Pentadecanoic Acid (C15:0), an Essential Fatty Acid, Shares Clinically Relevant Cell-Based Activities with Leading Longevity-Enhancing Compounds

Another not so new antiaging compound to add to our already bulky ‘wish list’.

Peer reviewed study: Pentadecanoic acid (C15:0) activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway

“Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n=36 activities in 10 of 12 cell systems) and rapamycin (n=32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFɑ, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds”.

Just for your info, there is already a supplement containing it Fatty15. Maker (Seraphina Therapeutics) involved in the study:

"Funding
This work was funded in part by the Office of Naval Research (Agreement No. N00014-2109-0002); NJS data analysis efforts are supported in part by NIH grants U19 AG023122, UH3 AG064706, U19 AG065169.

But:
Conflicts of Interest

S.V.-W. is a co-founder of and employed by Epitracker, Inc and Seraphina Therapeutics, Inc, which hold exclusive licensing rights from the U.S. Navy to commercialize odd-chain saturated fatty acids as human and animal health products. NJS is a co-founder of and consultant to Seraphina Therapeutics, Inc.

One scientific study mentioned in their site (Blog) to support their claims as antiageing. Cited in another post below.

For more info please visit the source link

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I immediately looked where to source. ChatGPT was less than helpful:

Pentadecanoic acid, also known as C15:0, is a saturated fatty acid with 15 carbon atoms. It can be found in various natural sources, including:

  1. Dairy Products: Some dairy products, such as butter and cheese, contain small amounts of pentadecanoic acid. It’s often found as a minor component of the fatty acids in these foods.

  2. Milk: Pentadecanoic acid is present in trace amounts in cow’s milk and can be derived from the fatty acids in the milk fat.

  3. Ruminant Meats: Meat from ruminant animals like cows, sheep, and goats can contain pentadecanoic acid, as it is formed during the microbial fermentation of feed in the rumen of these animals.

It’s worth noting that pentadecanoic acid is typically not a major component of the fatty acids in these foods but rather a minor one. A diet rich in dairy products and ruminant meats may contribute to its intake, but it’s not considered a primary dietary source of this fatty acid.

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From Nature’s Scientific Reports: Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health

Abstract

As an emerging dietary essential fatty acid, pentadecanoic acid (C15:0) is expected to have bioactive metabolites with broad health benefits. Here, we evaluated pentadecanoylcarnitine, an endogenous C15:0 metabolite, for dose dependent cell-based activities, including measurement of its effects on 148 clinically relevant biomarkers across twelve primary human cell systems mimicking various disease states. Mechanisms of action for pentadecanoylcarnitine were also assessed across 78 cell-based target assays. Pentadecanoylcarnitine had dose-dependent anti-inflammatory activities, including lower IL-1α, ITAC, MCP-1, and IP-10, across five cell systems relevant to treating cardiovascular, immune, neoplastic, pulmonary, and skin diseases. Targeted assays showed pentadecanoylcarnitine as a full-acting cannabinoid 1 and 2 receptor agonist (EC50 3.7 and 3.2 µM, 111% and 106% maximum activity compared to the positive control, respectively). Pentadecanoylcarnitine also had 5-HT1A and 5-HT1B receptor agonist and histamine H1 and H2 receptor antagonist activities. In summary, pentadecanoylcarnitine, a second discovered full-acting endocannabinoid, had broad pleiotropic activities relevant to regulating inflammation, pain, mood, and sleep. This study’s findings further the need to evaluate the potential health impacts of C15:0 nutritional deficiencies caused by population-wide avoidance of all dietary saturated fats, including C15:0.

Longevity only mentioned once.

Maker (Seraphina Therapeutics) involved in the study:

Competing interests

S.V. is a co-founder of and employed by Epitracker, Inc and Seraphina Therapeutics, Inc, which hold exclusive licensing rights from the U.S. Navy to commercialize odd-chain saturated fatty acids as human and animal health products. J.R. is employed by Epitracker.

