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Supnut
NIACIN
(Nicotinic acid, B3)

GENERAL:

Vitamin B3 (Niacin) is necessary for proper circulation, healthy skin, and is important for the proper functioning of the nervous system. It is involved in the normal formation of stomach fluids and secretion of bile, along with the synthesis of the sex hormones.
It may help lower triglycerides, cholesterol and is considered helpful for schizophrenia and other mental illnesses. Note: A "flush" may occur after intaking niacin. It is usually harmless, diminishes after 30 minutes or so, and can be reduced by taking niacin with a meal and an extra glass of water. A no-flush variety of niacin (inositol hexaniacinate) does not cause flushing, but is more expensive. Niacinamide (a synthetic form of niacin) also does not cause flushing, however there is some disagreement as to whether niacinamide would yield all the benefits of niacin.
Niacin is a water-soluble nutrient that participates in over 50 metabolic functions in the body important in the release of energy from carbohydrates?
Deficiency Symptoms: Headaches, insomnia, loss of appetite, low blood sugar, dizziness, halitosis, diarrhea, depression, canker sores, fatigue, and dementia. Pellagra is the most well-known deficiency disease.
Absorption Enhancers: B-Complex, vitamin B1, vitamin B2, vitamin C, phosphorus.
Absorption Antagonists: Alcohol, coffee, caffeine, excess sugar/carbohydrate intake, antibiotics, sulfa drugs.
Best Food Sources: Whole grains; organ meats, especially liver; fish; nuts; eggs; green vegetables such as broccoli; carrots; brewer’s yeast; legumes.


Hypoglycemic

Both nicotinic acid (NA) and the adenosine receptor agonist phenylisopropyladenosine (PIA) are potent antilipolytic agents. We have evaluated the ability of these compounds to lower plasma glucose concentration in 450-g male diabetic rats. Diabetes was induced by intravenous streptozotocin, and the rats were studied 7-10 days later. Mean (+/- SE) fasting glucose decreased 4 h after subcutaneous injections of PIA at 0 and 2 h. A similar change in plasma glucose level was also seen in rats injected with NA. The decrease in the concentration of plasma glucose in both instances was preceded by marked sustained reductions in plasma free fatty acid (FFA) concentrations; FFA decreased in PIA-injected rats and in response to NA. With injection of normal saline, neither plasma glucose nor FFA concentrations decreased in diabetic rats. There was no change in the plasma insulin concentration of rats that had hypoglycemic responses to PIA or NA. In vitro glucose uptake was determined in isolated adipocytes, and both PIA and NA were shown to increase basal and maximal insulin-stimulated glucose uptake. The stimulating effect of the two compounds was similar, and the magnitude of the effect was comparable in adipocytes from either normal or diabetic rats. As a result, neither NA nor PIA could restore the defects in glucose transport to normal in adipocytes from diabetic rats. Insulin-stimulated glucose uptake was assessed in vivo by determining the steady-state glucose response of diabetic rats to a continuous infusion of insulin and glucose and was found to be significantly enhanced in response to NA compared with NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 2962514


Glucocorticoids, oral contraceptives and nicotinic acid are associated with glucose intolerance, and the main cause of the glucose intolerance induced by these drugs is insulin resistance
PMID: 10707579

In this study the effect of two drugs [etomoxir and nicotinic acid (NA)] on plasma glucose, free-fatty acid (FFA), and triglyceride (TG) concentrations was determined in rats with streptozocin (STZ)-induced diabetes. The two compounds modify FFA metabolism by different mechanisms, etomoxir (ethyl-2-[6-(4-cholorophenoxyl)-hexyl]oxirane-2-carboxylate) by inhibiting hepatic fatty acid oxidation, and NA by inhibiting lipolysis in adipose tissue.

The acute administration of either etomoxir or NA lowered plasma glucose concentrations in diabetic rats by approximately 150 mg/dl (P less than .001) in 4 h.

Because plasma insulin concentrations did not change in response to either drug, whether administered singly or in combination, these metabolic effects do not result from a change in insulin secretion. These results suggest that modulation of FFA metabolism at the level of the adipocyte or the liver can have dramatic effects on carbohydrate and lipid metabolism.

PMID: 3275556


BACKGROUND: High doses of niacin have been shown to impair glucose control in patients with non--insulin-dependent diabetes mellitus (NIDDM). We undertook a study to determine if low-dose niacin has a similar effect.

