Pentadecanoic Acid As Effective for Aging as Rapamycin?

[DeStrider]

Pentadecanoic Acid (C15:0), an Essential Fatty Acid, Shares Clinically...

Research Worth Sharing, July 2024 Edition

Results showed that C15:0 and rapamycin performed comparably in promoting positive, dose-dependent, clinically relevant effects across the activities tested, with C15:0 showing significant effects for 36 activities in 10 of 12 cell systems and rapamycin showing significant effects in 32 activities in 12 of 12 cell systems. Both compounds outperformed metformin (17 activities) and acarbose (5 activities). C15:0 and rapamycin, both of which inhibit mTOR, were found to share many cellular processes, overlapping in 24 significant activities including reductions in markers of chronic inflammation, cell proliferation, autoimmune activity, fibrosis, and others. These results indicate that C15:0 can counteract cellular processes related to aging and disease to a comparable degree as rapamycin, suggesting that C15:0 may therefore have positive effects on longevity,

[desertshores]

Well, I am getting some in my dairy products. I have always drunk only whole-fat milk.

“Further, an 18-year longitudinal study including over 25,000 individuals demonstrated that children fed whole fat milk had a lower risk of having obesity compared to children who were provided fat-free or 1% fat milk, and multiple studies have demonstrated associations between higher dietary intake of full-fat dairy and reduced risk of type 2 diabetes and cardiovascular disease7,8,9. As such, there is a need re-evaluate potential health risks versus benefits of dietary dairy fats.”

C15:0 is a dual, partial PPAR α/δ agonist
C15:0 had no off-target pharmacological activities
C15:0 repaired mitochondrial function
C15:0 was non-cytotoxic across multiple primary human cell lines
C15:0 reduced proinflammatory and profibrotic states in human cell systems
C15:0 supplementation attenuated anemia, liver iron deposition, and severity of liver fibrosis in our in vivo NASH model
Daily oral C15:0 maintained safety in vivo at high doses over 14 days
Low-dose daily oral C15:0 attenuated a pro-inflammatory state and lowered glucose and cholesterol in vivo
Daily oral C15:0 attenuated anemia, inflammation, liver iron overload and NASH in vivo

This link may have been posted previously. If so I apologize.

https://www.nature.com/articles/s41598-020-64960-y

[AgentSmith]

I don’t know about the marketing, but the first (sponsored) Google result:

Essential Fatty Acid Supplement: C15:0 | fatty15

$460/year. Roughly the same as a year of Zydus brand rapamycin? Same order of magnitude at least.

[DeStrider]

I think there’s less expensive ways of getting C15:0.

[Alpha]

@AgentSmith

https://fatty15.com/

Where I live and getting rapamycin from a US source, I pay considerably more than $460 a year.
(I note that I could introduce grapefruit juice and do a series of tests to check if I get the levels I need.)

My questions.

• Could C15:0 and rapamycin complement each other?
• If yes, could one lower the amount of rapamycin by taking both?
• If yes, could one might even lower the effective dose of C15:0?

Interesting stuff.

Thoughts appreciated.

[baimayangji]

How about using MACKLIN’s chemical reagents. On Chinese websites, MACKLIN provides pentadecanoic acid reagents, cas: 1002-84-2, with a purity of 98%. 10 grams cost just over $20, which is very cheap

[Curious]

My main concerns are:

• If we rather easily can get C15 through diet. Why pay?

Top 100 Foods With Pentadecanoic Acid (15:0) - Care Omnia Nutrition

“Results showed that C15:0 and rapamycin performed comparably in promoting positive, dose-dependent, clinically relevant effects across the activities tested, with C15:0 showing significant effects for 36 activities in 10 of 12 cell systems and rapamycin showing significant effects in 32 activities in 12 of 12 cell systems”

• It looks like C15 acts through many of the pathways that Rapamycin also act on. But is that the whole truth? The systems they compare might only have been chosen to grab our attention. Are the systems they compare the ones that are crucial for the effects of C15 and Rapamycin? What other systems do rapamycin and C15 act on?

• If C15 and rapamycin actually share many pathways that are vital for increased healthspan and lifespan? Why take both?

• I have not seen a study that improves the health or life span of mammals.

This being said, I find C15 interesting. And it makes me consider if I get enough through food. I will probably stay away from C15 until we get some positive data from mice.

[JazzMann]

Hey @DeStrider

I read the Attia email yesterday and all the other papers have been discussed previously and almost all are written by the Fatty15 folks. It was unclear if Attia was discussing a new independent study? Where did you pick up the Rich Miller (ITP) had also been evaluating Pentadecanoic acid?
Thx

[DeStrider]

I just checked again. Attia mentioned Dr. Miller in discussing Rapamycin and other ITP results in an earlier episode in the blurb only. That’s what happens when you slim too quickly.

[AgentSmith]

@DeStrider

I think there’s less expensive ways of getting C15:0.

