Prof. Iris Shai

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Research Projects

Dietary Randomized Control Trials

The S. Daniel Abraham International Center for Health and Nutrition has undisputedly become a leader in dietary RCTs. A team of researchers led by Prof. Iris Shai has conducted several high profile trials and performed large-scale follow-up studies in the Israeli Defense Forces (IDF) over the past decade: the Dietary Intervention Randomized Controlled Trial (DIRECT), the Cardiovascular Diabetes and Ethanol (CASCADE) Randomized Control Trial (and its pilot alcohol trial), the Central Whole-Body MRI Randomized Control Trial, and the Metabolic, Lifestyle, and the Nutrition Assessment in Young Adults (MELANY) IDF study.

The results of these studies have been published in top professional journals (including the highly regarded New England Journal of Medicine), as well as mainstream media (The New York Times, CNN, etc.).  Study outcomes have already had an impact on the assessment, treatment, and prevention of cardio-metabolic disease, and research findings from these studies are cited today by researchers and clinicians around the world. A description of the DIRECT study follows, along with a brief summary of the three other trials.   

The Dietary Intervention Randomized Controlled Trial (DIRECT)

The dramatic increase in obesity worldwide underscores the urgent need to test the effectiveness and safety of widely used weight-loss diets, and DIRECT compared the effectiveness and safety of three restricted-calorie nutritional protocols (low-carbohydrate, Mediterranean, and low-fat diets).

Common limitations of dietary trials include high attrition, small size, and short duration.   DIRECT addressed all of these points in that it was a long-term (two-year), large scale (322 participants) study with conditions put in place to limit attrition and promote dietary adherence; the retention rate was high - 96% through the first year and 85% through the second year.  The model of intervention for all participants was the same and included the use of dietary group sessions, spousal support, food labels, and monthly weighing in the workplace.

Comprehensive evaluation included measurements of weight, waist circumference, blood pressure, and extensive blood tests (measuring lipids, inflammatory biomarkers, insulin, glucose, hemoglobin, liver enzyme, total cholesterol, high-density-lipoprotein (HDL) cholesterol, low-density-lipoprotein (LDL) cholesterol, triglycerides, etc.)  Adherence to the diets was evaluated by a food-frequency questionnaire, and physical activity was measured. 

Researchers found that the Mediterranean and low-carb diets were effective alternatives to the low-fat diet in terms of weight loss and safety.  They found that among all diet groups, weight loss was greater for those who completed the study, and that even moderate weight loss had health benefits.  Increased improvement in the levels of some biomarkers over time was observed, even after participants achieved maximum weight loss, suggesting that a healthy diet has benefits beyond weight reduction.  The research also points to the benefits of behavioral approaches that yield weight loss which in this study were found to be similar to those obtained with pharmacotherapy.  Results were published in The New England Journal of Medicine in 2008, and have been cited hundreds of times since then in research performed by other researchers.  The research made the headlines in newspapers across the US and was reported online and on TV and radio as well. 

In addition, DIRECT contributed to further research demonstrating that two-year weight loss diets can induce a significant regression of atherosclerosis.  In collaboration with Canadian colleagues, BGU researchers utilized a novel imaging technique, cutting-edge 3D ultrasound, which detected sensitive changes in atherosclerosis, demonstrating the impact of sustained dietary change.  This research was published in the prestigious journal of the American Heart Association, Circulation. 

Furthermore, an additional follow-up study to DIRECT confirms the long-lasting, favorable post-intervention effects (despite weight regain) of the diets.  This “halo” effect, reflected in improved total cholesterol and triglyceride levels, points to the sustained healthful influence of dietary modification. 

The Cardiovascular Diabetes and Ethanol (CASCADE) Randomized Control Trial

The health effects of wine have been the subject of much discussion with speculation that moderate alcohol intake is good for you.  CASCADE will verify this and evaluate the long-term effects of moderate wine consumption.  The BGU study which followed 224 participants with type 2 diabetes over a two-year period is the largest evaluation of its kind in the world.  Participants were evaluated on an extensive list of measures, and evaluation techniques range from the basic (scale) to the cutting edge (3D ultrasound and a continuous glucose monitoring system). 

