pathway (but not modulators of the PKC-, PKA-, and protein tyrosine kinase-mediated pathways) inhibited nicotinic acid transport into both HepG2 cells and human primary hepatocytes. Maintenance of HepG2 cells (for 48 h) in growth medium oversupplemented with nicotinic acid (or nicotinamide) did not affect the subsequent transport of [(3)H]nicotinic acid into HepG2 cells. These results show, for the first time, the existence of a specific and regulated membrane carrier-mediated system for nicotinic acid transport in human liver cells.

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“…In pharmacological doses, niacin reduces plasma triglycerides, cholesterol, and atherogenic apolipoprotein B (apoB)-containing lipoproteins and increases antiatherogenic apoA-I-containing high-density lipoprotein level, thus preventing atherosclerotic cardiovascular disease (10,11). Humans have access to niacin from endogenous and exogenous sources (1,9). The endogenous source of niacin is provided via the metabolic conversion of amino acid tryptophan to niacin.…”

mentioning

confidence: 99%

Mechanism and regulation of human intestinal niacin uptake

Nabokina¹,

Kashyap²,

Said³

2005

American Journal of Physiology-Cell Physiology

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The mechanism of uptake of dietary niacin (nicotinic acid) by intestinal epithelial cells is not well understood, and nothing is known about regulation of the uptake process. In this investigation, we used human-derived intestinal epithelial Caco-2 cells and purified intestinal brush-border membrane vesicles (BBMVs) isolated from human organ donors to assess niacin uptake. Our findings show niacin uptake by Caco-2 cells to be 1) temperature and energy dependent; 2) Na ϩ independent, but highly dependent on extracellular acidic pH; 3) saturable as a function of concentration, with an apparent K m of 0.53 Ϯ 0.08 M; 4) severely inhibited by the membrane-impermeable sulfhydryl group of reagents; and 5) highly specific for niacin but not affected by monocarboxylic acids. A marked trans stimulation in [ 3 H]niacin efflux from preloaded Caco-2 cells by unlabeled niacin in the incubation buffer was also observed. These findings suggest the involvement of a specialized, pH-dependent, carrier-mediated mechanism for human intestinal niacin uptake. This suggestion was confirmed in studies with native human intestinal BBMVs. We also examined possible regulation of niacin uptake by Caco-2 cells via specific intracellular regulatory pathways. The results show that while the PKA-, PKC-, and Ca 2ϩ / calmodulin-mediated regulatory pathways play no role in regulating niacin uptake, a role for a protein tyrosine kinase (PTK)-mediated pathway is apparent. The results of these studies show for the first time the existence of a specialized, acidic pH-dependent, carriermediated system of niacin uptake by human intestinal epithelial cells that operates at the micromolar (physiological) range of niacin. The results also suggest the possible involvement of a PTK-mediated pathway in the regulation of niacin uptake. intestinal transport; transport mechanism; transport regulation NIACIN (NICOTINIC ACID), a water-soluble vitamin, acts as a precursor to the synthesis of the coenzymes NAD and NADP, which are involved in important reactions that maintain the redox state of cells (e.g., glycolysis, pentose phosphate shunt) (8, 9). In pharmacological doses, niacin reduces plasma triglycerides, cholesterol, and atherogenic apolipoprotein B (apoB)-containing lipoproteins and increases antiatherogenic apoA-I-containing high-density lipoprotein level, thus preventing atherosclerotic cardiovascular disease (10, 11). Humans have access to niacin from endogenous and exogenous sources (1, 9). The endogenous source of niacin is provided via the metabolic conversion of amino acid tryptophan to niacin. The exogenous source is provided through the diet by absorption in the intestine.The mechanism involved in the intestinal absorption of dietary niacin, and its regulation, is not well understood. Previous studies in laboratory animals have reported the mechanism to function either via simple diffusion of the undissociated form of nicotinic acid (according to the pH partition hypothesis and assisted by acid microclimate at the luminal surface of the intestine) ...

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GI Absorption of Niacin in Humans

Cited by 53 publications

References 7 publications

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives

Mechanism of nicotinic acid transport in human liver cells: experiments with HepG2 cells and primary hepatocytes

Mechanism and regulation of human intestinal niacin uptake

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