Effect of a ketogenic diet versus Mediterranean diet on glycated hemoglobin in individuals with prediabetes and type 2 diabetes mellitus: The interventional Keto-Med randomized crossover trial.
Level 2 - randomized trial
Individual randomized crossover trial
PubMed 35641199 · doi:10.1093/ajcn/nqac154
What was done
The Keto-Med randomized crossover trial compared a well-formulated ketogenic diet (WFKD) to a Mediterranean-plus diet (Med-Plus) in 40 adults with prediabetes or type 2 diabetes mellitus. Participants followed each diet for 12 weeks in random order. Both diets shared core features (incorporating nonstarchy vegetables, avoiding added sugars and refined grains), but Med-Plus included legumes, fruits, and whole intact grains, which WFKD excluded. The primary outcome was percentage change in glycated hemoglobin (HbA1c) after 12 weeks on each diet. Secondary outcomes included percentage changes in body weight, fasting insulin, blood glucose, continuous glucose monitor readings, blood lipids, and nutrient intake.
What was found
In the primary analysis of 33 participants with complete data, HbA1c values did not differ between the two diets at 12 weeks. Triglycerides decreased significantly more on WFKD than on Med-Plus (-16% [SEM, 4%] vs -5% [SEM, 6%]; P = 0.02). LDL cholesterol increased on WFKD while decreasing on Med-Plus (+10% [SEM, 4%] vs -5% [SEM, 5%]; P = 0.01). Weight decreased by 8% (SEM, 1%) on WFKD vs 7% (SEM, 1%) on Med-Plus, and HDL cholesterol increased by 11% (SEM, 2%) vs 7% (SEM, 3%), but both outcomes showed a significant diet-by-order interaction. Participants had lower intakes of fiber and 3 nutrients on WFKD, and 12-week follow-up suggested Med-Plus was more sustainable.
Why it matters
When added sugars and refined grains are eliminated from both dietary patterns, adding legumes, fruits, and whole grains in a Mediterranean-style diet achieves equivalent glycemic control to a strict ketogenic diet without raising LDL cholesterol or restricting nutrient and fiber intake.
Limits
The sample size was small (33 analyzed from 40 enrolled), intervention duration was limited to 12 weeks per phase, and significant diet-by-order interactions were observed for body weight and HDL cholesterol. Long-term cardiovascular outcomes were not evaluated.
Cited by
- supports In the Keto-Med crossover trial comparing a ketogenic diet to a Mediterranean diet over 24 weeks with a 12-week free-choice follow-up, participants consistently shifted toward the Mediterranean diet pattern during the free-choice period.
- partial In a randomized controlled trial, simply cutting free and added sugars while keeping whole food carbohydrates produced fat loss, a 10% reduction in LDL cholesterol, no change in ApoB, and no disruption to the gut microbiome.