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I think I found it :blush:

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That only has 100 mg per capsule.

https://www.si.com/showcase/nutrition/fatty15-review

Fatty15 At a Glance

  • Single-ingredient formula containing 100 milligrams of FA15 (C15:0)
  • Formulated to promote healthy aging
  • One capsule per day serving size
  • Vegan-friendly supplement

It is claimed that you get more from butter

Foods High in Pentadecanoic acid (per 100 g edible portion)

Unsalted butterUnsalted butter 880 mg
Salted butterSalted butter 830 mg
Fermented butterFermented butter 820 mg
Cream (milk fat)Cream (milk fat) 450 mg
Cattle, Imported beef (rib loin, fat, raw)Cattle, Imported beef (rib loin, fat, raw) 450 mg
Cattle, Beef, dairy fattened steer (rib loin, fat, raw)Cattle, Beef, dairy fattened steer (rib loin, fat, raw)
410 mg
Natural cheese (cheddar)Natural cheese (cheddar) 390 mg
Whipping cream (milk fat)Whipping cream (milk fat) 380 mg

or cheese (parmesan or cheddar).

I don’t know how reliable the first source is. Assuming its reliability, 10 grams of butter gives you 88 mg of C15. At 15 grams (one tablespoon), that is 132 mg.

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Well feed it to Ora Biomedical then

They mention these in the background part of the intro in the actual paper, would be interesting to look when time as this should have examples actual human data it seems:

Large, prospective cohort studies have linked higher circulating concentrations of C15:0 to lower risks of developing chronic diseases, including cardiovascular disease, heart failure, and type 2 diabetes3,4,5. Further, higher dietary intake and circulating concentrations of C15:0 have been associated with lower mortality and greater longevity5,6,7.

From some of the human (non trial) data:

We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, **higher 15:0 was associated with lower incident CVD risk in a linear dose–response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case–cohort, or nested case–control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively.

At the same time:

** Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels.

And

Conclusions

In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.

From

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Apparently, some crude Schizochytrium alga oils are very high in C15:0. The composition will depend on strain and culture conditions, so one would want to find a supplier who knows their product’s breakdown.

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Yep, a good idea. But, IMHO, everything regarding algae has a possible downside. And it is its high iodine content, which has a troublesome relationship with our thyroid. And some people can met hypothyroidism, hyperthyroidism, etc … with high levels of iodine present in most marketed algae. On the other hand, regarding oils as the one you mention, as refined products, I’d hope suppliers get rid of this ‘dark side’ as Schizochytrium looks like a good natural source of C15:0.

Thanks for the heads up.

Pentadecanoic Acid is a HDAC6 inhibitor. Not necessarily a good thing. HDAC inhibitors trigger dna damage and inhibit dna repair.

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HDAC Inhibitor Sodium Butyrate Attenuates the DNA Repair in Transformed but Not in Normal Fibroblasts

Abstract

Many cancer therapy strategies cause DNA damage leading to the death of tumor cells. The DNA damage response (DDR) modulators are considered as promising candidates for use in combination therapy to enhance the efficacy of DNA-damage-mediated cancer treatment. The inhibitors of histone deacetylases (HDACis) exhibit selective antiproliferative effects against transformed and tumor cells and could enhance tumor cell sensitivity to genotoxic agents, which is partly attributed to their ability to interfere with DDR. Using the comet assay and host-cell reactivation of transcription, as well as γH2AX staining, we have shown that sodium butyrate inhibited DNA double-strand break (DSB) repair of both endo- and exogenous DNA in transformed but not in normal cells. According to our data, the dysregulation of the key repair proteins, especially the phosphorylated Mre11 pool decrease, is the cause of DNA repair impairment in transformed cells. The inability of HDACis to obstruct DSB repair in normal cells shown in this work demonstrates the advantages of HDACis in combination therapy with genotoxic agents to selectively enhance their cytotoxic activity in cancer cells.

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Adding C15:0 to the short list of Essential Fatty Acids is a very big deal.

I’ve been taking C15:0 for a while. The study takes a bit of reading but I find it compelling.

