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Biomedical subjects

Peter J H Jones

Publications and source records attributed to Peter J H Jones.

At least 19 recordsLinked to original sources

Cholic acid supplementation enhances cholesterol absorption in humans.

BACKGROUND & AIMS: Qualitative and quantitative changes in intralumenal bile acid composition may alter cholesterol absorption and synthesis and low-density lipoprotein (LDL) receptor expression. The role of cholic acid (CA) in cholesterol absorption in humans remains unclear and, thus, was examined in the current study. METHODS: In a crossover design outpatient study, 12 adults aged 24-36 years took 15 mg/kg/day (CA) or no bile acid supplement (control) while being fed a controlled diet (AHA heart-healthy diet). A liquid meal of defined composition was given on day 14 of the diet, and lumenal samples were collected. Thereafter, cholesterol absorption and cholesterol fractional synthetic rate (FSR) were assessed by stable isotopic methods from days 16 to 20. RESULTS: With CA treatment, bile was enriched significantly with CA (P < 0.0004) to 60.2% +/- 2.4% (mean +/- SEM) compared with 43.3% +/- 2.4% for controls. CA plus diet treatment significantly increased (P = 0.013) cholesterol absorption (72.6% +/- 2.9%) compared with diet treatment alone (60.4% +/- 2.9%). Percentage micellar cholesterol was increased by CA plus diet treatment vs. diet alone after meal ingestion (P = 0.004). Plasma total and high-density lipoprotein (HDL) and LDL cholesterol was unchanged with CA treatment. CONCLUSIONS: Thus, enrichment in lumenal bile with CA results in an increase in cholesterol absorption, an effect potentially mediated by enhanced cholesterol solubilization in micelles.

Absorption↗

Unesterified plant sterols and stanols do not affect LDL electrophoretic characteristics in hypercholesterolemic subjects.

The extent to which sterols and stanols modulate LDL particle size is unknown. We examined the effects of supplementation with unesterified plant sterols and stanols on several LDL electrophoretic characteristics. Healthy hypercholesterolemic subjects (n = 14) consumed each of four experimental diets contained plant sterols (S), plant stanols (SN), a 50:50 mixture of sterols and stanols (SSN), or cornstarch (control) in a randomized crossover design. The butter component of the diet was blended with unesterified sterols and stanols at a dose of 1.8 g/d. The LDL particles were characterized by polyacrylamide gradient gel electrophoresis of whole plasma. LDL cholesterol (LDL-C) concentrations decreased by 8.8, 13.6, and 13.1% in the S, SN, and SSN groups, respectively (P < 0.01) with a significant increase of 4.3% in the control group. None of the treatments with sterols and stanols induced significant changes in LDL peak particle diameter or in the cholesterol levels of the small LDL subfraction (<25.5 nm). The reduction in plasma LDL-C levels with SN consumption was due mainly to a decrease (P < 0.05) in the concentration of cholesterol in the large subfraction (>26.0 nm). The significant reduction in plasma LDL-C concentrations by sterol and stanol consumption in subjects was not paralleled by any beneficial changes in LDL electrophoretic characteristics.

Cholesterol, HDL↗

Phytosterols in low- and nonfat beverages as part of a controlled diet fail to lower plasma lipid levels.

Dietary phytosterols have been shown to reduce plasma cholesterol concentrations when consumed in different food matrices, but their effectiveness in nonfat or low-fat beverages has not been established. The objective of this study was to examine whether phytosterols alter plasma lipid levels when incorporated into nonfat or low-fat beverages. Fifteen moderately hypercholesterolemic men and women consumed three precisely controlled diets for periods of 21 days each in random order. Diets contained either a nonfat placebo beverage (NF), a beverage that is nonfat with added phytosterols (NFPS), or a beverage that is low in fat with added phytosterols (LFPS). Total cholesterol concentrations were not different between groups at endpoint, decreasing (P < 0.05) equally by 8.5%, 11.6%, and 10.1% with NF, NFPS, and LFPS consumption, respectively. There was no effect of dietary treatment on LDL cholesterol concentrations, which decreased over time (P < 0.05) by 5%, 10.4%, and 8.5% with NF, NFPS, and LFPS, respectively. HDL cholesterol and triacylglycerol concentrations were unaffected by the diets. Provision of phytosterols as part of nonfat and low-fat beverages did not exert any greater hypocholesterolemic effect than a nonfat placebo beverage. These results show that intake of phytosterols in a low-fat beverage format is not efficacious for lipid level modification.

