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PubMed | University of Manitoba, University of Granada, Richardson Center for Functional Foods and Nutraceuticals and Science 37
Type: Journal Article | Journal: Lipids | Year: 2016

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that regulates cholesterol metabolism by promoting LDL receptor degradation in the liver and has recently been proposed as a therapeutic target in the management of hyperlipidaemia. We investigated the impact of dietary fat on the metabolism of sterols and on plasma PCSK9 concentrations to explore likely clinical usefulness. In a post hoc analysis of a double-blind randomised crossover controlled feeding trial, the Canola Oil Multicenter Intervention Trial (COMIT), volunteers (n = 54) with at least one condition related to metabolic syndrome consumed diets with one of the following treatment oils in beverages: (1) conventional canola oil (Canola); (2) canola oil rich in docosahexanoic acid (DHA) (CanolaDHA); and (3) high-oleic acid canola oil (CanolaOleic). The enrichment in oleic acid resulted in lower plasma cholesterol concentration compared with diets enriched in DHA. Contrarily, DHA-enriched oil significantly decreased plasma PCSK9 and triacylglycerols levels, but increased circulating levels of sterols. The variations in lathosterol, sitosterol, and campesterol indicate that plasma PCSK9 levels are sensitive to changes in cholesterol synthesis and/or absorption. There was a significant correlation between plasma PCSK9 levels and plasma triacylglicerol and apolipoprotein B levels, which was not affected by dietary fat. Therefore, our results suggest that the impact of dietary fats should not be discarded as complementary treatment in the management of patients with hyperlipidaemia. These findings should be considered in the analysis of ongoing studies and may represent a cautionary note in the treatment of patients with cardiovascular risk.

Ramprasath V.R.,Richardson Center for Functional Foods and Nutraceuticals | Ramprasath V.R.,University of Manitoba | Eyal I.,Enzymotec | Zchut S.,Enzymotec | And 2 more authors.
Lipids in Health and Disease | Year: 2013

Background: Due to structural differences, bioavailability of krill oil, a phospholipid based oil, could be higher than fish oil, a triglyceride-based oil, conferring properties that render it more effective than fish oil in increasing omega-3 index and thereby, reducing cardiovascular disease (CVD) risk. Objective. The objective was to assess the effects of krill oil compared with fish oil or a placebo control on plasma and red blood cell (RBC) fatty acid profile in healthy volunteers. Participants and methods. Twenty four healthy volunteers were recruited for a double blinded, randomized, placebo-controlled, crossover trial. The study consisted of three treatment phases including krill or fish oil each providing 600 mg of n-3 polyunsaturated fatty acids (PUFA) or placebo control, corn oil in capsule form. Each treatment lasted 4 wk and was separated by 8 wk washout phases. Results: Krill oil consumption increased plasma (p = 0.0043) and RBC (p = 0.0011) n-3 PUFA concentrations, including EPA and DHA, and reduced n-6:n-3 PUFA ratios (plasma: p = 0.0043, RBC: p = 0.0143) compared with fish oil consumption. Sum of EPA and DHA concentrations in RBC, the omega-3 index, was increased following krill oil supplementation compared with fish oil (p = 0.0143) and control (p < 0.0001). Serum triglycerides and HDL cholesterol concentrations did not change with any of the treatments. However, total and LDL cholesterol concentrations were increased following krill (TC: p = 0.0067, LDL: p = 0.0143) and fish oil supplementation (TC: p = 0.0028, LDL: p = 0.0143) compared with control. Conclusions: Consumption of krill oil was well tolerated with no adverse events. Results indicate that krill oil could be more effective than fish oil in increasing n-3 PUFA, reducing n-6:n-3 PUFA ratio, and improving the omega-3 index. Trial registration. ClinicalTrials.gov, NCT01323036. © 2013 Ramprasath et al.; licensee BioMed Central Ltd.