CONCLUSION: Low-dose [500 mg three times daily for 2 months ] niacin increases fasting blood sugar in patients with stable NIDDM. [non--insulin-dependent diabetes mellitus] (they call that low dose?!?)
PMID: 11862304


NA significantly reduced the glucose infusion rate required to maintain euglycaemia in all subjects (placebo vs NA; 31.5+/-4.2 vs. 26.2+/-4.6 micromol/kg/min, P = 0.002) associated with a decrease in non-oxidative glucose disposal.
PMID: 10980588

ingestion of niacin-bound chromium and natural antioxidants such as grape seed proanthocyanidin extract has been demonstrated to improve insulin sensitivity and/or ameliorate free radical formation and reduce the signs/symptoms of chronic age-related disorders including syndrome X.
PMID: 12074977

Nicotinamide is being used in trials to prevent or delay the development of clinical IDDM. A related compound, niacin, has been shown to cause insulin resistance in normal subjects, resulting in increased insulin secretion. This study was designed to answer the question: Does the short-term administration of nicotinamide cause insulin resistance in subjects who have a high risk of developing IDDM? Eight islet cell antibody-positive (ICA+) relatives of IDDM patients were given nicotinamide at a dose of 2 g/day for 2 weeks. Measurements of first-phase insulin release, insulin sensitivity, glucose effectiveness, and the constant for glucose disappearance (Kg) were measured at baseline, at the end of 2 weeks of therapy, and after subjects had been off therapy for at least 2 weeks. Nicotinamide administration caused a 23.6% decrease in insulin sensitivity (P = 0.02). This decrease was associated with a fall in Kg despite increased insulin secretion.
PMID: 8866571

To determine whether downregulation of Gi proteins is associated with insulin resistance, we incubated isolated adipocytes with N6-(2-phenylisopropyl)adenosine (PIA; an A1-adenosine receptor agonist; 300 nM), prostaglandin E1 (PGE1; 3 microM), or nicotinic acid (1 mM) for 4 days in primary culture. The cells were washed, and the rate of glucose transport (2-deoxy-[3H]glucose uptake) was measured after incubation with various concentrations of insulin for 45 min. Both PIA and PGE1 (which downregulate Gi) decreased the maximal responsiveness of the cells to insulin by approximately 30% and caused a rightward shift in the dose-response curve. By contrast, nicotinic acid (which does not downregulate Gi) did not alter the insulin sensitivity of the cells. Prolonged treatment of adipocytes with either PIA or PGE1 (but not nicotinic acid) rendered the cells completely resistant to the antilipolytic effect of insulin. The ability of insulin to stimulate autophosphorylation of the beta-subunit of the insulin receptor was decreased by approximately 30% in PIA-treated cells, and the dose-response curve was shifted to the right. Similarly, the ability of the receptor to phosphorylate poly(Glu4-Tyr1) was decreased by approximately 35%. This decrease in tyrosine kinase activity of the receptor may account for the decrease in insulin sensitivity of glucose transport but cannot account for the complete loss of antilipolysis. The findings suggest both a direct and indirect involvement of Gi proteins in insulin action.

PMID: 9277377

NA-induced insulin resistance in this study is (a) less than previously reported; (cool.gif not associated with changes in insulin secretory responsiveness, but is © influenced by an individually variable NA effect on fasting NEFA levels.
PMID: 8903118

Hyperinsulinemia, in association with NA infusion (NA study) brings about a significantly greater stimulation of total glucose disposal in both pregnant (approximately 30%) and nonpregnant (approximately 35%) rabbits compared with the control study. A more pronounced inhibition of hepatic glucose production occurred in NA study in pregnant rabbits (approximately 30 vs. approximately 10%) but it did not reach a statistical significance, whereas there was a total inhibition in nonpregnant rabbits.
PMID: 8476036

The literature seams a bit confused, some sources claim and increase in insulin levels while other claim no change. While it acts to both lower glycerides and glucose levels, it appears to in most cases to induct insulin resistance [although I didn’t really see a good explanation as to why… perhaps this could be counteracted] and as one study mentioned it decreases lipolysiswhich of course would be bad.

It is said that increases in fat intake lead to an increase in insulin concentrations…. Perhaps lowering glycerides effects this equation in some manner?

The “niacin-bound chromium and natural antioxidants such as grape seed proanthocyanidin extract” sounds interesting and should be looked into further although I do not know what compounds specifically they are referring to.


Leptin stimulant



The effect of 3 days of intensive treatment with acipimox, an antilipolytic nicotinic acid derivative, on plasma leptin levels was studied in eight patients with Type 2 diabetes mellitus in a double-blind, placebo-controlled, cross-over study. Acipimox reduced plasma free fatty acids (FFA) markedly and lowered plasma triglycerides, glucose and insulin. Plasma leptin levels were elevated in all eight patients during 3 days of acipimox treatment (mean increase+/-s.e.: 2.38+/-0.57ng/ml, P<0.005) and the 24h mean effect of acipimox on leptin levels increased during the experimental period (P<0.03). The effect on plasma insulin and glucose resembled a mirror image of the effect on plasma leptin during 3 days of treatment. The suggestion that leptin mediates insulin resistance and may be involved in the development of the diabetic syndrome cannot be supported by the present results. It has been reported that FFA stimulates leptin secretion. Surprisingly, despite a markedly reduced FFA level, leptin concentration increased in the present study. We suggest that a primary acipimox effect is to increase leptin secretion, and that this prevails over the reduced FFA stimulus.
PMID: 11022182

Significantly, antilipolytic agents other than insulin (adenosine, nicotinic acid, acipimox, and orthovanadate) did not mimic the acute stimulatory effects of insulin on leptin secretion under these conditions. We conclude that norepinephrine specifically inhibits insulin-stimulated leptin secretion not only via the low-affinity beta3-adrenoceptors but also via the high-affinity beta1/beta2-adrenoceptors. Moreover, it is suggested that 1) activation of phosphodiesterase III by insulin represents an important metabolic step in stimulation of leptin secretion, and 2) lipolytic hormones competitively counterregulate the stimulatory effects of insulin by activating the adenylate cyclase system.

