What is metabolic syndrome and what does the scientific evidence say is the best cure?
Metabolic syndrome is defined according to the National Cholesterol Education Programme (NCEP) and International Diabetes Foundation (IDF) as when a person has central obesity plus any two of the following factors, 1) raised triglycerides ≥150 mg/dL (1.7mmol/L) or specific treatment for this lipid abnormality, 2) reduced HDL cholesterol <40 mg/dL in males or <50mg/dL in females or a specific treatment for this lipid abnormality, 3) raised blood pressure with systolic pressure ≥130 or diastolic ≤85mm Hg, 4) having a fasting plasma glucose level ≥100mg/dL or finally, 5) a waist circumference (for Europeans) of ≥94cm for men or ≥80cm for women (with variance based on ethnicity). It has also been called Insulin resistance syndrome, syndrome X and cardiometabolic syndrome. It is a clustering of metabolic abnormalities that have been found to increase the risk of type two diabetes, stroke and CVD. Abdominal obesity is thought to be the central component and is associated with chronic inflammation.
There have been many studies investigating the effects of lifestyle interventions on metabolic syndrome. Both Ford (Ford et al., 2008), a prospective study with 5 cohorts and 42,419 people showed a 3.53–4.42 increased risk of type 2 diabetes and Mottillo, (Mottillo et al., 2010) systematic review and metanalysis of 87 studies with 951083 (a respectable sample size) people which highlighted the increase of CVD mortality by up to 2 times or 1.5x to all causes of mortality, showed the need for lifestyle intervention with metabolic syndrome. As did the Hirode and Wong study (Hirode & Wong, 2020) which showed the growing trends in the number of people with metabolic syndrome, with the worrying trend in young people demonstrated in the study of 26609 young people by Nolan (Nolan et al., 2017) with metabolic syndrome found in 5–7% of all young people, 1/3 of which had low HDL levels.
The Diabetes Prevention Programme (DPP) RCT (USA) highlighted the benefits of lifestyle intervention on metabolic disease and associated risk outcomes. The study (Knowler et al., 2002) by Knowler, of 3234 people with a mean age of 51 years of age with an average BMI of 34 with impaired glucose tolerance at risk of type 2 diabetes, 53% of which had metabolic syndrome compared a placebo group to a group on the diabetes sensitizing drug Metformin and an intensive lifestyle intervention group (see figure 1) with an average follow up at 2.8 years. It found that intensive lifestyle interventions such as 150 minutes of physical exercise prescribed per week and individual lifestyle coaches, behavioural education, supervised physical activity with motivational strategies and tailored nutritional support, were superior to pharmacological intervention for the prevention of diabetes Lifestyle intervention reduced diabetes by 58% whereas the metformin by 31% as compared with placebo.
Secondary analysis of this data by Orchard (Orchard et al., 2005), showed that lifestyle intervention and metformin, both reduced the incidence of Metabolic syndrome, among the 47% of participants who did not have it at baseline, but the impact of lifestyle intervention was much more marked, with a reduction of 41% in the lifestyle group and 17% in the metformin group with a 29% in incidence in the lifestyle group compared to the metformin group. Therefore lifestyle intervention was most effective in reversing metabolic syndrome. In the 53% who already had metabolic syndrome, after a 3.2-year follow-up, 18% of the placebo group, 23% of the metformin group and 38% of the lifestyle group, no longer had metabolic syndrome. The lifestyle intervention was superior for both resolution of metabolic syndrome as well as the prevention.
As well as the Orchard study, there have been other trials which have demonstrated the effectiveness of dietary intervention plus physical activity for preventing and reversing metabolic syndrome. The 2004 SUN (Esposito & Giugliano, 2014; Giugliano et al., 2008) RCT study by Esposito and team, highlighted the benefits of the Mediterranean diet on endothelial function and inflammatory markers in patients with metabolic syndrome. The study in 180 people (a very small Italian cohort which may not be representative of a global population) compared those with a diet high in wholegrains, unsaturated fats, fibre, fruits, nuts and olive oil, to that of a control group which was a moderately low fat diet. Both groups increased their level of physical activity by at least 60% and there was no difference in this between groups (so physical activity level was not a confounder in this study). Body weight decreased more in the intervention (4kg weight loss compared to 1.2kg) group more than the control group. At 2 years after follow up, 40 patients in the intervention group still had metabolic disease, compared to 78 in the control group. So it was concluded that a Mediterranean diet was effected in reducing metabolic syndrome and associated risk conditions.
Similarly, the Azadbakter et al study (Azadbakht et al., 2005) aimed to determine the dietary interventions associated with stopping hypertension (DASH) diet on metabolic risks in patients with metabolic syndrome. This RCT was conducted in 116 people with metabolic syndrome (as per the NCEP ATPIII criteria) and it compared the dash diet (high in magnesium, calcium, potassium and low in added sodium, saturated fat and cholesterol and added sugars) to a weigh-reducing diet (which emphasized healthy food choices) and control of usual care. A study limitation is that it was very short in duration as it was only 6 months long. The study found that the prevalence of metabolic syndrome for those on the Dash diet was 65% compared to 81% in the weight loss diet and 100% in the control. The effects of reducing metabolic risks were significant even after concluding the Dash diet (Filippou et al., 2020) as per the ANOVA, suggesting that the dash diet is very effective in reducing metabolic syndrome.