MacKay D.S.,Richardson Center for Functional Foods and Nutraceuticals | MacKay D.S.,U.S. Department of Agriculture | Eck P.K.,U.S. Department of Agriculture | Gebauer S.K.,U.S. Department of Agriculture | And 4 more authors.
American Journal of Clinical Nutrition | Year: 2015

Background: The benefits of plant sterols (PSs) for cholesterol lowering are hampered by large heterogeneity across individuals, potentially because of genetic polymorphisms. Objective: We investigated the impact of candidate genetic variations on cholesterol response to PSs in a trial that recruited individuals with high or low endogenous cholesterol synthesis, estimated by lathosterol to cholesterol (L:C) ratio. Design: Mildly hypercholesterolemic adults preselected as possessing either high endogenous cholesterol synthesis (n = 24; mean ± SEM: L:C ratio = 2.03 ± 0.39 mmol/mmol) or low endogenous cholesterol synthesis (n = 39; mean ± SEM: L:C ratio = 0.99 ± 0.28 mmol/mmol) consumed 2 g PS/d or a placebo for 28 d by using a dual-center, single-blind, randomized crossover design. Cholesterol synthesis and change in cholesterol absorption were measured with stable isotopic tracers. Candidate single-nucleotide polymorphisms and apolipoprotein E (APOE) isoform were assessed by TaqMan genotyping assay. Results: The cholesterol fractional synthesis rate was higher (P , 0.001) in participants with high endogenous cholesterol synthesis (mean ± SEM: placebo: 9.16% ± 0.47%; PSs: 9.74% ± 0.47%) than in participants with low endogenous cholesterol synthesis (mean ± SEM placebo: 5.72% ± 0.43%; PS: 7.10% ± 0.43%). Low-density lipoprotein (LDL) cholesterol lowering in response to PSs was associated with individuals- genotypes. Cholesterol 7 alpha-hydroxylase (CYP7A1-rs3808607) T/T homozygotes showed no LDL cholesterol lowering (mean ± SEM: 20.05 ± 0.07 mmol/L, P = 0.9999, n = 20), whereas the presence of the G-allele associated with LDL cholesterol response in a dosedependent fashion (mean ± SEM G/T: 20.22 ± 0.06 mmol/L, P = 0.0006, n = 35; G/G: 20.46 ± 0.12 mmol/L, P = 0.0009, n = 8). Similarly, APOE e3 carriers (mean ± SEM: 20.13 ± 0.05 mmol/L, P = 0.0370, n = 40) responded less than APOE e4 carriers (mean ± SEM: 20.31 ± 0.07 mmol/L, P , 0.0001, n = 23). Moreover, genoset CYP7A1-rs3808607 T/T/APOE e3 was associated with nonresponsiveness (mean ± SEM: +0.09 ± 0.08 mmol/L, P = 0.9999, n = 14). rs5882 in cholesteryl ester transfer protein (CETP) and rs4148217 in ATP-binding cassette subfamily G member 8 (ABCG8) did not associate with LDL cholesterol lowering. Cholesterol absorption decreased as a result of PS consumption, but this decrease was not related to circulating LDL cholesterol concentrations, cholesterol synthesis phenotype, or genotypes. Conclusion: CYP7A1-rs3808607 and APOE isoform are associated with the extent of reduction in circulating LDL cholesterol in response to PS consumption and could serve as potential predictive genetic markers to identify individuals who would derive maximum LDL cholesterol lowering with PS consumption. The trial was registered at clinicaltrials.gov as NCT01131832. © 2015 American Society for Nutrition.

Onuh J.O.,University of Manitoba | Girgih A.T.,Richardson Center for Functional Foods and Nutraceuticals | Aluko R.E.,University of Manitoba | Aluko R.E.,Richardson Center for Functional Foods and Nutraceuticals | And 2 more authors.
Food Research International | Year: 2013

Enzymatic hydrolysates from chicken skin protein were investigated for their in vitro inhibitions of angiotensin converting enzyme (ACE) and renin activities. Enzyme hydrolysis of the chicken skin protein from the thigh and breast muscles was done using alcalase or a combination of pepsin/pancreatin (PP) at enzyme concentrations of 1-4%. The chicken skin protein hydrolysates (CSPH) were then fractionated by membrane ultrafiltration into different molecular weight peptides (<1, 1-3, 3-5 and 5-10. kDa). Results showed that degree of hydrolysis (DH) of the hydrolysates increased significantly with protease concentration for all the samples (72.61-81.88%) and correlated positively with peptide yield. The alcalase hydrolysates generally had significantly higher (p < 0.05) ACE-inhibitory activity when compared to PP hydrolysates. ACE inhibition was inversely related to size of ultrafiltration membrane peptides. A moderate renin-inhibitory activity was observed (15-36%), which was dependent on the type of protease; the PP hydrolysates showed significantly higher (p < 0.05) inhibition than alcalase hydrolysates. These results suggest that CSPH can be considered a potential ingredient for the development of functional foods and nutraceuticals that can attenuate catalytic activities of ACE and renin. © 2013 Elsevier Ltd.

