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Potential Factors Influencing the Effects of Anthocyanins on Blood Pressure Regulation in Humans: A Review.
Vendrame, S, Klimis-Zacas, D
Nutrients. 2019;11(6)
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Anthocyanins (ACNs) are plant compounds belonging to the flavonoid group of polyphenols and are naturally occurring in a number of foods. They are responsible for the red, blue and purple pigmentation within plant foods, such as blueberries and raspberries and are known to contain therapeutic compounds. Several studies have investigated the anti-inflammatory, antioxidant and blood pressure modulation properties within ACNs, however, results for blood pressure modulation, unlike those for anti-inflammatory and antioxidant properties have been mixed and less consistent. This paper reviews 66 human intervention trials exploring the effects of various forms of ACNs, like whole berries, concentrates and freeze-dried powders in order to identify the singular variables related to blood pressure modulation in order to further investigate. Having looked at a number of variables within the trials, researchers concluded that ACNs do in fact contain blood pressure lowering properties, but further research into varying factors including dose effect, synergistic effects, absorption and metabolism and the functionality of the individuals gut microbiota is needed to clarify results further.
Abstract
Dietary intake of anthocyanins (ACNs) is associated with a reduced risk of cardiovascular and coronary heart disease. While the anti-inflammatory, antioxidant, and lipid-lowering effects of ACN consumption have been consistently reported, their effect(s) on blood pressure regulation is less consistent and results from human studies are mixed. The objective of this review is attempting to identify potential patterns which may explain the variability in results related to blood pressure. To do so, we review 66 human intervention trials testing the effects on blood pressure of purified ACN or ACN-rich extracts, or whole berries, berry juices, powders, purees and whole phenolic extracts, from berries that are rich in ACN and have ACNs as predominant bioactives. Several factors appear to be involved on the mixed results reported. In particular, the baseline characteristics of the population in terms of blood pressure and total flavonoid intake, the dose and duration of the intervention, the differential effects of individual ACN and their synergistic effects with other phytochemicals, the ACN content and bioavailability from the food matrix, and individual differences in ACN absorption and metabolism related to genotype and microbiota enterotypes.
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The Effect of Electrolytes on Blood Pressure: A Brief Summary of Meta-Analyses.
Iqbal, S, Klammer, N, Ekmekcioglu, C
Nutrients. 2019;11(6)
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Hypertension is the major leading risk factor for atherosclerosis and several diseases, especially renal and cardiovascular disorders, including myocardial infarction, stroke, and heart failure. The aim of this study was to summarize meta-analyses studying the effect and associations of electrolytes as supplements or diets on human blood pressure or risk for hypertension throughout the last years. The study is a review that summarizes meta-analyses of publications studying the effect or association between electrolytes and blood pressure. Meta-analyses of randomized controlled trials or observational studies were included in this review. The major findings of this review indicate that: 1. Sodium (salt) reduction and a higher intake of potassium have convincing blood pressure lowering effects, 2. Higher magnesium intake is suggested to possibly reduce blood pressure, especially in patients with hypertension, and 3. Sufficient calcium intake confers a protective effect regarding the risk for gestational hypertension. Authors conclude that lowering sodium and increasing potassium intake would exert convincing blood pressure lowering effects, especially in hypertensive patients.
