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Gut Microbiota-Derived Metabolites and Cardiovascular Disease Risk: A Systematic Review of Prospective Cohort Studies.
Sanchez-Gimenez, R, Ahmed-Khodja, W, Molina, Y, Peiró, OM, Bonet, G, Carrasquer, A, Fragkiadakis, GA, Bulló, M, Bardaji, A, Papandreou, C
Nutrients. 2022;14(13)
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Cardiovascular disease (CVD) remains a major public health issue. Identification of circulating biomarkers with prognostic value may help to both identify pathophysiological processes relevant to CVD development and improve preventive cardiovascular risk reduction efforts. The aim of this study was to identify the association of circulating levels of microbial metabolites with CVD incidence. This study is a systematic review of twenty-one studies of which 19 were prospective cohort studies, one study included one nested case-control study and one study included two nested case–control studies. Results show that: - associations of trimethylamine N-oxide (TMAO) [molecular metabolite derived from the gut flora] and subsequent risk of CV outcomes were supported by some but not all prospective studies. - inconsistent results were also obtained for secondary bile acids in relation to CVD and related outcomes, and CVD/all-cause mortality. - with regards to branched-chain amino acids (BCAAs), their associations with CV outcomes were robust amongst most of the studies. Authors conclude that their findings show inconsistent results for TMAO and bile acids but robust ones for the relationships between BCAAs and CVD. Thus, further studies are needed to investigate whether circulating microbial metabolites could be an intervention target for CVD.
Abstract
Gut microbiota-derived metabolites have recently attracted considerable attention due to their role in host-microbial crosstalk and their link with cardiovascular health. The MEDLINE-PubMed and Elsevier's Scopus databases were searched up to June 2022 for studies evaluating the association of baseline circulating levels of trimethylamine N-oxide (TMAO), secondary bile acids, short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), tryptophan and indole derivatives, with risk of cardiovascular disease (CVD). A total of twenty-one studies were included in the systematic review after evaluating 1210 non-duplicate records. There were nineteen of the twenty-one studies that were cohort studies and two studies had a nested case-control design. All of the included studies were of high quality according to the "Newcastle-Ottawa Scale". TMAO was positively associated with adverse cardiovascular events and CVD/all-cause mortality in some, but not all of the included studies. Bile acids were associated with atrial fibrillation and CVD/all-cause mortality, but not with CVD. Positive associations were found between BCAAs and CVD, and between indole derivatives and major adverse cardiovascular events, while a negative association was reported between tryptophan and all-cause mortality. No studies examining the relationship between SCFAs and CVD risk were identified. Evidence from prospective studies included in the systematic review supports a role of microbial metabolites in CVD.
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What is the best diet for cardiovascular wellness? A comparison of different nutritional models.
Migliaccio, S, Brasacchio, C, Pivari, F, Salzano, C, Barrea, L, Muscogiuri, G, Savastano, S, Colao, A
International journal of obesity supplements. 2020;10(1):50-61
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Cardiovascular disease (CVD) is the leading cause of death in developed countries. There are many studies linking unhealthy nutrition and lifestyles to CVD, so there is a need to modify these factors. Different types of diet exist, or have been established, to optimise the approach such as the Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension diet (DASH), vegetarian diet, ketogenic diet, and Japanese diet. This review looks at the aspects of the diets. It evaluates the factors that increase CVD risk and the potential application and benefits of nutritional protocols. The diets are discussed along with factors such as energy excess, saturated fat intake, free sugars and refined starches intake, dietary fibre intake, fruit and vegetable intake, Polyunsaturated fatty acids (PUFA): omega-3, Monounsaturated fatty acids (MUFA), anthocyanins, vitamins and sedentary behaviour. The authors conclude that the MeDi has the best nutritional pattern. It includes whole grains, pulses, fiber and PUFAs without completely excluding food of animal origin such as meat, fish, dairy products, eggs, and limits alcohol consumption. The MeDi also includes conviviality and physical activity.
