Association of periodic fasting with lower severity of COVID-19 outcomes in the SARS-CoV-2 prevaccine era: An observational cohort from the INSPIRE registry
This observational longitudinal cohort study found that routine low-frequency periodic fasting for an average of >40 years was associated with a lower risk of COVID-19.
Benjamin Horne et al | Intermittent Fasting | Pandemic & Science
WHAT IS ALREADY KNOWN ON THIS TOPIC
⇒ During a period of energy restriction, fasting controls inflammation by dampening the cytokine cascade, it enhances autophagy, and it switches the metabolic source of energy from glucose to fats, including by increasing circulating free fatty acids such as linoleic acid.
⇒ The SARS-CoV-2 receptor binding domains bind linoleic acid in pockets that, when bound, reduce spike protein affinity for ACE 2.
⇒ Repeated fasting boosts basal levels of some parameters related to inflammation control and host defence 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 observational longitudinal cohort study found that routine low-frequency periodic fasting for an average of >40 years was associated with a lower risk of COVID-19, measured as a composite of hospitalisation or mortality after COVID-19 diagnosis.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
⇒ Intermittent fasting should be further evaluated for potential short-term and long-term preventive or therapeutic use as a complementary approach to vaccines and antiviral therapies for reducing COVID-19 severity.
Abstract
Objectives
Intermittent fasting boosts some host defence mechanisms while modulating the inflammatory response. Lower-frequency fasting is associated with greater survival and lower risk from COVID-19-related comorbidities. This study evaluated associations of periodic fasting with COVID-19 severity and, secondarily, initial infection by SARS-CoV-2.
Design
Prospective longitudinal observational cohort study.
Setting
Single-centre 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 for the primary outcome if they tested positive for SARS-CoV-2 during March 2020 to February 2021 (n=205) or, for the secondary outcome, if they had any SARS-CoV-2 test result (n=1524).
Interventions
No treatment assignments were made; individuals reported their personal history of routine periodic fasting across their life span.
Main outcome measures
A composite of mortality or hospitalisation was the primary outcome and evaluated by Cox regression through February 2021 with multivariable analyses considering 36 covariables. The secondary outcome was whether a patient tested positive for SARS-CoV-2.
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 to 0.90) favouring fasting. Multivariable analyses confirmed this association. Other predictors of hospitalisation/mortality were age, Hispanic ethnicity, prior MI, prior TIA and renal failure, with trends for race, smoking, hyperlipidaemia, coronary disease, diabetes, heart failure and 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 hospitalisation 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.