Pentadecanoic acid (C15:0), a fatty acid from grass-fed animals may be essential - several studies

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C-15:0 may be an essential fatty acid - review Dec 2024

New insights on pentadecanoic acid with special focus on its controversial essentiality: A mini-review
Biochimie Volume 227, Part B, Dec 2024, Pages 123-129 https://doi.org/10.1016/j.biochi.2024.10.008

Pentadecanoic acid (C15:0, PDA) is an odd and minor fatty acid that has been neglected in the literature until the last decade. Indeed, as a specific fatty acid of dairy fat, PDA was only used as a biomarker of dairy fat consumption. Lately, PDA was first correlated negatively with the incidence of metabolic syndrome disorder, then its physiological effects have been investigated as a protective fatty acid. PDA supplementation has been demonstrated as negatively correlated with elevated levels of leptin, plasminogen activator inhibitor-1 and insulin, and has been shown to exhibit sensitizing insulin effects with activation of AMPK pathway. PDA also reduced the severity of metabolic dysfunction-associated steatohepatitis (MASH), notably through reduced alanine transaminase and pro-inflammatory cytokines levels. The final effect described for PDA is its ability to display anti-inflammatory properties in several pathology models. Hence, considering these multiple effects, the presence of PDA could be associated with a healthier physiological state, this raises the question of whether the presence of PDA in the body, in adequate quantities, is needed to participate to health maintenance. PDA is not synthesized in sufficient quantities endogenously, so it must be provided by the diet, mainly through dairy fat, although other types of food can also contribute to the dietary intake of PDA. Essential fatty acids are described as not being endogenously synthesized in sufficient and required quantities to maintain physiological health.

Thus, PDA might gather both conditions to be described as essential, yet further investigations on both criteria are needed to enhance knowledge on this odd chain fatty acid with promising impact as potential protective supplement nutrient.
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C15:0 — Found in Dairy — May Be an Essential Fat - Mercola Aug 2024

Includes a 1 hour video by Venn-Watson

• "C15:0, also known as pentadecanoic acid, is an odd-chain saturated fat primarily found in dairy products, some fish, and certain plants. The story of C15:0's importance begins in an unlikely place — with dolphins."
• "Dr. Stephanie Venn-Watson, a veterinary epidemiologist, was brought on board the Navy's Marine Mammal program about 20 years ago to help understand aging in dolphins and protect their health. The Navy has been caring for a population of dolphins for over 60 years, and these dolphins are living much longer in captivity (40 to 50+ years) compared to their wild counterparts (around 20 years)."
• "Dr. Venn-Watson's research suggests that when your C15:0 levels drop below 0.2% of total fatty acids in your cell membranes, you enter a state she calls "Cellular Fragility Syndrome." This syndrome is characterized by fragile red blood cells, anemia, iron overload in the liver, and increased risk of conditions like Type 2 diabetes, cardiovascular disease and fatty liver disease. It's a domino effect that starts at the cellular level and cascades into systemic health issues."
• "The impact of C15:0 deficiency is far-reaching and multifaceted. The "Cellular Fragility Syndrome" resulting from C15:0 deficiency is characterized by a cascade of health issues. It starts with fragile red blood cells susceptible to lipid peroxidation, leading to anemia and dysmetabolic iron overload syndrome (DIOS). This iron overload can trigger ferroptosis in the liver, potentially leading to advanced nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)."
• "The syndrome also encompasses insulin resistance, metabolic syndrome, Type 2 diabetes, and cardiovascular disease. Perhaps most alarmingly, it includes systemic iron overload and ferroptosis, which can accelerate aging and tissue damage throughout your body. It's a complex web of interconnected health issues, all potentially stemming from a deficiency in this one crucial fat."
• "Based on the available research, your cell membranes require more than 0.2% C15:0 to ensure cellular stability. Optimal circulating C15:0 concentrations should be between 0.4% to 0.64% of total fatty acids. C15:0 deficiency is defined as 0.21% or less of total circulating fatty acids"

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The Cellular Stability Hypothesis: Evidence of Ferroptosis and Accelerated Aging-Associated Diseases as Newly Identified Nutritional Pentadecanoic Acid (C15:0) Deficiency Syndrome - June 2024