Abstract
Nutrition is known to exert an undeniable impact on blood pressure with especially salt (sodium chloride), but also potassium, playing a prominent role. The aim of this review was to summarize meta-analyses studying the effect of different electrolytes on blood pressure or risk for hypertension, respectively. Overall, 32 meta-analyses evaluating the effect of sodium, potassium, calcium and magnesium on human blood pressure or hypertension risk were included after literature search. Most of the meta-analyses showed beneficial blood pressure lowering effects with the extent of systolic blood pressure reduction ranging between -0.7 (95% confidence interval: -2.6 to 1.2) to -8.9 (-14.1 to -3.7) mmHg for sodium/salt reduction, -3.5 (-5.2 to -1.8) to -9.5 (-10.8 to -8.1) mmHg for potassium, and -0.2 (-0.4 to -0.03) to -18.7 (-22.5 to -15.0) mmHg for magnesium. The range for diastolic blood pressure reduction was 0.03 (-0.4 to 0.4) to -5.9 (-9.7 to -2.1) mmHg for sodium/salt reduction, -2 (-3.1 to -0.9) to -6.4 (-7.3 to -5.6) mmHg for potassium, and -0.3 (-0.5 to -0.03) to -10.9 (-13.1 to -8.7) mmHg for magnesium. Moreover, sufficient calcium intake was found to reduce the risk of gestational hypertension.
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Systematic review of palm oil consumption and the risk of cardiovascular disease.
Ismail, SR, Maarof, SK, Siedar Ali, S, Ali, A
PloS one. 2018;13(2):e0193533
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Palm oil, the most widely consumed vegetable oil in the world, derives from the palm tree fruit with a balanced ratio of unsaturated and saturated fatty acids. Studies have shown an association between high contents of saturated fats in palm oil with the detrimental atherogenic profile. The review aims at synthesising the available evidence reporting the association of palm oil consumption with cardiovascular disease risk and cardiovascular disease-specific mortality, including specifically Coronary Heart Disease (CHD) and stroke. The authors systematically searched three databases up to June 2017 without restriction on setting or language. Published interventional and observational studies that evaluated palm oil consumption with coronary heart disease or stroke in adults were searched. Separate searches were performed depending on the outcome. The study did not find a clear association between palm oil consumption and risk or mortality of cardiovascular disease, namely coronary heart disease and stroke. The health effects found between association of palm oil consumption and risk of coronary heart disease were not unique to just palm oil consumption as other food items were also included in the analysis. The review could not establish strong evidence for or against palm oil consumption relating to cardiovascular disease risk and cardiovascular disease-specific mortality. A healthy overall diet is suggested for good cardiometabolic health.
Abstract
BACKGROUND The high amount of saturated fatty acids (SFA) coupled with the rising availability and consumption of palm oil have lead to the assumption that palm oil contributes to the increased prevalence of cardiovascular diseases worldwide. We aimed at systematically synthesising the association of palm oil consumption with cardiovascular disease risk and cardiovascular disease-specific mortality. METHODS We systematically searched Central, Medline and Embase databases up to June 2017 without restriction on setting or language. We performed separate searches based on the outcomes: coronary heart disease and stroke, using keywords related to these outcomes and palm oil. We searched for published interventional and observational studies in adults (Age: >18 years old). Two investigators extracted data and a consensus was reached with involvement of a third. Only narrative synthesis was performed for all of the studies, as the data could not be pooled. RESULTS Our search retrieved 2,738 citations for stroke with one included study and 1,777 citations for coronary heart disease (CHD) with four included studies. Palmitic acid was reported to be associated with risk of myocardial infarction (MI) (OR 2.76; 95%CI = 1.39-5.47). Total SFA intake was reported to be not significant for risk of MI. Varying intake of fried foods, highest contributor to total SFA with 36% of households using palm oil for frying, showed no significant associations to risk of MI. Odds of developing first non-fatal acute MI was higher in palm oil compared to soybean oil with 5% trans-fat (OR = 1.33; 95%CI = 1.09-1.62) than palm oil compared to soybean oil with 22% trans-fat (OR = 1.16; 95%CI = 0.86-1.56). Nevertheless, these risk estimates were non-significant and imprecise. The trend amongst those taking staple pattern diet (characterised by higher palm oil, red meat and added sugar consumption) was inconsistent across the factor score quintiles. During the years of 1980 and 1997, for every additional kilogram of palm oil consumed per-capita annually, CHD mortality risk was 68 deaths per 100,000 (95% CI = 21-115) in developing countries and 17 deaths per 100,000 (95%CI = 5.3-29) in high-income countries, whereas stroke was associated with 19 deaths per 100,000 (95%CI = -12-49) and 5.1 deaths per 100,000 (95% CI: -1.2-11) respectively. The evidence for the outcomes of this review were all graded as very low. The findings of this review should be interpreted with some caution, owing to the lack of a pooled effect estimate of the association, significant bias in selection criteria and confounding factors, inclusion of other food items together with palm oil, and the possible out-dated trend in the ecological study. CONCLUSION In view of the abundance of palm oil in the market, quantifying its true association with CVD outcomes is challenging. The present review could not establish strong evidence for or against palm oil consumption relating to cardiovascular disease risk and cardiovascular disease-specific mortality. Further studies are needed to establish the association of palm oil with CVD. A healthy overall diet should still be prioritised for good cardiometabolic health.
