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Targeted approach in nutrition to address risk factors in metabolic syndrome

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01 December 2015

Metabolic syndrome is a disorder of energy utilization and storage, diagnosed by the coincidence of overweight or obesity with disturbances of lipid and sugar metabolism and hypertension. Subclinical inflammation and a fatty liver are further components typically associated with this condition. Metabolic syndrome substantially increases the risk of developing cardiovascular disease and diabetes. Diets targeting weight loss by restricting either carbohydrate or fat intake are an effective approach to improve most conditions associated with metabolic syndrome, but the benefit is not successfully achieved over longer periods. Therefore, a balanced diet rich in nutrients improving metabolism may represent a successful strategy. The role of several related nutrients has been presented and discussed during the 12th European Nutrition Conference (FENS 2015) in Berlin.

Metabolic syndrome (insulin resistance syndrome, syndrome X) is characterized by large waist circumference – due to abdominal obesity and associated with non-alcoholic fatty liver disease – high blood pressure, dyslipidemia and an abnormal fasting plasma glucose level or insulin resistance. Excess abdominal fat leads to increasing fat accumulation in the liver. Hypertension, dyslipidemia and insulin resistance develop, and glucose metabolism is impaired. Serum uric acid levels are elevated and increase the risk of gout, and a prothrombotic state and an inflammatory state develop. Patients have an increased risk of obstructive sleep apnea, non-alcoholic steatohepatitis, chronic kidney disease, polycystic ovary syndrome, and erectile dysfunction.

Fatty liver disease is a global and unresolved public health issue. We differentiate alcoholic fatty liver disease caused by heavy alcohol consumption from non-alcoholic fatty liver disease (NAFLD) which is the result of fat accumulation in the liver. NAFLD has become the most common cause of chronic liver disease in developed as well as in developing countries. There is emerging evidence that NAFLD affects other organs as well and so increases the risk of non-communicable diseases such as type 2 diabetescardiovascular and chronic kidney disease. There is encouraging data that particular micronutrients, such as vitamin E, can beneficially impact the onset and course of fatty liver disease. Also, the polyunsaturated fatty acids (omega-3s) EPA and DHA may lower the risk, progression and severity of NAFLD, and they may also be a therapeutic option for this condition.

Another global health risk is hypertension. Hypertension affects over 1 billion individuals globally and is the leading cause of mortality worldwide. Recent findings suggest that marginal riboflavin status may have adverse functional effects and long-term health consequences in specific population groups with a specific genotype. Although poor riboflavin status – based on dietary intake data – is not generally considered a problem in developed countries, some evidence is emerging – based on biomarker data – to suggest that suboptimal riboflavin status may be more prevalent than is generally reported. Given that this genetic predisposition for hypertension is correctable by riboflavin with considerable clinical and economic implications, further studies are needed to explore this gene-nutrient interaction and riboflavin status in different populations.

Fatty fish, fish oils and their concentrates, and some algal oils are particularly rich sources of long chain, highly unsaturated omega-3 fatty acids, e.g., eicosapentaenoic acid (EPA) and docosahexaenoioc acid (DHA). Intakes of EPA and DHA are typically low and much below recommended intakes. Increased content of EPA and DHA in blood lipids, blood cells and tissues can modify the structure of cell membranes, the function of membrane proteins and can alter patterns of gene expression. Through these actions EPA and DHA act to beneficially modify a number of risk factors for cardiovascular disease (CVD), including blood pressure, platelet reactivity and thrombosis, plasma triglyceride concentrations, vascular function, heart rate and heart rate variability, and inflammation. Thus they play a key role in prevention and slowing progression of several conditions associated with metabolic syndrome. Furthermore, pharmaceutical and supplemental niacin are used to treat hypercholesterolemia and to reduce the risk of cardiovascular disease.

Nutrients improving metabolism without significant weight loss may represent an alternative strategy to manage metabolic syndrome. This may be achieved by targeting nutrient sensors such as hormonal systems, inflammatory receptors and nutrient-sensitive transcription factors. Among the hormonal systems, incretins are realistic targets due to their differential location in the gut. The glucose-dependent insulinotropic polypeptide (GIP) system appears to trigger increased inflammation and fatty liver disease in overweight or obese subjects. Nutrients which bypass the GIP-releasing K-cells in the upper intestine represent a suitable strategy which can be achieved with alpha-glucosidase inhibitors or slowly cleaved sugars such as isomaltulose. This strategy has been used successfully in humans and was shown to improve lipid metabolism in longer-term trials. Moreover, significant effects on hepatic glucose production were shown in type 2 diabetic humans. The low Glycemic Index (GI) concept appears to involve some components of incretin modulation but is also affected by gastric emptying and therefore appears to involve several mechanisms.

Representatives of bioactive lipids, peptides, phenolic derivatives and sulfur compounds have all been shown to have potential benefits in CVD prevention by targeting blood pressure reduction, platelet function, endothelial function or cardiovascular inflammation. Water-soluble tomato concentrate (WSTC, FruitFlow) was awarded an authorized health claim by EFSA in 2009, on the basis of a set of mechanistic and intervention studies demonstrating consistent reduction of human platelet aggregability also present in metabolic syndrome, resulting in benefits to blood flow.

As demonstrated, nutritional approaches are influential in modifying metabolic syndrome and the disease risks associated with it – beyond or in addition to improvements in energy balance.

Author: Szabolcs Peter


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