Does Intermittent Fasting 2-3 Days a Week Drop Markers of Heart Disease?

One of the hottest trends in health promotion and the media is intermittent fasting (IF), properly defined as not eating or eating very little (fasting mimicking diet FMD) for 24 hours or more. IF extends healthspan and lifespan in rodents, and has been associated with metabolic benefits in humans, yet results so far have been inconsistent. More data is needed as several randomized studies have failed to confirm a major health benefit to IF despite the popularity. 


In the new study, the effects of IF-induced weight loss on metabolic and molecular determinants of healthy aging were tested.

A randomized clinical trial was performed in overweight men and women (30 to 65 yo, average 49 y), to test the effects of 6-mo IF. Fifty participants were randomized to IF (n = 28) or usual diet (n = 22) group. The primary outcome was the assessment of change in serum C-reactive protein (CRP) levels (inflammation marker) from baseline to 6 months; secondary outcomes where changes in insulin sensitivity using oral glucose tolerance (OGTT)-based indexes, and plasma metabolomics and gene expression changes of colon mucosa.


Participants in the IF group were prescribed by the study dietitians a fasting regimen, that consisted in 3 non-consecutive days per week, if their BMI was higher than 28 kg/m2, whereas participants with BMI between 24 and 27.9 kg/m2 were asked to fast for 2 non-consecutive days per week, for the entire duration of the study.

All IF participants were asked to skip breakfast, lunch, dinner, snacks, and calorie-containing beverages on the fast days, but they were allowed to consume at lunch and dinner non-starchy raw and/or cooked vegetables ‘ad libitum’, dressed with a 19 maximum of two tablespoons of olive oil (~240 kcal) plus vinegar or lemon juice.

Noncaloric drinks, such as black coffee, unsweetened tea or zero-calorie soda, were allowed. Because non-starchy vegetables contain very small quantities of bioavailable calories, proteins, fats and carbohydrates, this ‘vegetable fasting-mimicking’ protocol (that does not require counting calories) was selected to mimic water-only fasting while minimizing participants’ social life disruption.

During the ‘feast’ days, research volunteers were asked to consume their habitual diet without overcompensation of calories. Strategies to implement fast day planning, recipes for salads and cooked vegetables were covered at the weekly meetings with the dietitians.


No difference in serum levels of CRP or multiple other inflammatory markers was observed over this period despite a significant IF-induced 8% weight loss.

IF caused a statistically significant but clinically irrelevant small improvement in OGTT-derived insulin sensitivity indexes.

Preliminary multi-omic data analysis suggests that a non-linear relationship exists between IFi nduced weight loss and inhibition of multiple key nutrient-sensing aging pathways.


More trials are needed to understand the impact of different degrees of energy restriction on metabolic and molecular health in humans, and how fasting should be complemented with diet quality changes during the feast days to maximize clinical and longevity outcomes.

Previously, studies on intermittent fasting in animal models found lowered risk of cardiovascular disease, diabetes, inflammation and other illnesses.

The lead researcher commented: “Our research shows this isn’t the same in humans, who do not have the same response to limiting calories on alternate days when associated with usual diets.”

Dr. Joel Kahn

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