Adult↗

Effect of ursodeoxycholic acid on cholesterol absorption and metabolism in humans.

Qualitative and quantitative changes in intraluminal bile acid composition may alter cholesterol absorption and synthesis and LDL receptor expression. In a randomized crossover design outpatient study, 12 adults aged 24-36 years took 15 mg/kg/day ursodeoxycholic acid (UDCA) or no bile acid supplement (control) for 20 days while being fed a controlled diet (AHA Step II). A liquid meal of defined composition was then given and luminal samples collected. Cholesterol absorption and cholesterol fractional synthetic rate (FSR) were assessed by stable isotopic methods. With UDCA treatment, bile was enriched significantly (P < 0.0001) to 40.6 +/- 2.6% (mean +/- SEM) compared with 2.2 +/- 2.6% for controls. Regardless, plasma total, HDL, and LDL cholesterol were unchanged with UDCA treatment. Intraluminal cholesterol solubilized in the aqueous phase during the entire collection was decreased (P = 0.012) in UDCA-treated subjects (101.0 +/- 7.2 mg/ml/120 min) compared with controls (132.5 +/- 7.2 mg/ml/120 min.). Percent micellar cholesterol was increased in UDCA-treated versus controls after meal ingestion. No changes were found in cholesterol absorption, FSR, or LDL receptor mRNA with UDCA treatment compared with controls. Thus, despite marked enrichment in luminal bile with UDCA and decreased cholesterol solubilization, no differences in cholesterol absorption or metabolism are found when diet and genetic differences in absorption are carefully controlled.

Adult↗

Phytosterols and human lipid metabolism: efficacy, safety, and novel foods.

Plant sterols have been known for several decades to cause reductions in plasma cholesterol concentrations. These plant materials have been granted a conditional health claim in the United States regarding their effects in the prevention of cardiovascular disease and are being sold in functional foods in several countries in Europe as well as in the United States and Australia. It is generally suggested that daily consumption of approximately 2 g of plant sterols can lower cholesterol concentrations as part of a dietary prevention strategy. However, phytosterols have been added and tested for their cholesterol-lowering effects mainly in spreads. Consumption of these high-fat foods seemingly flies in the face of current recommendations for the promotion of heart health, which suggest lowering total fat and energy intake to maintain weight. Hence, new food formulations are being evaluated using phytosterols incorporated into low-fat and reduced-fat food items. The purpose of this review is to examine the cholesterol-lowering efficacy of plant sterols, focusing on novel food applications, their mechanism of action, and safety. These novel food formulations include new solubilization processes that lead to improved uses for plant sterols, as well as new foods into which phytosterols have been incorporated, such as breads, cereals, and beef. Such new foods and formulations should pave the way for greater use of phytosterols in heart health promotion, increasing the longer-term potential for the creation of innovative functional foods containing plant sterols and their derivatives.

Animals↗

Consumption of an oil composed of medium chain triacyglycerols, phytosterols, and N-3 fatty acids improves cardiovascular risk profile in overweight women.

Medium chain triacylglycerols (MCT) have been suggested as efficacious in weight management because they possess greater thermogenic qualities relative to long chain triacylglycerols; however, MCT may also increase circulating lipid concentrations, possibly increasing risk of cardiovascular disease (CVD). The present objective was to examine the effect of a diet supplemented with a functional oil (FctO) composed of energy expenditure-enhancing MCT (50% of fat), cholesterol-lowering phytosterols (22 mg/kg body weight), and triacylglycerol-suppressing n-3 fatty acids (5% of fat), versus a beef tallow-based diet (BT), on plasma lipid and aminothiol concentrations. In a randomized, single-blind, crossover design, partially-inpatient trial, 17 overweight women consumed each oil as part of a controlled, supervised, targeted energy balance diet for 27 days, with 4 or 8 weeks of washout between phases. Mean plasma total cholesterol concentration was lower (P <.0001), by 9.1%, on FctO (4.37 +/- 0.20 mmol/L) versus BT (4.80 +/- 0.20 mmol/L). Mean plasma low-density lipoprotein (LDL) cholesterol was also lower (P <.0001) following FctO (2.39 +/- 0.15 mmol/L) versus BT (2.86 +/- 0.16 mmol/L), representing a 16.0% difference between diets. High-density lipoprotein (HDL) cholesterol and circulating triacylglycerol concentrations remained unaffected by treatment. Ratios of HDL:LDL and HDL:total cholesterol were higher (P <.01) by 22.0% and 11.0%, respectively, on FctO versus BT. Plasma total homocysteine remained unchanged with FctO, but decreased (P <.05) with control, hence higher (P <.05) end points were observed with FctO (6.95 +/- 0.33 micromol/L) versus BT (6.27 +/- 0.28 micromol/L). Plasma glutathione increased (P <.05) by 0.44 micromol/L with FctO supplementation. In conclusion, despite equivocal effects on homocysteine levels, consumption of a functional oil composed of MCT, phytosterols, and n-3 fatty acids for 27 days improves the overall cardiovascular risk profile of overweight women.