PMID: 12055093

This was about all there was on leptin, once I know what the niacin-bond chromium compound is I will look to see if it has any effect on leptin like the analogue does.


Growth Hormone stimulant

Recent studies in adult volunteers have demonstrated that the free fatty acid reduction induced by acipimox, a nicotinic acid analog, stimulated GH secretion per se and enhanced in an additive manner the GH secretion elicited by such different stimuli as pyridostigmine, GHRH and GHRP-6.

These results indicate that: 1) following the administration of a single oral dose of acipimox, significant GH secretion was elicited in healthy short prepubertal children; 2) the combined administration of acipimox plus L-Dopa did not, however, enhance the GH secretion of this group of children; 3) acipimox was well tolerated with minimal side effects
PMID: 11085190

It has previously been shown that nicotinic acid (NA)-induced depression of free fatty acids (FFA) stimulates the secretion of GH and glucagon. To evaluate this hormonal response further, we studied the influence of different doses of glucose administered by continuous iv infusion on the GH and glucagon increase during NA-induced FFA depression. In ten male non-obese volunteers, FFA depression by the infusion of NA (2.3 g over a period of 210 min) resulted in a late rise (from 150 min on) of GH (From 1.1 to 25.9 ng/ml) and an early increase (from 30 min on) of glucagon (from 71.7 to 138.2 pg/ml). When glucose was infused (approximately 60, 120 and 180 g, respectively, over a period of 270 min) during NA-induced FFA depression, the GH rise was reduced and delayed in relation to the amount of glucose infused, but could not be completely abolished (maximal GH concentration during the three NA-plus-glucose infusions: 16.5, 8.0 and 6.1 ng/ml, respectively). The glucagon rise was entirely reversed by the high glucose dose. Insulin did not rise during NA infusion alone. Its secretion in response to glucose infusion was not significantly influenced by FFA depression. Thus, during NA-induced FFA depression the secretion of two lipolytic hormones--GH and glucagon--is stimulated while the secretion of the lipogenetic hormone insulin remains low. Glucose has an inhibitory effect on the GH and glucagon response which, however, is different for each of the hormones.

PMID: 838844

Perhaps increased Glucagon is the cause of the insulin sensitivity?

Two chemically unrelated inhibitors of lipolysis were used in order to differentiate between the effect of FFA depression and a possible FFA-unrelated drug effect, respectively, on the plasma concentrations of GH, cortisol, and glucagon. Saline infusion served as a control experiment. In eight healthy male volunteers, a similar FFA depression by either iv infusion of nicotinic acid (3-pyridine-carboxylic acid, NA) or oral intake of an adenosine derivative, N(6)-allyl-N(6)-cyclohexyl-adenosine (AD-D), was followed by a significant GH increase (to 22.1 +/- 6.2 and 9.6 +/- 2.9 ng/ml at 240 and 270 min, respectively). Due to the large scatter of the GH concentrations during NA infusion, these responses were not significantly different. No GH increase occurred when the FFA depression was prevented by addition of a lipid infusion. In contrast, plasma cortisol and glucagon both increased significantly (by 107.4 micrograms/liter at 270 min and by 48.4 pg/ml at 60 min, respectively) during NA- but not during AD-D-induced FFA depression. Addition of the lipid infusion abolished the cortisol increase during NA infusion but had no influence on basal cortisol concentrations during AD-D intake. It lowered glucagon to values slightly below basal concentrations when added to the NA infusion and more markedly during AD-D administration. The results provide evidence that 1) depression of plasma FFA per se stimulates the secretion of GH, and 2) the increase of cortisol and glucagon during NA infusion is probably unrelated to the FFA depression. Hence, the stimulatory effect of FFA lack on glucagon secretion needs to be reconsidered.

