Stanford University: Keto and Mediterranean diets both help manage diabetes, but one is easier to maintain

A low-carbohydrate diet is generally recommended for people who have Type 2 diabetes or who are at risk of developing the disease. But there isn’t wide agreement on how low to go in carbohydrate consumption or which carbohydrate foods to include, and little research is available to help people make informed decisions.

A new trial by investigators at Stanford Medicine has compared two popular low-carb diets — ketogenic and Mediterranean — in their effect on blood glucose, cardiometabolic risk factors, weight loss and nutrition, as well as how easily people can adhere to them.

The ketogenic diet is an ultra-low-carb, very high-fat diet that involves a drastic reduction in carbohydrate intake. The Mediterranean diet is a low-carb, moderately high-fat diet that emphasizes vegetables, legumes, fruits, whole grains, olive oil and fish.

Both diets received high marks in controlling blood glucose levels and aiding weight loss, but the ketogenic diet was lower in several nutrients, particularly fiber, and was more difficult for study participants to follow in the long run, according to findings published May 31 in the American Journal of Clinical Nutrition.

Low-carb diets for diabetes
“The main issue in diabetes is the inability to manage your blood glucose, and the biggest effect on your blood glucose is your diet,” said Christopher Gardner, PhD, the Rehnborg Farquhar Professor, a professor of medicine and the director of nutrition at the Stanford Prevention Research Center, who is the lead author of the study.

Americans get roughly half their daily calories from carbohydrates, with about 80% of those carb calories coming from added sugars and refined grains — think soda, candies, bagels, pastries and pizza crust.

To manage or prevent diabetes, the American Diabetes Association recommends the Mediterranean diet and other low-carb diets, as long as they minimize added sugars and refined grains and include non-starchy vegetables.

The ultra-low-carb ketogenic diet fulfills these criteria. But its dramatic rise in popularity in recent years has nutritionists like Gardner concerned.

Christopher Gardner

“The lower in carbs you go, the more you’re wiping out entire food groups that are considered very nutrient dense and healthy,” he said, noting that to achieve an extreme restriction of carbohydrates, the ketogenic diet prohibits legumes, fruits and whole grains. “What is it about this diet that would be so compelling that you would give up some of those central tenets of health and nutrition?”

Eating for science
In the new study, conducted from June 2019 to December 2020, Gardner and his team recruited 40 adults with Type 2 diabetes or prediabetes to try both the ketogenic diet and the Mediterranean diet. Half the participants started with the ketogenic diet, and the other half with the Mediterranean diet. After 12 weeks, the groups switched and tried the other diet for 12 weeks. This crossover design allowed participants to act as their own controls.

In the ketogenic diet phase, participants followed a version known as the well-formulated ketogenic diet. They were advised to limit carbs to 20-50 grams/day (about 80% less than usual) and proteins to 1.5 grams per kilogram of their ideal body weight per day, and to consume as much as they wanted in fats. They were asked to consume at least three servings of non-starchy vegetables a day.

In the Mediterranean diet phase, participants were advised to follow a mostly plant-based diet that included vegetables, legumes, fruits, whole grains, nuts and seeds, as well as fish for animal protein and olive oil for fat.

Both diets encouraged eating lots of vegetables and eliminating added sugars and refined grains as much as possible. The main question, Gardner said, was whether the keto diet offered additional health benefits from eliminating legumes, fruits and whole grains.

To set the participants up for success, the study sent ready-to-eat food to both groups during the first four weeks of each diet through the food delivery service Methodology. Short of feeding people all their meals in a lab, this approach was the best way to maximize adherence to the diets, Gardner said.

For the remaining eight weeks, participants were responsible for choosing and preparing their own food, giving researchers insight into how people realistically follow the diets. The participants were encouraged to be honest in reporting how well they were following the diets. “Don’t feel that you have to impress us,” they were told.

Similar clinical benefits
At various points, researchers collected blood samples to evaluate blood glucose control, lipid control, body weight and other clinical measures. Throughout the study, participants also were interviewed on their adherence to and satisfaction with the diets. Thirty-three participants completed the study, with several dropping out due to COVID-19 disruptions.

The researchers found that both diets improved blood glucose control, as indicated by similar drops in HbA1c levels (9% on keto and 7% on Mediterranean). Weight loss was also similar (8% on keto and 7% on Mediterranean), as were improvements in fasting insulin and glucose, HDL cholesterol, and the liver enzyme ALT.

Each diet had one other statistically significant benefit: LDL cholesterol increased on the keto diet and decreased on the Mediterranean diet — a point for Mediterranean. Triglyceride decreased on both diets, but it dropped more on the keto diet — a point for keto.
In nutrient levels, the ketogenic diet provided less fiber; thiamin; vitamins B6, C, D and E; and phosphorus. Only vitamin B12 was higher on the ketogenic diet.

Diets in the real world
As expected, when food was delivered, participants stuck to both diets relatively well, scoring an average of 7.5 on a 10-point adherence scale. When participants had to provide their own food, adherence on both diets dropped about two points on average.

“The one thing everybody did pretty well was limiting added sugar and refined grains. That was the main message for both diets,” Gardner said.

“The keto diet was more polarizing,” he said. “What we were hearing is that some people just couldn’t do the keto because it was too restrictive.” Yet a few may have found it simpler, at least initially, to focus just on avoiding carbs, according to Gardner.

There’s no reason to restrict heart-healthy, quality carbohydrate foods.
When the research team checked in with the participants three months after the trial, on average, they had maintained lower blood glucose levels and weight loss. Notably, they were eating closer to a Mediterranean diet than to a keto diet. Even the participants who had followed the keto diet nearly perfectly during the trial largely gave it up afterward.

The takeaway, Gardner said, is that there was no additional overall health benefit to cutting out legumes, fruits and whole grains to achieve an ultra-low-carb diet. For people with diabetes or prediabetes, the less restrictive Mediterranean diet was similarly effective in controlling glucose and likely more sustainable.

“Restricting added sugars and refined grains and emphasizing the inclusion of vegetables should be the focus,” Gardner said. “There’s no reason to restrict heart-healthy, quality carbohydrate foods above and beyond.”

Gardner is a member of the Stanford Cardiovascular Institute, the Stanford Wu Tsai Human Performance Alliance, the Stanford Maternal and Child Health Research Institute, and the Stanford Cancer Institute.