Adult↗

The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century.

It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.

Animals↗

Medium-chain triglycerides increase energy expenditure and decrease adiposity in overweight men.

OBJECTIVE: The objectives of this study were to compare the effects of diets rich in medium-chain triglycerides (MCTs) or long-chain triglycerides (LCTs) on body composition, energy expenditure, substrate oxidation, subjective appetite, and ad libitum energy intake in overweight men. RESEARCH METHODS AND PROCEDURES: Twenty-four healthy, overweight men with body mass indexes between 25 and 31 kg/m(2) consumed diets rich in MCT or LCT for 28 days each in a crossover randomized controlled trial. At baseline and after 4 weeks of each dietary intervention, energy expenditure was measured using indirect calorimetry, and body composition was analyzed using magnetic resonance imaging. RESULTS: Upper body adipose tissue (AT) decreased to a greater extent (p < 0.05) with functional oil (FctO) compared with olive oil (OL) consumption (-0.67 +/- 0.26 kg and -0.02 +/- 0.19 kg, respectively). There was a trend toward greater loss of whole-body subcutaneous AT volume (p = 0.087) with FctO compared with OL consumption. Average energy expenditure was 0.04 +/- 0.02 kcal/min greater (p < 0.05) on day 2 and 0.03 +/- 0.02 kcal/min (not significant) on day 28 with FctO compared with OL consumption. Similarly, average fat oxidation was greater (p = 0.052) with FctO compared with OL intake on day 2 but not day 28. DISCUSSION: Consumption of a diet rich in MCTs results in greater loss of AT compared with LCTs, perhaps due to increased energy expenditure and fat oxidation observed with MCT intake. Thus, MCTs may be considered as agents that aid in the prevention of obesity or potentially stimulate weight loss.

Adipose Tissue↗

Alpha-lipoic acid and cardiovascular disease.

Alpha-lipoic acid (ALA) has been identified as a powerful antioxidant found naturally in our diets, but appears to have increased functional capacity when given as a supplement in the form of a natural or synthetic isolate. ALA and its active reduced counterpart, dihydrolipoic acid (DHLA), have been shown to combat oxidative stress by quenching a variety of reactive oxygen species (ROS). Because this molecule is soluble in both aqueous and lipid portions of the cell, its biological functions are not limited solely to one environment. In addition to ROS scavenging, ALA has been shown to be involved in the recycling of other antioxidants in the body including vitamins C and E and glutathione. Not only have the antioxidant qualities of this molecule been studied, but there are also several reports pertaining to its blood lipid modulating characteristics, protection against LDL oxidation and modulation of hypertension. Therefore, ALA represents a possible protective agent against risk factors of cardiovascular disease (CVD). The objective of this review is to examine the literature pertaining to ALA in relation to CVD and describe the most powerful actions and potential uses of this naturally occurring antioxidant. Despite the numerous studies on ALA, many questions remain relating to the use of ALA as a supplement. There is no consensus on dosage, dose frequency, form of administration, and/or preferred form of ALA. However, collectively the literature increases our understanding of the potential uses for supplementation with ALA and identifies key areas for future research.

Antioxidants↗

Consumption of a functional oil rich in phytosterols and medium-chain triglyceride oil improves plasma lipid profiles in men.

Medium-chain triglycerides (MCT) have been proposed as weight-lowering agents, although there is some concern regarding their hyperlipidemic effect. This study evaluates the effects of a combination of MCT oil, phytosterols and flaxseed oil [functional oil (FctO)] on plasma lipid concentrations and LDL particle size. Twenty-four healthy overweight men (body mass index 28.2 +/- 0.4 kg/m(2)) consumed controlled diets designed to maintain weight for two periods of 29 d each. Diets contained 40% of energy as fat, 75% of which was added fat, either FctO or olive oil (OL). Body composition and blood samples were analyzed at the baseline and the endpoint of each period. Total cholesterol concentration decreased 12.5% (-0.68 mmol/L; P < 0.05) when subjects consumed FctO and 4.7% when they consumed OL. Similarly, FctO consumption lowered LDL cholesterol concentrations by 13.9%, whereas OL consumption did not. There was no difference in absolute change in LDL-cholesterol between FctO and OL consumption. Peak LDL particle size was greater in those who consumed FctO than in those who consumed OL (P < 0.05), with no effect of diet on proportion of large, medium or small particles. We conclude that those who consume a diet containing FctO have a better lipid profile than those who consume a diet rich in OL, which also leads to a larger lipoprotein particle size. Functional oil consumption can therefore help reduce the risk of cardiovascular disease.

