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Low-carbohydrate, high animal fat and protein diets have been promoted for weight loss and diabetes treatment. We therefore tested the effect of a low-carbohydrate vegan diet in diabetes as a potentially healthier and more ecologically sustainable low-carbohydrate option.We sought to compare the effectiveness of a low-carbohydrate vegan diet with a moderate-carbohydrate vegetarian diet on weight loss and metabolic measures in diabetes.One hundred and sixty-four male and female participants with type 2 diabetes were randomly assigned to advice on either a low-carbohydrate vegan diet, high in canola oil and plant proteins, or a vegetarian therapeutic diet, for 3 mo, with both diets recommended at 60% of calorie requirements. Body weight, fasting blood, blood pressure, and 7-d food records, to estimate potential greenhouse gas emissions, were obtained throughout the study with tests of cholesterol absorption undertaken at baseline and end of study on 50 participants.Both low-carbohydrate vegan and vegetarian diets similarly but markedly reduced body weight (-5.9 kg; 95% CI: -6.5, -5.28 kg; and -5.23 kg; 95% CI: -5.84, -4.62 kg), glycated hemoglobin (-0.99%; 95% CI: -1.07, -0.9%; and -0.88%; 95% CI: -0.97, -0.8%), systolic blood pressure (-4 mmHg; 95% CI: -7, -2 mmHg; and -6 mmHg; 95% CI: -8, -3 mmHg), and potential greenhouse gas emissions, but only for potential greenhouse gas emissions was there a significant treatment difference of -0.63 kgCO2/d (95% CI: -0.99, -0.27 kgCO2/d) favoring the low-carbohydrate vegan diet.Low-carbohydrate vegan and vegetarian diets reduced body weight, improved glycemic control and blood pressure, but the more plant-based diet had greater potential reduction in greenhouse gas emissions.Trial registration number: clinicaltrials.gov identifier NCT02245399.

Postprandial hypotension (PPH) has been reported to be associated with syncope, falls, adverse cardiovascular outcomes, and increased all-cause mortality. It has been reported to have an incidence as high as 30% in the elderly and persons with diabetes. We therefore performed a meta-analysis to determine the relation of PPH with cardiovascular disease (CVD) events and all-cause mortality.Our objective was to conduct a systematic review and meta-analysis of cohort and cross-sectional studies to determine the association of PPH with CVD and all-cause mortality.We searched the databases MEDLINE, EMBASE, and Cochrane library up to 13 April 2022 for prospective cohort and cross-sectional studies that examined the association of PPH with CVD outcomes and all-cause mortality. Data were analyzed using the generic inverse variance method with a random-effects model. Grading of Recommendations, Assessment, Development, and Evaluation approach assessed the certainty of evidence.Seven studies that included 2389 participants met our inclusion criteria. PPH was associated with each outcome individually, including increased all-cause mortality, total CVD, CVD mortality, and stroke. CVD outcomes and all-cause mortality combined were also associated with PPH (RR: 1.52; 95% CI: 1.05, 2.18; P = 0.03; I2 = 77%). The certainty of evidence was graded as very low due to significant heterogeneity and the limited number of studies.This assessment indicates an association of PPH with CVD and all-cause mortality. Further studies are required to improve CVD and mortality estimates, but the potential seriousness of CVD and all-cause mortality as outcomes of PPH justifies more screening, diagnosis, and research.

Aims/hypothesis Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes. Methods We searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle–Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA1c, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. Results We included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with ‘small important’ reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I2=88%, pQpp<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] −0.26 mmol/l [95% CI −0.52, −0.00], pMD=0.05; substantial heterogeneity: I2=89%, pQp<0.05). For the other outcomes there were ‘trivial’ reductions or no effect. The certainty of the evidence was low for total CVD incidence and LDL-cholesterol; moderate to high for CVD mortality, established lipid targets, adiposity markers, glycaemic control, blood pressure and inflammation; and low for all other outcomes, with evidence being downgraded mainly because of imprecision and inconsistency. Conclusions/interpretation Adherence to Nordic dietary patterns is associated with generally small important reductions in the risk of major CVD outcomes and diabetes, which are supported by similar reductions in LDL-cholesterol and other intermediate cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes. Registration ClinicalTrials.gov NCT04094194. Funding Diabetes and Nutrition Study Group of the EASD Clinical Practice. Graphical abstract

Context Excess calories from free sugars are implicated in the epidemics of obesity and type 2 diabetes. Honey is a free sugar but is generally regarded as healthy. Objective The effect of honey on cardiometabolic risk factors was assessed via a systematic review and meta-analysis of controlled trials using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Data Sources MEDLINE, Embase, and the Cochrane Library databases were searched up to January 4, 2021, for controlled trials ≥1 week in duration that assessed the effect of oral honey intake on adiposity, glycemic control, lipids, blood pressure, uric acid, inflammatory markers, and markers of nonalcoholic fatty liver disease. Data Extraction Independent reviewers extracted data and assessed risk of bias. Data were pooled using the inverse variance method and expressed as mean differences (MDs) with 95%CIs. Certainty of evidence was assessed using GRADE. Data Analysis A total of 18 controlled trials (33 trial comparisons, N = 1105 participants) were included. Overall, honey reduced fasting glucose (MD = −0.20 mmol/L, 95%CI, −0.37 to −0.04 mmol/L; low certainty of evidence), total cholesterol (MD = −0.18 mmol/L, 95%CI, −0.33 to −0.04 mmol/L; low certainty), low-density lipoprotein cholesterol (MD = −0.16 mmol/L, 95%CI, −0.30 to −0.02 mmol/L; low certainty), fasting triglycerides (MD = −0.13 mmol/L, 95%CI, −0.20 to −0.07 mmol/L; low certainty), and alanine aminotransferase (MD = −9.75 U/L, 95%CI, −18.29 to −1.21 U/L; low certainty) and increased high-density lipoprotein cholesterol (MD = 0.07 mmol/L, 95%CI, 0.04–0.10 mmol/L; high certainty). There were significant subgroup differences by floral source and by honey processing, with robinia honey, clover honey, and raw honey showing beneficial effects on fasting glucose and total cholesterol. Conclusion Honey, especially robinia, clover, and unprocessed raw honey, may improve glycemic control and lipid levels when consumed within a healthy dietary pattern. More studies focusing on the floral source and the processing of honey are required to increase certainty of the evidence. Systematic Review Registration PROSPERO registration number CRD42015023580.

