John L. Sievenpiper’s research while affiliated with St. Michael's Hospital and other places

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Publications (295)


Perspective: Current Scientific Evidence and Research Strategies in the Role of Almonds in Cardiometabolic Health
  • Article

November 2024

Current Developments in Nutrition

Paula R. Trumbo

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Jamy Ard

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France Bellisle

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James Hill

The flow of the literature on the effect of extracted pulse proteins on blood lipids. apoB, apolipoprotein B; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; non-HDL-C, non-high-density lipoprotein cholesterol; TG, triglyceride.
A summary plot of the effect of extracted pulse proteins on blood lipids in randomized controlled trials. Data are expressed as weighted mean differences with 95% confidence intervals of the summary effect estimates using the generic inverse variance method modeled by random effect (≥5 trial comparisons) or fixed effect (<5 trial comparisons) meta-analyses. The between-study heterogeneity was assessed using the Cochran Q statistic, where PQ < 0.100 was considered statistically significant, and quantified by the I² statistic, where I² ≥ 50% was considered evidence of substantial heterogeneity. The effect estimates of total extracted pulse proteins from different sources are denoted as diamonds. The effect estimates of individual extracted pulse protein types are denoted as squares. Any statistically significant reductions are highlighted in green. The grading of recommendations, assessment, development, and evaluation (GRADE) of randomized controlled trials are rated as having a “high” certainty of evidence and can be downgraded by 5 domains and upgraded by 1 domain. The white squares represent no downgrades, filled black squares indicate a single downgrade or upgrade for each outcome, and the black square with a white “2” indicates a double downgrade for each outcome. a Because all included trials were randomized controlled trials, the certainty of the evidence was graded as high for all outcomes by default and then downgraded or upgraded based on prespecified criteria. Criteria for downgrades included risk of bias (ROB) (downgraded if most trials were considered to be at high ROB); inconsistency (downgraded if there was substantial unexplained heterogeneity: I² ≥ 50%; PQ < 0.10); indirectness (downgraded if there were factors absent or present relating to the participants, interventions, or outcomes that limited the generalizability of the results); imprecision (downgraded if the 95% confidence intervals crossed the minimally important difference (MID) for harm or benefit set at 0.1 mmol/L (5%) for LDL-C, non-HDL-C, HDL-C, and TG and ± 0.04 g/L for apoB [32,33,34,35], or there was a concern with the robustness of the estimate resulting from sensitivity analyses); and publication bias (downgraded if there was evidence of publication bias based on the funnel plot asymmetry and/or significant Egger’s or Begg’s test (p < 0.10) with the confirmation of evidence of small study effects by adjustment using the trim-and-fill analysis of Duval and Tweedie [42]). The criteria for upgrades included a significant dose–response gradient that supports the direction of the pooled effect estimate. Please see Supplemental Table S7 for details on the GRADE assessment. b For the interpretation of the magnitude, we used the MIDs (see a) to assess the importance of the magnitude of our point estimate using the effect size categories according to the new GRADE guidance [51,52,53] as follows: a large effect (≥5× MID); moderate effect (≥2× MID); small important effect (≥1× MID); and trivial/unimportant effect (<1 MID). Please see Supplemental Table S7 for details on the GRADE assessment. * Owing to the difference in the directionality of HDL-C compared with the other outcomes with regards to signal for benefit or harm, the sign for the MD was changed. apoB, apolipoprotein B; CI, confidence interval; GRADE, grading of recommendations, assessment, development, and evaluation; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; MD, mean difference; N, number; non-HDL-C, non-high-density lipoprotein cholesterol; PMD, p-value of the mean difference; PQ, p-value of the heterogeneity; ROB, risk of bias; TG, triglycerides.
Continuous meta-regression analysis for the effect of extracted pulse proteins by the proportion of females *.
Effects of Extracted Pulse Proteins on Lipid Targets for Cardiovascular Risk Reduction: Systematic Review and Meta-Analysis of Randomized Controlled Trials
  • Article
  • Full-text available

November 2024

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21 Reads

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets. Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through April 2024 for trials of ≥3-weeks. The primary outcome was low-density lipoprotein-cholesterol (LDL-C). The secondary outcomes were other lipid targets. Independent reviewers extracted data and assessed the risk of bias. Subgroup analyses included by pulse type and the certainty of evidence was assessed using GRADE. Results: Seven included trials (14 trial comparisons, n = 453) with a median of 4-weeks duration and dose of 35 g/day showed that extracted pulse proteins decreased LDL-C by −0.23 mmol/L (95% confidence interval: −0.36 to −0.10 mmol/L, p < 0.001). Similar effects were observed for non-high-density lipoprotein-cholesterol and apolipoprotein B. No interactions were found by pulse type. Subgroup analyses revealed effect modification by sex, with greater proportions of females seeing greater reductions. GRADE was generally moderate. Conclusions: Extracted pulse proteins likely result in moderate reductions in LDL-C and other lipid targets. Future studies on various types of extracted pulse proteins including assessments by sex are warranted.

