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

Abstract

ObjectivesIntermittent 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.DesignProspective longitudinal observational cohort study.SettingSingle-centre secondary care facility in Salt Lake City, Utah, USA with follow-up across a 24-hospital integrated healthcare system.ParticipantsPatients 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).InterventionsNo treatment assignments were made; individuals reported their personal history of routine periodic fasting across their life span.Main outcome measuresA 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.ResultsSubjects 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).ConclusionsRoutine 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.Trial registrationClinicaltrials.gov, NCT02450006 (the INSPIRE registry).

Importance of Intermittent Fasting Regimens and Selection of Adequate Therapy on Inflammation and Oxidative Stress in SARS-CoV-2 Infection

“…To date, no RCTs have investigated the effects of IF on SARS-CoV-2 infection or severity of COVID-19 outcomes, although epidemiologic evidence regarding periodic fasting suggests that fasting in some forms may prevent severe COVID-19 outcomes such as hospitalization and death [ 71 ], perhaps in part, through the control of hyper-inflammation. The impacts of IF on markers of inflammation and oxidative stress are summarized below:…”

Pathogenic Mechanisms of the Severe Acute Respiratory Syndrome Coronavirus 2 and Potential Direct and Indirect Counteractions by Intermittent Fasting

“…This intriguing capability includes metabolic improvements that are observed when lower-frequency intermittent fasting is utilized, such as a regimen of once-per-week 24-hour water-only fasting from which substantial weight loss did not occur [ 8 ]. Very low-frequency once-per-month periodic fasting has also been studied in observational analyses for health outcomes of fasting conducted primarily for religious purposes [ 9 , 10 , 14 ]. Such very low-frequency fasting is unlikely to result in substantial weight loss, and observational studies showed that people who reported to routinely engage in such periodic fasting had similar weight and body mass index to those who did not fast routinely [ 9 , 10 ].…”

“…Such very low-frequency fasting is unlikely to result in substantial weight loss, and observational studies showed that people who reported to routinely engage in such periodic fasting had similar weight and body mass index to those who did not fast routinely [ 9 , 10 ]. Many people (35–40%) in those studies who engaged in periodic fasting for religious purposes had participated in the behavior for >40 years (or about 67% of their lifespan) [ 9 , 10 , 14 ], thereby potentially training their bodies to respond optimally to any length of fasting. Associations of periodic fasting were found with lower risks of coronary heart disease and diabetes in cross-sectional observational analyses [ 9 ].…”

“…With the occurrence of the coronavirus disease 2019 (COVID-19) pandemic, periodic fasting was found to be associated with lower risk of hospitalization or mortality after the diagnosis of COVID-19 [ 14 ]. In a population of 1524 patients undergoing evaluation by coronary angiography for the presence of coronary artery disease during February 2013 to March 2020, 512 reported participation in routine periodic fasting for >40 years (average age was 63 years) and 1012 did not fast routinely, while 1319 tested negative for SARS-CoV-2 at community test facilities after the onset of the pandemic and 205 tested positive [ 14 ]. Periodic fasting was not associated with infection by SARS-CoV-2 (14.3% of fasters versus 13.0% of non-fasters were positive, odds ratio: 1.11, p = 0.51) [ 14 ].…”

“…In a population of 1524 patients undergoing evaluation by coronary angiography for the presence of coronary artery disease during February 2013 to March 2020, 512 reported participation in routine periodic fasting for >40 years (average age was 63 years) and 1012 did not fast routinely, while 1319 tested negative for SARS-CoV-2 at community test facilities after the onset of the pandemic and 205 tested positive [ 14 ]. Periodic fasting was not associated with infection by SARS-CoV-2 (14.3% of fasters versus 13.0% of non-fasters were positive, odds ratio: 1.11, p = 0.51) [ 14 ]. Among those who tested positive, though, people who engaged in periodic fasting had a lower risk of the composite event of hospitalization or mortality after their COVID-19 test (HR = 0.61, 95% confidence interval 0.42, 0.90; p = 0.013) [ 14 ].…”