While the results of the study are currently under review, the study was referenced in The New York Times as early as 2009 with the headline “Alcohol’s Good for You?  Some Scientists Doubt it.”  The article went on to say, “The bottom line is there has not been a single study done on moderate alcohol consumption and mortality outcomes that is a ‘gold standard’…The Israeli scientists are now working with an international team to begin a larger two-year trial.” 

Researchers hope the published results will once again place BGU in the headlines in professional journals and the general press.  In the meantime however, adjunct research has been published in Diabetes Care (2012), centered on abdominal fat distribution (more specifically superficial subcutaneous fat) in patients with type 2 diabetes. Until now, the association between subcutaneous adipose tissue and obesity-related illness has been unclear.  BGU researchers looked at participants’ abdominal MRIs and observed a distinct protective fat sub-depot linking this body fat composition to type 2 diabetes.  The study adds to the understanding of abdominal fat distribution patterns, including newly implicated “sub-depots,” and their relation to glycemic control and cardiovascular risk in diabetic patients.  Research to develop effective interventions that can alter abdominal fat distribution may help determine whether fat distribution patterns reflect obesity-related disease or whether they indicate a risk factor for such disease. 

 

The Central Whole-Body MRI Randomized Control Trial

BGU researchers were the first in the world to quantify that not all body fat is equal in preliminary studies (described above).  Following up on these findings, the recently completed Central Whole-Body MRI trial addresses whether dietary intervention can positively impact the body’s fat depots.  278 participants were followed for 1.5 years during which they maintained healthy low-carb or Mediterranean diets.  Utilizing whole-body MRI, researchers thoroughly analyzed fat composition including:  abdominal fat compartments and hepatic, pericardial, cervical, pancreatic, muscular fat, renal fat, etc.

Results of the study will address the question of whether lifestyle (dietary intervention) can affect body fat composition and minimize the amount of fat stored in harmful locations.  The research may explain why individuals that look the same on the outside (similar weight and waist circumference) may have very different levels of cardio-metabolic health, and more importantly, study outcomes may contribute to the ability to alter body fat patterns by diet or help determine who is at risk for cardio-metabolic disease. 

The Metabolic, Lifestyle, and Nutrition Assessment in Young Adults (MELANY) Follow-Up Study

The MELANY study which followed 37,000 youngsters for 17 years, from the year before conscription into the Israel Defense Forces (IDF), was recently published in The New England Journal of Medicine.  Results show a substantial risk of obesity-related disorders (including heart disease) in young adulthood among those with a somewhat elevated, but within the normal range, body mass index (BMI) at age seventeen.  Researchers found that baseline BMI at adolescence can help predict the early occurrence of heart disease and type 2 diabetes in young adulthood.  The study showed that BMI in adolescence is a risk factor for cardio-metabolic disease, even if the teenager is not in the obese range at the time.  The study also found that increased BMI over time corresponded to an increased risk for type 2 diabetes and heart disease. 

Long-term, large-scale studies such as this offer the opportunity to identify patterns and change over periods of time, identify risk factors, and other information which can be used in the future to improve disease prevention and detection.

 

Related Cardio-Metabolic Health Research

Medical research is a long and arduous process which may or may not culminate in the performance of an RCT. In fact, the bulk of medical research takes place behind the scenes and in the lab, long before the involvement of human subjects in an RCT.  The RCTs conducted by researchers at the S. Daniel Abraham International Center for Health and Nutrition have been enriched and made possible by the groundwork laid by fellow researchers.  For example, it was such complementary research that advanced sophisticated imaging techniques, enabling our RCT team to study adipose tissue associated with different organs in the body.  Preliminary research also pointed to abdominal adipose tissue as a harbinger of the detrimental health effects of obesity and led to the identification of specific biomarkers associated with cardio-metabolic disease. 

Members of the S. Daniel Abraham International Center for Health and Nutrition have also played a role in the research underpinning the large scale RCTs conducted by the Center.  This research is fundamental in its own right, serving as the basis for prestigious international collaboration and contributing to the development of applications as well.