PMID: 6345570

The influence of ketone body infusion on the serum GH and glucagon response to FFA depression and insulin hypoglycemia was investigated in 10 healthy men. Intravenous infusion of nicotinic acid induced suppression of both FFA and ketone bodies. This was accompanied by a delayed GH increase to 21.1 +/- 6.9 ng/ml (at 300 min). During an additional beta-hydroxybutyrate (OHB) infusion, FFA remained depressed, but ketone bodies were elevated, and the GH response was abolished (maximum 5.6 +/- 1.6 ng/ml). During infusion of OHB alone, FFA were suppressed. GH increased significantly, although less markedly than during suppression of both FFA and ketone bodies (to 9.3 +/- 3.1 ng/ml at 270 min). No GH rise occurred when both FFA and ketone bodies were kept elevated by the addition of a lipid infusion. The GH rise in response to insulin hypoglycemia was not changed by an OHB infusion (43.2 +/- 4.6 vs. 48.0 +/- 7.3 ng/ml). However, OHB increased the net GH output by significantly delaying the return to basal concentrations in the presence of a reduced FFA rebound. An effect of OHB infusion on the plasma glucagon concentration during all experiments was small, and its physiological significance is doubtful. These results confirm that FFA depression induces delayed GH secretion. They suggest that this is not wholly dependent on concomitant depression of ketone bodies. On the other hand, when ketone bodies are elevated, the GH response to FFA depression is diminished or absent. The net GH response to changes in lipid substrates probably depends on the concentration of both FFA and ketone bodies.

PMID: 6348066

The purpose of this study was to assess how selected physiological and performance responses are affected when the normal increase in plasma free fatty acid concentration during exercise is blunted by ingesting nicotinic acid. On four occasions, 10 subjects cycled at 68 +/- 1% VO2peak for 120 min followed by a timed 3.5-mile performance task. Every 15 min during exercise, subjects ingested 3.5 ml.kg LBM-1 of one of four beverages: 1) water placebo (WP), 2) WP + 280 mg nicotinic acid.l-1 (WP + NA), 3) 6% carbohydrate-electrolyte beverage (CE), and 4) CE + NA. Ingestion of nicotinic acid (WP + NA and CE + NA) blunted the rise in FFA associated with WP and CE; in fact, NA ingestion effectively prevented FFA from rising above rest values. The low FFA levels with NA feeding were associated with a 3- to 6-fold increase in concentrations of human growth hormone throughout exercise. The mean performance time for CE (10.7 min) was significantly less than for WP (12.2 min) and WP + NA (12.8 min), but did not differ from CE + NA (11.4 min). The results indicate that blunting the normal rise in FFA alters the hormonal response to exercise and reduces the capacity to perform high-intensity exercise.
PMID: 7564973




Glucagon

Total glucose uptake during exercise was greater (P <.05) in NA (1,876 +/- 161 micromol.kg(-1)) than in CON (1,525 +/- 107 micromol.kg(-1)). Total fat oxidation was reduced (P <.05) by approximately 32% during exercise in NA. Total carbohydrate oxidized was approximately 42% greater (P <.05) in NA (412 +/- 40 mmol) than CON (290 +/- 37 mmol), of which, approximately 16% (20 +/- 10 mmol) could be attributed to glucose. Plasma insulin and glucagon were similar between trials. Catecholamines were higher (P <.05) during exercise in NA. In summary, during prolonged moderate exercise in untrained women, reduced FFA availability results in a compensatory increase in carbohydrate oxidation, which appears to be due predominantly to an increase in glycogen utilization, although there was a small, but significant, increase in whole body glucose uptake.
PMID: 11288047

In order to assess the ability of nicotinic acid to decrease plasma glucose concentration, normal individuals were given continuous four hour infusions of either nicotinic acid (NA), somatostatin (SRIF), NA + SRIF, or 0.9% NaCl (Saline). Plasma non-esterified fatty acid (NEFA) concentration decreased to about one-fourth of the basal value in response to either NA or NA + SRIF, associated with statistically significant decreases in plasma glucose concentration. The ability of NA and NA + SRIF to decrease plasma glucose concentration was seen despite the fact that plasma insulin concentrations also fell significantly during both infusions. Although plasma glucose concentration fell significantly in response to both NA and NA + SRIF, the effect of NA + SRIF was approximately twice as great as that seen with NA alone. The augmented hypoglycaemic effect of NA + SRIF as compared to NA alone was associated with a concomitant fall in plasma glucagon concentration. In contrast, plasma glucose concentration did not change following Saline, and was actually higher than baseline after the infusion of SRIF alone. These results provide evidence that NA can lower plasma glucose concentration in normal volunteers, and suggests that this is mediated by the NA-associated decrease in plasma NEFA concentration.

