John L. Sievenpiper

2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult

Since the publication of the 2012 guidelines new literature has emerged to inform decision-making. The 2016 guidelines primary panel selected a number of clinically relevant questions and has produced updated recommendations, on the basis of important new findings. In subjects with clinical atherosclerosis, abdominal aortic aneurysm, most subjects with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy is recommended. For all others, there is an emphasis on risk assessment linked to lipid determination to optimize decision-making. We have recommended nonfasting lipid determination as a suitable alternative to fasting levels. Risk assessment and lipid determination should be considered in individuals older than 40 years of age or in those at increased risk regardless of age. Pharmacotherapy is generally not indicated for those at low Framingham Risk Score (FRS; <10%). A wider range of patients are now eligible for statin therapy in the FRS intermediate risk category (10%-19%) and in those with a high FRS (> 20%). Despite the controversy, we continue to advocate for low-density lipoprotein cholesterol targets for subjects who start therapy. Detailed recommendations are also presented for health behaviour modification that is indicated in all subjects. Finally, recommendation for the use of nonstatin medications is provided. Shared decision-making is vital because there are many areas in which clinical trials do not fully inform practice. The guidelines are meant to be a platform for meaningful conversation between patient and care provider so that individual decisions can be made for risk screening, assessment, and treatment.

Heterogeneous effects of fructose on blood lipids in individuals with type 2 diabetes: systematic review and meta-analysis of experimental trials in humans

OBJECTIVE Because of blood lipid concerns, diabetes associations discourage fructose at high intakes. To quantify the effect of fructose on blood lipids in diabetes, we conducted a systematic review and meta-analysis of experimental clinical trials investigating the effect of isocaloric fructose exchange for carbohydrate on triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol in type 1 and 2 diabetes. RESEARCH DESIGN AND METHODS We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant trials of ≥7 days. Data were pooled by the generic inverse variance method and expressed as standardized mean differences with 95% CI. Heterogeneity was assessed by χ2 tests and quantified by I2. Meta-regression models identified dose threshold and independent predictors of effects. RESULTS Sixteen trials (236 subjects) met the eligibility criteria. Isocaloric fructose exchange for carbohydrate raised triglycerides and lowered total cholesterol under specific conditions without affecting LDL cholesterol or HDL cholesterol. A triglyceride-raising effect without heterogeneity was seen only in type 2 diabetes when the reference carbohydrate was starch (mean difference 0.24 [95% CI 0.05–0.44]), dose was >60 g/day (0.18 [0.00–0.37]), or follow-up was ≤4 weeks (0.18 [0.00–0.35]). Piecewise meta-regression confirmed a dose threshold of 60 g/day (R2 = 0.13)/10% energy (R2 = 0.36). A total cholesterol–lowering effect without heterogeneity was seen only in type 2 diabetes under the following conditions: no randomization and poor study quality (−0.19 [−0.34 to −0.05]), dietary fat >30% energy (−0.33 [−0.52 to −0.15]), or crystalline fructose (−0.28 [−0.47 to −0.09]). Multivariate meta-regression analyses were largely in agreement. CONCLUSIONS Pooled analyses demonstrated conditional triglyceride-raising and total cholesterol–lowering effects of isocaloric fructose exchange for carbohydrate in type 2 diabetes. Recommendations and large-scale future trials need to address the heterogeneity in the data.

Konjac-Mannan and American Ginsing: Emerging Alternative Therapies for Type 2 Diabetes Mellitus

Despite significant achievements in treatment modalities and preventive measures, the prevalence of diabetes has risen exponentially in the last decade. Because of these limitations there is a continued need for new and more effective therapies. An increasing number of people are using dietary and herbal supplements, even though there is a general lack of evidence for their safety and efficacy. Consequently, science based medical and government regulators are calling for more randomized clinical studies to provide evidence of efficacy and safety. Our research group has selected two such promising and functionally complementary therapies for further investigation as potentially emerging alternative therapies for type 2 diabetes: Konjac-mannan (KJM) and American ginseng (AG). We have generated a mounting body of evidence to support the claim that rheologically-selected, highly-viscous KJM, and AG with a specific composition may be useful in improving diabetes control, reducing associated risk factors such as hyperlipidemia and hypertension, and ameliorating insulin resistance. KJM has a demonstrated ability to modulate the rate of absorption of nutrients from the small bowel, whereas AG has post-absorptive effects. Consequently, it appears that KJM and AG are acting through different, yet complementary, mechanisms: KJM by increasing insulin sensitivity and AG likely by enhancing insulin secretion. Before the therapeutic potential of KJM and AG as novel prandial agents for treatment of diabetes can be fully realized, further controlled trials with larger sample sizes and of longer duration are required. A determination of the active ingredients in AG, and the rheology-biology relationship of KJM are also warranted.

Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials.

