Formulas makes a pantetheine capsule. They supplied these studies.)
(Jarrow Formulas makes a pantetheine capsule. They supplied these studies.)
WHAT IS IT?
Pantethine is the stable form of pantetheine, the active form of the vitamin Pantothenic acid.
This is the fundamental component of Coenzyme A (CoA) which transports fatty acids into the
mitochondria of cells. It is one of the most important enzymes in the body and is also critical for
many other functions ranging from antibody synthesis to maintaining blood sugar levels. The
pathway of pantethine is much shorter than pantothenic acid.
WHAT DOES IT DO?
while increasing the good HDL cholesterol. Pantothenic acid has no such activity.
In studies, Pantethine reduced serum triglycerides by 32% (the most of any substance,) total
by 19% and LDL cholesterol by 21%. It also raised HDL cholesterol by 23%!
Pantethine acts by inhibiting cholesterol synthesis and accelerating the use of fat as an energy
source. Several studies have shown impressive lipid lowering effects in diabetics, without side effects.
impairs insulin action and is unsuitable for diabetics.
Although no studies have been done with it, the weight loss effects of
acid may be
Comparison of the efficacy of pantethine, acipimox, and bezafibrate on plasma lipids and index of
cardiovascular risk in diabetics with dyslipidemia
Atherosclerotic manifestations are more common and precocious in diabetics than in the general population. Due to the increased cardiovascular risk, a primary or secondary (to diabetes mellitus) lipoprotein disorder in diabetics has to be carefully considered. 27 diabetics (15 NIDDM and 12 IDDM) with dyslipidemia (14 type IV, 8 type IIa and 5 type IIb) were divided in 3 groups and treated with 3 different hypolipemic drugs (Group A: pantethine 600 mg/day; Group B: acipimox 500 mg/day; Group C: bezafibrate 600 mg/day) to test their efficacy and acceptancy. Body weight, Hb A1-c, serum lipoproteins have been measured before and during the 6 months treatment. A significant variation of lipidemic pattern was observed in Group C: a decrease of cholesterol (-20%), triglycerides (-40%), LDL (-24.4%) and apo B (-26.8%) with an increase of HDL (+23.6%). Pantethine and acipimox were more effective on triglycerides (-37.7% and -23.3% respectively). Cardiovascular risk (CT tot/CT HDL) was significantly reduced with acipimox and normalized with bezafibrate. Tonutti L, Taboga C, Noacco C. Comparison of the efficacy of pantethine, acipimox, and bezafibrate on plasma lipids and index of cardiovascular risk in diabetics with dyslipidemia. Minerva Med 1991;82:657-663.
and clinical studies with cysteamine and pantethine related to the central
1. Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (HuntingtonÕs disease, prolactin-secreting adenomas) indications in clinical practice. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, ParkinsonÕs disease, instead of cysteamine) are discussed. Vecsei L, Widerlov E. Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system. Prog Neuropsychopharmacol Biol Psychiatry 1990;14:835-862.
Treatment of hyperlipemia in diabetic patients on dialysis with a physiological substance
Hyperlipemia is a very frequent complication of the diabetic patient on dialysis. There is difficulty of treatment with the diet, because the dietary restriction already imposed on these patients and the secondary effects and toxicity of the available drugs in uremics aggravate the problem. We have treated 22 diabetic patients on dialysis (8 on hemodialysis and 14 on continuous ambulatory peritoneal dialysis) suffering from hyperlipemia with pantethine, a physiological substance and coenzyme A precursor in the Krebs cycle. With the administration of an oral dose of 900 mg/day we obtained a reduction of total cholesterol (275 +/- 72 vs. 231 +/- 54 mg/dl; p less than 0.001), very-low-density lipoprotein (VLDL)-cholesterol (66 +/- 36 vs. 46 +/- 18 mg/dl; p less than 0.01) and triglycerides (332 +/- 182 vs. 227 +/- 90 mg/dl; p less than 0.01) at 2 months. High-density lipoprotein (HDL)-cholesterol did not change, but the total cholesterol/HDL-cholesterol ratio decreased significantly (p less than 0.05). Total cholesterol, VLDL and triglycerides showed a progressive and significant reduction at 4 and 6 months. No changes were observed in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, uric acid, blood glucose and glycosylated hemoglobin. Gastric discomfort in 2 patients and pruritus in another one were the secondary effects related. Pantethine was shown to be a very effective hypolipemic agent in diabetic patients on dialysis with a great tolerance. Coronel F, Tornero F, Torrente J, et al. Treatment of hyperlipemia in diabetic patients on dialysis with a physiological substance. Am J Nephrol 1991;11:32-36.
