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Pantethine as a Cholesterol-Lowering Agent
Abstracted by Marcia J. Egles, MD, October 18, 2011 from Pantethine, a derivative of vitamin B5 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 by John A. Rumberger, Joseph Napolitano, Isao Azumano,T. Kamiya, M. Evans in Nutrition Research 31(August, 2011) 608-615.(1)
Pantethine, a form of vitamin B5 or pantothenic acid, has been shown to slightly lower cholesterol levels in a recent sixteen week small clinical trial in healthy North American subjects (1). All B vitamins are important in cell metabolism, helping the body convert carbohydrates and fats into energy. Vitamin B5 is known to be involved in cholesterol metabolism. Vitamin B5 is widely present in foods and presents no classic nutritional deficiency diseases (such as beriberi, pellagra, or pernicious anemia) as with those of other B vitamins. No significant deleterious side-effects have been reported with pantethine (3).
A randomized, placebo-controlled, multicenter trial in Japan of 201 high cardiovascular risk individuals in 1986 demonstrated that 600 milligrams per day of pantethine over 16 weeks lowered LDL-C ( low density lipoprotein cholesterol) by 15%, lowered triglycerides by 14%, and raised HDL-C ( high density lipoprotein cholesterol i.e. “good cholesterol”) by 17% from baseline (2). Several small trials reporting pantethine’s efficacy in safely lowering cholesterol were published in 1981 to 1991, largely from Italy, as noted in a 2005 review published (3). No pantethine studies at all were published in the decade following 1991, and very little over the next ten years (3).
The new study directs attention towards pantethine’s merits as a cholesterol lowering measure in low–risk patients for whom diet and other lifestyle changes are an appropriate initial therapy. The current United States guidelines for cholesterol are published in the “Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults" (ATP III, 4). The ATP III recommends that an initial approach for an individual with abnormally elevated LDL-C should start with the therapeutic lifestyle change (“TLC”) diet.The diet restricts saturated fats, cholesterol, sodium and calories. The details of the diet may be found in reference 4 or at http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi, from the National Institute of Health.
Emphasizing the dietary guidelines of ATP-III, the study is the first well-controlled recent clinical trial of pantethine and its effects on blood cholesterol. Generally healthy adults who were taking no cholesterol altering medications were recruited from two sites, one in London, Ontario and one in Brandenberg, Florida. Approximately eighty per cent of the 120 final subjects were female, 95 % white, with an average age of 47, and an average total cholesterol blood level of 195 milligrams per deciliter at screening. In order to minimize concerns of dietary influences between the two treatment groups, all the subjects were to follow a TLC diet for the 16 week trial and for 4 weeks prior.   After the 4 week TLC diet before the start of the trial, the subjects on average showed a 6% improvement in total cholesterol. The TLC diet used in the study was the most basic phase without the added fiber or soy protein options.
The subjects were divided randomly into two groups, the treatment group taking by mouth 300 milligrams of pantethine pills twice per day for the first 8 weeks of the study, then increasing to a 900 milligram total dose per day for the next 8 weeks of the 16 week study. The control group consumed placebo pills packaged identically to the pantethine.   Both groups continued on the TLC diet.
Compared with placebo, the pantethine subjects showed significant ( p less than 0.005) and sustained reductions in total cholesterol and LDL-C.   Over and above the effect of diet alone, total cholesterol was reduced 3 per cent, or 6milligrams per deciliter, and LDL-C 4 per cent or 4 milligrams per deciliter. No additional reductions were achieved by the higher 900 milligram dose. No significant adverse reactions were detected. Nausea occurred at the same rate in both the placebo and pantethine groups.
Though of small magnitude, the results are noteworthy as prior studies have shown that for each one milligram per deciliter drop in LDL-C, there is a beneficial one per cent reduction in overall future cardiovascular risk (5). The study authors concluded that pantethine may be of value particularly in some, clinically low risk, patients for whom more potent cholesterol-lowering pharmaceuticals, with their inherent risks, may not be appropriate (1).                                                                                                                                                                                                                                                  
1. John A. Rumberger, et al, Pantethine, a derivative of vitamin B5 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. Nutrition Research 31( 2011) 608-615. Available online at www.sciencedirect.com.
2. Hata Y, Goto Y, Ide H, Tsuji M, Takahashi S, Itakura H, et al. Effects of pantethine on serum lipids and apoproteins—I. Results of a multicenter cooperative study. Geriat Med 1986;24:1139-50.
3. McRae MP. Treatment of hyperlipoproteinemia with pantethine: a review and analysis of efficacy and tolerability. Nutr Res 2005;25: 319-33.
4. Third Report of the National Cholesterol Education Program (NCEP) Expert panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143-421
5. Gotto A. Treating hypercholesterolemia: looking forward. Clin Cardiol 2003;26(Suppl I):I21-8.