Adult↗

Role of isoflavones in the hypocholesterolemic effect of soy.

Epidemiologic data suggest an inverse relationship between the consumption of soy isoflavones and cardiovascular disease risk. The aims of this review are to determine if isoflavones play a role in the hypocholesterolemic effect of soy and whether the studies realized with that scope were adequately designed. In humans, most studies have been performed in postmenopausal women. The results are inconsistent, however; some studies show a decrease in total cholesterol and low-density lipoprotein concentrations, and an increase in high-density lipoprotein levels, and other investigations fail to show any beneficial effect of soy isoflavones on lipid profiles. In most studies, beneficial effects could not be attributed with certainty to soy isoflavones. If these components have any health-protecting effect in humans, it is small in comparison with the effect of soy protein itself. There are currently not enough data to recommend the consumption of isoflavone supplements to lower plasma cholesterol levels.

Animals↗

Role of policosanols in the prevention and treatment of cardiovascular disease.

Policosanols are a mixture of aliphatic alcohols derived from purified sugar cane. When administered at 5 to 20 mg/day, policosanols have been shown to decrease the risk of atheroma formation by reducing platelet aggregation, endothelial damage, and foam cell formation in animals. Additionally, policosanols have been shown to lower total and low-density lipoprotein (LDL) cholesterol levels by 13 to 23% and 19 to 31%, respectively, while increasing high-density lipoprotein (HDL) cholesterol from 8 to 29%. Policosanols are thought to improve lipid profiles by reducing hepatic cholesterol biosynthesis while enhancing LDL clearance. When compared with statins, policosanols exhibit comparable cholesterol-lowering effects at much smaller doses. The mixture is well tolerated when administered to animals; however, a more precise safety profile is needed for humans. In summary, policosanols are a promising resource in the prevention and therapy of cardiovascular disease (CVD), but these results need to be confirmed in independent laboratories.

Anticholesteremic Agents↗

Impact of bedtime snack composition on prevention of nocturnal hypoglycemia in adults with type 1 diabetes undergoing intensive insulin management using lispro insulin before meals: a randomized, placebo-controlled, crossover trial.

OBJECTIVE: To determine the impact of four bedtime (HS) snack compositions on nocturnal glycemic control, including frequency of hypoglycemia (<4 mmol/l) and morning hyperglycemia (>10 mmol/l), in adults with type 1 diabetes using lispro insulin before meals and NPH insulin at bedtime. RESEARCH DESIGN AND METHODS: Substitutions of 15 g carbohydrate (one starch exchange) for an equivalent amount of uncooked cornstarch or pure protein were compared to a standard snack (control: two starch + one protein exchange) and to no snack (placebo) in 15 adults using a randomized, cross-over design. All snacks were equivalent in kcal, fat, and total available glucose. An intravenous facilitated hourly blood glucose sampling during the night (11:00 P.M. to 7:00 A.M.). RESULTS: The glycemic level at bedtime (<7, 7-10, and >10 mmol/l) mediated the effects observed. A total of 14 hypoglycemic episodes, in 60% of patients, and 23 morning hyperglycemic episodes occurred over 50 nights. Most hypoglycemic episodes (10 of 14, 71%) occurred with no snack compared to any snack (P < 0.001) and at HS levels of <7 mmol/l (P = 0.05). The standard and protein snacks resulted in no nocturnal hypoglycemia at all HS glucose levels (P < 0.001). Only HS glucose >10 mmol/l was protective against hypoglycemia, even in the absence of a snack (P = 0.05); 46% of morning hyperglycemic episodes were associated (r = 0.37, P = 0.07) with this HS glucose level. CONCLUSIONS: The need for and composition of an HS snack depends on the HS glucose such that no snack is necessary at levels >10 mmol/l. At levels between 7 and 10 mmol/l, any snack is advised, and at <7 mmol/l, a standard or protein snack is recommended.

Adult↗

Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810].