of the roles of the substances in serum lipids and their constitutive fatty
The newly-generated lipid mediators include products of arachidonate metabolism, prostaglandins and leukotrienes. In this study, serum lipids and fatty acids, including arachidonic acid (C20:4) were examined in 12 normal subjects (6 males and 6 females) and 23 subjects with chronic urticaria (6 males and 17 females), including 17 who made an excellent or good recovery (4 males and 13 females). The results indicated a relationship between chronic urticaria and serum lipids and fatty acids. The omega 6 (n-6) and omega 3 (n-3) series of polyunsaturated fatty acids and lipid peroxidation were suggested that may be one of the mediators in chronic urticaria. Pantethine, glutathione and ascorbic acid were effective in controlling chronic urticaria. Kobayashi S. Investigation of the roles of the substances in serum lipids and their constitutive fatty acids in chronic urticaria. J Dermatol 1989;16:196-206.
Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children
Following a brief outline of current knowledge concerning atherosclerosis and its treatment, the authors describe the results obtained by treating with pantethine (900-1200 mg daily for 3 to 6 months) a series of 7 children and 65 adults suffering from hypercholesterolemia alone or associated with hypertriglyceridemia (types IIa and IIb of FredricksonÕs classification). Pantethine treatment produced significant reduction of the better known risk factors (total cholesterol, LDL-cholesterol, triglycerides, and apo-B) and a significant increase of HDL-cholesterol (signally HDL2) and apolipoprotein A-I. The authors conclude with a discussion of these results and of the possible role of pantethine in the treatment of hyperlipoproteinemia, in view of its perfect tolerability and demonstrated therapeutic effectiveness. Bertolini S, Donati C, Elicio N, et al. Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children. Int J Clin Pharmacol Ther Toxicol 1986;24:630-637.
Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age
Cardiovascular diseases are the main cause of death also in women. Their incidence, rapidly growing in the peri-menopausal period, is related to serum levels of total cholesterol and its LDL fraction. It was also shown that the peroxidation of LDL is an additional factor in the genesis of atherosclerotic vascular disease. As long-term treatments with synthetic lipid-lowering drugs may cause undesirable side effects, while pantethine is known to be well tolerated, we treated 24 hypercholesterolemic women (total serum cholesterol greater than or equal to 240 mg/dl), in perimenopausal age (range: 45-55 years, mean +/- SD = 51.6 +/- 2.4) with 900 mg/day of pantethine. This is a precursor of coenzyme A, with an antiperoxidation effect in vivo, and our aim was to confirm its lipid lowering activity in this particular type of patients. After 16 weeks of treatment, significant reductions of total cholesterol, LDL-cholesterol and LDL-C/HDL-C ratio could be observed. No remarkable changes of the main laboratory parameters (fasting blood sugar, B.U.N., creatinine, uric acid) were seen. Efficacy percentages of the treatment were about 80%. None of the patients complained of adverse reactions due to the treatment with pantethine. In conclusion, we suggest that pantethine should be considered in the long-term treatment of lipid derangements occurring in the perimenopausal age. Binaghi P, Cellina G, Lo Cicero G, et al. Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age. Minerva Med 1990;81:475-479.
Pantethine, diabetes mellitus and atherosclerosis. Clinical study of 1045 patients
After a review of the clinical studies on the treatment of diabetic patients with pantethine, the authors discuss the results obtained in a postmarketing surveillance (PMS) study on 1045 hyperlipidemic patients receiving pantethine (900 mg/day on average). Of these patients, 57 were insulin-dependent (Type I) and 241 were non insulin-dependent (Type II) diabetics. Beyond the epidemiological considerations made possible by a PMS study, the authors show that pantethine brought about a statistically significant and comparable improvement of lipid metabolism in the three groups of patients, with very good tolerability. Pantethine should therefore be considered for the treatment of lipid abnormalities also in patients at risk such as those with diabetes mellitus. Donati C, Bertieri RS, Barbi G. Pantethine, diabetes mellitus and atherosclerosis. Clinical study of 1045 patients. Clin Ter 1989;128:411-422.
Lowering effect of pantethine on plasma beta-thromboglobulin and lipids in diabetes mellitus
Pantethine in a dosage of 600 mg for the first 3 months, and in a dosage of 1200 mg for the second 6 months was given to 16 diabetics in whom plasma beta-thromboglobulin was raised (greater than 50 ng/ml). Plasma beta-TG levels decreased significantly with pantethine treatment for 9 months. Plasma triglyceride, total cholesterol, apo E and apo CII levels decreased significantly after 9 months. Plasma LDL-C and atherogenic index (LDL-C/HDL-C ratio or apo B/apo AI ratio) tended to decrease with treatment. It is concluded that administration of pantethine may be beneficial in the prevention of diabetic angiopathy because of its lowering effect on plasma beta-TG, lipids and apolipoproteins. Eto M, Watanabe K, Chonan N, Ishii K. Lowering effect of pantethine on plasma beta-thromboglobulin and lipids in diabetes mellitus. Artery 1987;15:1-12.