Background: Adverse associations of low-and no-calorie sweetened beverages (LNCSBs) with cardiometabolic outcomes in observational studies may be explained by reverse causality and residual confounding. Purpose: To address these limitations we used change analyses of repeated measures of intake and substitution analyses to synthesize the association of LNCSBs with cardiometabolic outcomes. Study Selection: MEDLINE, EMBASE, and the Cochrane Library were searched up to 10 June 2021 for prospective cohort studies ≥1-year follow-up duration in adults. Outcomes included changes in clinical measures of adiposity, risk of overweight/obesity, metabolic syndrome, diabetes, cardiovascular disease, and total mortality. Data Extraction: Two independent reviewers extracted data, assessed study quality, and certainty of evidence using GRADE. Data was pooled using random-effects model and expressed as mean difference (MD) or risk ratio (RR) and 95% CI. Data Synthesis: Fourteen cohorts (416,830 participants) met the eligibility criteria. Change in LNCSB intake was associated with lower weight (5 cohorts, 136,206 participants; MD, -0.008 [95% CI: -0.014, -0.002] kg/y). Substitution of LNCSBs for sugar-sweetened beverages (SSBs) was associated with lower weight (3 cohorts, 165,579 participants; MD, -0.12 [95% CI: -0.14, -0.01] kg/y) and lower incidence of obesity (1 cohort, 15,765 participants; RR, 0.88 [0.88, 0.89]), coronary heart disease (6 cohorts, 233,676 participants; RR, 0.89 [95% CI: 0.81, 0.98]), CVD mortality (1 cohort, 118,363 participants; RR, 0.95 [95% CI: 0.90, 0.99]), and total mortality (1 cohort, 118,363 participants; RR, 0.96 [95% CI: 0.94, 0.98]) with no adverse associations across other outcomes. Substitution of water for SSBs showed lower weight (3 cohorts, 165,579 participants; MD, -0.10 [95% CI: -0.13, -0.06] kg/y), lower waist circumference (1 cohort, 173 participants; MD, -2.71[95% CI: -4.27, -1.15] cm/y) and percent body fat (1 cohort, 173 participants; MD, -1.51 [95% CI: -2.61, -0.42] %/y), and lower incidence of obesity (1 cohort, 15,765 participants; RR, 0.85 [95% CI: 0.75, 0.97]) and diabetes (3 cohorts, 281,855 participants; RR, 0.96 [95% CI: 95% CI: 0.94, 0.98]). Substitution of LNCSBs for water showed no adverse associations. Limitations: The evidence was low to very low certainty owing downgrades for imprecision, indirectness and/or inconsistency. Conclusions: LNCSBs were not associated with cardiometabolic harm in analyses that model the exposure as change or substitutions. The available evidence provides some indication that LNCSBs in their intended substitution for SSBs may be associated with cardiometabolic benefit, comparable to the standard of care, water.

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.

Nuts are nutrient-rich foods that contain many bioactive compounds that are beneficial for cardiovascular health. Higher consumption of nuts has been associated with a reduced risk of several cardiovascular diseases (CVD) in prospective cohort studies, including a 19% and 25% lower risk of CVD incidence and mortality, respectively, and a 24% and 27% lower risk of coronary heart disease incidence and mortality, respectively. An 18% lower risk of stroke mortality, a 15% lower risk of atrial fibrillation, and a 19% lower risk of total mortality have also been observed. The role of nuts in stroke incidence, stroke subtypes, peripheral arterial disease and heart failure has been less consistent. This narrative review summarizes recommendations for nuts by clinical practice guidelines and governmental organizations, epidemiological evidence for nuts and CVD outcomes, nut-containing dietary patterns, potential mechanisms of nuts and CVD risk reduction, and future research directions, such as the use of biomarkers to help better assess nut intake. Although there are still some uncertainties around nuts and CVD prevention which require further research, as summarized in this review, there is a substantial amount of evidence that supports that consuming nuts will have a positive impact on primary and secondary prevention of CVD.

Diabetes is a continuously growing global concern affecting >10% of adults, which may be mitigated by modifiable lifestyle factors. Consumption of nuts and their inclusion in dietary patterns has been associated with a range of beneficial health outcomes. Diabetes guidelines recommend dietary patterns that incorporate nuts; however, specific recommendations related to nuts have been limited. This review considers the epidemiological and clinical evidence to date for the role of nut consumption as a dietary strategy for the prevention and management of type 2 diabetes (T2D) and related complications. Findings suggest nut consumption may have a potential role in the prevention and management of T2D, with mechanistic studies assessing nuts and individual nut-related nutritional constituents supporting this possibility. However, limited definitive evidence is available to date, and future studies are needed to elucidate better the impact of nuts on the prevention and management of T2D.

Background: Fructose-containing sugars as sugar-sweetened beverages (SSBs) may increase inflammatory biomarkers. Whether this effect is mediated by the food matrix at different levels of energy is unknown. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials on the effect of different food sources of fructose-containing sugars on inflammatory markers at different levels of energy control. Methods: MEDLINE, Embase, and the Cochrane Library were searched through March 2022 for controlled feeding trials ≥ 7 days. Four trial designs were prespecified by energy control: substitution (energy matched replacement of sugars); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced). The primary outcome was C-reactive protein (CRP). Secondary outcomes were tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Independent reviewers extracted data and assessed risk of bias. GRADE assessed certainty of evidence. Results: We identified 64 controlled trials (91 trial comparisons, n = 4094) assessing 12 food sources (SSB; sweetened dairy; sweetened dairy alternative [soy]; 100% fruit juice; fruit; dried fruit; mixed fruit forms; sweetened cereal grains and bars; sweets and desserts; added nutritive [caloric] sweetener; mixed sources [with SSBs]; and mixed sources [without SSBs]) at 4 levels of energy control over a median 6-weeks in predominantly healthy mixed weight or overweight/obese adults. Total fructose-containing sugars decreased CRP in addition trials and had no effect in substitution, subtraction or ad libitum trials. No effect was observed on other outcomes at any level of energy control. There was evidence of interaction/influence by food source: substitution trials (sweetened dairy alternative (soy) and 100% fruit juice decreased, and mixed sources (with SSBs) increased CRP); and addition trials (fruit decreased CRP and TNF-α; sweets and desserts (dark chocolate) decreased IL-6). The certainty of evidence was moderate-to-low for the majority of analyses. Conclusions: Food source appears to mediate the effect of fructose-containing sugars on inflammatory markers over the short-to-medium term. The evidence provides good indication that mixed sources that contain SSBs increase CRP, while most other food sources have no effect with some sources (fruit, 100% fruit juice, sweetened soy beverage or dark chocolate) showing decreases, which may be dependent on energy control. Clinicaltrials.gov: (NCT02716870).

