Self-selected meal composition alters the relationship between same-day caloric intake and appetite scores in humans during a long-term ad-libitum feeding study.

PURPOSE: To determine the effect of an off-protocol meal during a long-term ad libitum feeding study on changes in total caloric consumption and ratings of hunger and satiety. METHODS: During the ad libitum portion of a 16 weeks research high-protein feeding study, 19 participants were allowed to eat up to one self-selected meal (SSM) a week instead of an intervention diet meal. The SSM was assessed for total caloric and macronutrient composition and compared to the intervention diet for 3 days before and after the SSM day. Visual analog scores rating daily hunger and fullness were collected and compared as well. RESULTS: On the SSM day, the mean ± SD daily caloric intake increased by 262 ± 332 kcal compared to the previous study days (P < 0.001), with no changes in subjective appetite scores. The following day there was a slight but significant reduction in intake (- 58 ± 85 kcal, P = 0.008) compared to the average pre-SSM day with no change in appetite scores. On the SSM day, percent protein intake was inversely associated mean daily caloric intake (r2 = 0.22, P = 0.03). CONCLUSIONS: During a long-term, ad-libitum high-protein feeding study, one SSM lower in protein increased daily total caloric consumption with no impact on appetite ratings and incomplete caloric consumption during subsequent days. These data suggest that during ad-libitum feeding, a single meal change in protein content impacts the relationships between daily level of hunger, satiety and calorie intake. GOV ID: NCT05002491 (retrospectively registered 07/20/2021).

Effects of dietary cholesterol and simvastatin on cholesterol synthesis in Smith-Lemli-Opitz syndrome.

Deficient cholesterol and/or excessive 7-dehydrocholesterol (7-DHC) may be responsible for the pathology of Smith-Lemli-Opitz syndrome (SLOS). Both high-cholesterol diets given to ameliorate cholesterol deficiency while decreasing 7-DHC and cholesterol-enriched diets plus simvastatin to further decrease sterol synthesis have been used as potential therapies. However, the effect of dietary cholesterol and simvastatin on cholesterol synthesis in SLOS has not been reported. Twelve subjects with SLOS enrolled in the study: Nine had received a high cholesterol diet (HI) for 3 y and three were studied after 4 wk on a low cholesterol diet (LO). Cholesterol fractional synthesis rate (FSR) was measured after oral administration of deuterium oxide, using gas chromatography isotope ratio mass spectrometry. FSR was lower in HI compared with LO (HI: 1.46 +/- 0.62%/d; LO: 4.77 +/- 0.95%/d; p < 0.001). Three HI subjects were retested after 0.8 y taking simvastatin (HI + ST). Simvastatin tended to reduce FSR and significantly decreased (p < 0.01) plasma 7-DHC compared with cholesterol supplementation alone. The study demonstrates the utility of the deuterium incorporation method to understand the effect of therapeutic interventions in SLOS. The data suggest that dietary cholesterol supplementation reduces cholesterol synthesis in SLOS and further support the rationale for the combined treatment of SLOS with a cholesterol-enriched diet and simvastatin.

Plasma plant sterol levels do not reflect cholesterol absorption in children with Smith-Lemli-Opitz syndrome.

OBJECTIVE: To test the hypothesis that there is a correlation between the ratio of plant sterols to cholesterol in plasma and dietary cholesterol absorption in children with Smith-Lemli-Opitz syndrome (SLOS), a cholesterol synthesis disorder. STUDY DESIGN: We obtained measurements of cholesterol absorption with a direct radioisotope cholesterol absorption method during 9 visits of children with SLOS. We measured plasma sterols in 22 children with SLOS and 16 control children, and we measured dietary intake of cholesterol and sitosterol (n=11 SLOS). RESULTS: The correlations of 2 plasma plant sterol ratios (sitosterol/cholesterol and campesterol/cholesterol) with direct cholesterol absorption measurement were poor (R= -0.33 and R= -0.25, respectively), significantly lower than the published correlation in adults (R=0.73; P< .02). CONCLUSIONS: Although the ratios of plant sterols to cholesterol in plasma has been used as a surrogate for cholesterol absorption in adults and children, these ratios may not accurately reflect cholesterol absorption in children with SLOS. These ratios should not be used as a surrogate for cholesterol absorption in children without further validation.

Increased nonsterol isoprenoids, dolichol and ubiquinone, in the Smith-Lemli-Opitz syndrome: effects of dietary cholesterol.

Smith-Lemli-Opitz syndrome (SLOS) is an inherited autosomal recessive cholesterol deficiency disorder. Our studies have shown that in SLOS children, urinary mevalonate excretion is normal and reflects hepatic HMG-CoA reductase activity but not ultimate sterol synthesis. Hence, we hypothesized that in SLOS there may be increased diversion of mevalonate to nonsterol isoprenoid synthesis. To test our hypothesis, we measured urinary dolichol and ubiquinone, two nonsterol isoprenoids, in 16 children with SLOS and 15 controls, all fed a low-cholesterol diet. The urinary excretion of both dolichol (P < 0.002) and ubiquinone (P < 0.02) in SLOS children was 7-fold higher than in control children, whereas mevalonate excretion was comparable. In a subset of 12 SLOS children, a high-cholesterol diet decreased urinary mevalonate excretion by 61% (P < 0.001), dolichol by 70% (P < 0.001), and ubiquinone by 67% (P < 0.03). Our hypothesis that in SLOS children, normal urinary mevalonate excretion results from increased diversion of mevalonate into the production of nonsterol isoprenoids is supported. Dietary cholesterol supplementation reduced urinary mevalonate and nonsterol isoprenoid excretion but did not change the relative ratios of their excretion. Therefore, in SLOS, a secondary peripheral regulation of isoprenoid synthesis may be stimulated.

Effects of weight loss on changes in insulin sensitivity and lipid concentrations in premenopausal African American and white women.

BACKGROUND: Few studies have tested the hypothesis that changes in disease risk factors are more closely associated with changes in visceral fat than with changes in other adipose tissue depots, particularly in subjects with different ethnic or racial backgrounds. OBJECTIVE: We describe changes in triacylglycerol, total cholesterol, HDL cholesterol, LDL cholesterol, insulin sensitivity (S(i)), visceral fat, and subcutaneous abdominal adipose tissue (SAAT) with weight loss in premenopausal, overweight [body mass index (in kg/m(2)): 27-30], African American (n = 19) and white (n = 18) women. DESIGN: Assessments were performed before and after diet-induced weight loss to a BMI < 25. Body composition and body fat distribution were assessed with dual-energy X-ray absorptiometry and computed tomography, respectively; S(i) was assessed with an intravenous-glucose-tolerance test and minimal modeling. RESULTS: White women lost significantly more visceral fat and less SAAT than did African American women despite similar weight losses (approximately 13 kg). Mixed-model analysis indicated significant effects of time (ie, weight loss) on S(i), triacylglycerol, HDL cholesterol, and LDL cholesterol and of race on triacylglycerol. Time x race interaction terms were not significant. After adjustment for either total body or visceral fat, time was not related to any outcome variable; however, race remained significantly related to triacylglycerol. CONCLUSIONS: With weight loss, moderately overweight African American and white women experienced significant improvements in S(i) and lipids. The beneficial effects of weight loss did not differ with race and could not be attributed to a specific body fat depot. Lower triacylglycerol concentrations among African American women are independent of both obesity status and body fat distribution.