Background/Objectives:In the absence of consistent clinical evidence, there are concerns that fructose contributes to non-alcoholic fatty liver disease (NAFLD). To determine the effect of fructose on markers of NAFLD, we conducted a systematic review and meta-analysis of controlled feeding trials.Subjects/Methods:We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library (through 3 September 2013). We included relevant trials that involved a follow-up of ⩾7 days. Two reviewers independently extracted relevant data. Data were pooled by the generic inverse variance method using random effects models and expressed as standardized mean difference (SMD) for intrahepatocellular lipids (IHCL) and mean difference (MD) for alanine aminotransferase (ALT). Inter-study heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic).Results:Eligibility criteria were met by eight reports containing 13 trials in 260 healthy participants: seven isocaloric trials, in which fructose was exchanged isocalorically for other carbohydrates, and six hypercaloric trials, in which the diet was supplemented with excess energy (+21–35% energy) from high-dose fructose (+104–220 g/day). Although there was no effect of fructose in isocaloric trials, fructose in hypercaloric trials increased both IHCL (SMD=0.45 (95% confidence interval (CI): 0.18, 0.72)) and ALT (MD=4.94 U/l (95% CI: 0.03, 9.85)).Limitations:Few trials were available for inclusion, most of which were small, short (⩽4 weeks), and of poor quality.Conclusions:Isocaloric exchange of fructose for other carbohydrates does not induce NAFLD changes in healthy participants. Fructose providing excess energy at extreme doses, however, does raise IHCL and ALT, an effect that may be more attributable to excess energy than fructose. Larger, longer and higher-quality trials of the effect of fructose on histopathological NAFLD changes are required.

Soy Protein Reduces Serum Cholesterol by Both Intrinsic and Food Displacement Mechanisms

The apparently smaller LDL cholesterol (LDL-C)-lowering effect of soy in recent studies has prompted the U.S. FDA to reexamine the heart health claim previously allowed for soy products. We therefore attempted to estimate the intrinsic and extrinsic (displacement) potential of soy in reducing LDL-C to determine whether the heart health claim for soy continues to be justified. The intrinsic effect of soy was derived from a meta-analysis using soy studies (20-133 g/d soy protein) included in the recent AHA Soy Advisory. The extrinsic effect of soy in displacing foods higher in saturated fat and cholesterol was estimated using predictive equations for LDL-C and NHANES III population survey data with the substitution of 13-58 g/d soy protein for animal protein foods. The meta-analysis of the AHA Soy Advisory data gave a mean LDL-C reduction of 0.17 mmol/L (n = 22; P < 0.0001) or 4.3% for soy, which was confirmed in 11 studies reporting balanced macronutrient profiles. The estimated displacement value of soy (13-58 g/d) using NHANES III population survey data was a 3.6-6.0% reduction in LDL-C due to displacement of saturated fats and cholesterol from animal foods. The LDL-C reduction attributable to the combined intrinsic and extrinsic effects of soy protein foods ranged from 7.9 to 10.3%. Thus, soy remains one of a few food components that reduces serum cholesterol (>4%) when added to the diet.

Supplementation of Conventional Therapy with the Novel Grain Salba ( Salvia hispanica L. ) Improves Major and Emerging Cardiovascular Risk Factors in Type 2 Diabetes: Results of a Randomized Controlled Trial

OBJECTIVE—To determine whether addition of Salba (Salvia hispanica L.), a novel whole grain that is rich in fiber, α-linolenic acid (ALA), and minerals to conventional treatment is associated with improvement in major and emerging cardiovascular risk factors in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS—Using a single-blind cross-over design, subjects were randomly assigned to receive either 37 ± 4 g/day of Salba or wheat bran for 12 weeks while maintaining their conventional diabetes therapies. Twenty well-controlled subjects with type 2 diabetes (11 men and 9 women, aged 64 ± 8 years, BMI 28 ± 4 kg/m2, and A1C 6.8 ± 0.9%) completed the study. This study was set in the outpatient clinic of the Risk Factor Modification Center, St. Michael’s Hospital, Toronto, Canada. RESULTS—Compared with the control treatment, Salba reduced systolic blood pressure (SBP) by 6.3 ± 4 mmHg (P < 0.001), high-sensitivity C-reactive protein (hs-CRP) (mg/l) by 40 ± 1.6% (P = 0.04), and vonWillebrand factor (vWF) by 21 ± 0.3% (P = 0.03), with significant decreases in A1C and fibrinogen in relation to the Salba baseline but not with the control treatment. There were no changes in safety parameters including liver, kidney and hemostatic function, or body weight. Both plasma ALA and eicosapentaenoic polyunsaturated fatty acid levels were increased twofold (P < 0.05) while consuming Salba. CONCLUSIONS—Long-term supplementation with Salba attenuated a major cardiovascular risk factor (SBP) and emerging factors (hs-CRP and vWF) safely beyond conventional therapy, while maintaining good glycemic and lipid control in people with well-controlled type 2 diabetes.

