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Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year

ByCrossFit May 22, 2019

Note: This trial is an additional review of data previously discussed on

This 2018 trial, funded by Virta Health, tested the impact of a high-compliance ketogenic diet on atherosclerotic biomarkers in Type 2 diabetics.

Atherogenic dyslipidemia refers to a particular lipoprotein pattern that has been linked to cardiovascular disease. Key biomarkers include high triglycerides, low HDL-C, and an increased concentration of small LDL particles (i.e., high small LDL-P). This pattern is prevalent in patients with Type 2 diabetes, which suggests many diabetic patients are at higher cardiovascular disease risk than traditional risk markers (i.e., LDL-C) would indicate.

Carbohydrate restriction has been shown to consistently resolve atherogenic dyslipidemia. However, as noted in other Virta-funded studies, the pragmatic value of carbohydrate restriction, and especially of the severe carbohydrate restriction required for a ketogenic diet, is limited by the fact that compliance with ketogenic diets in free-living (i.e., real-world) populations is low. This trial was designed to overcome this compliance issue and directly test the impact of a ketogenic diet, followed properly over a year, on markers of cardiovascular disease.

In this trial, 262 Type 2 diabetics were counseled to follow a diet that would achieve and sustain nutritional ketosis (i.e., blood BHB of 0.5 – 3.0 mmol/L). Each subject was given personalized, dynamic dietary guidance by a health coach who continuously communicated with each subject and tracked biomarkers via an app. As such, the specific diet varied by subject but generally involved 1.5 g/kg of protein intake and <30 g of carbohydrate intake per day, alongside non-starchy vegetables, multivitamins, and adequate fluids. There was no deliberate caloric restriction. Of the original 262 subjects, 218 completed one year of treatment.

A wide variety of atherosclerosis biomarkers were tracked. Selected changes included (all figures refer to mean reductions; all listed changes were statistically significant):

  • 24.4% decrease in triglycerides
  • 18.1% increase in HDL-C (and a -29.1% decrease in HDL-C/triglyceride ratio)
  • 38.9% decrease in large VLDL particle number and 20.8% decrease in small LDL particle number
  • 9.9% increase in LDL-C
  • 4.8% decrease in systolic blood pressure and 4.3% decrease in diastolic blood pressure
  • 39.3% reduction in hsCRP (a marker of inflammation)

There were no significant changes in total LDL particle number or ApoB.

Taken collectively, this trial demonstrated that one year of compliance with a ketogenic diet led to a variety of shifts in subjects’ lipid profiles. With the exception of an increase in LDL-C, all other shifts showed either a neutral or beneficial effect on overall cardiovascular risk. The simultaneous decreases in inflammation (i.e., a 39% reduction in hsCRP) and blood pressure further support a decrease in cardiovascular risk.

Note: The authors noted that a small number of participants (<1%) experienced adverse effects related to cardiovascular risk as assessed by lipid profile changes, which suggests that subjects should be monitored while following a ketogenic diet.

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