PMID: 1358776

Lowering of the plasma FFA level in intact fasted rats by infusion of nicotinic acid (NA) caused essentially complete ablation of insulin secretion (IS) in response to a subsequent intravenous bolus of arginine, leucine, or glibenclamide (as previously found using glucose as the beta-cell stimulus). However, in all cases, IS became supranormal when a high FFA level was maintained by co-infusion of lard oil plus heparin. Each of these secretagogues elicited little, if any, IS from the isolated, perfused "fasted" pancreas when tested simply on the background of 3 mM glucose, but all became extremely potent when 0.5 mM palmitate was also included in the medium. Similarly, IS from the perfused pancreas, in response to depolarizing concentrations of KCl, was markedly potentiated by palmitate. As was the case with intravenous glucose administration, fed animals produced an equally robust insulin response to glibenclamide regardless of whether their low basal FFA concentration was further reduced by NA. In the fasted state, arginine-induced glucagon secretion appeared to be independent of the prevailing FFA concentration. The findings establish that the essential role of circulating FFA for glucose-stimulated IS after food deprivation also applies in the case of nonglucose secretagogues. In addition, they imply that (i) a fatty acid-derived lipid moiety, which plays a pivotal role in IS, is lost from the pancreatic beta-cell during fasting; (ii) in the fasted state, the elevated level of plasma FFA compensates for this deficit; and (iii) the lipid factor acts at a late step in the insulin secretory pathway that is common to the action of a wide variety of secretagogues.

PMID: 9616208


NA has no direct effect on GNG. [gluconeogenesis]

This was the limited info I could find on NA acting directly with glucagons, as you can see it does not seam to stimulate it indirectly so that would rule out glucagons as being the cause if insulin resistance. While theory is knocked down another question has become apparent.

The NA clears the blood of fatty acids and then suppresses their use for energy, this led to a decrease in exercise performance in women but what about their metabolism? Is it being slowed down or is the glycolysis substituting completely for the lost energy? My understanding is that glucose provides fast energy then fat which is why you slow down after you have been working for a while, so I would assume then that the glucose getting used here is not getting used fast enough to compensate for the lack in lipolysis .

I also do not understand the method by which NA inhibits lipolysis , is it from the adipose tissue receiving and in flux of FA or by some other means?

It appears that insulin is can counteract the anitlipolytic action of NA although to what extent I can’t say and I am not sure if this is directly or indirectly through the stimulate of GH which would then promote fat burning, but this hints that if we can find a way around the other negative (NA causing insulin resistance) then using this with and insulin spiking meal could be still have potential.


To go off subject for a moment, they mention arginine releasing glucagons as mentioned here as well
Arg exerts its vascular actions also through NO-independent effects, including membrane depolarization, syntheses of creatine, proline and polyamines, secretion of insulin, growth hormone, glucagon and prolactin, plasmin generation and fibrinogenolysis, superoxide scavenging and inhibition of leukocyte adhesion to nonendothelial matrix.
PMID: 11053497

Now if arginine stimulates both insulin and glucagons I wonder which one wins out? Perhaps they effect of it alone gives no net increase in either making its use as an insulin potentiator rather useless.

PMID: 9927497


Vasodilator

The next property of NA we will look at is the vasodialation or flush it causes. Pharocopia has this information.

Niacin: A flush occurs due to histamine release from mast cells, 20 minutes after ingestion lasting up to 1 to 1 and ˝ hours. This usually lessens after 3 days and may disappear at higher doses. Decrease by taking niacin with meals, raising dosage slowly, or taking 300mg aspirin 15 - 30 minutes before ingestion of niacin. Can raise uric acid levels by competing with uric acid for renal excretion. Gouty symptoms or uric acid stone formation is rare though. Can see deterioration in oral glucose tolerance. Hepatic toxicity is rare but may occur with doses over 3 gm/day. Can see with sustained-release niacin, which can also cause bleeding with a prolonged thrombin time and lactic acidosis with nausea and vomiting. Other side effects reported with niacin include pruritus, hyperpigmentation, rash, acanthosis nigricans, nausea, diarrhea, aggravation of peptic ulcers, hypotension and atrial fibrillation.



Cardiostimulation produced by noradrenaline, glucagon, or tachycardia on the isolated perfused rat heart produced a metabolic coronary dilatation that was potentiated by nicotinic acid or its amide [NIC; 0.05-1.0 mM] without affecting the cardiostimulation. Reactive hyperaemia to brief coronary occlusion was unaffected by NIC, thus confirming that its vasodilator mechanism is of a different nature than that leading to metabolic coronary dilatation. It is suggested that NIC may be of significance as an adjuvant in the treatment of certain types of coronary insufficiencies.

PMID: 6232626

From personal experience I can tell you that a strong histamine flush (from 1gram) causes extreme redness to the entire body, you feel pressure in your face from it, and when you rub against anything it prickles. At only 250 I have had the flush occur at virtually the same magnitude. I personally do not find it all that uncomfortable as long as I don’t move around a lot, It gives you a warm but not hot feeling that can be actually quiet pleassent.

Now for those of you who follow my posts you have probably seen me mention my theory before but I will restate it here.

Wearing socks to stimulate vassodialtion in the extremities helps one fall asleep

A cold room helps one to fall asleep

Anithistamines specifically H1 antagonists causes drowsiness

H1 stimulation (I may have my receptors confused here) causes vassodialation of the extremities

Niacin causes vassodialation

Sleep depravation is related to niacin deficiency (PMID: 2062264, PMID: 1809857)

Melatonin peaks at the same time in which body temperature is at its lowest.