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No Difference between the Efficacy of High-Nitrate and Low-Nitrate Vegetable Supplementation on Blood Pressure after 16 Weeks in Individuals with Early-Stage Hypertension: An Exploratory, Double-Blinded, Randomized, Controlled Trial

September 2024

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41 Reads

Dietary inorganic nitrate lowers blood pressure (BP) in healthy individuals through improved nitric oxide (NO) bioavailability. However, there is limited evidence examining the long-term effects of dietary nitrate for managing hypertension. We aimed to determine whether the sustained intake of dietary nitrate improved BP and cardiovascular disease (CVD) risk factors in individuals with early-stage hypertension. The Dietary Nitrate (NO3) on BP and CVD Risk Factors (DINO3) Trial was a multi-center, double-blinded, parallel, randomized, controlled trial in participants with elevated BP. Participants were supplemented with high-nitrate (HN) (~400 mg nitrate) or low-nitrate (LN) vegetable powder (~50 mg nitrate) on top of their usual diets for 16 weeks. The primary outcome was office systolic BP at 16 weeks. The secondary outcomes were 24 h ambulatory BP, central BP, heart-rate-corrected augmentation index (AIx75), carotid–femoral pulse wave velocity (cf-PWV), lipids, and high-sensitivity C-reactive protein (hs-CRP). Sixty-six participants were randomized at baseline (39M:27F, age: 51.5 ± 10.8 years, BMI:27.9 ± 3.2 kg/m²). In an intention-to-treat analysis, no differences were observed between HN and LN groups in terms of office systolic BP at 16 weeks (3.91 ± 3.52 mmHg, p = 0.27) or secondary outcomes. In this exploratory study, sustained HN vegetable supplementation did not exhibit more favorable vascular effects than LN vegetable supplementation in individuals with elevated BP.



Participant flow from both trials. Dietary and HbA1c data were available at baseline and 6 months in 267 participants. Abbreviations: C, Control arm (high fibre dietary advice); DMGI, Diabetes Management with a low Glycemic Index diet study; DM-MRI, DM-Magnet Residence Imagining study; T, Test arm (low glycemic index dietary advice).
Correlation of change in the c-PDS and change in HbA1c. β: −0.04% per c-PDS point, 95% CI: −0.07 to −0.02, p = 0.001. Abbreviations: CI, confidence interval; c-PDS, clinical Portfolio Diet Score; HbA1c, hemoglobin A1c.
Baseline characteristics of participants in the included trials.
Pooled baseline intake of the Portfolio Diet measured by the c-PDS at baseline and end (6 months) along with the corresponding change in the pooled trials.
Multiple linear regression analysis of associated change of the c-PDS and HbA1c.
The Portfolio Diet and HbA1c in Adults Living with Type 2 Diabetes Mellitus: A Patient-Level Pooled Analysis of Two Randomized Dietary Trials

August 2024

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62 Reads

(1) Background: The Portfolio Diet, a dietary pattern of cholesterol-lowering foods, is also rich in low glycemic index (GI) foods. While strong evidence supports clinically meaningful reductions in cholesterol, evidence on the relationship between the Portfolio Diet and diabetes management is lacking. (2) Objective: To evaluate the relationship between the Portfolio Diet and glycated hemoglobin (HbA1c) as a determinant of glycemic control among adults living with type 2 diabetes mellitus (T2DM). (3) Methods: Patient-level data was pooled from two randomized dietary trials of low glycemic index interventions compared to high cereal fibre control diets in adults living with T2DM where HbA1c was collected (clinicaltrials.gov identifiers: NCT00438698, NCT00438698). Dietary exposure was assessed using weighed 7-day diet records. Adherence to the Portfolio Diet and its pillars (nuts and seeds, plant protein, viscous fibre, plant sterols, monounsaturated fatty acid [MUFA] oils) was determined using the validated clinical Portfolio Diet Score (c-PDS). Multiple linear regression was used to assess the association between change in the c-PDS and change in HbA1c over 6-months with covariate adjustments. (4) Results: A total of 267 participants, predominantly White (67%) and male (63%), were included, with a mean ± standard error age of 62 ± 0.5 years, baseline BMI of 30.2 ± 0.3 kg/m², HbA1c of 7.08 ± 0.03%, and a c-PDS of 4.1 ± 0.3 points out of 25. Change in the c-PDS was significantly associated with a change in HbA1c (β: −0.04% per point, 95% CI: −0.07, −0.02, p = 0.001). A 7.5-point (30%) increase in the c-PDS was associated with a 0.3% reduction in HbA1c. Of the individual pillars, a 1-point change in nut and seeds intake (β: −0.07%, 95% CI: −0.12, −0.02, p = 0.009) or in plant protein intake (β: −0.11%, 95% CI: −0.18, −0.03, p = 0.009) was associated with a change in HbA1c. Further analysis of plant protein intake revealed that an increase in dietary pulse intake, a particularly low-GI food, was significantly associated with a reduction in HbA1c (β: −0.24% per 1-cup points cooked pulses (226 g) or 2 c-PDS points, 95% CI: −0.45, −0.03, p = 0.028). (5) Conclusions: Among adults living with T2DM, the Portfolio Diet was associated with lower HbA1c over a 6-month period, predominantly driven by two pillars: nuts and seeds and plant protein, particularly dietary pulses. These data have implications for including the Portfolio Diet in dietary recommendations for glycemic control in T2DM. A trial demonstrating the direct causal effect of the Portfolio Diet in a diverse group is warranted.