IntroductionCurrent health claims recognize the ability of oat ß-glucan to lower blood cholesterol; however, its ability to improve glycemic control is less certain. We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to update the evidence on the effect of oats and oat ß-glucan on glycemic control in individuals with diabetes.Research design and methodsMEDLINE, EMBASE and Cochrane were searched (June 2021) for RCTs of ≥2 weeks investigating the effect of oat ß-glucan on glycemic control in diabetes. The outcomes were hemoglobin A1c (HbA1c), fasting glucose, 2-hour postprandial glucose (2h-PG) from a 75 g oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR) and fasting insulin. Independent reviewers extracted the data and assessed the risk of bias. Data were pooled using the generic inverse variance method. Heterogeneity was assessed (Cochran Q) and quantified (I2). Pooled estimates were expressed as mean difference (MD) with 95% CI. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach.ResultsEight trial comparisons (n=407) met the eligibility criteria. All trials were in adults with type 2 diabetes who were predominantly middle-aged, overweight and treated by antihyperglycemic medications or insulin. A median dose of 3.25 g of oat ß-glucan for a median duration of 4.5 weeks improved HbA1c (MD, −0.47% (95% CI −0.80 to −0.13), pMD=0.006), fasting glucose (−0.75 mmol/L (−1.20 to –0.31), pMDMD=0.003) and HOMA-IR (−0.88 (−1.55 to –0.20), pMD=0.011). There was a non-significant reduction in fasting insulin (−4.30 pmol/L (−11.96 to 3.35), pMD=0.271). The certainty of evidence was high for fasting glucose, moderate for HOMA-IR and fasting insulin (downgraded for imprecision), and low for HbA1c and 2h-PG (downgraded for imprecision and inconsistency).ConclusionsConsumption of oats and oat ß-glucan results in generally small improvements in established markers of fasting and postprandial glycemic control beyond concurrent therapy in adults with type 2 diabetes. The current evidence provides a very good indication for reductions in fasting glucose and less of an indication for reductions in HbA1c, 2h-PG, fasting insulin and HOMA-IR in this population.Trial registration numberNCT04631913.

Background: Fructose providing excess calories in the form of sugar sweetened beverages (SSBs) increases markers of non-alcoholic fatty liver disease (NAFLD). Whether this effect holds for other important food sources of fructose-containing sugars is unclear. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials of the effect of fructose-containing sugars by food source at different levels of energy control on non-alcoholic fatty liver disease (NAFLD) markers. Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through 7 January 2022 for controlled trials ≥7-days. Four trial designs were prespecified: substitution (energy-matched substitution of sugars for other macronutrients); addition (excess energy from sugars added to diets); subtraction (excess energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE. We included 51 trials (75 trial comparisons, n = 2059) of 10 food sources (sugar-sweetened beverages (SSBs); sweetened dairy alternative; 100% fruit juice; fruit; dried fruit; mixed fruit sources; sweets and desserts; added nutritive sweetener; honey; and mixed sources (with SSBs)) in predominantly healthy mixed weight or overweight/obese younger adults. Total fructose-containing sugars increased IHCL (standardized mean difference = 1.72 [95% CI, 1.08 to 2.36], p < 0.001) in addition trials and decreased AST in subtraction trials with no effect on any outcome in substitution or ad libitum trials. There was evidence of influence by food source with SSBs increasing IHCL and ALT in addition trials and mixed sources (with SSBs) decreasing AST in subtraction trials. The certainty of evidence was high for the effect on IHCL and moderate for the effect on ALT for SSBs in addition trials, low for the effect on AST for the removal of energy from mixed sources (with SSBs) in subtraction trials, and generally low to moderate for all other comparisons. Conclusions: Energy control and food source appear to mediate the effect of fructose-containing sugars on NAFLD markers. The evidence provides a good indication that the addition of excess energy from SSBs leads to large increases in liver fat and small important increases in ALT while there is less of an indication that the removal of energy from mixed sources (with SSBs) leads to moderate reductions in AST. Varying uncertainty remains for the lack of effect of other important food sources of fructose-containing sugars at different levels of energy control.

Importance: There are concerns that low- and no-calorie sweetened beverages (LNCSBs) do not have established benefits, with major dietary guidelines recommending the use of water and not LNCSBs to replace sugar-sweetened beverages (SSBs). Whether LNCSB as a substitute can yield similar improvements in cardiometabolic risk factors vs water in their intended substitution for SSBs is unclear.Objective: To assess the association of LNCSBs (using 3 prespecified substitutions of LNCSBs for SSBs, water for SSBs, and LNCSBs for water) with body weight and cardiometabolic risk factors in adults with and without diabetes.Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through December 26, 2021.Study Selection: Randomized clinical trials (RCTs) with at least 2 weeks of interventions comparing LNCSBs, SSBs, and/or water were included.Data Extraction and Synthesis: Data were extracted and risk of bias was assessed by 2 independent reviewers. A network meta-analysis was performed with data expressed as mean difference (MD) or standardized mean difference (SMD) with 95% CIs. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to assess the certainty of the evidence.Main Outcomes and Measures: The primary outcome was body weight. Secondary outcomes were other measures of adiposity, glycemic control, blood lipids, blood pressure, measures of nonalcoholic fatty liver disease, and uric acid.Results: A total of 17 RCTs with 24 trial comparisons were included, involving 1733 adults (mean [SD] age, 33.1 [6.6] years; 1341 women [77.4%]) with overweight or obesity who were at risk for or had diabetes. Overall, LNCSBs were a substitute for SSBs in 12 RCTs (n = 601 participants), water was a substitute for SSBs in 3 RCTs (n = 429), and LNCSBs were a substitute for water in 9 RCTs (n = 974). Substitution of LNCSBs for SSBs was associated with reduced body weight (MD, -1.06 kg; 95% CI, -1.71 to -0.41 kg), body mass index (MD, -0.32; 95% CI, -0.58 to -0.07), percentage of body fat (MD, -0.60%; 95% CI, -1.03% to -0.18%), and intrahepatocellular lipid (SMD, -0.42; 95% CI, -0.70 to -0.14). Substituting water for SSBs was not associated with any outcome. There was also no association found between substituting LNCSBs for water with any outcome except glycated hemoglobin A1c (MD, 0.21%; 95% CI, 0.02% to 0.40%) and systolic blood pressure (MD, -2.63 mm Hg; 95% CI, -4.71 to -0.55 mm Hg). The certainty of the evidence was moderate (substitution of LNCSBs for SSBs) and low (substitutions of water for SSBs and LNCSBs for water) for body weight and was generally moderate for all other outcomes across all substitutions.Conclusions and Relevance: This systematic review and meta-analysis found that using LNCSBs as an intended substitute for SSBs was associated with small improvements in body weight and cardiometabolic risk factors without evidence of harm and had a similar direction of benefit as water substitution. The evidence supports the use of LNCSBs as an alternative replacement strategy for SSBs over the moderate term in adults with overweight or obesity who are at risk for or have diabetes.