Metabolites 2024, 14(7), 355; https://doi.org/10.3390/metabo14070355
by Stephanie Venn-Watson 1,2ORCID
1 Seraphina Therapeutics Inc., San Diego, CA 92106, USA
2 Epitracker Inc., San Diego, CA 92106, USA

Ferroptosis is a newly discovered form of cell death caused by the peroxidation of fragile fatty acids in cell membranes, which combines with iron to increase reactive oxygen species and disable mitochondria. Ferroptosis has been linked to aging-related conditions, including type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). Pentadecanoic acid (C15:0), an odd-chain saturated fat, is an essential fatty acid with the primary roles of stabilizing cell membranes and repairing mitochondrial function. By doing so, C15:0 reverses the underpinnings of ferroptosis.
Under the proposed “Cellular Stability Hypothesis”, evidence is provided to show that cell membranes optimally need >0.4% to 0.64% C15:0 to support long-term health and longevity. A pathophysiology of a newly identified nutritional C15:0 deficiency syndrome (“Cellular Fragility Syndrome”) is provided that demonstrates how C15:0 deficiencies (≤0.2% total circulating fatty acids) can increase susceptibilities to ferroptosis, dysmetabolic iron overload syndrome, type 2 diabetes, cardiovascular disease, and NAFLD. Further, evidence is provided that C15:0 supplementation can reverse the described C15:0 deficiency syndrome, including the key components of ferroptosis. Given the declining dietary intake of C15:0, especially among younger generations, there is a need for extensive studies to understand the potential breadth of Cellular Fragility Syndrome across populations.
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There are several of vendors on Amazon for those who do not get grass-fed dairy or meat (goats, cows, etc.)

Note: Cost/capsule varies by 20X: $0.08 to $1.67

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Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems - May 2022

Stephanie K. Venn-Watson, Camden N. Butterworth
PLOS x https://doi.org/10.1371/journal.pone.0268778

A growing body of evidence supports that pentadecanoic acid (C15:0), an odd-chain saturated fat found in butter, is an essential fatty acid that is necessary in the diet to support long-term metabolic and heart health. Here, dose dependent and clinically relevant cell-based activities of pure C15:0 (FA15TM) were compared to eicosapentaenoic acid (EPA), a leading omega-3 fatty acid, as well as to an additional 4,500 compounds. These studies included 148 clinically relevant biomarkers measured across 12 primary human cell systems, mimicking various disease states, that were treated with C15:0 at four different concentrations (1.9 to 50 μM) and compared to non-treated control systems. C15:0 was non-cytotoxic at all concentrations and had dose dependent, broad anti-inflammatory and antiproliferative activities involving 36 biomarkers across 10 systems. In contrast, EPA was cytotoxic to four cell systems at 50 μM. While 12 clinically relevant activities were shared between C15:0 and EPA at 17 μM, C15:0 had an additional 28 clinically relevant activities, especially anti-inflammatory, that were not present in EPA. Further, at 1.9 and 5.6 μM, C15:0 had cell-based properties similar to bupropion (Pearson’s scores of 0.78), a compound commonly used to treat depression and other mood disorders. At 5.6 μM, C15:0 mimicked two antimicrobials, climabazole and clarithromycin (Pearson’s scores of 0.76 and 0.75, respectively), and at 50 μM, C15:0 activities matched that of two common anti-cancer therapeutics, gemcitabine and paclitaxel (Pearson’s scores of 0.77 and 0.74, respectively). In summary, C15:0 had dose-dependent and clinically relevant activities across numerous human cell-based systems that were broader and safer than EPA, and C15:0 activities paralleled common therapeutics for mood disorders, microbial infections, and cancer. These studies further support the emerging role of C15:0 as an essential fatty acid.
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Pentadecanoic acid and T2 Diabetes - Dec 2014

Serum pentadecanoic acid (15:0), a short-term marker of dairy food intake, is inversely associated with incident type 2 diabetes and its underlying disorders
The American Journal of Clinical Nutrition Volume 100, Issue 6 , Dec 2014, Pages 1532-1540 https://doi.org/10.3945/ajcn.114.092544

Background:
Growing evidence suggests that dairy consumption is associated with lower type 2 diabetes risk. However, observational studies have reported inconsistent results, and few have examined dairy’s association with the underlying disorders of insulin resistance and β-cell dysfunction.