Do I have to draw you a picture?
Unfortunately I can find little research to directly support that there is indeed a direct connection between melatonin and histamine.


Liver toxicity
The final consideration on NA is liver toxicity


Marked lowering of plasma total and low-density lipoprotein cholesterol levels that occur during treatment of dyslipidemia with pharmacologic doses of nicotinic acid result from hepatotoxicity. Therefore, a marked reduction in low-density lipoprotein may suggest generalized liver toxicity and drug treatment should be discontinued.

PMID: 9527102

We report a case of severe liver injury occurring on two occasions in a patient ingesting large doses of nicotinic acid. The liver architecture was markedly distorted, with both massive and submassive lobular collapse and marked cholestasis. Complete resolution of biochemical and histologic abnormalities occurred after withdrawal of these drugs.

PMID: 6823602


A 46-year-old man began taking nicotinic acid, 3 g daily, for hypercholesterolemia. A month later, he developed clinical and biochemical evidence of modest hepatocellular injury, and therapy was stopped. It was restarted 6 weeks later, and 10 weeks after that, the patient presented with fulminant hepatic failure, which resolved rapidly after cessation of nicotinic acid therapy. We suggest that nicotinic acid was the cause of his liver disease, that this case is of particular note because of the rather short period of therapy before the onset of liver injury and the severity of the hepatic failure, and that the probable increased use of nicotinic acid for serum cholesterol control makes it especially important for physicians and their patients to be alert to the signs of hepatotoxicity.

PMID: 3680913

Nicotinic acid has a proven efficacy in the treatment of hypercholesterolemia. Therapeutic use of this water-soluble B vitamin has resulted in a survival benefit among patients enrolled in the Coronary Drug Project. Conversely, nicotinic acid has been associated with a high side-effect profile when used at therapeutic doses. Nevertheless, there are no previously reported cases of hematemesis temporally associated with nicotinic acid use. The authors report the case of a previously healthy 20-year-old man who developed hematemesis and hepatitis 1 week after self-initiating the daily consumption of 6 g of nicotinic acid. Supportive therapy and discontinuing nicotinic acid resulted in rapid clinical improvement in this patient. The clinical circumstances suggest a possible causal relationship between nicotinic acid consumption and his presenting problems. The use of large doses of nicotinic acid may be rapidly complicated by hematemesis and hepatitis.

PMID: 2801756

I do not know minimum dose at which live function becomes impaired, nor do I know the lowest effective dose for causing glucose uptake or GH secretion although the study witth the women would have had them taking around 2.5 grams. The RDA for B3 is 15mg, the minimum dose at which flush can occur is 50mg. Most Niacin supplements I have seen are 250mg pills. I would assume that the effects are dose dependant and that one could therefore utilize NA at a dose lower then what would cause liver problems and still get some of the benefits.

For anyone who whishes to try the flush, I would assume that repeated flushing could deplete histamine stores in the mast cells faster then they could be replenished, I do not know the consequences of this but taking l-histadine would likely help to maintain histamine levels.
virtualcyber
There has been additional studies on niacin, and anti-aging effects.

Niacin comes in two forms (1) niacinamide and (2) just plain niacin. There has been some research which indicates that both forms are relevant to anti-aging.

================================================

The first study, subnut, you already have cited -- it talks about reduced mortality rate. But its efficacy is couched in view of patients with heart problems. To understand other implications, take a look at

http://www.life-enhancement.com/displayart.asp?ID=676

For niacinamide, visit

http://www.life-enhancement.com/displayart.asp?id=671

================================================

Niacin seems to convert to NAD (nicotinamide adenine dinucleotide) which is apparently involved in "gene silencing." It is interesting that while increased NAD increases lifespan of worms and yeast, the administration of niacin also seems to indicate increased lifespan
at http://intelegen.com/nutrients/niacin.htm, even though the article talks about it in the context of heart disease ...

Niacinamide seems to actually _REVERSE_ aging process. The speculation is that niacinamide is involved in "gene peeling."
nightop
QUOTE(virtualcyber @ Aug 6 2002, 07:25 AM)
There has been additional studies on niacin, and anti-aging effects.

Niacin comes in two forms (1) niacinamide and (2) just plain niacin.  There has been some research which indicates that both forms are relevant to anti-aging.

================================================

The first study, subnut, you already have cited -- it talks about reduced mortality rate.  But its efficacy is couched in view of patients with heart problems.  To understand other implications, take a look at

http://www.life-enhancement.com/displayart.asp?ID=676

For niacinamide, visit

http://www.life-enhancement.com/displayart.asp?id=671

================================================

Niacin seems to convert to NAD (nicotinamide adenine dinucleotide) which is apparently involved in "gene silencing."  It is interesting that while increased NAD increases lifespan of worms and yeast, the administration of niacin also seems to indicate increased lifespan
at http://intelegen.com/nutrients/niacin.htm, even though the article talks about it in the context of heart disease ...