This is an update of the previous 2018 systematic review and meta-analysis of vitamin and mineral supplementation on cardiovascular disease outcomes and all-cause mortality. New randomized controlled trials and meta-analyses were identified by searching the Cochrane library, Medline, and Embase, and data were analyzed using random effects models and classified by the Grading of Recommendations Assessment Development and Evaluation approach. This updated review shows similar findings to the previous report for preventive benefits from both folic acid and B vitamins for stroke and has been graded with moderate quality. No effect was seen for the commonly used multivitamins, vitamin D, calcium, and vitamin C, and an increased risk was seen with niacin (with statin) for all-cause mortality. Conclusive evidence for the benefit of supplements across different dietary backgrounds, when the nutrient is sufficient, has not been demonstrated.

The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, β-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.

To determine the association of total and added fructose-containing sugars on cardiovascular (CVD) incidence and mortality.MEDLINE, EMBASE and Cochrane Library were searched from January 1, 1980, to July 31, 2018. Prospective cohort studies assessing the association of reported intakes of total, sucrose, fructose and added sugars with CVD incidence and mortality in individuals free from disease at baseline were included. Risk estimates were pooled using the inverse variance method, and dose-response analysis was modeled.Eligibility criteria were met by 24 prospective cohort comparisons (624,128 unique individuals; 11,856 CVD incidence cases and 12,224 CVD mortality cases). Total sugars, sucrose, and fructose were not associated with CVD incidence. Total sugars (risk ratio, 1.09 [95% confidence interval, 1.02 to 1.17]) and fructose (1.08 [1.01 to 1.15]) showed a harmful association for CVD mortality, there was no association for added sugars and a beneficial association for sucrose (0.94 [0.89 to 0.99]). Dose-response analyses showed a beneficial linear dose-response gradient for sucrose and nonlinear dose-response thresholds for harm for total sugars (133 grams, 26% energy), fructose (58 grams, 11% energy) and added sugars (65 grams, 13% energy) in relation to CVD mortality (P.05). The certainty of the evidence using GRADE was very low for CVD incidence and low for CVD mortality for all sugar types.Current evidence supports a threshold of harm for intakes of total sugars, added sugars, and fructose at higher exposures and lack of harm for sucrose independent of food form for CVD mortality. Further research of different food sources of sugars is needed to define better the relationship between sugars and CVD. REGISTRATION: clinicaltrials.gov, NCT01608620.

To determine the effect on blood pressure of dietary advice to consume a combination of plant-based cholesterol-lowering foods (dietary portfolio).For 1 year, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (22.5 g/1000 kcal). There was no control group. Seven-day diet record, blood pressure and body weight were monitored initially monthly and later at 2-monthly intervals throughout the study.Fifty subjects completed the 1-year study. When the last observation was carried forward for non-completers (n=9) or those who changed their blood pressure medications (n=7), a small mean reduction was seen in body weight 0.7+/-0.3 kg (P=0.036). The corresponding reductions from baseline in systolic and diastolic blood pressure at 1 year (n=66 subjects) were -4.2+/-1.3 mm Hg (P=0.002) and -2.3+/-0.7 mm Hg (P=0.001), respectively. Blood pressure reductions occurred within the first 2 weeks, with stable blood pressures 6 weeks before and 4 weeks after starting the diet. Diastolic blood pressure reduction was significantly related to weight change (r=0.30, n=50, P=0.036). Only compliance with almond intake advice related to blood pressure reduction (systolic: r=-0.34, n=50, P=0.017; diastolic: r=-0.29, n=50, P=0.041).A dietary portfolio of plant-based cholesterol-lowering foods reduced blood pressure significantly, related to almond intake. The dietary portfolio approach of combining a range of cholesterol-lowering plant foods may benefit cardiovascular disease risk both by reducing serum lipids and also blood pressure.

Background and aim Compared to a DASH-type diet, an intensively applied dietary portfolio reduced diastolic blood pressure at 24 weeks as a secondary outcome in a previous study. Due to the importance of strategies to reduce blood pressure, we performed an exploratory analysis pooling data from intensively and routinely applied portfolio treatments from the same study to assess the effect over time on systolic, diastolic and mean arterial pressure (MAP), and the relation to sodium (Na + ), potassium (K + ), and portfolio components. Methods and results 241 participants with hyperlipidemia, from four academic centers across Canada were randomized and completed either a DASH-type diet (control n = 82) or a dietary portfolio that included, soy protein, viscous fibers and nuts (n = 159) for 24 weeks. Fasting measures and 7-day food records were obtained at weeks 0, 12 and 24, with 24-h urines at weeks 0 and 24. The dietary portfolio reduced systolic, diastolic and mean arterial blood pressure compared to the control by 2.1 mm Hg (95% CI, 4.2 to −0.1 mm Hg) (p = 0.056), 1.8 mm Hg (CI, 3.2 to 0.4 mm Hg) (p = 0.013) and 1.9 mm Hg (CI, 3.4 to 0.4 mm Hg) (p = 0.015), respectively. Blood pressure reductions were small at 12 weeks and only reached significance at 24 weeks. Nuts, soy and viscous fiber all related negatively to change in mean arterial pressure (ρ = −0.15 to −0.17, p ≤ 0.016) as did urinary potassium (ρ = −0.25, p = 0.001), while the Na + /K + ratio was positively associated (ρ = 0.20, p = 0.010). Conclusions Consumption of a cholesterol-lowering dietary portfolio also decreased blood pressure by comparison with a healthy DASH-type diet. Clinical Trial Reg. No. NCT00438425, clinicaltrials.gov.