Therapeutic efficacy of pantothenic acid preparations in ischemic heart disease patients
The therapeutic effectiveness of the pantothenic acid drugs: calcium pantothenate and pantethine, was studied in 182 patients with coronary heart disease and stable angina of effort. It is shown that both the drugs produce favourable effects on certain parameters of hemodynamics, on the metabolism of lipids, riboflavin and ascorbic acid. It is recommended that the administration of calcium pantothenate in a dose of 300 mg/day, during 3 weeks, be included into the combined treatment of coronary patients with no manifest disorders of lipid metabolism. Patients with manifest hyperlipidemia should be administered pantethine in a dose of 500 mg/day. Borets VM, Lis MA, Pyrochkin VM, et al. Therapeutic efficacy of pantothenic acid preparations in ischemic heart disease patients. Vopr Pitan 1987 Mar-Apr;(2):15-17.
Effect of oral treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia In a single-blind, crossover, completely randomized study, the effects of oral treatment with pantethine or placebo on fatty acid composition of plasma and platelet phospholipids were investigated in 10 IIa hyperlipoproteinemic patients. A significant decrease of total cholesterol and total phospholipids was observed both in plasma and in platelets after a twenty-eight-day treatment. In plasma, pantethine induced a decrease of the ratio sphingomyelin/phosphatidylcholine. Moreover, a relative increase of n3-polyunsaturated fatty acids both in plasma and in platelet phospholipids and a decrease of arachidonic acid in plasma phospholipids were observed. These results indicate that pantethine can affect plasma and platelet lipid composition with possibly favorable influences on the determinants of cell membrane fluidity. Prisco D, Rogasi PG, Matucci M, et al. Effect of oral treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia. Angiology 1987;38:241-247.
Hyperlipidemia, diabetes and atherosclerosis: efficacy of treatment with pantethine
The hypolipidemizing effects of pantethine were investigated by the authors in 37 hypercholesterolemic and/or hypertriglyceridemic patients. Of these, 21 were also diabetic, in a satisfying glucidic compensation, in order to verify the action of this drug also in this metabolic condition. The study was carried out for three months and during this period the patients were given pantethine at the dose of 600 mg/day orally. At the 30th, the 60th, the 90th day of treatment the following parameters were controlled: cholesterolemia, HDL cholesterol, apolipoproteins A and B, triglyceridemia, systolic and diastolic arterial pressure, uricemia, body weight. Thirty days after suspending the treatment, the parameters were controlled again to detect a possible rebound effect. The results were analyzed on the whole case-record, subdividing the patients in dislipidemic and diabetic-dislipidemic, and on the basis of the FredricksonÕs classification. Pantethine induced in all groups a quick and progressive decrease of cholesterolemia, triglyceridemia, LDL cholesterol and Apolipoproteins B with increased HDL cholesterol and Apolipoproteins A. After suspending the treatment, there is a clear inversion of the state of these parameters. The authors conclude that the present work shows that pantethine, a natural and atoxic substance, an important component of Coenzyme A, is efficacious in determining a clear tendency towards normalization of the lipidic values. Arsenio L, Caronna S, Lateana Met al. Hyperlipidemia, diabetes and atherosclerosis: efficacy of treatment with pantethine. Acta Biomed Ateneo Parmense 1984;55:25-42.
Effectiveness of long-term treatment with pantethine in patients with dyslipidemia
A one-year clinical trial with pantethine was conducted in 24 patients with established dyslipidemia of FredricksonÕs types II A, II B, and IV, alone or associated with diabetes mellitus. The treatment was well tolerated by all patients with no subjective complaints or detectable side effects. Blood lipid assays repeated after 1, 3, 6, 9, and 12 months of treatment revealed consistent and statistically significant reductions of all atherogenic lipid fractions (total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B) with parallel increases of high-density lipoprotein cholesterol and apolipoprotein A. The results were equally good in patients with uncomplicated dyslipidemia and in those with associated diabetes mellitus. The authors conclude that pantethine (a drug entity related to the natural compound, pantetheine) represents a valid therapeutic support for patients with dyslipidemia not amenable to satisfactory correction of blood lipids by diet alone. Arsenio L, Bodria P, Magnati G, et al. Effectiveness of long-term treatment with pantethine in patients with dyslipidemia. Clin Ther 1986;8:537-545.