Abstract
Cardiovascular diseases (CVD) represent to date the leading cause of mortality in both genders in the developed countries. In this context, a strong need for CVD prevention is emerging through lifestyle modification and nutrition. In fact, several studies linked CVD with unhealthy nutrition, alcohol consumption, stress, and smoking, together with a low level of physical activity. Thus, the primary aim is to prevent and reduce CVD risk factors, such as impaired lipid and glycemic profiles, high blood pressure and obesity. Different types of diet have been, therefore, established to optimize the approach regarding this issue such as the Mediterranean diet, Dietary Approaches to Stop Hypertension diet (DASH), vegetarian diet, ketogenic diet, and Japanese diet. Depending on the diet type, recommendations generally emphasize subjects to increase vegetables, fruits, whole grains, and pulses consumption, but discourage or recommend eliminating red meat, sweets, and sugar-sweetened beverages, along with processed foods that are high in sugar, salt, fat, or low in dietary fiber. In particular, we evaluated and compared the peculiar aspects of these well-known dietary patterns and, thus, this review evaluates the critical factors that increase CVD risk and the potential application and benefits of nutritional protocols to ameliorate dietary and lifestyle patterns for CVD prevention.
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Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability.
Mas-Capdevila, A, Teichenne, J, Domenech-Coca, C, Caimari, A, Del Bas, JM, Escoté, X, Crescenti, A
Nutrients. 2020;12(5)
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Cardiovascular diseases (CVDs) cause around 31% of all deaths worldwide. Certain dietary patterns have been associated with a reduction in CVDs and so the use of natural-based products has gained importance as a preventive strategy. Hesperidin is a bioactive compound found in high levels in citrus fruits. The reported beneficial properties include antitumor, antioxidant, anti-inflammatory; cholesterol and glucose lowering effects. Many animal studies show multiple beneficial effects but are inconclusive in human studies. The aim of this review is to describe the effects of hesperidin on CVD factors and to highlight the individual differences in its bioavailability and effectiveness. The gut bacteria play an important role in this. Hesperidin is not broken down by the normal digestive process and reaches the colon largely intact. It is the job of the gut bacteria to break it down into bioavailable substances that can be absorbed and utilised. The discrepancies observed in some of the results from human clinical trials may be partly due to individual differences, including that of the gut bacteria. Further clinical trials should be considered as well as classifying individuals according to individual differences in metabotypes.
Abstract
Recently, hesperidin, a flavonone mainly present in citrus fruits, has emerged as a new potential therapeutic agent able to modulate several cardiovascular diseases (CVDs) risk factors. Animal and in vitro studies demonstrate beneficial effects of hesperidin and its derived compounds on CVD risk factors. Thus, hesperidin has shown glucose-lowering and anti-inflammatory properties in diabetic models, dyslipidemia-, atherosclerosis-, and obesity-preventing effects in CVDs and obese models, and antihypertensive and antioxidant effects in hypertensive models. However, there is still controversy about whether hesperidin could contribute to ameliorate glucose homeostasis, lipid profile, adiposity, and blood pressure in humans, as evidenced by several clinical trials reporting no effects of treatments with this flavanone or with orange juice on these cardiovascular parameters. In this review, we focus on hesperidin's beneficial effects on CVD risk factors, paying special attention to the high interindividual variability in response to hesperidin-based acute and chronic interventions, which can be partly attributed to differences in gut microbiota. Based on the current evidence, we suggest that some of hesperidin's contradictory effects in human trials are partly due to the interindividual hesperidin variability in its bioavailability, which in turn is highly dependent on the α-rhamnosidase activity and gut microbiota composition.
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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.
Ferrucci, L, Fabbri, E
Nature reviews. Cardiology. 2018;15(9):505-522
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Inflammageing is a term used to describe elevated blood inflammatory markers that leads to frailty and increases an individual’s risk for heart disease, kidney disease and other physical and mental illnesses. Whether inflammageing is causal in heart disease is still uncertain. This large review of 310 papers aimed to understand the causes and role of inflammageing in heart disease and other illnesses associated with ageing. Causes of inflammageing were discussed and mechanisms are not fully understood. Genetic susceptibility, obesity, gut microbiota, gut permeability, when cells can no longer divide, and chronic infections were all implicated. The role of inflammageing in heart disease was a focus and the authors deduced that it was likely to be both causal and a result of heart disease. However, the administration of anti-inflammatories in heart disease has not always proved a successful treatment. Possible causes of inflammageing are likely to be linked and cumulative and although inflammation may cause age related diseases, its role in protecting the body means that its benefits outweigh its consequences. It was concluded that controlling inflammageing may prevent heart disease and other diseases associated with ageing. This study could be used by healthcare professionals to help understand what inflammageing is and its role in age related diseases.
