A recent study published in Life Metabolism has revealed that intermittent fasting (IF) can significantly reduce platelet activation, potentially lowering the risk of cardiovascular disease (CVD). This breakthrough research highlights the impact of IF on platelet-related processes and the gut microbiota, offering new insights into how dietary patterns can improve cardiovascular health.
Cardiovascular disease, which causes over 20 million deaths annually, is primarily driven by heart attacks and strokes resulting from blocked arteries. Atherosclerosis, elevated cholesterol levels, and increased blood glucose are key risk factors for CVD, all of which contribute to enhanced platelet aggregation and a heightened risk of thrombosis. Despite the availability of antiplatelet drugs, many patients continue to suffer from heart attacks triggered by platelet-induced coronary clots.
One promising approach to mitigating these risks is IF, a dietary strategy that involves reducing caloric intake by up to 60% on alternate days. Previous studies have shown that IF can improve outcomes for individuals with diabetes, high cholesterol, cancer, Alzheimer’s disease, and age-related health issues. Additionally, IF has been linked to improvements in blood pressure, cholesterol levels, and insulin resistance—factors crucial for cardiovascular health.
Study Design and Results
The study focused on coronary artery disease (CAD) patients, all of whom were on aspirin therapy. Participants were randomly assigned to either the IF or ad libitum (AL) group. The IF group followed a fasting regimen every other day, while the AL group maintained a standard diet. Blood samples were collected before and after a 10-day period to assess platelet activity. In parallel, in vivo experiments with genetically modified mice were conducted, with one group fasted every other day.
Results showed that IF effectively inhibited platelet activation and thrombus formation in both humans and mice. Further analysis of the gut microbiota in the IF group revealed elevated levels of orotate and indole-3-propionic acid (IPA). While orotate had no impact on platelet activation, IPA was found to play a significant role.
IPA: A Key Mediator of Platelet Inhibition
IPA, a metabolite produced by the bacterium Clostridium sporogenes, was identified as a key player in reducing platelet activation. In both in vivo and in vitro experiments, IPA demonstrated the ability to suppress platelet activation and delay thrombin formation, with effects comparable to those of the commonly prescribed antithrombotic drug clopidogrel. Notably, when IPA was combined with clopidogrel, the two compounds had a synergistic effect, further reducing thrombus formation.
The study also found that platelet aggregation in CAD patients decreased after 10 days of IF, and this reduction was inversely correlated with blood IPA levels. IPA’s inhibitory effect on platelet activation was shown to be mediated through its binding to the pregnane X receptor (PXR), which subsequently disrupted platelet-activating pathways, such as the Src/Lyn/Syk pathway. Blocking these pathways resulted in increased platelet aggregation, confirming IPA’s role in platelet suppression.
Gut Microbiota and IPA Production
IPA is primarily produced in the gastrointestinal tract by Clostridium sporogenes, a gram-positive bacterium. Mice treated with this bacterium showed higher IPA levels in their gut, plasma, and platelets, which corresponded to a reduction in platelet aggregation and a prolonged thrombus formation time. Importantly, IF was found to enhance the presence of C. sporogenes, whereas antibiotic treatment diminished IPA levels and led to increased platelet aggregation in IF mice.
These findings suggest that IF may mediate its cardiovascular benefits by altering the gut microbiota, promoting the production of IPA, and ultimately reducing platelet activation and thrombus formation.
Conclusion
The study concludes that IF has the potential to reduce platelet activation and arterial clot formation, providing a novel approach to improving cardiovascular health. By modifying the gut microbiota and increasing serum IPA levels, IF may offer a promising treatment for individuals with coronary atherosclerosis. However, further clinical studies are needed to confirm these findings and fully understand the therapeutic potential of IF in preventing cardiovascular events.
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