improves the lipid abnormalities of chronic hemodialysis patients: results
In the course of a post-marketing surveillance program on the effectiveness and tolerability of pantethine in the treatment of hyperlipidemia, the effects of the drug were explored in 31 patients with dyslipidemia undergoing chronic hemodialysis. The mean duration of treatment was 9 months (min. 7 months, max. 24 months), with oral doses of 600 to 1200 mg of pantethine daily (mean daily dosage 970 mg). Improvement was noted in terms of total blood cholesterol in the 7 patients with basal hypercholesterolemia (p less than 0.01) and highly significant reduction of serum triglycerides. No variations of HDL-cholesterol or total Apo-A were detected. None of the patients experienced any adverse effects from the treatment. In the light of extensive experience with the drug, plus the results of this study, the authors conclude by stressing the importance of an effective and readily tolerated product, such as pantethine, for the treatment of dyslipidemia in patients on chronic hemodialysis. Donati C, Barbi G, Cairo G, et al. Pantethine improves the lipid abnormalities of chronic hemodialysis patients: results of a multicenter clinical trial. Clin Nephrol 1986;25:70-74.
Changes in fatty acid composition of the single platelet phospholipids induced by pantethine treatment
In a single-blind cross-over study the effect of oral treatment with pantethine on plasma and platelet lipid composition was evaluated in 20 patients with dyslipidaemia (7 IIa, 7 IIb and 6 Iv type). In plasma significant decreases of total cholesterol and triglycerides with increase of high density lipoprotein-cholesterol were observed. In platelets pantethine treatment significantly reduced phospholipid and cholesterol content. In addition gas-chromatographic analysis showed a reduction of saturated and monounsaturated and a relative increase of polyunsaturated fatty acid content of platelet phospholipids. A selective relative increase was observed of some n-3 polyunsaturated fatty acids like eicosapentaenoic and docosahexaenoic acid whereas arachidonic acid decreased. The present study indicates a favourable influence of pantethine not only on plasma but also on platelet lipids which could be of value in delaying the development of atherosclerosis in dyslipidaemic patients. Gensini GF, Prisco D, Rogasi PG, et al. Changes in fatty acid composition of the single platelet phospholipids induced by pantethine treatment. Int J Clin Pharmacol Res 1985;5:309-318. Lowering of blood acetaldehyde but not ethanol concentrations by pantethine following alcohol ingestion: different effects in flushing and nonflushing subjects A rise in blood acetaldehyde concentrations following alcohol ingestion was significantly inhibited when healthy nonflushing subjects were administered a clinical dose of pantethine orally. However, similar findings were not observed in flushing (alcohol-sensitive) subjects lacking hepatic low Km aldehyde dehydrogenase (ALDH). The blood ethanol concentrations were not altered by this treatment in either flushing or nonflushing subjects. Acetaldehyde (45 microM) added in vitro to whole blood and plasma obtained 1 hr after pantethine administration disappeared as the incubation continued similarly as with blood and plasma obtained prior to pantethine treatment. Pantethine-related metabolites, such as taurine, pantetheine, coenzyme A, and pantothenate, activated ALDH in vitro. Hepatic acetaldehyde levels following ethanol loading of rats treated with pantethine were much lower than in untreated rats. The pantethine action observed only in nonflushing subjects might be due to an accelerated oxidation of acetaldehyde by the activation of low Km ALDH by pantethine-related metabolites formed in the liver. Watanabe A, Hobara N, Kobayashi M, et al. Lowering of blood acetaldehyde but not ethanol concentrations by pantethine following alcohol ingestion: different effects in flushing and nonflushing subjects. Alcohol Clin Exp Res 1985;9:272-276.
Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia
Pantethine (P), the stable disulphate form of pantetheine, major component and precursor of coenzyme A, was evaluated within a double-blind protocol (8 weeks for P or for a corresponding placebo) in 29 patients, 11 with type IIB hyperlipoproteinemia, 15 with type IV, and 3 with an isolated reduction of high density lipoprotein cholesterol (HDL-C) levels. In type IIB patients, P (300 mg t.i.d.) determined a highly significant lowering of plasma total and low density lipoprotein (LDL) associated cholesterol (-13.5% for both parameters). In the same patients, HDL-C levels increased about 10% at the end of treatment. Switching from P to placebo was associated with a rapid return to the baseline cholesterolemia. Both in type IIB and type IV patients, plasma triglyceride levels were reduced around 30%, when P was given as the first treatment; when it was preceded by placebo, reductions were less striking (respectively, -17.8% for type IIB and -13.0% for type IV, at the end of P treatment). HDL-C levels were not increased by P, either in type IV, and in the patients with low HDL cholesterolemia. In type IV, LDL cholesterol levels showed a variable response to P: they tended to increase when below 132 mg/dl, prior to treatment, and to be reduced when above this level. This study provides evidence for a significant hypocholesterolemic effect of P, a natural compound free of overt side effects. It also indicates that P may raise HDL-C levels in type IIB patients, while moderately reducing triglyceridemia. Gaddi A, Descovich GC, Noseda G,et al. Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia. Atherosclerosis 1984;50:73-83.