Niacinamide seems to actually _REVERSE_ aging process.  The speculation is that niacinamide is involved in "gene peeling."
[right][snapback]4237[/snapback][/right]


Found this old thread while searching for something related.

Interesting stuff, particularly the anti-aging effects.
dashforce
(Posted this in the other thread)

Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid.
Prostaglandins (Prostaglandins) 1989 Aug; 38(2): 263-74

Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.


Why does nicotinic acid cause flushing but not niacinamide? Anyone know?
micro2000
QUOTE (dashforce @ Mar 29 2008, 02:09 PM) *
(Posted this in the other thread)

Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid.
Prostaglandins (Prostaglandins) 1989 Aug; 38(2): 263-74

Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.


Why does nicotinic acid cause flushing but not niacinamide? Anyone know?


It states it in the article:

The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.

Edit: Sorry. Misread your question. Not sure why niacinamide does not share this effect with niacin.
thecrownedone
QUOTE (dashforce @ Mar 29 2008, 05:09 PM) *
(Posted this in the other thread)

Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid.
Prostaglandins (Prostaglandins) 1989 Aug; 38(2): 263-74

Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.


Why does nicotinic acid cause flushing but not niacinamide? Anyone know?


I didn't know what PGD2 was, so I found the following:

=======================================================
PGD2
The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.
from: http://www.online-medical-dictionary.org/PGD2.asp?q=PGD2
=======================================================

PGD2, or Prostaglandin 2—a by-product of mast cell degranulation that can cause joint pain and hormone problems
from: http://www.urticaria.thunderworksinc.com/pages/glossary.htm
=======================================================

Of the several dozen sleep-promoting substances thus far reported, prostaglandin (PG) D2, the primary subject of our investigation at the Molecular Behavioral Biology Department, is now accepted as the most potent endogenous sleep-promoting substance, with its mechanism of action most extensively characterized at the molecular level. PGD2 is produced at high levels in the brain-wrapping arachnoid and the ventral choroid plexus and secreted into the cerebrospinal fluid, after which it circulates in the brain as a sleep hormone. PGD2 also acts on PGD2 receptors, which is localized in the arachnoid of the forebrain fundus to activate the sleep center and selectively induce non-REM sleep, and has an important role in the recovery of fatigue.
...
We have found that naturalistic sleep is induced when prostaglandin D2 (PGD2), the principal prostaglandin produced in the central nervous system, is administered into the brains of animal. The sleep induced by PGD2 has been shown to be identical to physiological sleep as evidenced by electroencephalograms and animal behavioral observation. We have also demonstrated that the enzyme for the production of PGD2 in the brain is localized in the arachnoid membrane of the brain. We aim to continue to investigate the function of this enzyme and the cellular changes caused by PGD2 during sleep.

from: http://www.obi.or.jp/english/introduction/behavioral.html
======================================================


Doesn't sound so great, save the last notes.
dashforce
Lol -- but what about my nicotinic acid vs niacinamide Q? Bueller?
Jakeshorts
well nicotinic acid is a vasodialator and niacinamide isn't. If flushing is a result of vasodilation it would make sense that niacinamide wouldn't cause the flush. In fact niacinamide is used as an anti-inflammatory for acne treatment I believe.
dashforce
QUOTE (Jakeshorts @ Apr 1 2008, 12:39 PM) *
well nicotinic acid is a vasodialator and niacinamide isn't. If flushing is a result of vasodilation it would make sense that niacinamide wouldn't cause the flush. In fact niacinamide is used as an anti-inflammatory for acne treatment I believe.


Isn't the vasodilation due to prostaglandin release? If so, why is nicotinic acid and not niacinamide causing the reaction? They're two forms of getting the same vitamin...
Jakeshorts
Niacin is the mixture of both substances in question. I tried to look for evidence that niacinamide doesn't effect prostaglandin release but i was unable to produce a suitable citation. It is; however, generally accepted that this is the route of vasodilation of niacin and if niacinamide isn't causing vasodilation (which is documented) then I'd say it could be safely correlated as to not effect prostaglandin release.

Niacin itself is a pretty interesting compound. I found a source that cited it as being the #1 most prescribed lipid treatment. Interesting to say the least.

This is very bitch'n thread.

EDIT: Just reread through the thread... My first post was such a rehash. What a doofus. Thanks for the patience dash.
Kclone
So I one is taking antihistamines, would they be deficient in niacin since anti histamines block the action of niacin?
Jakeshorts
this may have been obvious to everyone BUT me... but in case it wasn't..

Int J Sports Med. 1997 Feb;18(2):83-8.Links
The effect of substrate utilization, manipulated by nicotinic acid, on excess postexercise oxygen consumption.Trost S, Wilcox A, Gillis D.
Department of Exercise and Sports Science, Oregon State University, Corvallis, USA.