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Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk.
Frühbeck, G, Catalán, V, Rodríguez, A, Gómez-Ambrosi, J
Adipocyte. 2018;7(1):57-62
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Obesity is medically defined as a condition of abnormal or excessive fat accumulation in adipose tissue, of sufficient extent to produce adverse health consequences. Presently, adipose tissue has emerged as an extremely active endocrine organ, based on its ability to secrete a plethora of biologically active adipokines [a class of cytokine mediators that are predominantly secreted by adipose cells] such as leptin and adiponectin. Furthermore, obesity is characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Thus, the adiponectin/leptin ratio has been suggested as a marker of adipose tissue dysfunction. A dysfunctional adipose tissue, evidenced by a lower adiponectin/ leptin ratio, is a clear contributor to the low-grade chronic inflammation associated with metabolic syndrome. Authors conclude that this ratio is highly and negatively correlated with markers of low-grade chronic inflammation emerging as a useful estimator of obesity- and metabolic syndrome- associated cardiometabolic risk.
Abstract
Obesity is currently the most extended metabolic disturbance worldwide favoring the development of cardiometabolic alterations such as type 2 diabetes, hypertension, and dyslipidemia. Obesity and the metabolic syndrome (MS) are characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Consequently, the adiponectin/leptin ratio has been suggested as a maker of adipose tissue dysfunction. This emerging biomarker correlates with insulin resistance better than adiponectin or leptin alone, or even HOMA and is decreased with increasing number of metabolic risk factors having been proposed as a predictive marker for the MS. Moreover, the adiponectin/leptin ratio is negatively correlated with markers of low-grade chronic inflammation. In this sense, an increase in this ratio has been related with reduced atherosclerosis risk as well as with a decreased risk of some types of cancer in epidemiological studies. In this commentary we propose new cutoffs to estimate obesity- and MS-associated cardiometabolic risk according to the adiponectin/leptin ratio and discuss different therapeutic strategies to increase this promising biomarker of metabolic risk.
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Spices and Atherosclerosis.
Tsui, PF, Lin, CS, Ho, LJ, Lai, JH
Nutrients. 2018;10(11)
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Cardiovascular disease (CVD) is one of the leading causes of death and disability in the world. Atherosclerosis, characterised by the accumulation of fat and inflammation in blood vessels, is the main feature of CVD. Common spices such as pepper, ginger, garlic, onion, cinnamon and chilli may have effects on the initiation and development of atherosclerosis. In this review, the authors focused on the potential protective effects of spices, in atherosclerosis and CVD. Most studies to date have been carried out either in cell culture or in animals. These have revealed various potential mechanisms by which spices exert their beneficial effects, including anti-oxidant, anti-atherogenic, anti-coagulant, anti-inflammatory and cholesterol-lowering properties. There are some human studies evaluating the effects of spices on high blood pressure. Although saffron, turmeric, and chilli pepper had no effect on blood pressure, cinnamon demonstrated significant blood pressure lowering effects in patients with diabetes. Garlic has been shown to have the potential to reduce blood pressure in patients with high blood pressure. These studies provide information on the beneficial roles of spices in reducing cardiovascular risk factors. The types of spices consumed vary across cultures, and currently there are no available population studies showing that consumption of spices is associated with reduction of CVD nor any recommendations for the amounts of spices to be consumed. The authors conclude that the consumption of spices should be encouraged across countries to promote good health.
