Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation.

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.

Pantothenic acid refeeding diminishes the liver, perinephrical fats, and plasma fats accumulated by pantothenic acid deficiency and/or ethanol consumption.

OBJECTIVE: Pantothenic acid (PaA) is a vitamin that is an integral part of coenzyme A (CoA). CoA is an essential coenzyme in fat metabolism. The aim of this study was to determine whether PaA deficiency causes the accumulation of tissue fats and, if so, can refeeding of PaA decrease such accumulated fat. METHODS: Weaning rats were fed the PaA-free diet for 30 d. Rats were then divided into two groups. One group was continuously fed the PaA-free diet, and the other was fed the PaA-containing diet for an additional 13 d. At the end of the experiment, liver fat and perinephric fat were weighed, and plasma triglyceride levels measured. An additional similar experiment was conducted in which rats consumed 15% ethanol instead of water. RESULTS: Fat that accumulated by consuming the PaA-free diet for 30 d was decreased by consuming the PaA-containing diet for an additional 13 d. Ethanol feeding elicited much greater accumulation of liver, perinephric, and plasma fats if rats were fed the PaA-free diet. In such cases, administration of PaA could decrease the accumulated fat. CONCLUSION: PaA deficiency causes fat accumulation, and readministration of PaA decreases the tissue fat in rats fed the pantothenic acid-free diet. Ethanol accelerated the accumulation of fat in rats fed the PaA-free diet. PaA could be beneficial for decreasing accumulated tissue fat.

Effects of pantothenic acid supplement on secretion of steroids by the adrenal cortex in female rats.

PURPOSE: The effect of pantothenic acid (PaA) supplementation on adrenal secretion of corticosterone and progesterone in female rats was investigated. METHODS: An in-vitro primary adrenal cell culture system was used. Pregnant rats were given 0.03% PaA in their drinking water throughout pregnancy and the period of lactation. In the first experiment, after weaning, female rats continued to receive 0.03% PaA treatment until 10 weeks of age. The animals were then decapitated and adrenal cells were cultured in the absence or presence of rat adrenocorticotropic hormone (ACTH) for 4 h. In the second experiment, adrenal cells from lactating rats on day 5 of lactation were cultured in the absence or presence of rat ACTH for 4 h. RESULTS: The effect of ACTH at 10-10 m on corticosterone and progesterone release was greater for PaA-treated cyclic rats than for control cyclic rats. The effect of ACTH at 10-10 m on corticosterone release was greater for PaA-treated lactating rats than for control lactating rats. Circulating ACTH and corticosterone levels in PaA-treated and control cyclic and lactating rats were no different. CONCLUSIONS: These results indicate that PaA supplementation induced hyperresponsiveness to ACTH stimulation in cyclic and lactating female rats. These results clearly demonstrated that PaA is an essential factor in adrenal steroidogenesis of female rats.

Pantethine, a derivative of vitamin B(5) used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled investigation.

Safety and efficacy of a biologically active derivative of vitamin B(5) (pantethine) on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) metabolism was studied in North American subjects at conventional low to moderate cardiovascular disease (CVD) risk. A total of 120 subjects initiated a therapeutic lifestyle change (TLC) diet 4 weeks before randomization (baseline) and maintained the diet throughout a 16-week study period; at baseline, subjects were randomized in a triple-blinded manner to either pantethine (600 mg/d, baseline to week 8, and 900 mg/d, weeks 9-16) or identically labeled, nonbiologically active placebo (n = 60 per group). We hypothesized that pantethine would lower TC and low-density lipoprotein in low-CVD-risk North American subjects in a similar manner as reported in high-CVD-risk subjects studied mainly in Italy and Japan. While sustaining a TLC diet and in comparison with placebo, pantethine demonstrated significant (P < .005) and sustained reductions (from baseline to week 16) in TC (6 mg/dL, 0.16 mmol/L, 3%), LDL-C (4 mg/dL, 0.10 mmol/L, 4%), and apolipoprotein B (4 mg/dL, 0.04 g/L, 5%). Our data suggest that pantethine supplementation for 16 weeks (600 mg/d for weeks 1-8 then 900 mg/d for weeks 9-16) is safe and significantly lowers TC and LDL-C over and above the effect of TLC diet alone. Although the absolute magnitude of these effects was small in these low- to moderate-risk North Americans (4-6 mg/dL), the results are noteworthy as prior studies have shown that, for each 1 mg/dL (0.026 mmol/L) reduction in LDL-C, there is a concomitant 1% reduction in overall future CVD risk.

Effects of pantothenic acid on testicular function in male rats.

Pantothenic acid (PaA) is a water-soluble vitamin required to sustain various physiological functions in animals. The physiological roles of PaA on testicular function, in particular, testicular endocrinology and sperm mortility, were investigated in rats. Male rats at 3 weeks of age were fed a PaA-free diet or a 0.0016% PaA diet (control) for 7 weeks. Total body weight, as well as the weights of the liver, kidney, pituitary, testis, epididymis, seminal vesicle and prostate; sperm motility; and the plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and corticosterone were measured in rats at 10 weeks of age. Body weight gain decreased from 5 weeks of age in rats fed the PaA-free diet compared with the control. The relative weights of the testes were significantly higher in the PaA-deficient group compared with the control group. Several parameters of sperm motility were significantly reduced in the PaA-deficient group compared with the control group. In addition, the plasma concentrations of testosterone and corticosterone were significantly lower in the PaA-deficient group compared with the control group, whereas the plasma concentrations of FSH and LH showed no change. These results clearly demonstrate that PaA is an essential factor in testicular endocrinology and sperm motility in male rats.

Effects of pantothenic acid supplementation on adrenal steroid secretion from male rats.

The effects of pantothenic acid-supplementation on the adrenal secretion of corticosterone and progesterone in male rats were investigated using an in vitro cell culture system. Male rats at 21 d of age were given 0.03% pantothenic acid in their drinking water for 9 weeks. After 9 weeks of treatment, the animals were decapitated, and adrenal cells were cultured in the absence or presence of rat adrenocorticotropic hormone (ACTH; 10(-15) to 10(-10) M) and/or ovine prolactin (oPRL; 10(-9) to 10(-7) M) for 4 h. Adrenal cells in pantothenic acid-treated rats exhibited higher basal levels of corticosterone and progesterone than control rats. The response of ACTH and/or PRL on corticosterone and progesterone release was higher in the pantothenic acid-treated rats than in the control rats. In addition, PRL increased the stimulatory effect of ACTH-induced corticosterone secretion in both normal and pantothenic acid-treated rats. These results clearly demonstrated that pantothenic acid supplementation stimulates the ability of adrenal cells in male rats to secrete corticosterone and progesterone. Additionally, these results also showed that pantothenic acid supplementation induced adrenal hyperresponsiveness to ACTH stimulation, and PRL further stimulated adrenal sensitivity to ACTH.