Thesis (Ph. D.)--Columbia University, 1916. / Vita. "Reprinted from the Journal of biological chemistry, vol. XXVII, no. 2, October, 1916."

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Reduced bioavailability in some formulations of phytosterols accounts for the variable results observed in LDL- C- lowering efficacy among trials. This study examined the effects of a water-dispersible formulation of free phytosterols (WD-PS) versus phytosterol esters (PS-esters) on plasma lipid and fat soluble vitamins concentrations in hypercholesterolemic individuals. Using a double-blind, randomized, crossover study, 47 hypercholesterolemics were provided for 4 wk: WD-PS-enriched yogurt (2g/d), PS-esters-enriched yogurt (2g/d), or yogurt alone (placebo), in a random order. Each study phase was separated by 4 wk washout intervals. Supplementation of WD-PS or PS-esters similarly decreased serum TC (7.7% and 6.3%, respectively) and LDL-C levels (11.7% and 11.6%, respectively, p<0.001). The ratio of TC/ HDL-C decreased for WD-PS (10.6%, p<0.05) but not for PS-esters. Moreover, WD-PS reduced serum TG (13.9%, p<0.05) as compared to PS-esters (0.6%). The results of the current study confirm the importance of the formulation of phytosterols in their bioavailability and efficacy.

Reduced bioavailability in some formulations of phytosterols accounts for the variable results observed in LDL- C- lowering efficacy among trials. This study examined the effects of a water-dispersible formulation of free phytosterols (WD-PS) versus phytosterol esters (PS-esters) on plasma lipid and fat soluble vitamins concentrations in hypercholesterolemic individuals. Using a double-blind, randomized, crossover study, 47 hypercholesterolemics were provided for 4 wk: WD-PS-enriched yogurt (2g/d), PS-esters-enriched yogurt (2g/d), or yogurt alone (placebo), in a random order. Each study phase was separated by 4 wk washout intervals. Supplementation of WD-PS or PS-esters similarly decreased serum TC (7.7% and 6.3%, respectively) and LDL-C levels (11.7% and 11.6%, respectively, p<0.001). The ratio of TC/ HDL-C decreased for WD-PS (10.6%, p<0.05) but not for PS-esters. Moreover, WD-PS reduced serum TG (13.9%, p<0.05) as compared to PS-esters (0.6%). The results of the current study confirm the importance of the formulation of phytosterols in their bioavailability and efficacy.

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The cholesterol-lowering effect of mixed linkage (1→3) (1→4)-β-D-glucans (β-glucan) from barley has been documented, yet the underlying mechanism responsible for this action and factors influencing it, such as physicochemical properties of β-glucan and genetic background of an individual, remain unclear.As a component of dietary fibre, β-glucan also has the potential to shift the gut microbial community, however, whether alterations in the gut microbiota are associated with the physiological effects of β-glucan have yet to be determined. This study was designed to assess the effects of β-glucan molecular weight (MW) and dose on loweringserum cholesterol levels and to elucidate its mechanism of action in human subjects. Additionally, this study examined gene-diet interactions as well as changes in the gut microbiota profile following consumption of barley foods. In a controlled four phase crossover trial, mildly hypercholesterolemic but otherwise healthy subjects (n =30) were randomly assigned to receive breakfasts containing 3g high MW (HMW), 5g low molecular weight (LMW), 3g LMW barley β-glucan or a control diet with wheat and rice (WR control), each for 5 weeks. The washout period between the phases was 4 weeks. The consumption of 3g/d HMW diet lowered total cholesterol (TC) compared with WR control diet (P =0.0046), but not the LMW diet at either 3g/d or 5g/d. Individuals with the SNP rs3808607-G allele of CYP7A1 had greater TC reduction in response to 3g/d HMW β-glucan diet compared to the individuals carrying homozygous TT alleles (P<0.01). Cholesterol absorption and synthesis were not changed, but bile acid synthesis increased by 3g/d HMW diet compared to the control. Consuming 3g HMW/d β-glucan altered gut microbiota at the phylum and genus levels and the impacted microbial members was correlated with favorable shifts of cardiovascular disease risk factors. In conclusion, physicochemical properties of β-glucan play critical roles in the cholesterol-lowering effect and gut microbiota alteration ability of β-glucan. The results suggest the increasing bile acid synthesis rather than inhibiting cholesterol absorption and synthesis is the mechanism responsible for the cholesterol reducing property of β-glucan.The altered microbiota profile by HMW β-glucan is associated with its physiological effect. / February 2016

