Human cholesterol synthesis measurement using deuterated water. Theoretical and procedural considerations.

Jones, Peter J H; Leitch, C. A.; Li, Z.-C.; Connor, William E.

doi:10.1161/01.atv.13.2.247

Cited by 68 publications

(84 citation statements)

References 29 publications

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“…Cholesterol synthesis rates were assessed after 24 h of deuterium water administration, using the deuterium incorporation approach (Jones et al, 1993). This method measures cholesterol synthesis as the rate of deuterium incorporation from body water into RBC membrane free cholesterol over a 24-h period.…”

Section: Study Design and Protocolmentioning

confidence: 99%

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Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans

et al. 2008

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Background/Objectives: To compare the efficacy of single versus multiple doses of plant sterols on circulating lipid level and cholesterol trafficking. Subjects/Methods: A randomized, placebo-controlled, three-phase (6 days/phase) crossover, supervised feeding trial was conducted in 19 subjects. Subjects were provided (i) control margarine with each meal; (ii) 1.8 g/day plant sterols in margarine with breakfast (single-BF) and control margarine with lunch and supper or (iii) 1.8 g/day plant sterols in margarine divided equally at each of the three daily meals (three times per day). Results: Relative to control, end point plasma low-density lipoprotein (LDL) cholesterol concentrations were lower (Po0.05) after consuming plant sterols three times per day but were not different when consumed once per day (3.43±0.62, 3.22±0.58 and 3.30 ± 0.65 mmol/l, control, three times per day and single-BF, respectively). Relative to the control, end point LDL level was 0.21±0.27 mmol/l (6%) lower (Po0.05) at the end of the three times per day phase. Cholesterol fractional synthesis rate was highest (Po0.05) after the three times per day phase (0.0827 ± 0.0278, 0.0834 ± 0.0245 and 0.0913 ± 0.0221 pool/day, control, single-BF and three times per day, respectively). Cholesterol-absorption efficiency decreased (Po0.05) by 36 and 39% after the three times per day and single-BF phase, respectively, relative to control. Conclusions: Present data indicate that to obtain optimal cholesterol-lowering impact, plant sterols should be consumed as smaller doses given more often, rather than one large dose.

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Section: Study Design and Protocolmentioning

confidence: 99%

“…FSR represents that fraction of the cholesterol pool that is synthesized in 24 h and is calculated as per the equation (Jones et al, 1993):…”

Section: Study Design and Protocolmentioning

confidence: 99%

Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans

et al. 2008

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“…18,21 Additionally, deuterium enrichment of plasma water was determined, as described elsewhere. 19 Fractional synthesis rate (FSR) of cholesterol over 24 h was determined using the following equation that corrects for cholesterol deuterium : protium ratio 21 :…”

Section: Cholesterol Biosynthesismentioning

confidence: 99%

“…The factor 0.478 reflects to ratio of labeled H atoms replaced by deuterium during in vivo biosynthesis. 21 Cholesterol turnover Turnover of plasma-free unesterified cholesterol is defined as the rate of influx from synthesis and dietary absorption compared with the rate of efflux from esterification, excretion or transfer from other body pools. 22 Therefore, turnover rates of erythrocyte-free cholesterol was determined after subtraction of baseline D 7 , [D 7 ]cholesterol enrichment of RBC at 12, 24, 48 and 72 h were fitted to exponential curves to determine the rate of decay.…”

Section: Cholesterol Biosynthesismentioning

confidence: 99%

Cholesterol metabolism and body composition in women: the effects of moderate weight loss