Onuh J.O.,University of Manitoba | Girgih A.T.,University of Manitoba | Aluko R.E.,University of Manitoba | Aluko R.E.,Richardson Center for Functional Foods and Nutraceuticals | And 2 more authors.
Food Chemistry | Year: 2014

Chicken thigh and breast skin proteins were hydrolysed using alcalase or a combination of pepsin and pancreatin (PP), each at concentrations of 1-4%. The chicken skin protein hydrolysates (CSPHs) were then fractionated by membrane ultrafiltration into different molecular weight peptides (<1, 1-3, 3-5 and 5-10 kDa) and analysed for antioxidant properties. Results showed that the CSPHs had a significantly (p < 0.05) lower scavenging activity against DPPH radicals when compared to reduced glutathione. The chicken breast skin hydrolysates had significantly higher DPPH scavenging activity than the chicken thigh skin hydrolysates. DPPH scavenging and metal ion chelation increased significantly (p < 0.05) from 29-40% to 86-89%, respectively with increasing proteolytic enzyme concentration. In contrast, the antioxidant properties decreased as peptide size increased. We conclude that CSPHs and their peptide fractions may be used as ingredients in the formulation of functional foods and nutraceuticals for the control and management of oxidative stress-related diseases.© 2013 Published by Elsevier Ltd.

Chen Y.,University of Manitoba | Thiyam-Hollander U.,University of Manitoba | Thiyam-Hollander U.,Richardson Center for Functional Foods and Nutraceuticals | Barthet V.J.,Canadian Grain Commission | Aachary A.A.,University of Manitoba
Journal of Agricultural and Food Chemistry | Year: 2014

Valuable phenolic antioxidants are lost during oil refining, but evaluation of their occurrence in refining byproducts is lacking. Rapeseed and canola oil are both rich sources of sinapic acid derivatives and tocopherols. The retention and loss of sinapic acid derivatives and tocopherols in commercially produced expeller-pressed canola oils subjected to various refining steps and the respective byproducts were investigated. Loss of canolol (3) and tocopherols were observed during bleaching (84.9%) and deodorization (37.6%), respectively. Sinapic acid (2) (42.9 μg/g), sinapine (1) (199 μg/g), and canolol (344 μg/g) were found in the refining byproducts, namely, soap stock, spent bleaching clay, and wash water, for the first time. Tocopherols (3.75 mg/g) and other nonidentified phenolic compounds (2.7 mg sinapic acid equivalent/g) were found in deodistillates, a byproduct of deodorization. DPPH radical scavenging confirmed the antioxidant potential of the byproducts. This study confirms the value-added potential of byproducts of refining as sources of endogenous phenolics. © 2014 American Chemical Society.

Jones P.J.,Richardson Center for Functional Foods and Nutraceuticals
Nutrition journal | Year: 2014

BACKGROUND: Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption.OBJECTIVE: The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins.METHODS: Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months.RESULTS: No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased β-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted β-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; β-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; β-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and β-sitosterol concentrations were negatively correlated (p < 0.001) with total and LDL-C levels.CONCLUSION: Results demonstrate that consuming a portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.

Rideout T.C.,Richardson Center for Functional Foods and Nutraceuticals | Harding S.V.,Richardson Center for Functional Foods and Nutraceuticals | Jones P.J.H.,Richardson Center for Functional Foods and Nutraceuticals | Jones P.J.H.,University of Manitoba
Molecular Nutrition and Food Research | Year: 2010

