These studies below show that reducing
the concentration of free
fatty acids (FFA) in the blood will increase the
responsiveness of the pituitary to Growth Hormone Releasing
Hormone (GHRH), in everyone and especially in the obese and
In these experiments the researchers used a drug called acipimox to reduce FFA. Acipimox is a nicotinic acid analogue. Nicotinic acid = Niacin = Vitamin B3. This means that niacin will have many of the same effects as acipimox. Other evidence shows that niacin does indeed have the expected effects. Niacin is very inexpensive and available anywhere vitamins are sold. (niacinamide is related but not identical and probably does not have the same effects)
FFA is a powerful mediator of GH
feedback which seems to work at the pituitary gland. High serum
GH causes high serum FFA, which directly or indirectly inhibits
further secretion of endogenous GH. Niacin or any other drug or
supplement that reduces FFA should therefore have the effect of
reducing the negative feedback.
Niacin is a water soluble B vitamin. It is considered reasonably safe in doses up to approximately one gram in non-sustained release form. However megadoses of niacin do present some risks to the liver, especially in multiple gram doses in sustained release form.
Doses in the 500 to 1000 mg range are safe for most people and should still have some FFA reducing effects, so niacin appears to be a promising supplement for people who supplement GH. For example if one normally injects GH in the morning then it might be a good idea to take niacin at bed time. In theory the reduction of FFA during sleep would enhance the release of endogenous GH. I do not however think this strategy should be used in place of cycling. The purpose would be to further reduce the risks that the practice of cycling is designed to reduce, while also enhancing total GH and IGF-1.
Another benefit might be a reduction of the risk of insulin resistance, which is a possible side-effect of GH therapy. In a recent study diabetics and non-diabetics taking acipimox at night realized significant improvements in insulin resistance and glucose tolerace. Niacin can also be effective in reducing cholesterol levels.
Ideally one would take several grams of niacin to gain the full FFA-reducing effects but I think doses in excess of about one gram should be taken only under the supervision of a physician. From the evidence I have seen I would avoid multiple gram doses of sustained release niacin completely, but doses of two to three grams of the non-sustained release form might be an acceptable risk for some people if under doctor's supervision.
Niacin can cause a harmless but
sometimes annoying "flushing" effect on the skin. The
flushing disappears in most people after a few days as the body
becomes accustomed to the niacin. People who want to take niacin
might want to start with smaller doses in the 50 mg range and
then increase the dosage gradually. Talk to your doctor before
moving up to higher doses.
Niacin is not without some risks, however, especially if taken in very large doses in excess of one gram, and in sustained release form.
This material is from http://www.pharminfo.com/pubs/msb/niacin.html
Reprinted from the April 1994 issue of Medical Sciences Bulletin , published by Pharmaceutical Information Associates, Ltd.
Niacin (nicotinic acid) is widely used for reducing serum cholesterol levels, in part because it is effective, and in part because it is available and cheap. In doses of 2 to 3 g daily, it reduces levels of total and high-density lipoprotein cholesterol (LDL-C) by an average of 20% to 30%, reduces triglyceride levels 35% to 55%, increases high-density lipoprotein cholesterol (HDL-C) 20% to 35%, and reduces Lp(a) lipoprotein. In primary prevention, niacin reduces total mortality as well as mortality from coronary artery disease; used in secondary prevention along with bile acid resins, it slows or reverses the progression of atherosclerosis. And it costs only about $2.00 for a 10-day supply. Does all this sound too good to be true? Results from a recent study by McKenney et al. (Medical College of Virginia School of Pharmacy) indicate that not all the news about niacin is good news. In therapeutic doses, niacin can be dangerous, particularly sustained-release niacin.
The Virginia researchers conducted a randomized, double-blind, parallel-group comparison of sustained-release (SR) and immediate-release (IR) niacin in 46 patients with hypercholesterolemia. The 36-week trial included a 6-week evaluation and instruction period followed by five 6-week treatment periods during which niacin was given in escalating doses (500 mg/day initially, increasing up to 3Êg/day). Both the IR niacin product (Rugby Laboratories, division of Marion Merrell Dow) and the SR niacin (Goldline Laboratories) were effective for improving the lipid profile. At the highest (3-g) dose, SR niacin reduced total cholesterol by about 40% and LDL-C by 50%, while IR niacin reduced total cholesterol by about 16% and LDL- C by about 22%. Both formulations at the 3-g dose reduced triglycerides by about 41%. IR niacin elevated HDL-C by 35% at the 3-g dose, while SR niacin elevated HDL-C by only 9.4%, a significant difference.