et al. 2007

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Objective: To determine how moderate weight loss protocol through diet and exercise may affect changes in body composition, to determine the effects of weight loss on cholesterol metabolism and to examine the relationship between cholesterol metabolism and changes in body composition. Design: Thirty-five otherwise healthy, hypercholesterolemic women completed a 24-week weight loss study. A 20% decrease in energy intake through diet and a 10% increase in energy expenditure by exercise were combined with motivational strategies to encourage weight loss. The diet was self-selected and comprised of 50-60% carbohydrates, 20% protein and o30% fat. Results: Participants lost an average of 11.772.5 kg (Po0.001). Whole body and regional losses in tissue mass occurred after weight loss. After weight loss, cholesterol fractional synthesis rate (FSR) decreased (P ¼ 0.003) 3.8679.33%, whereas rates of cholesterol absorption and turnover did not change (3.31719.4%, P ¼ 0.32 and À0.0176.20%, P ¼ 0.75, respectively). Changes in cholesterol turnover were positively correlated (r ¼ 0.44, P ¼ 0.01) with changes in FSR. Reductions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were predictive (b ¼ À5.04, r ¼ 0.38; P ¼ 0.03, and b ¼ À147, r ¼ 0.40; P ¼ 0.03, respectively) of increases in cholesterol turnover. Losses in skeletal muscle (SM) and upper-body SM predicted (b ¼ 6.82, r ¼ 0.36; P ¼ 0.04 and b ¼ 14.7, r ¼ 0.41; P ¼ 0.01, respectively) decreases in cholesterol absorption. Conclusions: Decreases in cholesterol synthesis after moderate weight loss are not compensated for by changes in cholesterol absorption or turnover. Changes in regional body composition were associated with variations in cholesterol metabolism. Understanding how weight loss affects cholesterol metabolism will help identify more effective treatment routes for overweight individuals undergoing weight loss resulting in earlier and more intensive therapy for the associated dyslipidemia.

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“…Methods for determination of endogenous cholesterol synthesis on the basis of deuterium incorporation have been well established 16,44,45 and are advantageous because they are direct, short-term, noninvasive methods, compared with intake balance methods [46][47][48] and isotopic kinetic decay analyses. [49][50][51] The efficacy of using erythrocyte cholesterol deuterium enrichment to study human lipid metabolism has been described previously.…”

Section: Discussionmentioning

confidence: 99%

Effects of Early Cholesterol Intake on Cholesterol Biosynthesis and Plasma Lipids Among Infants Until 18 Months of Age

et al. 2005

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Background. The endogenous cholesterol fractional synthesis rate (FSR) is related inversely to infant dietary cholesterol at 4 months of age; however, it remains to be established whether this effect is permanent, possibly contributing to later hypercholesterolemia. Objective. To determine whether levels of dietary cholesterol in infancy induced changes in FSR and plasma lipid levels that persisted at 18 months. Methods. A prospective clinical trial was conducted with 47 infants, from their first week of life until 18 months of age, who received human milk (HM) until weaned (n = 15) or were randomized to receive modified cow's milk formula (MCF) with added cholesterol (n = 15) or cow's milk formula (CF) (n = 17) for 12 months. Cholesterol contents of HM, MCF, and CF were 120, 80, and 40 mg/L, respectively. FSR and plasma lipid levels were measured at 4 and 18 months. Results. At 4 months, total cholesterol and low-density lipoprotein cholesterol levels were higher for infants fed HM and MCF, compared with CF. High-density lipoprotein cholesterol levels were higher in the MCF group than in the HM and CF groups. FSR in the HM group (0.034 ± 0.005 pools per day) was lower than that in the CF group (0.052 ± 0.005 pools per day). There was no difference between the HM and MCF (0.047 ± 0.005 pools per day) groups or between the MCF and CF groups. At 18 months, there were no differences in FSRs or plasma lipid profiles between the groups. Conclusion. Although cholesterol intake before weaning affects FSRs and plasma lipid profiles at 4 months, these differences do not persist after weaning to an unrestricted diet at 18 months. This provides additional evidence that there is no imprinting of FSR in infancy with differing dietary levels of cholesterol.

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Human cholesterol synthesis measurement using deuterated water. Theoretical and procedural considerations.

Cited by 68 publications

References 29 publications

Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans

Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans

Cholesterol metabolism and body composition in women: the effects of moderate weight loss

Effects of Early Cholesterol Intake on Cholesterol Biosynthesis and Plasma Lipids Among Infants Until 18 Months of Age

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