New study shows that raising levels of fatty acid C15:0 through supplementation can improve metabolic health and combat cellular aging.
A recent clinical trial has reported promising results on the role of C15:0 (pentadecanoic acid) supplementation in improving metabolic health and addressing a newly discovered condition known as Cellular Fragility Syndrome. This study, published in The Journal of Nutrition, demonstrates that supplementing with C15:0 can effectively raise C15:0 levels in the blood, subsequently improving liver and red blood cell health [1]. These findings, led by Dr Jeffrey Schwimmer, an expert in pediatric fatty liver disease at the University of California, San Diego and Rady Children’s Hospital, add a new dimension to our understanding of cellular aging and longevity.
Longevity.Technology: Cellular Fragility Syndrome is a condition characterized by a deficiency in C15:0, an essential fatty acid found predominantly in dairy fats. This deficiency compromises cell membrane stability, increasing susceptibility to ferroptosis – a form of cell death associated with the peroxidation of fragile fatty acids in cell membranes. Ferroptosis has been implicated in various aging-related conditions, including type 2 diabetes, cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). The Cellular Stability Hypothesis suggests that adequate levels of C15:0 are necessary to stabilize cell membranes and maintain mitochondrial function, thereby supporting long-term health and longevity.
The rise in popularity of weight-loss drugs like semaglutide (marketed as Wegovy for weight loss and Ozempic for diabetes) highlights a growing demand for interventions targeting obesity and related metabolic disorders. While these drugs have shown effectiveness, they can be expensive and often come with side effects. Preclinical and cell-based studies have suggested that C15:0 supplementation may offer a natural alternative by addressing physiological changes linked to inflammation, obesity and cardiometabolic disease [234]. Notably, higher C15:0 levels have been correlated with a lower risk of obesity [5], making it encouraging to see human trials beginning to explore its benefits; as studies progress, C15:0 could emerge as a valuable component in the broader strategy to combat metabolic conditions and improve overall health.
The recent randomized, double-blinded and placebo-controlled clinical trial included 30 young adults aged 18 to 24 with overweight or obesity and elevated liver enzymes indicative of impaired liver function. The participants, who actively avoided whole dairy fat, were administered fatty15 daily for 12 weeks. At the study’s outset, two-thirds of the participants had C15:0 levels below the proposed deficiency threshold of 5 μg/ml. Those who achieved C15:0 levels above this threshold exhibited significant reductions in liver enzyme levels (ALT and AST) and increases in hemoglobin levels, signaling improved liver and red blood cell health. Notably, these beneficial effects were not observed in the placebo group, and improved red blood cell health is a critical first expected effect in reversing Cellular Fragility Syndrome [1].
Schwimmer noted: “This study is an important step in confirming that C15:0 supplementation can effectively raise circulating C15:0 levels, potentially leading to improvements in metabolic health.” He further emphasized the potential role of C15:0 in managing metabolic dysfunctions common among patients with liver disease, diabetes and cardiovascular conditions. Dr Stephanie Venn-Watson, co-founder and CEO of Seraphina Therapeutics, echoed these sentiments, highlighting the study’s significance in addressing nutritional C15:0 deficiencies and their impact on Cellular Fragility Syndrome.
The implications of these findings are far-reaching, especially considering the growing prevalence of NAFLD, a condition marked by excessive fat accumulation in the liver. NAFLD has emerged as a significant public health concern, affecting one in three individuals globally, including one in ten children. The disease can progress to severe liver inflammation, cell damage and cirrhosis, making it a leading cause of liver cancer and a substantial contributor to cardiovascular mortality. The discovery that C15:0 can ameliorate some of the metabolic disturbances associated with NAFLD presents a compelling case for revisiting current dietary guidelines – particularly regarding the intake of odd-chain saturated fats like C15:0.
A date with the dairy
Historically, public health guidelines have recommended reducing saturated fat intake, including fats found in dairy products. However, this trial and previous research suggest that certain saturated fats, such as C15:0, may have protective effects against age-related cellular damage. The study’s findings align with previous research that demonstrated C15:0’s ability to support healthy LDL cholesterol levels, improve the gut microbiome and reduce body and liver fat beyond the benefits seen with caloric restriction or the Mediterranean diet.
The clinical trial’s outcomes underline the urgent need for further studies to understand the breadth of Cellular Fragility Syndrome across different populations and age groups. As Venn-Watson puts it: “There is an increasingly urgent need to revisit current nutritional guidelines around saturated fats, especially odd-chain saturated fats, to help people maintain healthy C15:0 levels and protect their long-term health.” This renewed focus on the potential health benefits of C15:0 could shift perspectives on dietary fats and contribute to more nuanced nutritional recommendations that consider the complex roles of different types of fatty acids in human health.
The study on fatty15 and C15:0 supplementation provides compelling evidence for its role in counteracting the adverse effects of Cellular Fragility Syndrome. By stabilizing cell membranes and protecting against ferroptosis, C15:0 supplementation may offer a valuable strategy for enhancing healthspan and mitigating the risk of chronic diseases associated with aging. As research in this area continues, it holds promise for developing new interventions that promote longevity and improve overall metabolic health.
READ MORE – Small but mighty: the fatty acid that packs a considerable longevity punch
[1] https://jn.nutrition.org/article/S0022-3166(24)00411-5/fulltext
[2] https://pubmed.ncbi.nlm.nih.gov/32424181/
[3] https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189965
[4] https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132117
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272531/
