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Keto vs Mediterranean diet and diabetes – Stanford randomised trial

Both the ketogenic and Mediterranean diets successfully cut blood sugar levels in patients with prediabetes or type 2 diabetes, according to a small randomised crossover trial. However, the former showed a reduced, less healthy intake of fibre and essential vitamins.

Among 33 adults, the well-formulated ketogenic diet (WFKD) resulted in a 9% drop in HbA1c values after 12 weeks, while the Mediterranean-plus diet (Med-Plus) resulted in a 7% drop, reported Christopher Gardner, PhD, of Stanford University in California, and colleagues.

Both diet types also led to decreases in weight (8% vs 7%, respectively), without any significant differences between the groups, they noted in the American Journal of Clinical Nutrition.

Both diets are considered “low carb” and are based on the foundation of limiting added sugars and refined grains, and consuming more non-starchy vegetables. However, WFKD avoids legumes, fruits and whole intact grains that are otherwise included in the Med-Plus diet.

“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 polarising,” he added. “What we were hearing is that some people just couldn’t do the keto because it was too restrictive."

As for cardiometabolic parameters, reports MedPage Today, the WFKD dieters saw a greater reduction in triglycerides – a 16% drop from baseline versus only a 5% drop for Med-Plus dieters (P=0.02). LDL cholesterol increased by 10% with the WFKD diet and decreased by 5% with Med-Plus, while HDL cholesterol increased by 11% with WFKD and 7% with Med-Plus.

However, the WFKD diet fell flat for nutrients, as those who stuck to this diet had lower intake of fibre; thiamine; vitamins B6, C, D, and E; and phosphorus compared with the Med-Plus dieters. Vitamin B12 levels were higher with WFKD.

“The lower in carbs you go, the more you’re wiping out entire food groups that are considered very nutrient dense and healthy,” Gardner said. “What is it about this diet that would be so compelling you would give up some of those central tenets of health and nutrition?

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

The San Francisco-based study included adults with prediabetes (HbA1c 5.7% to 6.4% or fasting glucose 100 to 125 mg/dL) or type 2 diabetes (HbA1c 6.5% or higher or fasting glucose 126 mg/dL or higher). The 33 participants were randomised evenly to each diet type for 12 weeks.

The researchers didn’t necessarily discourage weight loss, but there wasn’t a particular calorie restriction put on the participants. On average, participants consumed about 250 to 300 fewer calories per day compared with baseline.

Participants on the WFKD diet were instructed to sustain nutritional ketosis by limiting carbohydrates to 20g to 50g per day and proteins to around 1.5g/kg ideal body weight per day, with the remaining calories coming from fats. They were also told to consume more than three servings per day of non-starchy vegetables and maintain adequate mineral and fluid intake for the ketogenic state, with about 3g to 5g of sodium and 3g to 4g of potassium per day.

Med-Plus dieters were told to simply avoid added sugars and refined grains, while adhering to a chiefly plant-based diet.

A total of four adverse events were reported, with just one – an elevated alanine transaminase level on WFKD – considered to be possibly related to the study.

Study details

Effect of a ketogenic diet versus Mediterranean diet on glycated haemoglobin in individuals with prediabetes and type 2 diabetes mellitus: The interventional Keto-Med randomised crossover trial

Christopher Gardner, Matthew Landry, Dalia Perelman, Christina Petlura, Lindsay Durand, Lucia Aronica, Anthony Crimarco, Kristen Cunanan, Annie Chang, Christopher Dant, et al.

Published in The American Journal of Clinical Nutrition on 31 May 2022


Consensus has not been reached on what constitutes an optimal diet in individuals with prediabetes and type 2 diabetes mellitus (T2DM), especially between low-carbohydrate options.

We compared two low-carbohydrate diets with three key similarities (incorporating nonstarchy vegetables and avoiding added sugars and refined grains) and three key differences (incorporating compared with avoiding legumes, fruits, and whole, intact grains) for their effects on glucose control and cardiometabolic risk factors in individuals with prediabetes and T2DM.

Keto-Med was a randomised, crossover, interventional trial. Forty participants aged ≥18 years with prediabetes or T2DM followed the well-formulated ketogenic diet (WFKD) and the Mediterranean-plus diet (Med-Plus) for 12 weeks each, in random order. The diets shared the three key similarities noted above. The Med-Plus incorporated legumes, fruits, and whole, intact grains, while the WFKD avoided them. The primary outcome was the percentage change in glycated haemoglobin (HbA1c) after 12 weeks on each diet. Secondary and exploratory outcomes included percentage changes in body weight, fasting insulin, glucose, and blood lipids; average glucose from continuous glucose monitor (CGM), and nutrient intake.

The primary analysis was of 33 participants with complete data. The HbA1c values did not differ between diets at 12 weeks. Triglycerides decreased more for the WFKD [percentage changes, −16% (SEM, 4%) compared with −5% (SEM, 6%) for the Med-Plus; P = 0.02] and LDL cholesterol was higher for the WFKD [percentage changes, +10% (SEM, 4%) compared with −5% (SEM, 5%) for the Med-Plus; P = 0.01]. Weight decreased 8% (SEM, 1%) compared with 7% (SEM, 1%) and HDL cholesterol increased 11% (SEM, 2%) compared with 7% (SEM, 3%) for the WFKD compared with the Med-Plus, respectively; however, there was a significant interaction of diet × order for both. Participants had lower intakes of fibre and three nutrients on the WFKD compared with the Med-Plus. Twelve-week follow-up data suggest the Med-Plus is more sustainable.

HbA1c values were not different between diet phases after 12 weeks, but improved from baseline on both diets, likely due to several shared dietary aspects. The WFKD led to a greater decrease in triglycerides, but also had potential untoward risks from elevated LDL cholesterol and lower nutrient intakes from avoiding legumes, fruits, and whole, intact grains, as well as being less sustainable.


MedPage Today –Keto Versus Mediterranean Diet: Which Is Better for Diabetes? (Open Access)


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