I’ve inserted a few excerpts for the"time poor" but reading the whole paper is fascinating and well worth the effort. The tables showing the BioMAP test results are compelling.

C15:0 compounds:
To evaluate the repeatability and consistency of human cell phenotypic profiling with C15:0, two C15:0 compounds manufactured at different facilities, Seraphina Therapeutics (FA15TM, pentadecanoic acid 99%) and Millipore Sigma (Sigma-Aldrich Product W433400, pentadecanoic acid 99%), were compared using the BioMAP Diversity Plus Panel (Eurofins DiscoverX, Fremont, California USA).

The reference link to Fatty15 is already in this thread.

The tests included a well regarded EPA supplement.

There are excellent tables showing the comparisons. Spoiler alert, both C15:0 sources were very similar and in many cases, better than EPA.

Here’s a link to the Millipore Sigma product. It costs $340 for 100g.

BioMAP® Diversity PLUS panel is the platform for testing

The BioMAP® Diversity PLUS panel (Eurofins) uses 12 human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues. Quantitative measurements of 148 clinically relevant biomarker activities across this broad panel, along with comparative analysis of the biological activities of known bioactive agents in the BioMAP reference database, are used to predict the safety, efficacy and function of test agents. The reference database includes BioMAP profiles of over 4,500 compounds with known safety, efficacy and function.

Discussion

First paragraph only. The whole discussion is worth reading as it describes many of the potential beneficial findings of the study.

C15:0 is emerging as an essential fatty acid with pleiotropic and clinically relevant benefits that may help to stem chronic cardiometabolic, liver, and inflammatory diseases. Here, our study demonstrated broad and dose-dependent anti-inflammatory, immunomodulatory and antifibrotic activities of C15:0, including dose dependent activities involving 36 key biomarkers across 10 different human cell systems mimicking various disease states. Overall, these clinically relevant activities were repeated when evaluating two pure C15:0 compounds from different manufacturers.

Conclusion

Demonstrated broad and beneficial activities of C15:0, including many that were improved upon a leading omega-3, support C15:0’s role as an emerging essential fatty acid relevant to both physical and mental health. This study built on the existing literature of C15:0’s anti-cancer and antimicrobial properties, as well as being the first to demonstrate the potential for C15:0 to help manage depression and autoimmune diseases. Given the growing and repeated evidence of C15:0 as a beneficial odd-chain saturated fatty acid, there is a need to reevaluate current nutritional guidelines that continue to recommend lowered intake of all dietary saturated fats.

@Krister_Kauppi @RapAdmin I think C15:0 is a great candidate to be added near the top of the ITP list and should hopefully figure in your own testing plans and perhaps your personal regimes.

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A press release from Seraphina Therapeutics.

It always bugs me a little when companies charge more for supplements than I pay for my rapamycin…

Seraphina Therapeutics Founder shows essential nutrient rivals leading anti-aging drugs in clinically relevant benefits expected to extend human longevity.

SAN DIEGO, Oct. 30, 2023 /PRNewswire-PRWeb/ – A recently published study in the scientific journal Nutrients reveals that C15:0 (pentadecanoic acid), an odd-chain healthy saturated fat found in trace amounts in dairy fat, and the first essential fatty acid to be discovered in over 90 years (since omega-3), has anti-aging properties expected to extend human longevity that equal, and even surpass, leading prescription drug candidates.

While numerous studies have linked higher C15:0 levels to lower risks of type 2 diabetes, heart disease, nonalcoholic fatty liver disease, and cancer, only recently have the anti-aging mechanisms driving these C15:0 health benefits been revealed.

“In 2020, we discovered that C15:0 directly targets multiple hallmarks of aging and effectively repaired cells throughout the human body,” said Dr. Stephanie Venn-Watson, co-founder of Seraphina Therapeutics and the lead author of the recent Nutrients paper and earlier 'Nature’s Scientific Reports’ paper. “Paired with the mounting science on C15:0’s long-term health benefits, we hypothesized that this nutrient plays an essential role in supporting human longevity. We were delighted by the study’s results.”