Both formulations were associated with considerable side effects. Nine of the 23 patients assigned to IR niacin withdrew from the trial before completing the 3-g dose phase because of adverse reactions, including vasodilation (flushing, itching, rash), fatigue, and acanthosis nigricans (a wart-like skin eruption). Eighteen of the 23 patients in the SR niacin group withdrew before completing the 3-g dose phase because of gastrointestinal effects, fatigue, and hepatotoxicity. Thus, 39% of patients on IR niacin and 78% of those on SR niacin withdrew because of side effects.
More than half the patients in the SR niacin group showed evidence of hepatotoxicity. Liver aminotransferase levels were three times the upper limit in 12 of the 18 who withdrew, and 3 patients had symptoms of hepatic dysfunction (fatigue, nausea, anorexia). Toxicity appeared dose related; changes in liver function test results reached statistical significance by the time the dosage reached 1500 mg/day, and 9 of the 12 with substantial hepatotoxicity were taking 2 to 3 g/day. Hepato-toxicity did not develop in any patients taking IR niacin.
In recent years, numerous case reports have described hepatotoxicity linked to high-dose niacin therapy; almost all the patients were taking SR niacin. Toxicity was noted in some cases in as little as 1 week after initiating therapy, and in others as late as 48 months. Usually, toxicity resolved after drug discontinuation, but in some cases liver dysfunction progressed to stage 3 and 4 encephalopathy, and one patient required liver transplantation. Perhaps even more hepatotoxi- city would have developed in patients in the McKenney study if the trial had continued beyond 5 weeks. Other major side effects reported in the literature include activation of peptic ulcers, hyperuricemia and gout, and impaired glucose tolerance. While McKenney et al. noted no change in uric acid levels, they did see elevations in fasting glucose levels with increasing doses. The elevations were significant in the SR niacin group at doses of 2 g and over. By the end of the trial, six patients with normal glucose levels at baseline (three in each group) had fasting glucose levels above 7.8Êmmol/L (140 mg/dL). One patient taking IR niacin had a bleeding pep-tic ulcer, apparently from activation of peptic ulcer disease.
A number of products have been implicated in niacin-induced hepatotoxicity, including two prescription products: Nicobid from Rhone-Poulenc Rorer (Collegeville, PA) and Slo-Niacin from Upsher- Smith (Minneapolis). Other implicated products include Nature's Plus, Niatrol, Endur-Acin, and generic products from Rugby Laboratories (Rockville Center, NY), Major Pharmaceuticals (San Diego), and Goldline Laboratories (Ft. Lauderdale, FL). According to Goldline, their SR niacin is a generic version of Rhone-Poulenc's Nicobid. Neither Goldline nor Rhone-Poulenc promote their SR niacin for cholesterol reduction. Only two prescription products (both of them IR niacin) are approved for cholesterol reduction: Upsher-Smith's Niacor and Rhone-Poulenc's Nicolar. "All other IR dosage forms and all SR dosage forms are available as nonprescription drugs for the treatment of nicotinic acid deficiencies and are not regulated by the FDA," said McKenney et al. In many published cases, a patient went to the health food store for IR niacin because of the health claims and the price, switched to SR niacin because of side effects associated with IR niacin, and then had to visit the doctor because of symptoms that turned out to be caused by hepatotoxicity. "Given the degree of toxic effects we encountered," said the investigators, "we believe that allowing niacin to remain on the nonprescription market, where it may be used in high doses for cholesterol lowering without proper monitoring by trained health care professionals, presents a potentially serious public health problem."
This study poses some interesting questions. Why was SR niacin more effective than IR niacin in reducing LDL-C? Why was IR niacin more effective for increasing HDL-C? Do phar-macokinetic differences explain the efficacy and toxicity differences? Slower absorption of SR niacin may mean lower peak serum levels, but fewer side effects may mean higher total ingested dose. Increased hepatotoxicity with SR niacin may be due to steadier bathing of liver cells, and the hepato-toxicity may explain the cholesterol reductions.