(A) A scatter plot of the correlation between the dietary adherence to Portfolio Diet at week 24 measured by the reference method, shown as percentage, and the clinical-Portfolio Diet Score (c-PDS), shown as points (range, 0 to 25-points). (B) Bland–Altman plot visually presents the agreement between the c-PDS and the reference method of % adherence to the Portfolio Diet assessed by weighed 7-day diet records (week 24). The x-axis is the mean of the two methods, and the y-axis is the difference between the two methods. The red line is the mean difference and black lines represent upper and lower 95% limits of agreement. The Bland–Altman plot demonstrates reasonable agreement between the c-PDS and the reference method by dietary records. Clustering of datapoints closest to the origin of X-axis was attributed to the control group’s low adherence to the Portfolio Diet. c-PDS, clinical-Portfolio Diet Score; LDL-C low-density lipoprotein cholesterol.
A scatter plot showing the predictive validity of the clinical-Portfolio Diet Score using % change of LDL-C over 6 months as a biomarker of adherence. c-PDS, clinical-Portfolio Diet Score; LDL-C low-density lipoprotein cholesterol.
Simulation model to assess the validity of the clinical portfolio diet score used in the PortfolioDiet.app for dietary self-tracking: a secondary analysis of a randomized controlled trial in hyperlipidemic adults

August 2024

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44 Reads

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1 Citation

Introduction The Portfolio Diet combines cholesterol-lowering plant foods for the management of cardiovascular disease risk. However, the translation of this dietary approach into clinical practice necessitates a user-friendly method for patients to autonomously monitor their adherence. Objective This study aimed to develop and validate the clinical-Portfolio Diet Score (c-PDS) as a food-based metric to facilitate self-tracking of the Portfolio Diet. Methods Using a simulation model to estimate the c-PDS, the validity was assessed in a secondary analysis of a completed trial of the Portfolio Diet in 98 participants with hyperlipidemia over 6 months. Concurrent and predictive validity of the estimated c-PDS were assessed against the reference measure (weighed 7-day diet records) and concomitant changes in LDL-C from baseline to 6 months. Bland–Altman analysis was used to assess the limits of agreement between the two methods. Results The c-PDS was positively correlated with dietary adherence as measured using the 7-day diet records (r = 0.94, p < 0.001). The c-PDS was negatively correlated with change in LDL-C (r = −0.43, p < 0.001) with a 1-point increase in the c-PDS being associated with a − 0.04 mmol/L (CI:−0.06,−0.03; p < 0.001) or a 1.09% reduction in LDL-C. Visual evaluation of the Bland–Altman plots showed reasonable agreement. Conclusion These findings indicate good validity of the c-PDS for primary prevention in adults with hyperlipidemia. The predictive validity findings have informed the goals and messaging within the PortfolioDiet.app, a digital health application for delivering the Portfolio Diet. Future research will assess the effectiveness of the intended combination of the c-PDS and the PortfolioDiet.app in supporting behavior change.