In the recent study, pure C15:0 (FA15) went head-to-head against three leading longevity drug candidates: rapamycin, metformin, and acarbose. Independent, third-party tests of all four compounds were conducted and evaluated for dose-dependent effects on clinically relevant biomarkers across 12 human cell systems mimicking various chronic disease states.

Of the four compounds, the results showed that pure C15:0 delivered the most cell repairing benefits, closely followed by rapamycin. At their optimal doses, C15:0 and rapamycin shared an impressive 24 clinically relevant activities across 10 out of the 12 human cell systems evaluated. These benefits, including anti-inflammatory, anticancer, antifibrotic, and antimicrobial activities of both C15:0 and rapamycin, align well with previously published studies. C15:0 and rapamycin have also been shown to share the ability to inhibit mTOR, which has been targeted as a key means to extend human longevity.

Dr. Nicholas Schork, the study’s co-author and Principal Investigator for the National Institutes of Health’s Longevity Consortium, points out that “the numerous benefits of C15:0, that match and even surpass that of leading candidate longevity drugs, speak to the essentiality of C15:0 to our long-term health.” Dr. Schork shares, “Remarkably, while billions of dollars have been spent around the world on advancing anti-aging research, the secret to longevity may be much closer to home.”

As a particularly urgent point, population-wide C15:0 levels have been declining, caused by avoidance of whole fat cow’s milk over the past 40 years. Given its role as an essential nutrient, it is hypothesized that nutritional C15:0 deficiencies may be driving the rise in chronic diseases among younger people, including nonalcoholic fatty liver disease (NAFLD). The most recently discovered longevity-enabling activities of C15:0 suggests that nutritional C15:0 deficiencies may help explain why human lifespans have been shortening over recent years, too.

“While global health has been declining at an alarming rate, studies are increasingly supporting that we have a new and tangible hope - the ability to readily replenish our C15:0 levels, restore aspects of our long-term health, and extend longevity for all,” states Venn-Watson.

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HaHa, Amen to that RapAdmin!

Interestingly, C15:0 itself, doesn’t have a patent.

I’m pretty sure that the price will be forced down by competition. As outlined in my earlier link, Sigma-Aldrich (Merck), have already created a version of C15 and I’ve heard that others are following suit.

From the Ray Peat Forum, I read that another Lab has plans for the C15 lipid at a cost that, “… would be much cheaper than the fatty15 product”.

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There is a debate in the literature concerning whole milk vs skim. The reason I mention this is because whole milk and dairy product consumers get a significant amount of C15:0 in their diets. If you are a significant dairy product consumer you probably don’t need a C15:0 supplement. There are 80 mg. in an 8-ounce glass of whole milk. So, 2, 8 oz glasses of milk per day would give you 160 mg per day vs 100 mg of the C15:0 supplement.

“Our primary dietary source of C15:0 is from whole-fat dairy products"

N=1: I am 82 years old and in very good health. I have been a large dairy consumer my entire life because my parents and ancestors were large dairy consumers and I personally love dairy products. Especially, as I have grown older I have a decreased appetite and I use dairy products to get help get the daily calories I need.

If you are not lactose intolerant, whole milk, butter, and cheese are a way to get a significant amount of C15:0

I don’t think whole milk will shorten your lifespan.

To see what is in whole milk see the charts below and change the 100g selector to 1 cup as it is a more convenient measurement for most than 100g

https://fdc.nal.usda.gov/fdc-app.html#/food-details/746782/nutrients

.

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Skim milk was only fit for fattening pigs until the low fat craze.

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And it looks like whole milk consumption doesn’t affect CVD risk (at least according to this systemic review and meta-analysis). Sounds like companies that wanted to skim off the profits might have spread this rumour to get people buying their skimmed products? (my conspiracy two cents worth :slight_smile: )

Milk and Dairy Product Consumption and Cardiovascular Diseases: An Overview of Systematic Reviews and Meta-Analyses - PubMed (nih.gov)

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Might be a factor in the French paradox - the central position of butter in French cuisine.

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So my Heavy Cream Lattes are ok?

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