Background: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) markedly reduce serum cholesterol and have anti-inflammatory effects. The effect of cholesterol-lowering diets on inflammatory biomarkers is less well known. Objective: To compare the efficacy of a dietary combination (portfolio) of cholesterol-lowering foods vs a statin in reducing C-reactive protein (CRP) as a biomarker of inflammation linked to increased cardiovascular disease risk. Methods: In all, 34 hyperlipidemic subjects completed three 1-month treatments as outpatients in random order: a very low-saturated fat diet (control); the same diet with 20 mg lovastatin (statin); and a diet high in plant sterols (1.0 g/1000 kcal), soy protein (21.4 g/1000 kcal), viscous fibers (9.8 g/1000 kcal), and almonds (14 g/1000 kcal) (portfolio). Fasting blood samples were obtained at weeks 0, 2, and 4. Results: Using the complete data, no treatment reduced serum CRP. However, when subjects with CRP levels above the 75th percentile for previously reported studies (>3.5 mg/l) were excluded, CRP was reduced similarly on both statin, −16.3±6.7% (n=23, P=0.013) and dietary portfolio, −23.8±6.9% (n=25, P=0.001) but not the control, 15.3±13.6% (n=28, P=0.907). The percentage CRP change from baseline on the portfolio treatment (n=25) was greater than the control (n=28, P=0.004) but similar to statin treatment (n=23, P=0.349). Both statin and portfolio treatments were similar in reducing CRP and numerically more effective than control but only the change in portfolio was significant after the Bonferroni adjustment. Conclusions: A combination of cholesterol-lowering foods reduced C-reactive protein to a similar extent as the starting dose of a first-generation statin.

Background: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA)reductaseinhibitorsreduceserumcholesterolandareincreasinglyadvocatedinprimarypreventiontoachievereductionsinLDL cholesterol. Newer dietary approaches combining cholesterolloweringfoodsmayofferanotheroption,buttheseapproacheshave not been compared directly with statins in the same persons. Objective: The objective was to compare, in the same subjects, the cholesterol-loweringpotentialofadietaryportfoliowiththatofastatin. Design:Thirty-fourhyperlipidemicparticipantsunderwentallthree 1-mo treatments in random order as outpatients: a very-lowsaturated-fat diet (control diet), the same diet plus 20 mg lovastatin (statin diet), and a diet high in plant sterols (1.0 g/1000 kcal), soyprotein foods (including soy milks and soy burgers, 21.4 g/1000 kcal), almonds (14 g/1000 kcal), and viscous fibers from oats, barley, psyllium, and the vegetables okra and eggplant (10 g/1000 kcal) (portfolio diets). Fasting blood samples were obtained at 0, 2, and 4 wk. Results:LDL-cholesterol concentrations decreased by 8.51.9%, 33.3 1.9%, and 29.6 1.3% after 4 wk of the control, statin, and portfolio diets, respectively. Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk (P 0.013), 9 participants (26%) achieved their lowest LDLcholesterol concentrations with the portfolio diet. Moreover, the statin (n 27) and the portfolio (n 24) diets did not differ significantly (P 0.288) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff. Conclusions: Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention.Theymay,therefore,bridgethetreatmentgapbetweencurrent therapeutic diets and newer statins. Am J Clin Nutr 2005;81

Purpose: Herbal remedies high in phytoestrogens have been shown to reduce serum prostate specific antigen (PSA) and have been proposed as a treatment for prostate cancer. Soy proteins used to lower serum cholesterol are rich sources of phytoestrogens. Therefore, we assessed the effect of soy consumption on serum PSA in men who had participated in cholesterol lowering studies.Materials and Methods: For 3 to 4 weeks 46 healthy middle-aged men with a range of starting PSA values took soy (mean 44 gm. soy protein daily, 116 mg. isoflavones daily) or control foods, and a subgroup of men took a lower level of soy supplements for 3 months. PSA was measured at the start and end of each treatment.Results: Soy had no significant effect on serum total or free PSA, independent of PSA starting value or isoflavone intake. The lack of effect on PSA was seen, although soy intake was sufficient to reduce low-density lipoprotein cholesterol (5.8 ± 2.2%, p = 0.012), the estimated coronary heart disease risk (6.1 ± 2.8% for ...

BACKGROUND Many of the benefits of soy have been attributed to soy isoflavones. OBJECTIVE The objective was to determine the effects of high- and low-isoflavone soy-protein foods on both lipid and nonlipid risk factors for coronary artery disease (CAD). METHODS Forty-one hyperlipidemic men and postmenopausal women participated in a study with three 1-mo diets: a low-fat dairy food control diet and high- (50 g soy protein and 73 mg isoflavones daily) and low- (52 g soy protein and 10 mg isoflavones daily) isoflavone soyfood diets. All 3 diets were very low in saturated fat (< 5% of energy) and cholesterol (< 50 mg/d). Fasting blood samples were drawn and blood pressure was measured at the start and end of each diet. RESULTS No significant differences were seen between the high- and low-isoflavone soy diets. Compared with the control diet, however, both soy diets resulted in significantly lower total cholesterol, estimated CAD risk, and ratios of total to HDL cholesterol, LDL to HDL cholesterol, and apolipoprotein B to A-I. No significant sex differences were observed, except for systolic blood pressure, which in men was significantly lower after the soy diets than after the control diet. On the basis of blood lipid and blood pressure changes, the calculated CAD risk was significantly lower with the soy diets, by 10.1 +/- 2.7%. CONCLUSION Substitution of soyfoods for animal products, regardless of isoflavone concentration, reduces the CAD risk because of both modest reductions in blood lipids and reductions in oxidized LDL, homocysteine, and blood pressure.

