A fasting-mimicking diet shows unique benefits for cardiovascular health, study finds

In a recent article published in Npj Metabolic Health and Diseaseresearchers evaluated the effectiveness of a fasting-mimicking diet (FMD) versus a Mediterranean diet (MD) in reducing cardiovascular disease (CVD) risk among obese adults with hypertension.

Study: Fasting Mimicking Dietary Cycles vs Mediterranean Diet and Cardiometabolic Risk in Overweight and Obese Hypertensives: A Randomized Clinical Trial. Image credit: Foxys Forest Manufacture / Shutterstock.com

They conducted a single-center randomized clinical trial (RCT) in Tennessee, United States (US), at the Hypertension Institute (HTI) between September 2018 and May 2019.


Healthy eating habits may represent an effective strategy to protect the vascular endothelium. Aberrations of the vascular endothelium, such as impaired vasodilation, may contribute to atherosclerosis and hypertension.

In their previous work, the researchers demonstrated the safety, feasibility, and beneficial effects of intermittent (five-day/monthly) FMD on cardiometabolic risk factors in healthy, normal-weight and overweight adults. FMD is a low-calorie, low-protein, high-fat plant-based diet.

Similarly, studies have linked MD to multiple benefits, including CVD prevention. The Mediterranean diet is characterized by a high proportion of cereals, legumes, fruits/vegetables, moderate amounts of protein from fish and healthy fats obtained from olive oil,

FMD and MD diets also provide healthy fats ie. monounsaturated fats [MUFA] {eg oleic acid} and polyunsaturated fats [PUFA] {eg alpha-linolenic acid (omega-3); docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)}.

However, the fats in foot-and-mouth are only plant-based (nuts, algae oil), while those in foot-and-mouth are usually from animal sources.

About the research

In the current RCT, investigators compared the effectiveness of four monthly cycles of FMD versus continuous MD in obese hypertensive adults over four months.

They randomly assigned 44 and 40 subjects (of both sexes) aged 35 to 75 years to the FMD and MD arms, respectively, and assessed their endothelial function from baseline to the end of the intervention phase (V3) as indicated by the index of reactive hyperemia (RHI) and small and large arterial compliance scores (AC1/AC2). Second, they assessed changes in cardiometabolic factors.

Participants were included if they had a body mass index (BMI) ≥28 and a confirmed diagnosis of either endothelial dysfunction or low resistance artery (AC2). They excluded all participants with an EndoPAT® score/reactive hyperemia index (RHI) >2.0 and with severely altered blood pressure (BP) >180/105.

According to the study protocol, the team organized clinical visits to all participants at the following time points as follows: i) baseline; ii) 5–8 days after completion of the first FMD cycle; iii) 35–38 days after initiation of MD (V1); iv) 5–8 days after the end of the third FMD cycle or 95–98 days after the initiation of MD (V2); v) end of dietary interventions (V3); vi) three months after the end of dietary interventions (V4).

At each visit, the team asked about waist circumference (WC), body weight (BW) and height of all participants. They prohibited the consumption of caffeine, alcohol or tobacco six hours before the blood pressure measurement. Heart rate (HR) data were also collected.

Additionally, they quantified tumor necrosis factor-alpha (TNF alpha), insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6), and leptin levels in blood samples collected after an overnight fast of >12 hours.

They used these data to calculate the homeostasis model assessment of insulin resistance (HOMA-IR) and estimate the prevalence of all metabolic syndromes in the participants.

Participants in the FMD group consumed only the contents of the box provided to them. FMD is based on a person’s weight (not gender) and is supplemented with glycerol to compensate for the caloric deficit due to FMD. It provides a total caloric intake ranging from 1000–1100 kcal on day 1 to 700–800 kcal on days 2–5.

During periods between FMD cycles, participants followed their usual diet. On the other hand, participants in the MD group received guidelines based on a validated MD but were not required to follow them.

The team used several statistical methods to analyze the data, including comparisons of baseline characteristics using Spearman’s correlation test, intention-to-treat (ITT) analysis, and linear mixed models to assess the effects of time and treatment, accounting for baseline variation and time changes.

They used a t-test to calculate p-values ​​for the coefficients of two groups and to compare treatment effects between MD and FMD.


The FMD group showed a decrease in RHI, which may indicate a potential impairment of endothelial function. However, neither group showed improvements in AC1/AC2 measurements or changes in abnormal RHI (< 1.67).

According to Spearman’s correlation test, there was a non-significant correlation between RHI and age at onset.

The FMD group also showed a trend toward reduced biological age, cardiac age, and Protein Unstable Lesion Signature (PULS) heart test scores, assessing five-year stroke risk.

However, given the lack of changes in AC1/AC2, the reduced RHI likely represents a rejuvenating effect of FMD rather than impaired endothelial function. Therefore, further work is needed to clarify these findings.

At the study’s three-month follow-up, the FMD group showed decreased levels of insulin and HOMA-IR, while the MD group showed a greater decline in diabetes prevalence. This was an intriguing finding because at the start of the study, the MD group had almost twice as many patients with diabetes.

Additionally, the FMD group showed a marked decrease in body fat mass but not lean muscle mass at the end of the follow-up period, while the MD group showed a loss of over two pounds (lb) of lean muscle mass, suggesting adherence to this dietary regimen may lead to increased frailty in old age.

MD may have caused reduced protein and, more importantly, intake of some amino acids necessary for muscle growth; however, the paw did not interfere with the subject’s total dietary protein consumption.

Thus, the authors ruled out that an intermittent FMD regimen may preserve lean body mass more effectively than a continuous MD intervention.


Overall, the study results suggest that while FMD and MD interventions are effective in managing weight and improving cardiometabolic disease risk in obese hypertensive individuals, both have some unique effects.

FMD reduced RHI, a change associated with impaired vascular endothelial cell functional integrity or vascular rejuvenation, PULS cardiac score, estimated cardiac age, and unchanged arterial compliance. FMD reduced body fat mass; MD, on the contrary, causes a loss of lean body mass.

In addition, the researchers emphasized variety of the FMD menu to improve adherence to this diet, especially since many participants did not enjoy its taste but found intermittent dietary regimens more feasible than continuous ones.

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