Abstract
Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.
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Physical exercise, gut, gut microbiota, and atherosclerotic cardiovascular diseases.
Chen, J, Guo, Y, Gui, Y, Xu, D
Lipids in health and disease. 2018;17(1):17
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Cardiovascular diseases (CVD), such as heart attacks and strokes, are the leading cause for mortality worldwide. Many studies have shown beneficial effects of physical exercise on cardiovascular risk factors, such as high cholesterol, high blood pressure, abdominal obesity and diabetes. However, some of the mechanisms, by which these beneficial effects occur, are not well understood. It is believed that gut microbiota, affected by physical exercise, altering the intestinal environment, plays a role. This review paper summarised the current understanding on the effects of physical exercise on CVD, through its effects on the gut microbiota and intestinal function. The authors reviewed animal and human studies looking at how various types of exercise, such as high-intensity interval training (mice), running (rats and mice) and rugby (humans), affect diversity and distribution of microbes, metabolites produced by microbiota, intestinal wall integrity and systemic inflammation. Based on the reviewed papers, the authors concluded that, although further research is warranted, many studies confirm the premise that physical exercise can prevent CVD through modifying gut microbiota and alleviating systemic inflammation.
Abstract
Arteriosclerotic cardiovascular diseases (ASCVDs) are the leading cause of morbidity and mortality worldwide and its risk can be independently decreased by regular physical activity. Recently, ASCVD and its risk factors were found to be impacted by the gut microbiota through its diversity, distribution and metabolites. Meanwhile, several experiments demonstrated the relationship between physical exercise and diversity, distribution, metabolite of the gut microbiota as well as its functions on the lipid metabolism and chronic systematic inflammation. In this review, we summarize the current knowledge on the effects of physical exercise on ASCVD through modulation of the gut microbiota and intestinal function.
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Impact of vegan diets on gut microbiota: An update on the clinical implications.
Wong, MW, Yi, CH, Liu, TT, Lei, WY, Hung, JS, Lin, CL, Lin, SZ, Chen, CL
Ci ji yi xue za zhi = Tzu-chi medical journal. 2018;30(4):200-203
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Gut microbiota is defined as microbes that collectively inhabit the gut ecosystem. Several factors, including diet, age, birth mode, breast-feeding or formula-feeding, geography, exercise, alcohol consumption, and exposure to antibiotics may influence gut microbiota. Previous conventional culturing together with recent culture-independent molecular studies show that vegan diets appear to affect gut microbiota. Furthermore, recent literature also indicates that vegan diets may have various health benefits, including amelioration of metabolic syndrome, cardiovascular disease and rheumatoid arthritis. Authors conclude that these findings have their limitations. Thus, further research may help to clarify the complex mechanisms and interrelationships between vegan diets and gut microbiota.
Abstract
Numerous studies indicate that microbiota plays an important role in human health. Diet is a factor related to microbiota which also influences human health. The relationships between diet, microbiota, and human health are complex. This review focuses on the current literature on vegan diets and their unique impact on gut microbiota. We also report on the health benefits of a vegan diet for metabolic syndrome, cardiovascular disease, and rheumatoid arthritis concerning relevant impacts from gut microbiota. Despite evidence supporting the clinical relevance of vegan gut microbiota to human health, the whole mechanism awaits further investigation.
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Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies.
Azad, MB, Abou-Setta, AM, Chauhan, BF, Rabbani, R, Lys, J, Copstein, L, Mann, A, Jeyaraman, MM, Reid, AE, Fiander, M, et al
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2017;189(28):E929-E939
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Obesity is a major public health challenge that contributes to type 2 diabetes and cardiovascular disease. Evidence that sugar consumption is fuelling this epidemic has stimulated the increasing popularity of non-nutritive sweeteners including aspartame, sucralose and stevioside. The aim of this study was to synthesize evidence of whether routine consumption of non-nutritive sweeteners by adults and adolescents is associated with adverse long-term cardiometabolic effects. This study is a systemic review and meta-analysis of randomised controlled trials and prospective cohort studies. It includes 37 studies involving a total of 406910 individuals. The study shows that small RCTs with short follow-up (median 6 months) suggest that consumption of non-nutritive sweeteners is not consistently associated with decreases in body weight, BMI or waist circumference. However, in larger prospective cohort studies with longer follow-up periods (median 10 years), intake of non-nutritive sweeteners is significantly associated with modest long-term increases in each of these measures. Authors conclude that caution in the use of non-nutritive sweeteners is warranted until the long-term risks and benefits of these products are fully characterised.