This study sought to determine effects of high- and low-isoflavone soy protein foods on acute-phase proteins and proinflammatory cytokines and whether isoflavone phytoestrogens might act as estrogens, which enhance the immune response. Forty-one hypercholesterolemic men and postmenopausal women underwent three 1-month diets consisting of a low-fat dairy food control phase and high- and low-isoflavone soy food test phases (50 g/d and 52g/d soy protein, respectively, and 73 mg/d and 10 mg/d isoflavone, respectively). Diets were low in saturated fat (

BACKGROUND The US Food and Drug Administration (FDA) approved health claims for 2 dietary fibers, beta-glucan (0.75 g/serving) and psyllium (1.78 g/serving), on the assumption that 4 servings/d would reduce cardiovascular disease risk. OBJECTIVE We assessed the efficacy of this dose of fibers in reducing serum lipid risk factors for cardiovascular disease. DESIGN Sixty-eight hyperlipidemic adults consumed a test (high-fiber) and a control low-fat (25% of energy), low-cholesterol (

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

The effects of tree nuts on risk factors for coronary heart disease (CHD), in particular blood lipids, have been investigated in a number of studies and the beneficial effects are now recognized. The beneficial effects of nuts on CHD in cohort studies have also been clearly demonstrated. However, while there is also reason to believe the unique micro- and macronutrient profiles of nuts may help to control blood glucose levels, relatively few studies have investigated their role in diabetes control and prevention. Nuts are low in available carbohydrate, have a healthy fatty acid profile, and are high in vegetable protein, fiber and magnesium. Acute feeding studies indicate that when eaten alone nuts have minimal effects on raising postprandial blood glucose levels. In addition, when nuts are consumed with carbohydrate rich foods, they blunt the postprandial glycemic response of the carbohydrate meal. Despite the success of these acute studies, only a limited number of trials have been conducted with nuts in type 2 diabetes. These studies have either been of insufficient duration to observe changes in HbA1c, as the standard measure of glycemic control, or have been underpowered. Therefore, more long-term clinical trials are required to examine the role of nuts on glycemic control in patients with prediabetes and diabetes. Overall, there are good reasons to justify further exploration of the use of nuts in the prevention of diabetes and its micro- and macrovascular complications.

CHD is the leading cause of worldwide mortality. The prevalence of heart disease has been linked to the adoption of a sedentary lifestyle and the increased dietary dependence on saturated fats from animal sources and the intake of refined foods. Elevated blood cholesterol level is one of the major risk factors for CHD. While cholesterol-lowering drug therapy (statins) has been effective in reducing the risk of heart disease, there are those individuals who are unwilling or because of muscle pains or raised levels of liver or muscle enzymes are unable to take cholesterol-lowering medication. Fortunately, there is evidence linking a number of dietary components to CHD risk reduction. The strength of this evidence has prompted various regulatory bodies to advocate diet as the first line of defence for primary prevention of heart disease. It was therefore decided to combine four dietary components that have been shown to lower blood cholesterol concentrations (nuts, plant sterols, viscous fibre and vegetable protein) in a dietary portfolio in order to determine whether the combined effect is additive. In a metabolically-controlled setting this dietary portfolio has proved to be as effective as a starting dose of a first-generation statin cholesterol-lowering medication in reducing the risk of CHD. The dietary portfolio has also been shown to be effective in sustaining a clinically-significant effect in the long term under a 'real-world' scenario. However, success of the diet depends on compliance and despite the accessibility of the foods adherence has been found to vary greatly. Overall, the evidence supports the beneficial role of the dietary portfolio in reducing blood cholesterol levels and CHD risk.

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.

Nuts, including peanuts, are now recognized as having the potential to improve the blood lipid profile and, in cohort studies, nut consumption has been associated with a reduced risk of coronary heart disease (CHD). More recently, interest has grown in the potential value of including nuts in the diets of individuals with diabetes. Data from the Nurses Health Study indicates that frequent nut consumption is associated with a reduced risk of developing diabetes and cardiovascular disease. Randomized controlled trials of patients with type 2 diabetes have confirmed the beneficial effects of nuts on blood lipids also seen in nondiabetic subjects, but the trials have not reported improvement in A1c or other glycated proteins. Acute feeding studies, however, have demonstrated the ability of nuts, when eaten with carbohydrate (bread), to depress postprandial glycemia. Furthermore, there was evidence of reduced postprandial oxidative stress associated with nut consumption. In terms of dietary composition, nuts have a good nutritional profile, are high in monounsaturated fatty acids (MUFA) and PUFA, and are good sources of vegetable protein. Incorporation of nuts in the diet may therefore improve the overall nutritional quality of the diet. We conclude that there is justification to consider the inclusion of nuts in the diets of individuals with diabetes in view of their potential to reduce CHD risk, even though their ability to influence overall glycemic control remains to be established.

The glycemic index concept owes much to the dietary fiber hypothesis that fiber would reduce the rate of nutrient absorption and increase the value of carbohydrate foods in the maintenance of health and treatment of disease. However, properties and components of food other than its fiber content contribute to the glycemic and endocrine responses postprandially. The aim of the glycemic index classification of foods was therefore to assist in the physiological classification of carbohydrate foods which, it was hoped, would be of relevance in the prevention and treatment of chronic diseases such as diabetes. Over the past two decades low glycemic index diets have been reported to improve glycemic control in diabetic subjects, to reduce serum lipids in hyperlipidemic subjects and possibly to aid in weight control. In large cohort studies, low glycemic index or glycemic load diets (glycemic index multiplied by total carbohydrate) have also been associated with higher levels of high-density lipoprotein cholesterol, reduced C-reactive protein concentrations and with a decreased risk of developing diabetes and cardiovascular disease. More recently, some case-control and cohort studies have also found positive associations between the dietary glycemic index and the risk of colon, breast and other cancers. While the glycemic index concept continues to be debated and there remain inconsistencies in the data, sufficient positive findings have emerged to suggest that the glycemic index is an aspect of diet of potential importance in the treatment and prevention of chronic diseases.

Background: Cholesterol-lowering foods may be more effective when consumed as combinations rather than as single foods. Objectives: Our aims were to determine the effectiveness of consuming a combination of cholesterol-lowering foods (dietary portfolio) under real-world conditions and to compare these results with published data from the same participants who had undergone 4-wk metabolic studies to compare the same dietary portfolio with the effects of a statin. Design: For 12 mo, 66 hyperlipidemic participants were prescribed dietshighinplantsterols(1.0g/1000kcal),soyprotein(22.5g/1000 kcal),viscousfibers(10g/1000kcal),andalmonds(23g/1000kcal). Fifty-five participants completed the 1-y study. The 1-y data were also compared with published results on 29 of the participants who had also undergone separate 1-mo metabolic trials of a diet and a statin. Results: At 3 mo and 1 y, mean (SE) LDL-cholesterol reductions appeared stable at 14.0 1.6% (P 0.001) and 12.8 2.0% (P 0.001), respectively (n66). These reductions were less than those observed after the 1-mo metabolic diet and statin trials. Nevertheless, 31.8% of the participants (n 21 of 66) had LDL-cholesterol reductions of 20% at 1y( x SE: 29.7 1.6%). The LDLcholesterol reductions in this group were not significantly different from those seen after their respective metabolically controlled portfolio or statin treatments. A correlation was found between total dietary adherence and LDL-cholesterol change (r 0.42, P 0.001). Only 2 of the 26 participants with 55% compliance achieved LDL-cholesterol reductions 20% at 1 y. Conclusions: More than 30% of motivated participants who ate the dietary portfolio of cholesterol-lowering foods under real-world conditions were able to lower LDL-cholesterol concentrations 20%, which was not significantly different from their response to a first-generation statin taken under metabolically controlled conditions. Am J Clin Nutr 2006;83:582–91.