According to editorialist Louis Lasagna, the FDA has approved niacin for treating hypercholesterolemia, and the National Cholesterol Education Program recommends it for primary prevention. Niacin still has a role in managing dyslipidemia, said Lasagna, "but not on the basis of self-diagnosis and self- treatment." The Medical College of Virgin-ia cholesterol research center routinely evaluates the efficacy and safety of drugs for hypercholesterolemia. "The incidence and severity of adverse reactions experienced with both niacin dosage forms in the present study, but particularly with SR niacin, were much greater than any investigational drug we have evaluated for hypercholesterolemia," concluded McKen-ney et al. "If niacin were being evaluated for efficacy and safety and our experiences were replicated by others, we do not believe that it would be approved by the FDA for use in the management of hypercholesterolemia." (McKenney JM et al. JAMA. 1994;271:672-677. Lasagna L. JAMA. 1994;271:709-710)
|100||[Pharmacologic treatment of lipid metabolism disorders] (Gmi´nski J; Wiad Lek, 1996)|
|95||The control on growth hormone release by free fatty acids is maintained in acromegaly. (Lanzi R; J Clin Endocrinol Metab, 1999 Apr)|
|94||Effect of decreasing plasma free fatty acids by acipimox on hepatic glucose metabolism in normal rats. (Lee KU; Metabolism, 1996 Nov)|
|94||The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia [corrected and republished article originally printed in J Intern Med 1997 Feb;241(2):151-5] (Hoogerbrugge N; J Intern Med, 1998 May)|
|94||The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia [corrected and republished in J Intern Med 1998 May;243(5):151-6] (Hoogerbrugge N; J Intern Med, 1997 Feb)|
|94||Optimal metabolic conditions during fluorine-18 fluorodeoxyglucose imaging; a comparative study using different protocols. (Bax JJ; Eur J Nucl Med, 1997 Jan)|
|93||Effect of acute acipimox administration on the rates of lipid and glycogen synthesis in cachectic tumor-bearing rats. (Obeid OA; Nutr Cancer, 1997)|
|91||Effects of acipimox on haemorheology and plasma lipoproteins in patients with mixed hyperlipoproteinaemia. (Otto C; Br J Clin Pharmacol, 1998 Nov)|
|91||Tolerability and effects of high doses acipimox as additional lipid-lowering therapy in familial hypercholesterolemia. (Stuyt PM; Neth J Med, 1998 Nov)|
|79||Restoration of growth hormone (GH) response to GH-releasing hormone in elderly and obese subjects by acute pharmacological reduction of plasma free fatty acids. (Pontiroli AE; J Clin Endocrinol Metab, 1996 Nov)|
|76||Uncoupling of fatty acid and glucose metabolism in malignant lymphoma: a PET study. (Nuutinen J; Br J Cancer, 1999 May)|
|74||[Pharmacology of hypolipidemic agents] (F´ery F; Rev Med Brux, 1997 Feb)|
|55||Evidence for an inhibitory effect of physiological levels of insulin on the growth hormone (GH) response to GH-releasing hormone in healthy subjects. (Lanzi R; J Clin Endocrinol Metab, 1997 Jul)|
|54||Acipimox-mediated plasma free fatty acid depression per se stimulates growth hormone (GH) secretion in normal subjects and potentiates the response to other GH-releasing stimuli. (Peino R; J Clin Endocrinol Metab, 1996 Mar)|
|54||Impaired growth hormone secretion in obese subjects is partially reversed by acipimox-mediated plasma free fatty acid depression. (Cordido F; J Clin Endocrinol Metab, 1996 Mar)|
|53||Effect of acute pharmacological reduction of plasma free fatty acids on growth hormone (GH) releasing hormone-induced GH secretion in obese adults with and without hypopituitarism. (Cordido F; J Clin Endocrinol Metab, 1998 Dec)|
|53||Lowering fatty acids potentiates acute insulin response in first degree relatives of people with type II diabetes. (Paolisso G; Diabetologia, 1998 Oct)|
|53||The reduction in postprandial lipemia after exercise is independent of the relative contributions of fat and carbohydrate to energy metabolism during exercise. (Malkova D; Metabolism, 1999 Feb)|
|53||Effects of an acute decrease in non-esterified fatty acid levels on muscle glucose utilization and forearm indirect calorimetry in lean NIDDM patients. (Piatti PM; Diabetologia, 1996 Jan)|
|52||Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects. (Santomauro AT; Diabetes, 1999 Sep)|
|52||Long-term administration of acipimox potentiates growth hormone response to growth hormone-releasing hormone by decreasing serum free fatty acid in obesity. (Nam SY; Metabolism, 1996 May)|
|52||Acute pharmacological reduction of plasma free fatty acids enhances the growth hormone (GH)-releasing hormone-mediated GH secretion in patients with Cushing's syndrome. (Leal-Cerro A; J Clin Endocrinol Metab, 1997 Sep)|
|51||Long-term effects of a sustained-release preparation of acipimox on dyslipidemia and glucose metabolism in non-insulin-dependent diabetes mellitus. (Davoren PM; Metabolism, 1998 Mar)|
|51||Treatment possibility of hypercholesterolaemia associated with hypertriglyceridaemia. (Paragh G; Acta Biol Hung, 1997)|
|51||The effect of circulating non-esterified fatty acids on the entero-insular axis. (Ranganath L; Eur J Clin Invest, 1999 Jan)|