BACKGROUND: Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. METHODS: Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. RESULTS: Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p < 0.05) fecal isobutyric, isovaleric and propionic acids as well as the total amount of fecal short chain fatty acids. Kefir supplementation resulted in increased fecal bacterial content in the majority of the subjects. CONCLUSIONS: Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent.

Adult↗

Longer term effects of early dietary cholesterol level on synthesis and circulating cholesterol concentrations in human infants.

De novo endogenous cholesterol synthesis is an integral component of developing human infant adaptive mechanisms that regulate cholesterol homeostasis. Smaller central pools of cholesterol later in life may contribute to reduced low-density lipoprotein-cholesterol (LDL-C) concentrations in the plasma and thus reduce the risk of cardiovascular disease. Early infant adaptive mechanisms may theoretically result in altered central pools of cholesterol in later life. To examine the response of cholesterol homeostasis to long-term dietary cholesterol supplementation, endogenous cholesterol synthesis was studied in 81 full-term healthy neonates at 4 months or at 11 and 12 months of age. Thirty-two infants were breast-fed (BF) (6 males, 7 females), fed regular cows milk protein-based formula (RF) (6 males, 3 females) 0.85 mmol cholesterol/L (33 mg cholesterol/L), or fed regular cow milk protein-based formula with the addition of cholesterol (RF+cholesterol) (5 males, 5 females) 3.44 mmol cholesterol/L (133 mg cholesterol/L). Effects of cholesterol supplementation on cholesterol synthesis rates were evaluated at 4 months of age. Forty-nine other infants, BF (11 males, 6 females) fed RF (7 males, 12 females), or RF+cholesterol (6 males, 7 females) until 6 months of age were studied to test the hypothesis of imprinting using a cross-over design study with a 1-month 250 mg cholesterol/day challenge at 11 months of age. The incorporation rate of deuterium in body water into erythrocyte-free cholesterol over 48 hours was used as an index of cholesterol fractional synthetic rate (FSR) at 4, 11, and 12 months of age. Both plasma total- and LDL-C were higher (P <.04) in BF compared with RF+cholesterol and RF formula-fed groups at 4 months of age. Plasma cholesterol concentrations for all 3 groups were similar at 11 and 12 months of age. FSR (pools/d) was 4-fold higher (P <.0001) in both RF and RF+cholesterol compared with BF groups, but not different between RF and RF+cholesterol formula-fed groups. No differences in FSR before and after cholesterol challenge were observed within the 3 feeding groups at 11 and 12 months of age. However, synthesis rates from 4 months to 12 months increased (P <.03) in BF infants and decreased in both RF+cholesterol (P <.0001) and RF (P <.0001) fed groups. These results demonstrate relative insensitivity of synthesis rates and serum cholesterol concentrations to cholesterol challenge, irrespective of early dietary cholesterol intake in formula-fed and BF infants. These findings support the notion that early dietary cholesterol causes minimal changes in cholesterol metabolism about 6 months after dietary exposure in young infants.

Animals↗

No changes in serum fat-soluble vitamin and carotenoid concentrations with the intake of plant sterol/stanol esters in the context of a controlled diet.

Spreads enriched with plant sterol and stanol esters have been shown to possess similar cholesterol-lowering properties; however, their comparative capacity to alter circulating levels of other fat-soluble compounds has not been fully assessed. To compare actions of sterol and stanol ester consumption on serum fat-soluble vitamin and carotenoid concentrations, 15 hypercholesterolemic subjects were fed each of 3 fixed foods treatment diets over 21 days using a randomized crossover controlled design. Diets contained either (1) margarine (M), (2) margarine with sterol esters (MSE; 1.92 g/d), or (3) margarine with stanol esters (MSA; 1.76 g/d). No significant differences were found in initial or final serum fat-soluble vitamin and carotenoid concentrations among the 3 phases. Serum retinol and alpha- and gamma-tocopherol concentrations at baseline and endpoint and percentage changes relative to baseline for MSE and MSA were not significantly different from those of the M diet. After adjusting for total cholesterol reduction, no changes for alpha- and gamma-tocopherol were found. Serum vitamins D and K, lycopene, and lutein concentrations and percentage changes did not differ across diets. Serum concentrations at baseline and endpoint and percentage changes for alpha- and beta-cryptoxanthin and alpha- and gamma-carotene were not different among the diets, nor did serum alpha- and gamma-carotene concentrations to total cholesterol ratios differ. Serum lutein, beta-cryptoxanthin, and alpha-carotene concentrations increased over time. In conclusion, our results show no effect of consumption of esterified plant sterols or stanols on serum fat-soluble vitamin or carotenoid concentrations compared with a control diet.

Adult↗