Association of Periodic Fasting with Lower Severity of COVID-19 Outcomes in the SARS-CoV-2 Pre-Vaccine Era: An Observational Cohort from the INSPIRE Registry
Authors: Horne Benjamin D. , Muhlestein Joseph B. , May Heidi T. , Le Viet T. , Bair Tami L. , Knowlton Kirk U. , Anderson Jeffrey L. ,   the INSPIRE Registry Investigators
Published: March 2022

Objectives

Intermittent fasting boosts some mechanisms of host defense against infection while modulating the inflammatory response. Lower-frequency periodic fasting is associated with greater survival and lower risk of comorbidities that exacerbate COVID-19. This study evaluated the association of periodic fasting with COVID-19 severity and, secondarily, initial diagnosis of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Design

Prospective longitudinal observational cohort study.

Setting

Single-center secondary care facility in Salt Lake City, Utah, USA with follow-up across a 24-hospital integrated healthcare system.

Participants

Patients enrolled in the INSPIRE registry in 2013-2020 were studied if they had SARS-CoV-2 testing in March 2020-February 2021 and either tested positive (N=205) for the primary outcome evaluation or had a positive or negative test result for evaluation of the secondary outcome (n=1,524).

Interventions

No treatment assignments were made; individuals provided information about their personal practice and history of engaging in routine periodic fasting across their lifespan.

Main outcome measures

The association of periodic fasting with a composite of mortality or hospitalization as the primary outcome was evaluated by Cox regression through February 2021 and multivariable adjustments considered 36 covariables in INSPIRE patients diagnosed with COVID-19. Secondary analysis evaluated the association of fasting with testing positive for SARS-CoV-2 in INSPIRE patients evaluated for COVID-19 (n=1,524).

Results

Subjects engaging in periodic fasting (n=73, 35.6%) did so for 40.4±20.6 years (max: 81.9 years) prior to COVID-19 diagnosis. The composite outcome occurred in 11.0% of periodic fasters and 28.8% of non-fasters (p=0.013), with HR=0.61 (95% CI=0.42, 0.90) favoring fasting. Multivariable analyses confirmed this association. Other predictors of hospitalization/mortality were age, Hispanic ethnicity, prior MI, prior TIA, and renal failure, with trends for race, smoking, hyperlipidemia, coronary disease, diabetes, heart failure, and history of anxiety, but not alcohol use. In secondary analysis, COVID-19 was diagnosed in 14.3% of fasters and 13.0% of non-fasters (p=0.51).

Conclusions

Routine periodic fasting was associated with a lower risk of hospitalization or mortality in patients with COVID-19. Fasting may be a complementary therapy to vaccination that could provide immune support and hyperinflammation control during and beyond the pandemic.

Trial registration

clinicaltrials.gov, NCT02450006 (the INSPIRE registry)

What is already known on this topic

During a period of energy restriction, fasting controls inflammation by dampening the cytokine cascade and it switches the metabolic source of energy from glucose to fats, including by increasing circulating free fatty acids such as linoleic acid.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domains bind linoleic acid in pockets that, when bound, reduce spike protein affinity for the angiotensin-converting enzyme 2.

Repeated fasting boosts basal levels of some parameters related to inflammation control and host defense against infections, including galectin-3, and it ameliorates insulin resistance and cardiovascular risks such that periodic fasting is associated with greater survival and lower risk of heart failure, coronary artery disease, and type 2 diabetes.

What this study adds

This study evaluated the association of periodic fasting with severity of coronavirus disease 2019 (COVID-19) and with initial infection with SARS-CoV-2 in a population where a substantial proportion of people routinely engage in periodic dry or water-only fasting, primarily for religious purposes.

This observational epidemiologic study found that routine low-frequency periodic fasting for an average of >40 years was associated with a lower risk of a composite of hospitalization or mortality after COVID-19 diagnosis, suggesting that fasting deserves further investigation as a complementary approach along with vaccines for reducing COVID-19 severity.

The study also found no association of periodic fasting with the onset of SARS-CoV-2 infection.

Trial registration

The Intermountain INSPIRE registry (clinicaltrials.gov, NCT02450006)

Transparency

BDH affirms that the manuscript is an honest, accurate, and transparent account of the study being reported and that no important aspects of the study have been omitted.

Copyright

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