Fluoxetine, a common antidepressant, was found to protect mice from sepsis-induced death by enhancing metabolic defenses. The study revealed that fluoxetine promotes a shift in macrophage metabolism toward fatty acid oxidation, increasing mitochondrial respiration and ATP production. This metabolic boost enables macrophages to effectively clear bacterial infections and mitigate the harmful inflammation characteristic of sepsis, ultimately improving survival rates. The protective effect was dependent on activation of the serotonin 1A receptor, suggesting a potential mechanism linking the drug's antidepressant properties with its anti-septic action.
The concept of "minimum effective dose" (MED) applies beyond pharmacology to various life areas. It emphasizes achieving desired outcomes with the least possible effort or input. Whether it's exercise, learning, or personal productivity, identifying the MED avoids wasted resources and minimizes potential negative side effects from overexertion or excessive input. This principle encourages intentional experimentation to find the "sweet spot" where effort yields optimal results without unnecessary strain, ultimately leading to a more efficient and sustainable approach to achieving goals.
HN commenters largely agree with the concept of minimum effective dose (MED) for various life aspects, extending beyond just exercise. Several discuss applying MED to learning and productivity, emphasizing the importance of consistency over intensity. Some caution against misinterpreting MED as an excuse for minimal effort, highlighting the need to find the right balance for desired results. Others point out the difficulty in identifying the true MED, as it can vary greatly between individuals and activities, requiring experimentation and self-reflection. A few commenters mention the potential for "hormesis," where small doses of stressors can be beneficial, but larger doses are harmful, adding another layer of complexity to finding the MED.
Researchers have identified a naturally occurring molecule called BAM15 that acts as a mitochondrial uncoupler, increasing fat metabolism without affecting appetite or body temperature. In preclinical studies, BAM15 effectively reduced body fat in obese mice without causing changes in food intake or activity levels, suggesting it could be a potential therapeutic for obesity and related metabolic disorders. Further research is needed to determine its safety and efficacy in humans.
HN commenters are generally skeptical of the article's claims. Several point out that the study was performed in mice, not humans, and that many promising results in mice fail to translate to human benefit. Others express concern about potential side effects, noting that tampering with metabolism is complex and can have unintended consequences. Some question the article's framing of "natural" boosting, highlighting that the molecule itself might not be readily available or safe to consume without further research. A few commenters discuss the potential for abuse as a performance-enhancing drug. Overall, the prevailing sentiment is one of cautious pessimism tempered by hope for further research and development.
Summary of Comments ( 13 )
https://news.ycombinator.com/item?id=43078537
HN commenters discuss the study's limitations, noting the small sample size and the focus on a single antibiotic. They question the translatability of mouse studies to humans, emphasizing the differences in immune system responses. Some highlight the potential benefits of fluoxetine's anti-inflammatory properties in sepsis treatment, while others express concern about potential side effects and the need for further research before clinical application. The discussion also touches upon the complexity of sepsis and the challenges in finding effective treatments. Several commenters point out the known link between depression and inflammation and speculate on fluoxetine's mechanism of action in this context. Finally, there's skepticism about the presented mechanism, with some suggesting alternative explanations for the observed protective effects.
The Hacker News post titled "Fluoxetine promotes metabolic defenses to protect from sepsis-induced lethality" linking to a Science Advances article, has generated a moderate number of comments discussing various aspects of the study and its implications.
Several commenters focused on the complexity of sepsis and the challenges in finding effective treatments. One commenter highlighted the multi-factorial nature of sepsis, making it difficult to pinpoint a single therapeutic target. They emphasized that the existing arsenal against sepsis is limited, and new treatments are desperately needed. Another commenter echoed this sentiment, pointing out the high mortality rate associated with sepsis and the need for further research to validate the findings of the study. They expressed hope that this research could eventually lead to a new class of sepsis treatments.
Some comments delved into the specifics of the study itself. One commenter questioned the study's focus on mortality as the primary outcome, suggesting that other important factors, such as long-term morbidity and quality of life, should also be considered when evaluating potential sepsis treatments. Another commenter discussed the role of mitochondria in sepsis and how fluoxetine, typically used as an antidepressant, might be acting on these cellular powerhouses to provide protection. They mentioned the complexity of the metabolic pathways involved and the need for further research to fully understand the mechanisms at play.
The potential repurposing of fluoxetine for sepsis treatment was also a point of discussion. One commenter pointed out that fluoxetine is already a widely used and relatively safe drug, which could potentially expedite its clinical application for sepsis if the findings are confirmed in further studies. Another commenter cautioned against over-interpreting the results of a single study, emphasizing the need for rigorous clinical trials before drawing definitive conclusions about the efficacy of fluoxetine in treating sepsis. They also mentioned the possibility of unforeseen side effects when using fluoxetine in a critically ill population.
Finally, a few comments addressed the broader context of drug discovery and development. One commenter discussed the challenges of translating preclinical findings into effective clinical therapies, highlighting the high failure rate in drug development. Another commenter expressed skepticism about the hype surrounding potential new treatments for complex diseases like sepsis, emphasizing the importance of cautious optimism and rigorous scientific scrutiny.