Figure 1. (continued).
Figure 2. Shown are interventions. Recommendations from the Patients, Experience, Evidence, Research (PEER) guidelines are highlighted in (A) gray (weak recommendations) and (B) white (strong recommendations). The Canadian Cardiovascular Society (CCS) guidelines perspective is summarized in the last column and is colour-coded to convey strong similarities (green), similarities but with important additional factors outlined in the CCS guidelines (yellow), and discordances (red). apoB, apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; CVD, cardiovascular disease; DASH, dietary approaches to stop hypertension; FH, familial hypercholesterolemia; HDL-C, high-density lipoprotein; IMPROVE-IT trial, Improved Reduction of Outcomes: Vytorin Efficacy International Trial; IPE, icosapent ethyl; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; RCT, randomized controlled trial; TG, triglyceride; T2D, type 2 diabetes
Figure 2. (continued).
Figure 3. Shown are considerations in patients aged > 75 years. Recommendations from the Patients, Experience, Evidence, Research (PEER) guidelines are highlighted in gray (weak recommendations) and white (strong recommendations). The Canadian Cardiovascular Society (CCS) guidelines perspective is summarized in the last column and is colour-coded to convey strong similarities (green), and similarities but with important additional factors outlined in the CCS guidelines (yellow). Note that 2 of the recommendations from PEER are not captured by the current CCS guideline; these are highlighted in white. CV, cardiovascular; CVD, CV disease; PROSPER trial, Prospective Study of Pravastatin in the Elderly at Risk.
Prevention and Management of Cardiovascular Disease in Primary Care: A Comment on the PEER Simplified Lipid Guideline

June 2024

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37 Reads

CJC Open

Background In Canada, 2 guidelines provide guidance for the management of dyslipidemia. The Patients, Experience, Evidence, Research simplified lipid guidelines, intended for primary care practitioners, and the Canadian Cardiovascular Society guidelines, intended for all practitioners, are based on differing methodologies with distinct priorities and preferences. The disparate approaches may contribute to confusion among family practitioners and their co-managed patients, with the potential for compromised care, differing standards for training in the fundamentals of lipidology, and differing criteria that might be used in practice audits to evaluate quality of care. Methods The Patients, Experience, Evidence, Research (PEER) recommendations were considered by primary authors of the Canadian Cardiovascular Society guideline to identify areas of concordance, discordance, or agreement with qualifications. Results Discordance between the guidelines is greatest with respect to interpretation of the cholesterol profile, the implications of elevated triglyceride, the utility of apolipoprotein B and non-high-density lipoprotein-cholesterol measurements, the role of nonstatin medications, and the importance of assuring adherence and avoiding undertreatment through follow-up measurement of lipid profiles. The disparate importance attached to identification of patients with enhanced risk due to an elevated lipoprotein (a) level is also apparent. Conclusions This comparison attempts to reconcile key principles of practice, to foster both high quality of care and fully informed patient-centred decision-making.



Citations (61)


... ESHA, Salem, OR, USA). Adherence to the Portfolio Diet and its pillars was determined using the validated clinical Portfolio Diet Score (c-PDS), ranging from 0 to 25 points [34]. The c-PDS is a pre-defined scoring method developed for use in clinical practice and trial settings as part of a digital translational tool (PortfolioDiet.app) of the Canadian Cardiovascular Society guidelines for cardiovascular risk reduction [7,35]. ...

Reference:

The Portfolio Diet and HbA1c in Adults Living with Type 2 Diabetes Mellitus: A Patient-Level Pooled Analysis of Two Randomized Dietary Trials
Simulation model to assess the validity of the clinical portfolio diet score used in the PortfolioDiet.app for dietary self-tracking: a secondary analysis of a randomized controlled trial in hyperlipidemic adults

... Previous conclusions about MR products have mostly been drawn from randomized trials, where the focus has usually been placed on the efficacy of MR products on weight management or their safety for medical use [3,6,16,[19][20][21]. One systematic study summarized that incorporating MR into weight loss programs would benefit the users by reducing weight and cardiometabolic risks within a relatively short time of follow-up (longest follow-up time included: ≤52 weeks) [22]. However, another systematic review pointed out that the conclusions are inconsistent regarding long-term weight loss (>1 year) [23]. ...

Weight management using meal replacements and cardiometabolic risk reduction in individuals with pre-diabetes and features of metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials
  • Citing Article
  • May 2024

Obesity Reviews

... Notably, honey is approximately 70% more dense than sugar (Table S3), meaning 1 tsp of honey contains more sugar than 1 tsp of table sugar. The sugar content of the honey samples used in this study ranged between 79 and 81 g sugars/100 g honey, with the majority coming from the monosaccharides glucose (32%-37%) and fructose (38%-41%) (Table S4) (Oroian, 2013;Zhu et al., 2024). On the other hand, ordinary table sugar is at least 99% sucrose, a polysaccharide containing one glucose and one fructose unit. ...

