Fasting-mimicking diet shows unique benefits in cardiovascular health, study finds

In a recent article published in Npj Metabolic Health and Disease, researchers assessed the effectiveness of the fasting-mimicking diet (FMD) against the Mediterranean diet (MD) in reducing the risk for cardiovascular disease (CVD) among obese adults with hypertension.

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

Background

Healthy dietary habits may present an effective strategy to protect the vascular endothelium. Aberrations to the vascular endothelium, such as impaired vasodilation, can contribute to atherosclerosis and hypertension. 

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

Similarly, studies have associated MD with multiple benefits, including CVD prevention. The Mediterranean diet is characterized by a high proportion of cereals, legumes, fruits/vegetables, moderate quantities of proteins from fish, and olive oil-derived healthy fat,

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

However, the fats in FMD are only plant-based (nuts, algal oil), while those in MD tend to be from animal sources.

About the study

In the present RCT, researchers compared the effectiveness of four monthly cycles of FMD versus a continuous MD in obese adults with hypertension over four months.

They randomly allocated 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 reactive hyperemia index (RHI) and scores on small and large arterial compliance (AC1/AC2). Secondarily, they evaluated changes in cardiometabolic factors.

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

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

During each visit, the team enquired 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 BP measurement. Heart rate (HR) data was also collected. 

Furthermore, 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 overnight fasting of >12 hours.

They used this data to compute the homeostasis model assessment of insulin resistance (HOMA-IR) and assess the prevalence of any metabolic syndromes in participants.

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

During the periods between FMD cycles, participants followed their regular diet. On the other hand, participants in the MD group received guidelines based on a validated MD, but they were not bound to comply. 

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

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

Results

The FMD group exhibited a reduction in RHI, which might indicate potential impairment in endothelial function. However, neither group showed improvements in AC1/AC2 measures or changes in abnormal RHI (< 1.67).

Per Spearman's correlation test, there was a negligible correlation between RHI and age at baseline. 

The FMD group also exhibited a trend for reduced biological age, heart age, and the Protein Unstable Lesion Signature (PULS) cardiac test scores evaluating the five-year risk of stroke.

However, considering the lack of AC1/AC2 changes, a reduced RHI likely represented a rejuvenating effect of FMD rather than an impaired endothelial function. Thus, further work is needed to elucidate these findings.

During the three-month study follow-up, the FMD group showed decreased insulin and HOMA-IR levels, while the MD group showed a higher decline in the prevalence of diabetes. It was an intriguing revelation as the MD group had nearly double the subjects with diabetes at the study's beginning.

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

MD may have caused a decreased protein and, more importantly, some amino acid intake necessary for muscle growth; however, the FMD did not interfere with the overall protein consumption of the subject's diet.

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

Conclusions

Overall, the study findings suggested that while both FMD and MD interventions were effective in weight management and improving cardiometabolic disease risk in obese people with hypertension, both had some unique effects, too.

FMD decreased RHI, a change associated with impaired functional integrity of vascular endothelial cells or vascular rejuvenation, PULS cardiac score, calculated heart age, and unaltered arterial compliance. FMD decreased trunk fat mass; MD, on the contrary, caused loss of lean body mass.

Furthermore, the researchers emphasized diversifying the FMD menu to improve adherence to this diet, especially as many participants did not enjoy its taste but found periodic dietary regimens more feasible than continuous ones.

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.