The effect of pravastatin and atorvastatin on coenzyme Q10.

BACKGROUND: Coenzyme Q10 (CoQ10) is an antioxidant and plays an important role in the synthesis of adenosine triphosphate. Studies suggest that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce CoQ10 levels; however, no studies have directly compared HMG-CoA reductase inhibitors in a randomized crossover fashion. METHODS: Twelve healthy volunteers received either 20 mg pravastatin (P) or 10 mg atorvastatin (A) for 4 weeks in a randomized crossover fashion. There was a 4- to 8-week washout period between the 2 phases. CoQ10 levels and a lipid profile were obtained. RESULTS: There was no difference in CoQ10 levels from baseline to post-drug therapy for either P or A (0.61 +/- 0.14 vs 0.62 +/- 0.2 microg/mL and 0.65 +/- 0.22 vs 0.6 +/- 0.12 microg/mL, respectively; P >.05). There was a significant difference in low-density lipoprotein (LDL) levels from baseline to post-drug therapy for both P and A (97 +/- 21 vs 66 +/- 19 mg/dL and 102 +/- 21 vs 52 +/- 14 mg/dL, respectively; P <.01). There was no significant correlation between LDL and CoQ10. CONCLUSIONS: P and A did not decrease CoQ10 despite a significant decrease in LDL levels. These findings suggest that HMG-CoA reductase inhibitors do not significantly decrease the synthesis of circulating CoQ10 in healthy subjects. Routine supplementation of CoQ10 may not be necessary when HMG-CoA reductase inhibitor therapy is administered.

A clinical trial to selectively change dietary fat and/or energy intake in women: the Women's Diet Study.

Dietary fat and energy intake have been implicated in breast cancer etiology. To examine the relative importance of these dietary factors on markers of cancer risk in women, we designed an intervention trial to selectively decrease fat and/or energy intake in free-living, premenopausal women who were somewhat overweight. The study used a 2 x 2 factorial design to evaluate the independent and interactive effects of dietary fat and energy. The diets were nonintervention, low fat (15% of energy from fat, maintenance of energy intake), low energy (25% energy reduction), and combination low fat and low energy. We utilized an individualized counseling approach with self-selection of foods. Women on the low-fat and combination diets were asked to meet given daily goals for fat grams and food group exchanges, while women on the low-energy diet used only food group exchanges. Of the 113 premenopausal women randomized who were eligible for analysis, 43% were African-American. A total of 88 women completed the 12-week program, and adherence to the dietary goals was similar in both racial groups. Women on the low-fat diet were able to reduce dietary fat intake to 19% of energy by 4 weeks and to 17% by 12 weeks with a slight decrease in energy intake. Women on the low-energy diet met their energy reduction goals by four weeks while maintaining percentage of energy from fat. Women on the combination diet largely met their goals by four weeks as well. These data indicate that it is possible to selectively manipulate dietary fat and energy intake in women over a short period of time, which makes clinical studies on the relative effects of these two dietary variables on cancer risk biomarkers readily feasible.

Differential gender response produced by meal and ad lib feedings of a high-fat diet in Osborne-Mendel rats.

We investigated if there were gender differences in metabolic consequences produced by meal feeding of a high-fat (HF) diet in male and female Osborne-Mendel rats. An HF diet was fed either ad lib (AL) or in 1 meal (MF) during the last 3 h of the dark cycle for 4 weeks (lights off from 2400 h to 1200 h). All rats were sacrificed at 1 of 3 time-points: prior to MF rats receiving their food at 0900 h, after food was taken from MF groups at 1200 h or 1500 h. Food intake, body weight, body fat weight, retroperitoneal adipose tissue lipoprotein lipase activity, plasma cholesterol, or HDL-cholesterol levels did not differ between MF- and AL-fed groups, but were higher in male than in female rats. There were no differences between the male and female groups in plasma levels of insulin and glucose or systolic blood pressures. Plasma triglyceride levels at 1200 h were significantly different between MF and AL Groups within either gender, but this was not observed at 0900 h or 1500 h. Body weights were correlated with internal fat weights and plasma cholesterol levels in both males (r = 0.57, p < 0.05) and females (r = 0.59, p < 0.05). Hence, it is the amount of HF diet ingested, rather than the pattern of meal feeding, that was the most significant factor related to gender differences in weight gain, increases in fat mass, and metabolic differences.

Chronic weight cycling increases oxidative DNA damage levels in mammary gland of female rats fed a high-fat diet.

Oxidative DNA damage levels may be a marker of breast cancer risk that is modulated by diet. We examined the effects of a high-fat diet fed in varying feeding regimens on levels of 5-hydroxymethyl-2'-deoxyuridine (5-OHmU), an oxidized thymidine residue, in DNA from mammary gland of aging female rats. A total of 48 rats were randomly divided into four groups: ad libitum fed (AL), weight cycled above baseline (WC-G), weight cycled below baseline (WC-L), or energy restricted (ER) for 28 weeks. WC groups were fed repeated ad libitum/restricted amounts of the diet. At sacrifice, both WC groups had body weights similar to the ER group but higher levels of 5-OHmU (p < 0.01). 5-OHmU levels were higher in the WC groups than in the AL group, even though body weights of the WC groups were significantly lower (p < 0.001). These results indicate that a history of weight cycling, even when body weight is reduced, can have adverse effects on 5-OHmU levels in mammary gland DNA, a potential biomarker of cancer risk. Constant control of calories for the maintenance of body weight, therefore, may be more beneficial.

Changes in feeding efficiency and carcass composition in rats on repeated high-fat feedings.

Male and female Sprague-Dawley rats were fed ad libitum two cycles of 10 weeks of a high-fat (HF) diet, followed by 5 weeks of control chow (CH). During the initial 10 weeks (weeks 1-10) the HF fed male rats had an increased rate of weight gain and feeding efficiency (FE) in comparison to CH-fed controls. In the female HF-fed rats, the FE was higher during weeks 1-5 than that seen in CH-fed females. The male HF-fed rats had significantly higher levels of FE than the female HF-fed rats during the first 10 week period. At the end of the tenth week, the HF-fed rats weighed significantly more than CH-fed controls. HF-fed male rats gained more weight than HF-fed female rats. During the 5 week period (weeks 11-16) of CH feeding, the body weight of the HF-fed rats was reduced. At the end of week 16 there was no difference between the body weights of the CH and HF fed rats. During the second cycle of HF feeding (weeks 16-25) the HF-diet further increased body weight gain in both male and female rats compared with CH-fed controls. There was no reduction in FE in HF-fed male and female rats during this period when compared to the first ten week HF feeding period. After the last 5 week period (weeks 26-30) of CH feeding, the formerly HF-fed rats had similar body weights as the control rats, but still had more body fat than control rats.(ABSTRACT TRUNCATED AT 250 WORDS)