Saturated fat may hold the key to fixing Cellular Fragility Syndrome
According to a recently published study in The Journal of Nutrition, the essential odd-chain saturated fatty acid known as pentadecanoic acid (C15:0) and commercialized by Seraphina Therapeutics as fatty15 could reduce harmful liver enzymes associated with obesity and its comorbidities.
"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,” said Dr. Jeffrey Schwimmer, senior author on the study and leading expert in pediatric fatty liver disease research at the University of California, San Diego and Rady Children’s Hospital.
“While many questions remain, particularly regarding the optimal dosage and application in conditions like fatty liver disease, our findings indicate that C15:0 may have a role in managing the underlying metabolic dysfunction common among some patients with liver disease, diabetes and cardiovascular disease."
The research was supported by a grant from the National Institutes of Health and Seraphina Therapeutics.
The good odd-chain saturated fatty acid
It was through her work with older dolphins with higher cholesterol, insulin resistance and fatty liver disease at the Navy Marine Mammal Program from 2007 to 2017 that Stephanie Venn-Watson, DVM, MPH, a veterinary epidemiologist and co-founder at Seraphina Therapeutics, uncovered the potential health implications of C15:0 for reversing cellular aging.
In a 2020 paper published in Scientific Reports, she and her co-authors presented C15:0 as a potential essential fatty acid and the first to be discovered since omega-3 and omega-6 nearly a century ago.
With exclusively licensed patents from the U.S. Navy, Seraphina Therapeutics launched fatty15 in 2021 and has been hard at work destigmatizing saturated fat, which Dr. Venn-Watson explains “got a bad rap” because even-chain saturated fatty acids (especially C16:0 and C18:0) found in red meat, full fat dairy and palm oil have been associated with markers of heart disease, inflammation and type 2 diabetes.
“While we have been told to reduce our dietary intake of all saturated fats for over 50 years, this behavior has resulted in population-wide deficiencies in an essential odd-chain saturated fatty acid called C15:0 (pentadecanoic acid),” she said.
“Understanding that one in three people globally, including one in 10 children, have impaired metabolic and liver function, and evidence that replenishing C15:0 levels can help fix this global pandemic, there is an increasingly urgent need to reevaluate current nutritional guidelines around dietary saturated fats.”
C15:0, primarily sourced from whole fat dairy but also found in some ruminant meat, fish and plants, is described as a sturdy fatty acid that serves as an armor for cells in the body. Dr. Venn-Watson’s research has shown that C15:0 can strengthen cell membranes by 80% and repair mitochondrial function.
In a study published earlier this year in the journal Metabolites, she expanded her work to explore the relationship between ferroptosis—a newly discovered form of cell death brought on by lipid peroxidation—and the newly identified nutritional C15:0 deficiency syndrome, which Seraphina Therapeutics has termed Cellular Fragility Syndrome. As the company explains, when the body has low C15:0 levels, cell membranes become fragile, resulting in accelerated aging and increased risks to long-term red blood cell, metabolic, heart and liver health.
This latest study in humans led by Dr. Schwimmer set out to build upon the epidemiological, preclinical and cell-based studies to date linking C15:0 to reduced cardiovascular disease and diabetes risk and the potential to address physiological changes related to inflammation, obesity and cardiometabolic disease.
Study details
The double-blind, randomized, controlled, two-arm trial recruited 30 young adults between the ages of 18 and 24 years with overweight or obesity (BMI of 33.4 ± 5.3 kg/m2) and assigned them to consume either 200 mg of C15:0 or a placebo daily for 12 weeks.
The primary objective was to investigate changes in plasma C15:0 levels at the end of the study period and to assess safety and tolerability while measuring potential markers of physiological response as secondary outcomes.
“Notably, the mean plasma C15:0 increased significantly for the active treatment group relative to the placebo group,” the study reported. “Moreover, C15:0 supplementation was well tolerated without any significant adverse events.”
Recognizing the findings as preliminary, the researchers also linked supplementation to a significant decrease in gamma-glutamyl transferase (GGT), where high levels of GGT are associated with liver damage.
Of the participants in the C15:0 group, approximately half had a post-treatment plasma of 5 μg/mL or above—considered the “healthy zone”. These elevated levels were associated with potentially relevant improvements in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hemoglobin—markers of improved liver and red blood cell health.
“It's noteworthy, however, that the extent of this response exhibited substantial variability among individuals within the treatment group, with changes in circulating C15:0 spanning a range of -1.21 to 5.31 μg/mL,” the researchers wrote, hypothesizing that differences in C15:0 absorption or metabolism likely play a role and calling for future studies to address these discrepancies.
They also noted limitations including the relatively small sample size, the 12-week intervention duration, the examination of a single dosage regimen and lack of uniformity of metabolic parameters. In addition, factors such as dietary habits, physical exercise and age that may influence outcomes were not assessed in this pilot study.
“Dr. Schwimmer’s clinical trial further supports that many people have baseline C15:0 levels consistent with nutritional C15:0 deficiencies, and that fatty15 can help fix this deficiency to reverse key components of Cellular Fragility Syndrome,” Dr. Venn-Watson said. “This is an important milestone toward our global effort to restore healthy C15:0 levels, slow cellular aging and get our long-term health back on track.”
Looking ahead, she told NutraIngredients-USA that clinical trials will continue to investigate how fatty15 fixes a wide variety of conditions driven by Cellular Fragility Syndrome in addition to exploring potential benefits for cognitive health.
“Perhaps most importantly, we are working with scientific and medical leaders to prevent and treat nutritional C15:0 deficiencies and improve global health, including infants and youth,” she added.
The company shared that since launch, fatty15 has reached 130,000 customers with a 95% monthly retention rate and is on track to achieve a compound annual growth rate of 200% from 2021 to 2024. It also recently co-launched an at-home test in partnership with Genova Diagnostics to help physicians and consumers determine and monitor their C15:0 levels and is currently developing a higher-dose fatty15 for its rapidly growing health practitioner channel to meet individual patient needs.
Source: The Journal of Nutrition
doi: 10.1016/j.tjnut.2024.07.030
“C15:0 Supplementation in Young Adults with Overweight and Obesity: A Randomized Controlled Trial”
Authors: Miranda K. Robinson et al.