3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol. Newer dietary approaches combining cholesterol-lowering foods may offer another option, but these approaches have not been compared directly with statins in the same persons.The objective was to compare, in the same subjects, the cholesterol-lowering potential of a dietary portfolio with that of a statin.Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in random order as outpatients: a very-low-saturated-fat diet (control diet), the same diet plus 20 mg lovastatin (statin diet), and a diet high in plant sterols (1.0 g/1000 kcal), soy-protein foods (including soy milks and soy burgers, 21.4 g/1000 kcal), almonds (14 g/1000 kcal), and viscous fibers from oats, barley, psyllium, and the vegetables okra and eggplant (10 g/1000 kcal) (portfolio diets). Fasting blood samples were obtained at 0, 2, and 4 wk.LDL-cholesterol concentrations decreased by 8.5+/-1.9%, 33.3+/-1.9%, and 29.6+/-1.3% after 4 wk of the control, statin, and portfolio diets, respectively. Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk (P=0.013), 9 participants (26%) achieved their lowest LDL-cholesterol concentrations with the portfolio diet. Moreover, the statin (n=27) and the portfolio (n=24) diets did not differ significantly (P=0.288) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff.Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention. They may, therefore, bridge the treatment gap between current therapeutic diets and newer statins.

It was initially hypothesized that resistant starches, i.e., starch that enters the colon, would have protective effects on chronic colonic diseases, including reduction of colon cancer risk and in the treatment of ulcerative colitis. Recent studies have confirmed the ability of resistant starch to increase fecal bulk, increase the molar ratio of butyrate in relation to other short-chain fatty acids, and dilute fecal bile acids. However the ability of resistant starch to reduce luminal concentrations of compounds that are damaging to the colonic mucosa, including fecal ammonia, phenols, and N-nitroso compounds, still requires clear demonstration. As such, the effectiveness of resistant starch in preventing or treating colonic diseases remains to be assessed. Nevertheless, there is a fraction of what has been termed resistant (RS1) starch, which enters the colon and acts as slowly digested or lente carbohydrate in the small intestine. Foods in this class are low glycemic index and have been shown to reduce the risk of chronic disease. They have been associated with systemic physiological effects such as reduced postprandial insulin levels and higher HDL cholesterol levels. Consumption of low glycemic index foods has been shown to be related to reductions in risk of coronary heart disease and Type 2 diabetes. Type 2 diabetes has in turn been related to a higher risk of colon cancer. If carbohydrates have a protective role in colon cancer prevention this may lie partly in the systemic effects of low glycemic index foods. The colonic advantages of different carbohydrates, varying in their glycemic index and resistant starch content, therefore, remain to be determined. However, as recent positive research findings continue to mount, there is reason for optimism over the possible health advantages of those resistant starches, which are slowly digested in the small intestine.

The ability of dietary carbohydrates to affect blood glucose and insulin levels by dietary carbohydrates is best measured by the glycemic index (GI) and glycemic load (GL) which have been directly associated with risk of several chronic conditions, including cancer.Three case-control studies were conducted between 1992 and 2000 in Italy. The first one included 598 hospital patients with incident, histologically confirmed oral and pharyngeal cancer and 1491 controls admitted to the same hospital networks for acute, non-neoplastic diseases; the second study included 304 subjects with squamous cell oesophageal cancer and 743 controls; the third one included 460 cases with laryngeal cancer and 1088 controls. All subjects were interviewed using a validated food frequency questionnaire.The odds ratios (OR) of upper aero-digestive tract neoplasms for the highest versus the lowest quintile of dietary GI and GL were 1.5 (95% confidence interval [CI]: 1.1-2.0) and 1.8 (95% CI: 1.1-2.9), respectively. The associations were in the same direction for various cancer sites. The ORs were apparently stronger in women, in those with high body mass index and reporting low alcohol consumption.This study supports the hypothesis that high dietary GI and GL are associated with cancers of the upper aero-digestive tract.

ContextTo enhance the effectiveness of diet in lowering cholesterol, recommendations of the Adult Treatment Panel III of the National Cholesterol Education Program emphasize diets low in saturated fat together with plant sterols and viscous fibers, and the American Heart Association supports the use of soy protein and nuts.ObjectiveTo determine whether a diet containing all of these recommended food components leads to cholesterol reduction comparable with that of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).DesignRandomized controlled trial conducted between October and December 2002.Setting and ParticipantsForty-six healthy, hyperlipidemic adults (25 men and 21 postmenopausal women) with a mean (SE) age of 59 (1) years and body mass index of 27.6 (0.5), recruited from a Canadian hospital-affiliated nutrition research center and the community.InterventionsParticipants were randomly assigned to undergo 1 of 3 interventions on an outpatient basis for 1 month: a diet very low in saturated fat, based on milled whole-wheat cereals and low-fat dairy foods (n = 16; control); the same diet plus lovastatin, 20 mg/d (n = 14); or a diet high in plant sterols (1.0 g/1000 kcal), soy protein (21.4 g/1000 kcal), viscous fibers (9.8 g/1000 kcal), and almonds (14 g/1000 kcal) (n = 16; dietary portfolio).Main Outcome MeasuresLipid and C-reactive protein levels, obtained from fasting blood samples; blood pressure; and body weight; measured at weeks 0, 2, and 4 and compared among the 3 treatment groups.ResultsThe control, statin, and dietary portfolio groups had mean (SE) decreases in low-density lipoprotein cholesterol of 8.0% (2.1%) (P = .002), 30.9% (3.6%) (P