Abstract
BACKGROUND Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects. METHODS We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points. RESULTS From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference -0.37 kg/m2; 95% confidence interval [CI] -1.10 to 0.36; I2 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I2 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome. INTERPRETATION Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749.
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Associations between Yogurt Consumption and Weight Gain and Risk of Obesity and Metabolic Syndrome: A Systematic Review.
Sayon-Orea, C, Martínez-González, MA, Ruiz-Canela, M, Bes-Rastrollo, M
Advances in nutrition (Bethesda, Md.). 2017;8(1):146S-154S
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According to the WHO, overweight and obesity is defined as an excessive or abnormal fat accumulation that may affect human health. The prevalence of metabolic syndrome is growing which is mainly due to sedentary lifestyles, as well as the increasing prevalence of obesity. The aim of the study was to analyse the relation between yoghurt consumption and changes in weight or waist circumference and the risk of becoming overweight, obese or develop metabolic syndrome. This study is a systemic review based on 10 cohort studies, 1 of which included the results of 3 cohort studies. Results demonstrate that there was no detrimental affect of yoghurt consumption on weight status or on the risk of developing metabolic syndrome. The study also showed that high consumption of yoghurt in tandem with high consumption of fruit may be inversely associated with the development of metabolic syndrome. Authors conclude that further prospective studies and high-quality randomised control trials are required in order to confirm that yoghurt consumption may contribute to a reduction in adiposity indexes and the risk of metabolic syndrome.
Abstract
The role of yogurt consumption in the risk of developing overweight, obesity, or metabolic syndrome has been the subject of epidemiologic studies over the last 10 y. A comprehensive literature search on MEDLINE and ISI Web of Knowledge from 1966 through June 2016 was conducted to examine the relation between yogurt consumption and weight gain, as well as the risk of overweight, obesity, or metabolic syndrome, in prospective cohort studies. Ten articles met all the inclusion criteria and were included in our systematic review. Of the 10 cohort studies, 3 analyzed the relation between yogurt consumption and the risk of overweight or obesity, 8 analyzed changes in waist circumference or weight changes, 3 studied the association with the risk of developing metabolic syndrome, and 1 studied the probability of abdominal obesity reversion. Although an inverse association between yogurt consumption and the risk of developing overweight or obesity was not fully consistent or always statistically significant, all studies but one showed in their point estimates inverse associations between yogurt consumption and changes in waist circumference, changes in weight, risk of overweight or obesity, and risk of metabolic syndrome during follow-up, although not all estimates were statistically significant (2 studies). Prospective cohort studies consistently suggested that yogurt consumption may contribute to a reduction in adiposity indexes and the risk of metabolic syndrome. Therefore, there is a need for more prospective studies and high-quality randomized clinical trials to confirm this apparent inverse association.
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Association between plant-based diets and plasma lipids: a systematic review and meta-analysis.
Yokoyama, Y, Levin, SM, Barnard, ND
Nutrition reviews. 2017;75(9):683-698
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Plasma lipids play a prominent role in heart disease and modifiable factors such as diet and lifestyle can facilitate in preventing or developing hyperlipidemia. Previous research has suggested that vegetarian diets are associated with lower plasma lipid concentrations, however long-term impacts of consuming a plant-based diet (PBD) has not been studied. The aim of this research was to conduct a systematic review and meta-analysis for studies that have examined the relationship between PBDs and plasma lipids. Thirty observational studies and 19 clinical trials were included in this analysis and showed consumption of a PBD was significantly associated with lower total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), but not in triglyceride concentrations. Based on these results, the authors conclude PBDs could offer individuals and healthcare professionals an effective option for reducing heart disease. They also add that while dietary changes may not be as powerful as pharmaceutical drugs in reducing plasma lipids, dietary and pharmacologic interventions can work together.