Increased fat oxidation during the recovery period from exercise is thought to be a contributing factor for excess postexercise oxygen consumption (EPOC). In an attempt to study the effect of serum free fatty acid (FFA) availability during exercise and recovery on the EPOC, nicotinic acid, a potent inhibitor of FFA mobilization from adipose tissue, was administered to five trained male cyclists prior to, during, and after a bout of cycling at 65% VO2max. In the nicotinic acid trial, a 500 mg dose of nicotinic acid was ingested prior to exercise, and 100 mg doses were ingested at 15, 30, and 45 min exercise, and 30 min recovery. The cyclists also completed a trial under control conditions. Serum FFA, serum glycerol, RER and VO2 were monitored during rest, exercise, and recovery, each of which was 1-h in duration. Nicotinic acid ingestion prevented the increase in serum FFA that occurred during exercise in the control trial. FFA levels during the nicotinic acid trial were significantly lower than control values during both exercise and recovery. Serum glycerol levels were also significantly lower during exercise in the nicotinic acid trial, indicative of a reduction in lipolysis. RER was not significantly different at rest or during exercise; however, RER values were significantly lower during recovery in the control trial, indicative of greater fat oxidation. For both treatments, postexercise VO2 remained elevated above resting levels at the completion of the 1-h recovery period. However, the magnitude of EPOC was significantly reduced after FFA blockade with nicotinic acid (3.4 +/- 0.61 vs 5.5 +/- 0.71). These results support the hypothesis that increased FFA metabolism during exercise and recovery is an important contributing factor to the magnitude of EPOC.

PMID: 9081262 [PubMed - indexed for MEDLINE]
Mr.Kite
QUOTE (Jakeshorts @ Apr 18 2008, 07:06 AM) *
this may have been obvious to everyone BUT me... but in case it wasn't..

Int J Sports Med. 1997 Feb;18(2):83-8.Links
The effect of substrate utilization, manipulated by nicotinic acid, on excess postexercise oxygen consumption.Trost S, Wilcox A, Gillis D.
Department of Exercise and Sports Science, Oregon State University, Corvallis, USA.

Increased fat oxidation during the recovery period from exercise is thought to be a contributing factor for excess postexercise oxygen consumption (EPOC). In an attempt to study the effect of serum free fatty acid (FFA) availability during exercise and recovery on the EPOC, nicotinic acid, a potent inhibitor of FFA mobilization from adipose tissue, was administered to five trained male cyclists prior to, during, and after a bout of cycling at 65% VO2max. In the nicotinic acid trial, a 500 mg dose of nicotinic acid was ingested prior to exercise, and 100 mg doses were ingested at 15, 30, and 45 min exercise, and 30 min recovery. The cyclists also completed a trial under control conditions. Serum FFA, serum glycerol, RER and VO2 were monitored during rest, exercise, and recovery, each of which was 1-h in duration. Nicotinic acid ingestion prevented the increase in serum FFA that occurred during exercise in the control trial. FFA levels during the nicotinic acid trial were significantly lower than control values during both exercise and recovery. Serum glycerol levels were also significantly lower during exercise in the nicotinic acid trial, indicative of a reduction in lipolysis. RER was not significantly different at rest or during exercise; however, RER values were significantly lower during recovery in the control trial, indicative of greater fat oxidation. For both treatments, postexercise VO2 remained elevated above resting levels at the completion of the 1-h recovery period. However, the magnitude of EPOC was significantly reduced after FFA blockade with nicotinic acid (3.4 +/- 0.61 vs 5.5 +/- 0.71). These results support the hypothesis that increased FFA metabolism during exercise and recovery is an important contributing factor to the magnitude of EPOC.

PMID: 9081262 [PubMed - indexed for MEDLINE]

Wow, something to think about. But if you look at the first post, when it talks about nicotinic acid as a leptin stimulant, you will see that it reduced plasma FFA there. Another study above said that Nicotinic acid works by inhibiting lipolysis.
Jakeshorts
So what's the mean gain is fat isn't lost? LBM?
Mr.Kite
QUOTE (Jakeshorts @ Apr 19 2008, 11:12 AM) *
So what's the mean gain is fat isn't lost? LBM?

While that isnt a well formed sentence of english, I think the answer to your question is that Niacin prevents lipolysis and thus reduces fat loss.
Ras
Medice, cura te ipsum.
Benson
QUOTE (Ras @ Apr 19 2008, 08:03 PM) *
Medice, cura te ipsum.


Medicus curat...natura sanat.
Mr.Kite
non sequitur's are the name of the game
Jakeshorts
QUOTE (Ras @ Apr 19 2008, 08:03 PM) *
Medice, cura te ipsum.


hopefully this is latin for everyone makes typographical errors or 'he pointed that out in his original post'... either would suffice.
virtualcyber
QUOTE (Jakeshorts @ Apr 19 2008, 02:12 PM) *
So what's the mean gain is fat isn't lost? LBM?

It temporarily promotes glycolysis.

In the long run, it doesn't matter.
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