Herbal remedies high in phytoestrogens have been shown to reduce serum prostate specific antigen (PSA) and have been proposed as a treatment for prostate cancer. Soy proteins used to lower serum cholesterol are rich sources of phytoestrogens. Therefore, we assessed the effect of soy consumption on serum PSA in men who had participated in cholesterol lowering studies.For 3 to 4 weeks 46 healthy middle-aged men with a range of starting PSA values took soy (mean 44 gm. soy protein daily, 116 mg. isoflavones daily) or control foods, and a subgroup of men took a lower level of soy supplements for 3 months. PSA was measured at the start and end of each treatment.Soy had no significant effect on serum total or free PSA, independent of PSA starting value or isoflavone intake. The lack of effect on PSA was seen, although soy intake was sufficient to reduce low-density lipoprotein cholesterol (5.8 +/- 2.2%, p = 0.012), the estimated coronary heart disease risk (6.1 +/- 2.8% for 10 years, p = 0.032) and the serum concentration of oxidized low-density lipoprotein measured as conjugated dienes (9.5 +/- 3.4%, p = 0.008) in the 3 to 4-week study. In addition, the lack of effect of soy on PSA persisted for the 3 months of the extended study.At levels of soy intake which reduce low-density lipoprotein cholesterol any potential benefits of soy consumption on prostate cancer are likely to occur for reasons other than alterations in hormone activity.

Background— Although recent studies have indicated that nut consumption may improve levels of blood lipids, nuts are not generally recommended as snacks for hyperlipidemic subjects because of their high fat content. Furthermore, the effective dose is still unknown. Methods and Results— The dose-response effects of whole almonds, taken as snacks, were compared with low-saturated fat (P =0.018, and 9.4±1.9%, P P =0.001, and 12.0±2.1%, P P =0.034) and oxidized LDL concentrations (14.0±3.8%, P Conclusions— Almonds used as snacks in the diets of hyperlipidemic subjects significantly reduce coronary heart disease risk factors, probably in part because of the nonfat (protein and fiber) and monounsaturated fatty acid components of the nut.

OBJECTIVE—Cohort studies indicate that cereal fiber reduces the risk of diabetes and coronary heart disease (CHD). Therefore, we assessed the effect of wheat bran on glycemic control and CHD risk factors in type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 23 subjects with type 2 diabetes (16 men and 7 postmenopausal women) completed two 3-month phases of a randomized crossover study. In the test phase, bread and breakfast cereals were provided as products high in cereal fiber (19 g/day additional cereal fiber). In the control phase, supplements were low in fiber (4 g/day additional cereal fiber). RESULTS—Between the test and control treatments, no differences were seen in body weight, fasting blood glucose, HbA1c, serum lipids, apolipoproteins, blood pressure, serum uric acid, clotting factors, homocysteine, C-reactive protein, magnesium, calcium, iron, or ferritin. LDL oxidation in the test phase was higher than that seen in the control phase (12.1 ± 5.4%, P < 0.034). Of the subjects originally recruited, more dropped out of the study for health and food preference reasons from the control phase (16 subjects) than the test phase (11 subjects). CONCLUSIONS—High-fiber cereal foods did not improve conventional markers of glycemic control or risk factors for CHD in type 2 diabetes over 3 months. Possibly longer studies are required to demonstrate the benefits of cereal fiber. Alternatively, cereal fiber in the diet may be a marker for another component of whole grains that imparts health advantages or a healthy lifestyle.

The glycemic index concept is an extension of the fiber hypothesis, suggesting that fiber consumption reduces the rate of nutrient influx from the gut. The glycemic index has particular relevance to those chronic Western diseases associated with central obesity and insulin resistance. Early studies showed that starchy carbohydrate foods have very different effects on postprandial blood glucose and insulin responses in healthy and diabetic subjects, depending on the rate of digestion. A range of factors associated with food consumption was later shown to alter the rate of glucose absorption and subsequent glycemia and insulinemia. At this stage, systematic documentation of the differences that exist among carbohydrate foods was considered essential. The resulting glycemic index classification of foods provided a numeric physiologic classification of relevant carbohydrate foods in the prevention and treatment of diseases such as diabetes. Since then, low-glycemic-index diets have been shown to lower urinary C-peptide excretion in healthy subjects, improve glycemic control in diabetic subjects, and reduce serum lipids in hyperlipidemic subjects. Furthermore, consumption of low-glycemicindex diets has been associated with higher HDL-cholesterol concentrations and, in large cohort studies, with decreased risk of developing diabetes and cardiovascular disease. Case-control studies have also shown positive associations between dietary glycemic index and the risk of colon and breast cancers. Despite inconsistencies in the data, sufficient, positive findings have emerged to suggest that the dietary glycemic index is of potential importance in the treatment and prevention of chronic diseases.

Combining foods with recognized cholesterol-lowering properties (dietary portfolio) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions.To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low-density lipoprotein cholesterol (LDL-C) among participants following self-selected diets.A parallel-design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada (Quebec City, Toronto, Winnipeg, and Vancouver) randomized between June 25, 2007, and February 19, 2009, to 1 of 3 treatments lasting 6 months.Participants received dietary advice for 6 months on either a low-saturated fat therapeutic diet (control) or a dietary portfolio, for which counseling was delivered at different frequencies, that emphasized dietary incorporation of plant sterols, soy protein, viscous fibers, and nuts. Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months.Percentage change in serum LDL-C.In the modified intention-to-treat analysis of 345 participants, the overall attrition rate was not significantly different between treatments (18% for intensive dietary portfolio, 23% for routine dietary portfolio, and 26% for control; Fisher exact test, P = .33). The LDL-C reductions from an overall mean of 171 mg/dL (95% confidence interval [CI], 168-174 mg/dL) were -13.8% (95% CI, -17.2% to -10.3%; P.001) or -26 mg/dL (95% CI, -31 to -21 mg/dL; P.001) for the intensive dietary portfolio; -13.1% (95% CI, -16.7% to -9.5%; P.001) or -24 mg/dL (95% CI, -30 to -19 mg/dL; P.001) for the routine dietary portfolio; and -3.0% (95% CI, -6.1% to 0.1%; P = .06) or -8 mg/dL (95% CI, -13 to -3 mg/dL; P = .002) for the control diet. Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet (P.001, respectively). The 2 dietary portfolio interventions did not differ significantly (P = .66). Among participants randomized to one of the dietary portfolio interventions, percentage reduction in LDL-C on the dietary portfolio was associated with dietary adherence (r = -0.34, n = 157, P.001).Use of a dietary portfolio compared with the low-saturated fat dietary advice resulted in greater LDL-C lowering during 6 months of follow-up.clinicaltrials.gov Identifier: NCT00438425.