Abstract
CONTEXT Although a recent meta-analysis of randomized controlled trials showed that adoption of a vegetarian diet reduces plasma lipids, the association between vegetarian diets and long-term effects on plasma lipids has not been subjected to meta-analysis. OBJECTIVE The aim was to conduct a systematic review and meta-analysis of observational studies and clinical trials that have examined associations between plant-based diets and plasma lipids. DATA SOURCES MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for articles published in English until June 2015. STUDY SELECTION The literature was searched for controlled trials and observational studies that investigated the effects of at least 4 weeks of a vegetarian diet on plasma lipids. DATA EXTRACTION Two reviewers independently extracted the study methodology and sample size, the baseline characteristics of the study population, and the concentrations and variance measures of plasma lipids. Mean differences in concentrations of plasma lipids between vegetarian and comparison diet groups were calculated. Data were pooled using a random-effects model. RESULTS Of the 8385 studies identified, 30 observational studies and 19 clinical trials met the inclusion criteria (N = 1484; mean age, 48.6 years). Consumption of vegetarian diets was associated with lower mean concentrations of total cholesterol (-29.2 and -12.5 mg/dL, P < 0.001), low-density lipoprotein cholesterol (-22.9 and -12.2 mg/dL, P < 0.001), and high-density lipoprotein cholesterol (-3.6 and -3.4 mg/dL, P < 0.001), compared with consumption of omnivorous diets in observational studies and clinical trials, respectively. Triglyceride differences were -6.5 (P = 0.092) in observational studies and 5.8 mg/dL (P = 0.090) in intervention trials. CONCLUSIONS Plant-based diets are associated with decreased total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, but not with decreased triglycerides. SYSTEMATIC REVIEW REGISTRATION PROSPERO number CRD42015023783. Available at: https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015023783.
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A plant-based diet for the prevention and treatment of type 2 diabetes.
McMacken, M, Shah, S
Journal of geriatric cardiology : JGC. 2017;14(5):342-354
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Type 2 diabetes is rising worldwide and increasing evidence indicates that dietary and lifestyle choices are key drivers of insulin resistance. Research on plant-based diets (PBDs) shows lower rates of type 2 diabetes, obesity, hypertension, hyperlipidaemia, cardiovascular disease and cancer. The aim of this review is to analyze the evidence supporting the use of PBDs for the prevention and treatment of type 2 diabetes and explore potential mechanisms of action. The existing literature points to the fact that PBDs simultaneously reduce the risk factors for cardiovascular disease including obesity, hypertension, hyperlipidaemia and inflammation. The proposed mechanism by which PBDs reduce insulin resistance is through the high fiber, antioxidant and magnesium content, all of which have been shown to promote insulin sensitivity. Based on this analysis, the authors conclude the PBD is highly beneficial for preventing and treating type 2 diabetes. Additionally, the authors agree with the mounting evidence for utilising a PBD to reduce the burden of diabetes and improve health overall.
Abstract
The prevalence of type 2 diabetes is rising worldwide, especially in older adults. Diet and lifestyle, particularly plant-based diets, are effective tools for type 2 diabetes prevention and management. Plant-based diets are eating patterns that emphasize legumes, whole grains, vegetables, fruits, nuts, and seeds and discourage most or all animal products. Cohort studies strongly support the role of plant-based diets, and food and nutrient components of plant-based diets, in reducing the risk of type 2 diabetes. Evidence from observational and interventional studies demonstrates the benefits of plant-based diets in treating type 2 diabetes and reducing key diabetes-related macrovascular and microvascular complications. Optimal macronutrient ratios for preventing and treating type 2 diabetes are controversial; the focus should instead be on eating patterns and actual foods. However, the evidence does suggest that the type and source of carbohydrate (unrefined versus refined), fats (monounsaturated and polyunsaturated versus saturated and trans), and protein (plant versus animal) play a major role in the prevention and management of type 2 diabetes. Multiple potential mechanisms underlie the benefits of a plant-based diet in ameliorating insulin resistance, including promotion of a healthy body weight, increases in fiber and phytonutrients, food-microbiome interactions, and decreases in saturated fat, advanced glycation endproducts, nitrosamines, and heme iron.