Mediterranean diet can reverse metabolic disorder, lower risk of diabetes, obesity, heart disease

The Mediterranean diet doesn't just protect against heart disease: It may actually reverse metabolic syndrome, a cluster of symptoms linked to heart disease and diabetes.

The findings came from a study conducted by researchers from the Universitat Rovira i Virgili and the Hospital Universitari de Sant Joan de Reus in Reus, Spain.

"In this large, multicentre, randomized clinical trial involving people with high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil was associated with a smaller increase in the prevalence of metabolic syndrome compared with advice on following a low-fat diet," the researchers wrote.

"Because there were no between-group differences in weight loss or energy expenditure, the change is likely attributable to the difference in dietary patterns."

A heart-healthy diet

Metabolic syndrome refers to a cluster of symptoms that is associated with a higher risk of diabetes, cardiovascular disease and premature death, and affects about 25 percent of all adults globally. The condition can be diagnosed in anyone who has three or more symptoms. Symptoms include high blood sugar, high triglycerides, low HDL ("good") cholesterol, high blood pressure and central obesity (a large waist circumference).

The researchers wondered how the Mediterranean diet could affect metabolic syndrome, because the diet has previously been shown to reduce the risk of cardiovascular disease and type 2 diabetes, as well as lead to better health, longer life and less age-related cognitive decline. For example, a 2013 study published in the New England Journal of Medicine found that people who ate a Mediterranean diet were about 30 percent less likely to develop cardiovascular disease than people who ate a low-fat diet.

The Mediterranean diet has high quantities of olive oil, seeds and nuts, whole grains and beans; moderate to high quantities of dairy, primarily in the form of yogurt and cheese; moderate quantities of fish and poultry; low to moderate consumption of red wine; and low consumption of red meat.

Metabolic syndrome decreased 30 percent

In the new study, researchers randomly assigned 5,801 adults between the ages of 55 and 80 who were considered at high risk of developing heart disease to follow one of three diets: a low-fat diet (control group), a Mediterranean diet plus extra olive oil or a Mediterranean diet plus extra nuts. Participants were followed for an average of 4.8 years.

By the end of the study, there was no difference between the three groups in the numbers who had developed new cases of metabolic syndrome. This showed that, despite being higher in fat, the Mediterranean diet did not worsen metabolic outcomes.

The more surprising outcome came among patients who already had metabolic syndrome at the beginning of the study. Among the groups on one of the two Mediterranean diets, the incidence of metabolic syndrome actually fell by 28.2 percent. Participants receiving extra olive oil were more likely to see decreases in central obesity and blood sugar, whereas participants receiving extra nuts were more likely to see a decrease in central obesity alone.

"Mediterranean diets supplemented with olive oil or nuts were not associated with a reduced incidence of metabolic syndrome compared with a low-fat diet; however, both diets were associated with a significant rate of reversion of metabolic syndrome," the researchers wrote.

Increasingly, research is suggesting that the benefits of the Mediterranean diet also extend far beyond metabolic health. In a 2010 study conducted by researchers from the University of Navarra in Pamplona, Spain. The Mediterranean diet was found to lower the risk of developing depression by 30 percent -- even after researchers controlled for risk factors including anxiety, personality, lifestyle habits and family status.

Human Growth Hormone and Testosterone Therapy for Heart Failure

Human Growth Hormone (HGH) and testosterone supplementation have shown promising effects in patients with heart failure despite numerous small, short-term clinical trials showing mixed results. Selected patients may benefit from supplementation in addition to conventional therapy, in particular patients with documented hormonal deficiency (below or in the low-normal range). Patients with suspected HGH resistance may warrant pretreatment screening prior to supplementation to adjust dosing and possible direct IGF-1 administration in addition to HGH. However, from our knowledge, there are no direct studies with both HGH and IGF-1 supplementation in  heart failure, thus recommendations cannot be made regarding this dual therapeutic approach.

Minimal data exist for combined therapy of HGH and testosterone in the setting of heart failure. The studies using combined HGH and testosterone supplementation were mostly conducted in older men with testosterone and IGF-1 in lower ranges of normal. One study showed promising effects on the improvement of body composition and muscle performance,  while another study found no change in function, mood and body composition. However, the latter study observed improvements in balance and muscle IGF-1 gene expression. Future studies investigating combined HGH and testosterone therapy in patients with heart failure would be warranted in order to assess possible synergistic effects, which may be advantageous over monotherapy.

Testosterone treatment has been shown to exert beneficial effects in both men and women with heart failure with few adverse effects. In our patients with advanced heart failure and other comorbid conditions, we routinely screen for and treat testosterone deficiency. Approximately 20–30% of our heart failure patients, those with ventricular assist devices and patients with postorthotopic heart transplantation status, have received supplemental testosterone at some point. Anecdotally, the patients have improved nutritional status as well as improved functionality and sense of well being. Although our patients appear to show some clinical improvement with testosterone therapy, we currently do not have conclusive data to recommend testosterone therapy in heart failure patients. Despite the promising role of hormonal supplementation in Heart Failure, larger, long-term, randomized clinical trials are warranted to further assess efficacy and safety of manipulation of the hormonal imbalance in patients with chronic Heart Failure.

Patients with heart failure are often observed to have hormonal dysregulation. HGH/IGF-1 axis derangement and testosterone deficiency have been an area of great interest as an adjunctive therapy in patients with advanced heart failure. While early studies show that HGH supplementation in patients with heart failure enhances cardiac function resulting in improvement in clinical symptoms, subsequent studies did not demonstrate significant improvements in cardiac morphology, performance or clinical status. However, the studies have been small with relatively short study duration. Of note, the inconsistent data may be linked to HGH resistance in patients and this may affect the biochemical response to HGH therapy. Patients with HGH resistance were observed to have lower levels of IGF-1, thus combination therapy of both HGH and IGF-1 may be beneficial. Coadministration of HGH and IGF-1 in patients with heart failure have not been fully investigated, thus the efficacy and safety of this therapeutic approach remains uncertain.

The majority of adverse effects observed in patients on long-term HGH replacement therapy include edema, insulin resistance, arthralgia and myalgia. These adverse effects were often related to higher dosing; therefore, appropriate dosing will have to be addressed to minimize adverse effects but maximize beneficial outcomes. Because there are inconsistent data on efficacy and lack of long-term assessment on safety – large randomized clinical trials are needed to fully evaluate these issues before starting patients on HGH-replacement therapy.

Similarly, testosterone therapy in patients with heart failure shows improvement in functional status and prognosis. Multiple studies observe improvements in parameters such as LV performance, incremental shuttle walk test and mean peak oxygen consumption. The adverse effects of testosterone therapy have been associated with exacerbation of prostate cancer, atherosclerosis, unfavorable lipid profiles and polycythemia. These adverse effects were mainly observed when testosterone was administered at supraphysiological levels. Despite the positive benefits of testosterone replacement, the long-term efficacy and safety remains unclear and will need to be addressed prior to committing a patient to long-term therapy.

HGH and testosterone therapy have shown promising benefits in patients with heart failure. At present, many institutions, including our own, are actively participating in trials to reproduce the data observed in earlier studies. As more data are available and large clinical studies show consistent benefits with minimal adverse effects, hormonal supplementation may become an integral agent in the treatment of heart failure. If the benefits and safety are clearly established, patients may be prescreened for low levels of HGH and testosterone early on in their course of disease. This strategy may lead to earlier initiation of hormone therapy with hopes of improving functional status and quality of life.