Scientists have investigated why some individuals with obesity do not develop metabolic disorders despite their condition. A study from the Center for Human Nutrition in Missouri and Washington School of Medicine in Washington State examined three dietary approaches to determine if the balance of macronutrients influences metabolic health differently. Their findings indicated that a low-carbohydrate diet was most effective at reversing metabolic syndrome compared to Mediterranean and low-fat plant-based diets.
The study, published in Cell Metabolism, detailed a clinical trial comparing the Mediterranean diet, a low-carbohydrate diet, and a low-fat plant-based diet. The low-carb diet provided just 4% of calories from carbohydrates, 73% from fat, and 23% from protein. In contrast, the Mediterranean diet supplied 50% of energy from carbohydrates, 35% from fat, and 15% from protein, while the low-fat plant-based diet consisted of 70% carbohydrates, 15% fat, and 15% protein.
Comparing Metabolic Outcomes
The researchers recruited 55 volunteers who had metabolically unhealthy obesity—defined as a BMI over 30, intrahepatic triglyceride levels higher than 5.6%, a HbA1C level greater than 5.7% or a fasting glucose reading above 100 mg/dl. They excluded volunteers who were going through or who had been through menopause or had any conditions or illnesses that could affect their metabolism or interfere with the experiment. These included diabetes, PMOS, cancer, bariatric surgery, veganism, alcohol problems, pregnancy and more.
The researchers used a special randomization technique to ensure that the groups were very similar, making it easier to see if there were real differences at the end of the experiment. Seventeen would follow a very low-carbohydrate ketogenic diet; eighteen would eat Mediterranean style and 20 would try a very low-fat plant forward diet. Each participant picked up a weekly stock of frozen meal packages, carefully designed to conform to the requirements of each diet. The volunteers agreed to stick to the meal plans and log what they ate in an online diary, with expert advice from dietitians each week.
The researchers set the participants a challenge to lose 10% of their body weight by sticking to their individualized, dietitian-planned meals for around five months. Having shed the pounds, the volunteers continued on a maintenance meal plan for another 3-4 months.
Results of the Study
The researchers compared each participant’s metabolic markers at each time point, looking to see how the diets compared directly and examining the size of changes for each participant. The results showed that all three diets helped the volunteers lose weight, with an average loss of 11 kg, going from a mean BMI of around 39 kg/m2 to 35 Kg/m2. The researchers used dual-energy X-ray absorptiometry to evaluate each person’s body fat percentage before the start of the diet and then five months later.
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The researchers found that the macro nutrient ratios in the diets didn’t impact body composition when people lost weight, with around 73% of the weight lost being from fat. However, the low-carb ketogenic diet was particularly effective in improving liver insulin sensitivity, with participants gaining back significantly more insulin sensitivity in their liver than those on the Mediterranean or low-fat diet. The low-carb diet boosted liver insulin sensitivity to three times that of participants who lost weight on the other two plans.
The low-carb group showed statistically significant improvements in kidney function, measured by glomerular filtration rate, compared to the other two groups. After weight loss, half of the low-carb participants no longer met criteria for prediabetes, compared to 29% on the Mediterranean diet and just 7% on the low-fat diet. The findings suggest weight loss improves metabolic function across diets, but carbohydrate intake may play a key role in reversing prediabetic changes.
The study’s findings are based on a small group of participants, and other scientists will need to replicate and build on these results. However, the careful comparisons and serious attempts at controlling what participants ate over a long period showed that it is possible to pick up some clear differences. The researchers used a hyperinsulinemic-euglycemic clamp procedure with a radio-labelled glucose tracer to watch how each participant’s muscle cells sucked up glucose from their blood before and after losing weight.
Liver insulin sensitivity was evaluated using the hepatic insulin sensitivity index, showing how liver cells responded to insulin before and after participants lost weight. All three diets improved muscle insulin sensitivity by 50%, regardless of macronutrient ratios. The team emphasized liver insulin resistance as critical, as chronic dysfunction there can lead to fatty liver disease.
A low-carb diet may improve liver insulin sensitivity, which could help prevent metabolic diseases.