Without intervention, metabolic syndrome will progress until the hyperglycaemia leads to beta cell pancreatic burnout and a diagnosis of type 2 diabetes. Therefore insulin sensitivity is a potential target for the dietary intervention treatment of metabolic syndrome. Two studies looked at how modifying dietary fat and sugar impact metabolic syndrome. The RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) trial looked at the effect of changing the amount and type of fat and carbohydrate on insulin sensitivity and cardiovascular risk. The parallel design RCT with 5 groups across sites (Jebb et al., 2010) study, looked at the effects of the replacement of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates of high glycemic index (HGI) or low glycemic index (LGI). It looked (figure 2) at 548 participants who either had metabolic syndrome or were at high risk of metabolic syndrome. It found that after 6 months there was no differential effects on insulin sensitivity which was measured using a gold standard method called the intravenous glucose tolerance test (IGTT). The paper showed that there were greater improvements with low glycaemic diets compared to the low glycaemic index diets when fat content was kept low. There was improved insulin sensitivity with the low glycaemic index group. It also found no difference in weight control, triglycerides, blood pressure. However the low-fat diet reduced HDL-cholesterol whereas the high monousaturated fat diet reduced total cholesterol and the HDL-ratio improved. Overall it concluded that the amount and type of dietary carbohydrates had no difference in weight control, lipids and blood pressure.
The Lipgene study, (Tierney et al., 2011), compared 417 people on four specific fat-controlled diets for 3 months. One diet with high saturated (SFA) triglycerides content, one that was high in mono-unsaturated (MUFA) fats and two that were low-fat, high in complex carbohydrates (LFHCC) diets, with omega3 PUFA poly-unsaturated fatty acids supplements (1.2 g per day) or placebo (Tierney et al., 2011). It found that there was no significant difference in weight control or insulin sensitivity according to the intravenous glucose tolerance test (IGTT). However, the high saturated fat diet reduced triglycerides, and the high MUFA and high SFA diets increased HDL-cholesterol and lowered the triglyceride to HDL-cholesterol ratio. It concluded that adding fish oil supplements to a low-fat diet lowered triglycerides.
The meta-analysis of 12 cross-sectional cohort studies by Godos (Godos et al., 2017) found that a Mediterranean diet whole diet approach was better for the treatment of metabolic syndrome than a restrictive diet that was limited based on food group quality and quantity. It compared the Mediterranean diet +nuts with the Mediterranean diet + extra virgin olive oil. This was shown further in the PREDIMED study which looked at the Mediterranean diet and the risk of metabolic syndrome. It initially aimed to look at the effects of a Mediterranean diet on cardiovascular disease (CVD) endpoints. Secondary (Martínez-González et al., 2015). analysis showed no effect. However, of the 3392 participants with metabolic syndrome at baseline, those on the 2 Mediterranean diets were more likely to have this reversed than those on the control diet (HR 1.28/1.35 (95% CI 1.08/1,15–1.51/1.58).
The PURE (Prospective Urban Rural Epidemiology) study of 112922 people (a large cohort size) across continents looked at the effects of dairy on metabolic syndrome (Dehghan et al., 2018). It found that a higher intake of dairy (at least 2 servings per day) reduced metabolic syndrome by 24% with a dose-response observed. Higher intakes of high-fat dairy with low-fat dairy, compared to low-fat dairy alone, were associated with a higher reduced risk of metabolic syndrome and improved metabolic control. This study, a limitation of which is that it is a cross-sectional study with potential for dietary recall error, emphasized the benefits of looking at whole foods, rather than individual food groups, for the treatment of obesity and metabolic syndrome and associated risk factors. Whole foods may contain bioactive compounds which may provide additional anti-inflammatory benefits for example which go beyond the simple macronutrient contents.
Limitations in evidence lie in the fact that most of the studies are of a very short duration and so the long-term effects of remission to metabolic syndrome are not assessed. Additionally, the studies either have a small cohort size with potential for non-representation for a wider population, or are across geographic continents where differences in ethnicity, climate, culture and lifestyle behaviour potential confounders, are not observed. There is much further work that is needed to improve current scientific research study design.
Overall, it can be concluded based on current reputable scientific evidence from systematic meta-analysis reviews of RCT, that the best dietary interventions for metabolic syndrome and associated risk factors (including diabetes, cardiovascular disease and stroke risk) are those with holistic (whole diet and lifestyle) interventions with weight management and integrated dietary patterns such as in the Mediterranean diet and dash diet, whereas targeting specific parts of the diet and demonising them, such as fat and carbohydrate in isolation has less benefit. These diets have small effects which are probably seen after a longer duration.
Copyright Laura Campbell 12/03/2023
References
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