Global obesity is linked to chronic diseases including hypercholesterolemia, a cardiovascular disease risk factor, thus weight reduction in obesity is a key priority for combatting obesity. The cholesterol transporters ABCG5, ABCG8 and NPC1L1 mediate cholesterol trafficking across the intestinal wall, thus are important in regulating cholesterol metabolism and circulating levels. The objective of this study was to examine if single nucleotide polymorphisms (SNP) of cholesterol transporters ABCG5, ABCG8 and NPC1L1 are associated with changes in cholesterol synthesis and absorption and lipid parameters (LP) subsequent to weight loss (WtL) in overweight individuals. Eighty-nine individuals from two WtL trials (Trial A (n = 54) and Trial B (n = 35)) completed a 20-wk WtL period. After 10% WtL, lipid parameters excluding LDL-C were improved in Trial A, while all lipid parameters were ameliorated after 12% of WtL when Trial A and B were combined. Post-WtL, cholesterol synthesis (CS) was reduced; however, cholesterol absorption was not changed in either Trial A or the combined trials. Polymorphisms in ABCG8 V632A were associated with changes in TC and TG levels after WtL in both trial A and the combined data. SNPs in ABCG5 Q604E, ABCG8 T400K, were associated with changes in CS because of WtL in Trial A; however, the association is no longer seen in combined analysis. In conclusion, cardio-protective changes in LP due to weight loss were mediated by reductions in CS. Additionally, polymorphisms in ABCG8 were associated with amelioration in LP after WtL. Thus, the benefits in CVD risk subsequent to weight loss vary across individuals due to genetic factors associated with cholesterol trafficking.

Global obesity is linked to chronic diseases including hypercholesterolemia, a cardiovascular disease risk factor, thus weight reduction in obesity is a key priority for combatting obesity. The cholesterol transporters ABCG5, ABCG8 and NPC1L1 mediate cholesterol trafficking across the intestinal wall, thus are important in regulating cholesterol metabolism and circulating levels. The objective of this study was to examine if single nucleotide polymorphisms (SNP) of cholesterol transporters ABCG5, ABCG8 and NPC1L1 are associated with changes in cholesterol synthesis and absorption and lipid parameters (LP) subsequent to weight loss (WtL) in overweight individuals. Eighty-nine individuals from two WtL trials (Trial A (n = 54) and Trial B (n = 35)) completed a 20-wk WtL period. After 10% WtL, lipid parameters excluding LDL-C were improved in Trial A, while all lipid parameters were ameliorated after 12% of WtL when Trial A and B were combined. Post-WtL, cholesterol synthesis (CS) was reduced; however, cholesterol absorption was not changed in either Trial A or the combined trials. Polymorphisms in ABCG8 V632A were associated with changes in TC and TG levels after WtL in both trial A and the combined data. SNPs in ABCG5 Q604E, ABCG8 T400K, were associated with changes in CS because of WtL in Trial A; however, the association is no longer seen in combined analysis. In conclusion, cardio-protective changes in LP due to weight loss were mediated by reductions in CS. Additionally, polymorphisms in ABCG8 were associated with amelioration in LP after WtL. Thus, the benefits in CVD risk subsequent to weight loss vary across individuals due to genetic factors associated with cholesterol trafficking.