Effect of fructose on postprandial triglycerides: A systematic review and meta-analysis of controlled feeding trials

BACKGROUND In the absence of consistent clinical evidence, concerns have been raised that fructose raises postprandial triglycerides. PURPOSE A systematic review and meta-analysis was conducted to assess the effect of fructose on postprandial triglycerides. DATA SOURCES Relevant studies were identified from MEDLINE, EMBASE, and Cochrane databases (through September 3, 2013). DATA SELECTION Relevant clinical trials of ≥ 7-days were included in the analysis. DATA EXTRACTION Two independent reviewers extracted relevant data with disagreements reconciled by consensus. The Heyland Methodological Quality Score (MQS) assessed study quality. Data were pooled by the generic inverse variance method using random effects models and expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). DATA SYNTHESIS Eligibility criteria were met by 14 isocaloric trials (n = 290), in which fructose was exchanged isocalorically for other carbohydrate in the diet, and two hypercaloric trials (n = 33), in which fructose supplemented the background diet with excess energy from high-dose fructose compared with the background diet alone (without the excess energy). There was no significant effect in the isocaloric trials (SMD: 0.14 [95% CI: -0.02, 0.30]) with evidence of considerable heterogeneity explained by a single trial. Hypercaloric trials, however, showed a significant postprandial triglyceride raising-effect of fructose (SMD: 0.65 [95% CI: 0.30, 1.01]). LIMITATIONS Most of the available trials were small, short, and of poor quality. Interpretation of the isocaloric trials is complicated by the large influence of a single trial. CONCLUSIONS Pooled analyses show that fructose in isocaloric exchange for other carbohydrate does not increase postprandial triglycerides, although an effect cannot be excluded under all conditions. Fructose providing excess energy does increase postprandial triglycerides. Larger, longer, and higher-quality trials are needed. PROTOCOL REGISTRATION ClinicalTrials.gov identifier, NCT01363791.

Are dietary recommendations for the use of fish oils sustainable

People in developed countries have been encouraged in recent years to increase their intakes of fatty fish by at least 2–3-fold. The goal is to consume adequate amounts of the long-chain polyunsaturated omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for optimal

Glycemic index, glycemic load and glycemic response: An International Scientific Consensus Summit from the International Carbohydrate Quality Consortium (ICQC)

BACKGROUND AND AIMS The positive and negative health effects of dietary carbohydrates are of interest to both researchers and consumers. METHODS International experts on carbohydrate research held a scientific summit in Stresa, Italy, in June 2013 to discuss controversies surrounding the utility of the glycemic index (GI), glycemic load (GL) and glycemic response (GR). RESULTS The outcome was a scientific consensus statement which recognized the importance of postprandial glycemia in overall health, and the GI as a valid and reproducible method of classifying carbohydrate foods for this purpose. There was consensus that diets low in GI and GL were relevant to the prevention and management of diabetes and coronary heart disease, and probably obesity. Moderate to weak associations were observed for selected cancers. The group affirmed that diets low in GI and GL should always be considered in the context of diets otherwise understood as healthy, complementing additional ways of characterizing carbohydrate foods, such as fiber and whole grain content. Diets of low GI and GL were considered particularly important in individuals with insulin resistance. CONCLUSIONS Given the high prevalence of diabetes and pre-diabetes worldwide and the consistency of the scientific evidence reviewed, the expert panel confirmed an urgent need to communicate information on GI and GL to the general public and health professionals, through channels such as national dietary guidelines, food composition tables and food labels.

Associations of Glycemic Index and Load With Coronary Heart Disease Events: A Systematic Review and Meta-Analysis of Prospective Cohorts

Background Glycemic index (GI) and glycemic load (GL) have been associated with coronary heart disease (CHD) risk in some but not all cohort studies. We therefore assessed the association of GI and GL with CHD risk in prospective cohorts. Methods and Results We searched MEDLINE, EMBASE, and CINAHL (through April 5, 2012) and identified all prospective cohorts assessing associations of GI and GL with incidence of CHD. Meta-analysis of observational studies in epidemiology (MOOSE) methodologies were used. Relative measures of risk, comparing the group with the highest exposure (mean GI of cohorts=84.4 GI units, range 79.9 to 91; mean GL of cohorts=224.8, range 166 to 270) to the reference group (mean GI=72.3 GI units, range 68.1 to 77; mean GL=135.4, range 83 to 176), were pooled using random-effects models, expressed as relative risk (RR) with heterogeneity assessed by χ2 and quantified by I2. Subgroups included sex and duration of follow-up. Ten studies (n=240 936) were eligible. Pooled analyses showed an increase in CHD risk for the highest GI quantile compared with the lowest, with RR=1.11 (95% confidence interval [CI] 0.99 to 1.24) and for GL, RR=1.27 (95% CI 1.09 to 1.49), both with evidence of heterogeneity (I2>42%, P<0.07). Subgroup analyses revealed only a significant modification by sex, with the female cohorts showing significance for GI RR=1.26 (95% CI 1.12 to 1.41) and for GL RR=1.55 (95% CI 1.18 to 2.03). Conclusions High GI and GL diets were significantly associated with CHD events in women but not in men. Further studies are required to determine the relationship between GI and GL with CHD in men.