Scientists have worked extremely hard to understand the various aspects of the novel coronavirus, namely, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Recently, they evaluated the impact of intermittent fasting on COVID-19 disease severity. This study is available in BMJ Nutrition, Prevention & Health.
Studies have shown that fasting changes the pattern of energy utilization. This is because fasting is linked to the amount of consumption of glucose and glycogen that triggers gluconeogenesis and, subsequently, induces ketogenesis. Fasting promotes ketosis, which enhances the levels of fatty acids (e.g., linoleic acid and). Interestingly, studies have reported that the spike protein of the SARS-CoV-2 binds to linoleic acid, which leads to a reduction in the affinity of SARS-CoV-2 for ACE2. Hence, this finding suggests a significant relationship between fasting and a reduction in the severity of COVID-19.
A trial study associated with low-frequency intermittent fasting reported an increased amount of galectin-3 (a multifaceted protein), independent of weight changes, in a person who participated in a six-month Weekly One-Day Water-only Fasting Interventional (WONDERFUL) study.
Previous studies have reported that galectin-3 controls inflammation via proinflammatory actions, in response to acute infection. Therefore, galectin-3 has been associated with anti-inflammatory functions during acute infection. This protein lowers the risks of chronic metabolic disorders. Interestingly, scientists have detected an increased level of galectin-3 in patients with cardiac issues and diabetes.
Scientists have reported that galectin-3 binds to a wide range of pathogens and induces the innate immune system. Additionally, this protein is also capable of elevating the expression of human genes with antiviral capacities, inhibiting viral replication, and influencing respiratory infections.
Scientists hypothesized that an increase in the levels of galectin-3 could be the mechanistic link between prolonged fasting and reduction in COVID-19 severity. Previous studies have indicated that routine periodic fasting could lower the possibility of developing type 2 diabetes and coronary artery disease (CAD). Interestingly, patients with a history of fasting for more than 42 years showed greater survival with a lower risk of heart failure.
About the study
The main objective of the prospective observational cohort study was to evaluate whether periodic fasting is linked with severe COVID-19 symptoms. Researchers also studied if periodic fasting could predict the onset of SARS-CoV-2 infection.
In this study, the study cohort included patients who had a history of cardiac catheterization and participated in a socio-behavioral survey associated with periodic fasting behavior. Researchers included demographic details of the selected participants and also accounted for their work, exercise pattern, ethnicity, alcohol intake, and sleep behavior.
Scientists considered all participants of this study from the INSPIRE (Intermountain Healthcare Biological Samples Collection Project and Investigational Registry) database. Although a total of 8634 patients were enrolled in INSPIRE during the study period, 5795 patients fitted the criteria of the present study. Among the selected participants, 1682 patients were tested for COVID-19 infection. Out of the tested group, only 225 patients tested positive.
The authors reported that 1524 patients fasted periodically, i.e. fasted routinely for five years or more. Among them, 205 patients tested SARS-CoV-2 positive, and the rest of the patients tested negative. The study cohort considered in this study was before COVID-19 mass vaccination.
The current study reported that individuals with a history of routine periodic fasting for about 40 years or more showed a lower risk of hospitalization or death due to severe COVID-19 infection. This finding was true irrespective of age, race, or ethnicity. This result was also consistent with individuals with cardiac history and comorbidities.
The authors reported that periodic fasting could not predict if an individual could contract SARS-CoV-2 infection. The substantial variance in the rate of hospitalization and mortality due to COVID-19 infection was due to various factors, including medical, healthcare, age, political, and biological issues.
The authors believe that an elevated amount of linoleic acid that binds to the spike protein of SARS-CoV-2, reduces the number of infected cells or the SARS-CoV-2 virions in cells. This leads to a decrease in the COVID-19 infection severity. Similar benefits could be achieved by following ketogenic diets.
A previous study showed that galectin-3 triggers anti-inflammatory effects via the NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which might resist the hyperinflammation linked with SARS-CoV-2 infection.
One of the common symptoms after infection is loss of appetite, which might be due to the intrinsic mechanisms of the human body that initiates fasting to trigger the immune system. However, more research is required to validate the above observation.
One of the key limitations of this study is its observational nature, where the participant’s periodic fasting was not randomized to the behavior. Additionally, the fasting history was self-reported, which might cause bias. However, the study's findings strongly suggest that routine periodic fasting reduces the risk of hospitalization and mortality due to severe COVID-19 infection. Two key mechanisms by which fasting prevents severe infection are strengthening certain immunity pathways and controlling hyperinflammation.