To investigate emerging clinical data suggesting a triglyceride (TAG)-lowering response to plant sterol (PS) therapy, we characterized changes in TAG metabolism in 16 C57BL/6J mice fed a basal control diet (CON) or the CON diet supplemented with 2% PS for 6 wk. PS consumption reduced (p<0.05) plasma (-28%) and hepatic (-30%) TAG concentrations compared with CON mice. PS consumption increased (p<0.05) hepatic lipogenic gene expression (sterol-regulatory-element-binding protein 1c, 2.4-fold of CON; fatty acid synthase, 6.5-fold of CON) and de novo lipogenesis (4.51±70.72 versus 2.82±70.61%/day) compared with CON. PS consumption increased (p<0.05) fecal palmitate and stearate excretion and reduced body weight gain compared with CON mice. Although no change in the transcription of intestinal fatty acid absorptive genes was observed, peroxisome proliferator-activated receptor α mRNA was reduced (p<0.05, 2.0-fold of CON) in the PS-fed mice. In conclusion, PS-fed C57BL/6J mice showed pronounced reductions in plasma and hepatic TAG concentrations despite increases in hepatic lipogenic gene expression and de novo lipogenesis. Interference with intestinal fatty acid/TAG metabolism as suggested by increased fecal fatty acid loss and reduced weight gain may be associated with the TAG-lowering response to PS consumption. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Khattab R.Y.,Alexandria University | Eskin M.N.A.,University of Manitoba | Thiyam-Hollander U.,Richardson Center for Functional Foods and Nutraceuticals
JAOCS, Journal of the American Oil Chemists' Society | Year: 2014

A potent antioxidant, anti-inflammatory and anti-mutagenic agent; 4-vinyl-2,6-dimethoxyphenol (canolol) was obtained from canola meal in a significant yield via alkaline (NaOH)/enzymatic (ferulic acid esterase) hydrolysis followed by microwave-assisted decarboxylation. The hydrolysis was carried out either through using canola meal directly as a substrate or by using the 70 % aqueous methanolic extract filtrates. The hydrolyzed extracts underwent RP-HPLC analysis which showed that 81.0 and 94.8 % of the total phenolics were hydrolyzed to sinapic acid after the alkaline hydrolysis of the meal and the methanolic extracts, respectively. The enzymatic hydrolysis showed lower conversion rates (49.5 and 58.3 %). The hydrolyzed extracts were consequently decarboxylated using 8-diazabicyclo[5.4.0]undec-7-ene under microwave irradiation at different conditions. The HPLC profiling of decarboxylated extracts showed that using microwave at 300 Wof microwave power for 12 min brought the highest sinapic acid conversion to canolol (58.3 %) yielding 4.2 mg canolol from each gram of canola meal suggesting that the process could be commercially economical. © AOCS 2013.

Rideout T.C.,Richardson Center for Functional Foods and Nutraceuticals | Rideout T.C.,University of Manitoba | Harding S.V.,Richardson Center for Functional Foods and Nutraceuticals | Harding S.V.,University of Manitoba | And 4 more authors.
American Journal of Clinical Nutrition | Year: 2010

Background: The cholesterol-lowering effectiveness of plant sterol (PS) therapy is hindered by wide-ranging variability in LDL-cholesterol responsiveness across individuals. To capitalize on the LDL-cholesterol-lowering potential of PS in the clinical setting, it is paramount to characterize the metabolic factors that underlie this heterogeneity of responsiveness. Objective: The objective was to investigate the relation between cholesterol synthesis and plasma LDL-cholesterol reductions in response to PS consumption. Design: We evaluated previously conducted clinical PS interventions incorporating stable-isotope measures of cholesterol synthesis and conducted feeding studies in animal models of response (Syrian Golden hamsters) and nonresponse (C57BL/6J mice) to PS consumption. Results: From our clinical study population (n = 113), we identified 47 nonresponders (3.73 ± 1.10% change in LDL cholesterol) and 66 responders (-15.16 ± 1.04% change in LDL cholesterol) to PS therapy. The basal cholesterol fractional synthesis rate (FSR) as measured by direct deuterium incorporation was 23% higher (P = 0.003) in the nonresponder subgroup than in responders to PS therapy. The basal cholesterol FSR correlated (r = 0.22, P = 0.02) with the percentage change in LDL cholesterol after PS intervention. In support of our clinical observations, nonresponding mice showed a 77% higher (P = 0.001) basal cholesterol FSR than that of responding hamsters. Compared with control mice, PS-fed mice showed an increase in hepatic nuclear sterol regulatory element binding protein 2 abundance (1.3-fold of control, P = 0.04) and β-hydroxy-β-methylglutaryl coenzyme A reductase-mRNA expression (2.4-fold of control, P = 0.00). Conclusion: The results suggest that subjects with high basal cholesterol synthesis are less responsive to PS treatment than are subjects with low basal cholesterol synthesis. © 2010 American Society for Nutrition.

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