Objective:
We investigated the association of the dairy fatty acid biomarkers pentadecanoic acid (15:0) and trans-palmitoleic acid (trans 16:1n−7) with type 2 diabetes traits by evaluating 1) prospective associations with incident diabetes after 5 y of follow-up and 2) cross-sectional associations with directly measured insulin resistance and β-cell dysfunction.

Design:
The study analyzed 659 adults without diabetes at baseline from the triethnic multicenter Insulin Resistance Atherosclerosis Study (IRAS). Diabetes status was assessed by using oral-glucose-tolerance tests. Frequently sampled intravenous-glucose-tolerance tests measured insulin sensitivity (SI) and β-cell function [disposition index (DI)]. Serum fatty acids were quantified by using gas chromatography. Logistic and linear regression models were adjusted for demographic, lifestyle, and dietary variables.

Results:
Serum 15:0 was a significant biomarker for total dairy intake in the IRAS cohort. It was associated with a decreased incident diabetes risk (OR: 0.73, P = 0.02) and was positively associated with log SI (β: 0.84, P = 0.03) and log DI (β: 2.21, P = 0.02) in fully adjusted models. trans 16:1n−7 was a marker of total partially hydrogenated dietary fat intake and was not associated with outcomes in fully adjusted models.

Conclusions:
Serum 15:0, a marker of short-term intake of this fatty acid, was inversely associated with diabetes risk in this multiethnic cohort. This study may contribute to future recommendations regarding the benefits of dairy products on type 2 diabetes risk.
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Health benefits of Pentadecanoic acid - Perplexity AI Aug 2024

Pentadecanoic acid (C15:0) is an odd-chain saturated fatty acid that has been recognized for its potential health benefits. Here are some of the key health benefits associated with pentadecanoic acid:

1. Cardiometabolic Health: C15:0 is linked to improved cardiometabolic health, including lower risks of type 2 diabetes, heart disease, and nonalcoholic fatty liver disease. It helps in reducing cholesterol and triglyceride levels, which are crucial for cardiovascular health.
2. Anti-inflammatory and Antifibrotic Effects: C15:0 exhibits anti-inflammatory and antifibrotic properties. It activates AMPK and PPAR-α/δ, which are involved in metabolic regulation, and inhibits mTOR, JAK-STAT, and HDAC-6 pathways, contributing to its anti-inflammatory effects.
3. Longevity and Aging: Studies suggest that C15:0 may enhance healthspan and longevity. It has been compared to rapamycin, a known longevity-enhancing drug, for its cell-repairing benefits and potential to delay the onset of age-related diseases.
4. Metabolic Regulation: C15:0 supports metabolic health by improving mitochondrial function, stabilizing red blood cells, and regulating glucose metabolism. These activities help maintain healthy glucose and cholesterol levels.
5. Cellular Health: C15:0 enhances cellular resilience by incorporating into cell membranes, improving their stability and function. It also helps in maintaining cellular communication by activating PPARs, which are crucial for metabolism and immunity.
6. Potential Antimicrobial and Antidepressant Properties: C15:0 has shown antimicrobial effects against certain bacteria and fungi, and its properties have been likened to those of antidepressants, suggesting potential benefits for mood disorders.

Overall, pentadecanoic acid is emerging as a nutrient with broad health benefits, particularly in supporting metabolic health, reducing inflammation, and promoting longevity.

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30+ YouTube videos for "Pentadecanoic acid" OR C15:0 (A.K.A Fatty15)

• SATURATED FATS Truth: Essential Fatty Acids and the Discovery of C15:0 with Dr. Eric Venn-Watson
• This OUTPERFORMS Omega 3's (Pentadecanoic Acid - Fatty15)
• C15:0 update #1 | Human Studies and Ferroptosis
• C15 A Longevity Game Changer? | The Studies Reviewed
• Newly Discovered Super-Fat in Ghee | Dr. John Douillard's LifeSpa
• Newly Discovered Compound Improves Insulin Resistance AND Longevity | Dr. Venn-Watson 47 minutes

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