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.

(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.

Background Despite dietary recommendations to consume more plant foods for public and planetary health and the role that soy foods can play in plant-predominant diets, controversies around the effects of soy foods and their components, especially isoflavones, are a barrier to their intake. Given the cardioprotective effects and ability to alleviate menopausal symptoms, addressing this issue is particularly relevant to women. We therefore undertook a systematic review and meta-analysis of randomized controlled trials in postmenopausal women to determine the effect of soy isoflavones on measures of estrogenicity. Methods MEDLINE, Embase, and Cochrane Library were searched through July 2023 for randomized controlled trials 3-months investigating soy isoflavones versus non-isoflavone controls in postmenopausal women. The four outcomes included endometrial thickness (ET), vaginal maturation index (VMI), follicle-stimulating hormone (FSH), and estradiol. Independent authors extracted data and assessed risk of bias. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess certainty of evidence. Results We included 40 trials (52 trial comparisons, n=3285) assessing the effect of a median daily dose of 75 mg of soy isoflavones in substitution for non-isoflavone control over a median of 24 weeks. Isoflavones had no statistically significant effects on any of the measures of estrogenicity; ET (mean difference, -0.22mm [95% confidence interval, -0.45 to 0.01mm], P MD =0.059), VMI (2.31 [-2.14 to 6.75], P MD =0.310), FSH (-0.02IU/L [-2.39 to 2.35IU/L], P MD =0.987), and estradiol (1.61pmol/L [-1.17 to 4.38pmol/L], P MD =0.256). The certainty of evidence was high-to-moderate for all outcomes. Conclusion Current evidence provides a good indication that soy isoflavones do not have an estrogenic effect versus non-isoflavone controls on 4 measures of estrogenicity in postmenopausal women. This synthesis supports the classification of soy isoflavones as selective estrogen receptor modulators and that isoflavones differ clinically from the hormone estrogen where no assumptions about the health effects of soy foods or isoflavones should be based on an understanding of the effects of the hormone estrogen. Addressing public health concerns around soy foods may support their intake as high-quality plant protein foods with low environmental impact and cost, especially relevant for postmenopausal women, and aligning with sustainable dietary patterns and guidelines. Registration : PROSPERO (CRD42023439239)

Background: There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute metabolic and endocrine responses to NNS. To examine whether these mechanisms are operational under real-world scenarios, we conducted a systematic review and network meta-analysis of acute trials comparing the effects of non-nutritive sweetened beverages (NNS beverages) with water and sugar-sweetened beverages (SSBs) in humans. Methods: MEDLINE, EMBASE, and The Cochrane Library were searched through to January 15, 2022. We included acute, single-exposure, randomized, and non-randomized, clinical trials in humans, regardless of health status. Three patterns of intake were examined: (1) uncoupling interventions, where NNS beverages were consumed alone without added energy or nutrients; (2) coupling interventions, where NNS beverages were consumed together with added energy and nutrients as carbohydrates; and (3) delayed coupling interventions, where NNS beverages were consumed as a preload prior to added energy and nutrients as carbohydrates. The primary outcome was a 2 h incremental area under the curve (iAUC) for blood glucose concentration. Secondary outcomes included 2 h iAUC for insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon concentrations. Network meta-analysis and confidence in the network meta-analysis (CINeMA) were conducted in R-studio and CINeMA, respectively. Results: Thirty-six trials involving 472 predominantly healthy participants were included. Trials examined a variety of single NNS (acesulfame potassium, aspartame, cyclamate, saccharin, stevia, and sucralose) and NNS blends (acesulfame potassium + aspartame, acesulfame potassium + sucralose, acesulfame potassium + aspartame + cyclamate, and acesulfame potassium + aspartame + sucralose), along with matched water/unsweetened controls and SSBs sweetened with various caloric sugars (glucose, sucrose, and fructose). In uncoupling interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon responses similar to water controls (generally, low to moderate confidence), whereas SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses with no differences in postprandial ghrelin and glucagon responses (generally, low to moderate confidence). In coupling and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects similar to controls (generally, low to moderate confidence). Conclusions: The available evidence suggests that NNS beverages sweetened with single or blends of NNS have no acute metabolic and endocrine effects, similar to water. These findings provide support for NNS beverages as an alternative replacement strategy for SSBs in the acute postprandial setting.