Abstract
Cardiovascular disease is one of the leading causes of death and disability in the world. Atherosclerosis, characterized by lipid accumulation and chronic inflammation in the vessel wall, is the main feature of cardiovascular disease. Although the amounts of fruits and vegetables present in the diets vary by country, diets, worldwide, contain large amounts of spices; this may have positive or negative effects on the initiation and development of atherosclerosis. In this review, we focused on the potential protective effects of specific nutrients from spices, such as pepper, ginger, garlic, onion, cinnamon and chili, in atherosclerosis and atherosclerotic cardiovascular disease. The mechanisms, epidemiological analysis, and clinical studies focusing on a variety of spices are covered in this review. Based on the integrated information, we aimed to raise specific recommendations for people with different dietary styles for the prevention of atherosclerotic cardiovascular disease through dietary habit adjustments.
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The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review.
Boyle, NB, Lawton, C, Dye, L
Nutrients. 2017;9(5)
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15% of the population experience anxiety-related conditions at some point in their lives. Several studies have found a relationship between low magnesium (Mg) and an increased likelihood of stress and anxiety. This systematic review examined the available evidence for the effectiveness of Mg supplementation in reducing anxiety and stress. 18 studies were included in the review. Of the eight studies looking at Mg supplementation and anxiety, four reported positive results. Four of seven studies on premenstrual syndrome and one of two studies in people with high blood pressure reported positive effects of Mg on anxiety. Mg had no effect on postpartum anxiety in the study reviewed. The authors concluded that existing evidence is suggestive of a beneficial effect of Mg on anxiety. However, the quality of the existing evidence is poor. Well-designed randomised controlled trials are required to further confirm the effect of Mg supplementation on anxiety and stress.
Abstract
BACKGROUND Anxiety related conditions are the most common affective disorders present in the general population with a lifetime prevalence of over 15%. Magnesium (Mg) status is associated with subjective anxiety, leading to the proposition that Mg supplementation may attenuate anxiety symptoms. This systematic review examines the available evidence for the efficacy of Mg supplementation in the alleviation of subjective measures of anxiety and stress. METHODS A systematic search of interventions with Mg alone or in combination (up to 5 additional ingredients) was performed in May 2016. Ovid Medline, PsychInfo, Embase, CINAHL and Cochrane databases were searched using equivalent search terms. A grey literature review of relevant sources was also undertaken. RESULTS 18 studies were included in the review. All reviewed studies recruited samples based upon an existing vulnerability to anxiety: mildly anxious, premenstrual syndrome (PMS), postpartum status, and hypertension. Four/eight studies in anxious samples, four/seven studies in PMS samples, and one/two studies in hypertensive samples reported positive effects of Mg on subjective anxiety outcomes. Mg had no effect on postpartum anxiety. No study administered a validated measure of subjective stress as an outcome. CONCLUSIONS Existing evidence is suggestive of a beneficial effect of Mg on subjective anxiety in anxiety vulnerable samples. However, the quality of the existing evidence is poor. Well-designed randomised controlled trials are required to further confirm the efficacy of Mg supplementation.
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Cardio-Metabolic Benefits of Plant-Based Diets.