A comprehensive characterization of phenolics, amino acids and other minor bioactives of selected honeys and identification of botanical origin markers
  • Citing Article
  • March 2024

Journal of Food Bioactives

... Thank you for the opportunity to respond to the concerns raised by Ayoub-Charette et al. [1]. As they disclosed, the senior authors of this Comment have longstanding relationships with industry associations that promote the manufacture and sale of non-nutritive sweeteners (NNS), diet sodas, and other diet products. ...

Lack of Biological Plausibility and Major Methodological Issues Cast Doubt on the Association between Aspartame and Autism. Comment on Fowler et al. Daily Early-Life Exposures to Diet Soda and Aspartame Are Associated with Autism in Males: A Case-Control Study. Nutrients 2023, 15, 3772

... High-fructose diets, commonly from sugary beverages and sweets, disrupt the gut microbiota, favoring pro-inflammatory bacteria [157]. High glycemic diets also increase CVD risk by causing oxidative stress, LDL oxidation, inflammation, protein glycation, and procoagulant activity [143,158]. These findings highlight the importance of reducing refined and processed foods and increasing fiber-and polyphenol-rich foods to support a heart-healthy gut microbiota and reduce MI risk. ...

Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: a meta-analysis of mega cohorts of more than 100 000 participants
  • Citing Article
  • February 2024

... These outcomes were selected as they are the first steps within the hierarchical framework of food marketing effects [21]. Onehundred percent fruit juices are included as part of this study's definition of sugary drinks as they are metabolized similarly to added sugars, contributing to overall energy density of diets [36], and is supported by evidence which observed an association between 1 serving of 100% fruit juice and weight gain in children [37]. ...

Consumption of 100% Fruit Juice and Body Weight in Children and Adults: A Systematic Review and Meta-Analysis

... The samples dehydrated under these conditions had the highest potassium content. Moreover, both inulin and erythritol are compounds that, like potassium, have been shown to have positive effects on the cardiovascular system, including consumption being associated with reduced blood pressure [73], reduced risk of developing hypertension by 21% [74], reduced low-density lipoprotein (LDL) and triglyceride levels [75], and improved small vessel endothelial function, and reduced central aortic stiffness [76]. In order to compare the effect of the level of addition of the chemical form of potassium, 2.5 or 5.0% addition of potassium chloride was used. ...

The effects of inulin-type fructans on cardiovascular disease risk factors: systematic review and meta-analysis of randomized controlled trials

American Journal of Clinical Nutrition

... Acknowledgments: Components of this work were presented at the Canadian Cardiovascular Society's Vascular 2023 conference in October 2023 and the abstract was published by Elsevier Inc. [61]. ...

DCP080 THE ASSOCIATION BETWEEN THE CLINICAL PORTFOLIO DIET SCORE AND A1C IN TYPE 2 DIABETES MELLITUS: AN EXPLORATORY ANALYSIS OF TWO RANDOMIZED DIETARY TRIALS
  • Citing Article
  • October 2023

The Canadian journal of cardiology

... Se ha propuesto que el mecanismo de acción de estos compuestos es modular el metabolismo de lípidos, dentro de estos compuestos destacan el resveratrol, antocianinas, taninos hidrolizables y ácidos grasos poliinsaturados provenientes de alimentos 5 . Diversos estudios destacan los beneficios del consumo de compuestos bioactivos como el incremento de los niveles de colesterol unido a lipoproteínas de alta densidad (C-HDL), así como la reducción de las lipoproteínas aterogénicas (LDL) 6 . El propósito de este trabajo es analizar las terapias nutricionales que se han comprobado ser efectivas para regular el perfil lipídico, y otras condiciones como inflamación y estrés oxidativo, características fisiológicas comunes en pacientes VIH+ y que se exacerban con la presencia de lipodistrofia desencadenando algún factor de riesgo cardiovascular. ...

Portfolio Diet Score and Risk of Cardiovascular Disease: Findings From 3 Prospective Cohort Studies
  • Citing Article
  • October 2023

Circulation

... Although certain aspects of climate change, such as increased precipitation, may offer localized benefits, there are also adverse impacts, including reduced water availability and more frequent extreme weather events (Alcamo et al., 2007;Iglesias and Garrote, 2015). Given that climate change is recognized as one of the most significant environmental challenges of this century (KPMG International, 2012), there is a need to evaluate the impact and efficiency of water use in the agricultural sector (Civit et al., 2018;Chen et al., 2023;Fatichi et al., 2023). ...

Response to comment on “Relation of fruit juice with adiposity and diabetes depends on how fruit juice is defined: a re-analysis of the EFSA draft scientific opinion on the tolerable upper intake level for dietary sugars” by Chen et al. 2023

European Journal of Clinical Nutrition