pantetheine and Hypercholesterolemia

High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to 16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines.

Topics: Adult; Anticholesteremic Agents; Biomarkers; Cholesterol; Cholesterol, LDL; Combined Modality Therapy; Coronary Disease; Female; Florida; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Ontario; Pantetheine; Patient Selection; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

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.

Topics: Cholesterol, HDL; Cholesterol, LDL; Drug Evaluation; Female; Humans; Hypercholesterolemia; Menopause; Middle Aged; Pantetheine; Sulfhydryl Compounds; Triglycerides

Recent human studies suggest rapid in vivo hydrolysis of the lipid-lowering drug, pantethine, to the vitamin pantothenic acid and the small aminothiol compound, cysteamine. To test whether the active agent is a hydrolysis product, we repeated three experimental models of pantethine's effect with pantothenate and cysteamine. In vitro experiments with human fetal fibroblasts showed equivalent modulation of cholesterol and methyl sterol synthesis by pantethine, cysteamine, or cystamine (the disulfide of cysteamine), but pantothenate had no effect. Similarly, in vivo experiments with 0.5% cholesterol-fed rabbits showed oral pantethine or equimolar cystamine significantly lowered plasma cholesterol, while pantothenate, cystine, and 2-hydroxyethyl disulfide did not. Lastly, diabetic male rats (40 mg/kg streptozotocin) fed 0.1% pantethine and lower plasma free fatty acids after 2 weeks than controls, an effect not seen with pantothenate and largely duplicated by cystamine. The efficacy of pantethine has previously been attributed to altered vitamin metabolism and increased coenzyme A concentration. Pantethine did increase CoA levels 45% in rat liver homogenates while equivalent amounts of cystamine or pantothenate did not. However, a causal relationship between CoA levels and pantethine's action as a hypolipemic agent has never been shown. At least in 3 independent experimental models, the lipomodulating effect of pantethine appears instead to be mediated by the hydrolysis product cysteamine.

Topics: Animals; Cells, Cultured; Coenzyme A; Cysteamine; Diabetes Mellitus, Experimental; Humans; Hydrolysis; Hypercholesterolemia; Lipid Metabolism; Male; Pantetheine; Rabbits; Rats; Sulfhydryl Compounds

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 Fredrickson's 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.

Topics: Adolescent; Adult; Aged; Apolipoprotein A-I; Apolipoproteins A; Apolipoproteins B; Child; Cholesterol; Female; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Lipoproteins; Male; Middle Aged; Pantetheine; Sulfhydryl Compounds; Triglycerides

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/die 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 Fredrickson's 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.

Topics: Adolescent; Adult; Aged; Apolipoproteins; Arteriosclerosis; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Complications; Female; Humans; Hypercholesterolemia; Hyperlipoproteinemias; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Pantetheine; Sulfhydryl Compounds

Pantethine (P), a coenzyme A precursor, was administered to cholesterol-fed rabbits (0.5% cholesterol diet + 1% pantethine) for 90 days. At the end of treatment, plasma total cholesterol levels were reduced 64.7% and the HDL/total cholesterol ratio increased in P-treated animals; a significant rise of the apo A-I/A-II ratio was detected in HDL. VLDL lipid and protein levels were, on the other hand, reduced by P. The cholesterol-ester content of both liver and aortic tissues was not significantly affected by P. Although the total aortic area with evident plaques was reduced only 18.2%, the microscopical examination of sections from the major vessels of P-treated animals, showed a reduction in the severity of lesions, both in the aorta and in the coronary arteries. These findings suggest that P, in addition to significantly lowering plasma cholesterol levels in rabbits on an experimental diet, may modify lipid deposition in major arteries, possibly by affecting lipoprotein composition and/or exerting an arterial protective effect.

Topics: Animals; Aorta, Abdominal; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins A; Cholesterol, Dietary; Cholesterol, HDL; Coronary Vessels; Hypercholesterolemia; Isoelectric Focusing; Lipoproteins, HDL; Male; Pantetheine; Rabbits; Sulfhydryl Compounds

A high-cholesterol diet caused in rabbits a great increase in beta-migrating VLDL and a significant decrease in HDL 2 (43% of normal) and HDL 3 masses (64% of normal), without significant changes in HDL cholesterol values. Chemical analysis of the HDL subfractions indicated an abnormal lipid-protein composition in the hypercholesterolemic rabbits, an increase in cholesterol and a decrease in the contents of triglycerides and phospholipid. When these rabbits were treated for about 1 month with pantethine, and intermediate precursor of coenzyme A, the increase in cholesterol levels was effectively prevented in the beta-VLDL (11%) and LDL fractions (43%) but, conversely, HDL-cholesterol was significantly increased (151%). In a separate experiment, HDL 2 and HDL 3 masses were calculated to be increased to 186% and 193%, respectively, by pantethine treatment, when compared with those in control cholesterol-fed rabbits. Serum apolipoprotein AI antigen levels were also significantly increased by the treatment.

Topics: Animals; Cholesterol, Dietary; Hypercholesterolemia; Lipoproteins; Lipoproteins, HDL; Male; Pantetheine; Rabbits; Sulfhydryl Compounds