Kahleova, H, Levin, S, Barnard, N
Nutrients. 2017;9(8)
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Chronic disease, which includes cardiovascular disease, obesity, type 2 diabetes, hypertension, hyperlipidaemia and stroke, is the underlying cause of many health and economic burdens. There is ample evidence that proper nutrition, specifically plant-based diets (PBDs), are an effective strategy for reducing the burden of chronic disease. The aim of this narrative review is to summarise the most recent evidence on the efficacy of PBDs on various cardio-metabolic disease risk factors. This review found consistent, convincing evidence around PBDs improving body weight, glycaemic control, blood pressure and blood lipid profile, thus reducing the overall risk factors associated with chronic disease. Based on these findings, the authors conclude properly planned PBDs are an effective tool for preventing and treating cardio-metabolic disease and encourage PBDs to be recommended and promoted.
Abstract
Cardio-metabolic disease, namely ischemic heart disease, stroke, obesity, and type 2 diabetes, represent substantial health and economic burdens. Almost one half of cardio-metabolic deaths in the U.S. might be prevented through proper nutrition. Plant-based (vegetarian and vegan) diets are an effective strategy for improving nutrient intake. At the same time, they are associated with decreased all-cause mortality and decreased risk of obesity, type 2 diabetes, and coronary heart disease. Evidence suggests that plant-based diets may reduce the risk of coronary heart disease events by an estimated 40% and the risk of cerebral vascular disease events by 29%. These diets also reduce the risk of developing metabolic syndrome and type 2 diabetes by about one half. Properly planned vegetarian diets are healthful, effective for weight and glycemic control, and provide metabolic and cardiovascular benefits, including reversing atherosclerosis and decreasing blood lipids and blood pressure. The use of plant-based diets as a means of prevention and treatment of cardio-metabolic disease should be promoted through dietary guidelines and recommendations.
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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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Olive Polyphenols and the Metabolic Syndrome.
Saibandith, B, Spencer, JPE, Rowland, IR, Commane, DM
Molecules (Basel, Switzerland). 2017;22(7)
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Up to 25% of the world’s population has metabolic syndrome (MetS), characterised by a combination of high blood pressure, high blood sugar, obesity and abnormal levels of fats in the blood. People with MetS have an increased risk of developing type 2 diabetes and heart disease. The development of MetS is related to modifiable diet and lifestyle factors. This review presents evidence from previous studies investigating the relationship between consumption of olive products, and aspects of MetS, and discusses potential mechanisms linking olive consumption to improvements in markers of health. The authors found good evidence from previous human studies showing that the consumption of olives and olive oil lowers blood pressure in people diagnosed with high blood pressure. There is also good evidence that olives and olive oil can improve blood glucose levels in those with prediabetes and improve markers of lipid peroxidation. There is limited, but promising evidence for effects on dyslipidaemia and the inhibition of weight gain. Studies that used extra virgin olive oil (EVOO) used doses of up to 50g per day, well above the amount that is consumed habitually in most diets. Further evidence is needed to confirm the mechanisms and benefits of olive polyphenols, but the authors suggest that they may explain some of the metabolic benefits associated with a Mediterranean diet.
Abstract
Here, the effects of consuming polyphenol-rich olive products, including olive leaves, their crude extract, and extra virgin olive oil, on aspects of the metabolic syndrome are reviewed. We have sought to summarize the available scientific evidence from dietary intervention trials demonstrating a role for these phytochemicals in ameliorating aberrant glucose metabolism, high blood pressure and elevated blood lipids, and we discuss the potential mechanisms underpinning these observations. Searches for relevant literature published in English were conducted via PubMed and Science Direct. Based on published dietary intervention studies, there is convincing evidence to show that olive polyphenols, independently of olive lipids, reduce risk factors for metabolic syndrome, in particular by improving blood sugar and blood pressure control, and in reducing low density lipoprotein oxidation. There is more limited evidence to suggest that the consumption of olive polyphenols or related products can reduce body weight and visceral fat or impede weight gain, and similarly there are some limited data suggesting improved lipid profiles. There is some mechanistic data to support observations made in human volunteers, but further work is needed in this area. The consumption of olive polyphenols within the context of a healthy pattern of food intake may, in part, explain the reduced risk of metabolic disease associated with adherence to the Mediterranean diet.