For sure. Consumer Lab:

Getting C15:0 fatty acid from food

As noted earlier, some foods contain C15:0 fatty acid, but these same foods contain additional saturated fat, so eating large amounts to get C15:0 fatty acid could be unhealthy. The American Heart Association recommends that an adult not exceed about 13 grams of saturated fat per day. There is about 80 mg of C15:0 fatty acid in 1 cup of whole milk or 4 oz of raw ground beef (85% lean), but these products contain, respectively, about 4.6 to 6.5 grams of total saturated fat (FoodData Central, 4/1/2019; FoodData Central, 12/16/2019). Therefore, getting 300 mg per day of C15:0 from whole milk or 85% lean ground beef, respectively, would also correspond to getting more than 17 grams or 25 grams of saturated fat per day. However, eating enough to get just 100 mg (the amount in a daily serving of fatty15), would not exceed the limit but could certainly help push you over the limit, which is based on one’s total daily food intake.

[cl-user]

@desertshores

Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? | Scientific Reports

The authors in that paper are co-founders of the company selling C15:0 which financed the paper.

S.V. is a co-founder of and employed by Epitracker, Inc and Seraphina Therapeutics, Inc, which financed studies in this paper and hold exclusive licensing rights from the U.S. Navy to commercialize odd-chain saturated fatty acids as human and animal health products. R. Lumpkin’s work related to this study was also financed by Epitracker. E.A. Dennis is a member of the Scientific Advisory Board of Epitracker and holds equity.

BTW in that paper they hint that the dietary intake is sufficient:

the average baseline circulating C15:0 concentration in people is 24.9 µM74. These levels are consistent with our studies, which demonstrated cell-based PPARα/δ agonist, anti-inflammatory, antifibrotic, and mitochondrial protective C15:0 activities between 10 and 50 µM, with most of our studies demonstrating optimal activities at 20 µM. Human pharmacokinetic studies support that a single dose of 200 mg of C15:0 results in 20 µM circulating C15:0 concentrations (approximately 5 µg/ml)75. Further, the average reported dietary intake of C15:0, based on a population of women from the 1990s, was 220 ± 100 mg per day, which is consistent with the amount needed to achieve approximately 20 µM circulating C15:0 concentrations76. Combined, these studies support potential targeted circulating C15:0 concentrations from 20 to 30 µM.

Basically if you are healthy and eat well there is no need to supplement as getting too much of it is not optimal either.
The only category in this forum (*) that, maybe, needs supplementation would probably be strict vegans as C15:0 is found in animal foods like dairy and meat.

For instance just with my consumption of homemade whole milk kefir and yogurt in addition to lean meat I’m above 200mg of C15:0.

(*) I’m assuming there are not too many morbidly obese people here

[JuanDaw]

Mackerel (99 mg)or bluefin tuna sashimi (90 mg) would be good sources too,

Fishes and Shellfishes High in Pentadecanoic acid | Whole Food Catalog

[desertshores]

@cl-user

BTW in that paper they hint that the dietary intake is sufficient:

I agree. I don’t ever add a supplement to my stack unless there is strong scientific evidence that it has value.
So many of the studies are fraudulent or have vested interests.

BTW: I eat all of the top C15:0 foods on the list.

[JuanDaw]

Another supplement worth checking out - rutin.

https://ergo-log.com/this-analogue-of-rutin-extends-life-by-10-percent.html

From their 32nd week of life, mice were given lifelong drinking water in which researchers at Capital Medical University in Beijing had dissolved sodium rutinate. If the mice had been humans, they would have received about 160-240 milligrams of sodium rutinate daily.

Results
Rutin sodium, as the Chinese call the rutin analogue they use, extended the mean and maximum lifespan of the mice by 10 percent.

When the mice were middle-aged, they ran faster if they had been given rutin sodium. Moreover, after the researchers had placed them on a rotating axis, they tumbled down less quickly. This indicates that rutin sodium kept the mice physically and motor fit.

The mice that had been given rutin sodium also looked younger. Their fur was in better condition than that of the animals who had not been given rutin sodium. This also points to better health in aging mice.

Mechanism
As organisms age, the concentration of beta-galactose in their cells increases. Beta-galactose is a marker of cell aging at the molecular level. The researchers found less beta-galactose in the cells of older mice that had been given rutin sodium.

Full paper below.

https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15410

[Joseph_Lavelle]

@JuanDaw I was told by James Lavalle (a pharmacist I interviewed) that Rutin was an appetite suppressant. Perhaps there’s a bit of CR in these mouse results…?

[AnUser]

Previous threads:

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…

Replacing Omega-3 with C15:0 a Good Idea?

After reading a recent interview with longevity doctor Mark Hyman posted here, I’m considering replacing my daily fish oil Omega 3 supplement with C15:0 instead. I don’t want to add more stuff to my stack, but I am willing to replace things. From data I’ve found, C15:0 seems to be a better essential fatty acid supplement to take than omega 3 (but is certaily more expensive). What do you guys think? Additional info at this link:

C15:0 fatty acid

Great, a healthy excuse to put even more cream cheese on my lox bagel.

Why did you make a new one?

[JuanDaw]

After 8 months of sodium rutin supplementation, we found that sodium rutin treatment did not affect food intake and water consumption of the mice

The increase in insulin sensitivity may be one factor.

https://ergo-log.com/rutin-diabetes.html

[AlexKChen]

Does anyone do a high dose loading dose of this first? Given that it’s likely we’re deficient and it might make up for our deficiency sooner with a high loading dose? Is there a limit to the rate at which it gets incorporated?

[Karel1]

The first ingredient of a cheap block of hand soap is sodium palmate. The substances palmitinic acid and sodium palmitate are also very cheap to synthesize so it may be very cheap.
Eating the soap is not advisable(!)