C15:0 fatty acid

Looked into the supplement, and claims it has similar effect as rapamycin. Does anybody else have any information about this?

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Abstract

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, TNFα, 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.

Conclusion

In summary, our studies and prior literature show that C15:0 and rapamycin, a leading healthspan and longevity-enhancing intervention candidate, share numerous clinically relevant activities, including anti-inflammatory, anticancer, antifibrotic, antimicrobial, and mTOR-inhibiting activities. Further, as an AMPK activator, C15:0 also showed multiple similarities to metformin, especially at specific doses. Above and beyond in vitro and in vivo studies, C15:0 has the added benefit over rapamycin and metformin of having its associations with health studied in global meta-analyses of large prospective cohort studies that have taken place over decades, most of which included healthy individuals; these studies consistently show that people with higher circulating C15:0 concentrations have a lower risk of aging-associated conditions. Given the voluminous supporting literature, we propose C15:0 as a natural, effective, and safe odd-chain saturated fatty acid with strong evidence that this essential nutrient supports healthy aging and longevity in humans, with cell-based activities that are as good as, or better than, leading longevity-enhancing prescription therapeutics. Given population wide declining C15:0 levels, there is a need to evaluate the potential effects of nutritional C15:0 deficiencies on our healthspan and longevity.

Thoughts

Pretty extraordinary if this holds up.

Questions

  • Does anyone have an idea on C15:0 dosing for humans?
  • Delivery method
  • If oral, does it require enteric coating or encapsulation?
  • Could one “stack” it with rapamycin or possible alternate week to week?

Even more from Nature

Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential?
2020
https://www.nature.com/articles/s41598-020-64960-y

Abstract

Dietary odd-chain saturated fatty acids (OCFAs) are present in trace levels in dairy fat and some fish and plants. Higher circulating concentrations of OCFAs, pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0), are associated with lower risks of cardiometabolic diseases, and higher dietary intake of OCFAs is associated with lower mortality. Population-wide circulating OCFA levels, however, have been declining over recent years. Here, we show C15:0 as an active dietary fatty acid that attenuates inflammation, anemia, dyslipidemia, and fibrosis in vivo , potentially by binding to key metabolic regulators and repairing mitochondrial function. This is the first demonstration of C15:0’s direct role in attenuating multiple comorbidities using relevant physiological mechanisms at established circulating concentrations. Pairing our findings with evidence that (1) C15:0 is not readily made endogenously, (2) lower C15:0 dietary intake and blood concentrations are associated with higher mortality and a poorer physiological state, and (3) C15:0 has demonstrated activities and efficacy that parallel associated health benefits in humans, we propose C15:0 as a potential essential fatty acid. Further studies are needed to evaluate the potential impact of decades of reduced intake of OCFA-containing foods as contributors to C15:0 deficiencies and susceptibilities to chronic disease.

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I’ve been taking it for a couple years and I think it’s a good thing, though very expensive. I take fatty15:

If you find something cheaper or better, please post. I think probably a double dose is closer to what is needed, but I’m not spending that much.

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Have you identified any specific benefits and/or benefits over taking rapamycin?
Seems like one can get 90 days for $1.33 per dose.

Sorry, I take too much stuff and try too many things to notice a benefit. So it breaks the Desertshores rule. I don’t see any chance of harm and they tell a compelling story.

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

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Previous threads:

It’s not an essential fatty acid, that’s just marketing, there are two EFA’s that is Omega-3 and Omega-6.

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How does it affect LDL and LDL particle sizes?

their recommended dosage is 1 pill per day (100mg), but this seems way too small\

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While dose–response effects were present with C15:0 in the BioMAP panel, there were decreased activities at the highest dose (50 µM). While this could suggest that there were inconsistencies with the assay, this U-shaped activity profile of C15:0 is consistent with a true optimal active concentration of C15:0 at 17 to 20 µM. For example, when mitochondrial repair activities of C15:0 were assessed at 10, 20, 50, 100, and 200 µM, the optimal concentration for lowering mitochondrial reactive oxygen species production was 20 µM [2]. Similarly, while Trieu et al. showed a linear association between higher circulating C15:0 concentrations and lower risk of incident cardiovascular disease, there was a U-shaped association between circulating C15:0 concentration and risk of all-cause mortality; in this study, the lowest risk of mortality was among people with circulating C15:0 concentrations of 0.2 to 0.3% total fatty acids [11]. When including our current findings, these studies support the idea that C15:0 concentrations of 20 µM may be ideal for supporting human longevity.

A human population pharmacokinetic model, based on a series of studies involving oral administration of pure C15:0 to healthy adults and children, estimated that 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.

and the only 15:0 in iollo is Cholesteryl ester 15:0 7.53011539803889…

Oral C15:0 achieved active concentrations in vivo

Given that C15:0 demonstrated cell-based anti-inflammatory and antifibrotic activities between 6.7 and 20 µM (equal to 2.5 to 5 µg/ml), we first sought to understand oral doses of C15:0 needed to achieve these plasma concentrations in appropriate models. Here, 8- to 10-week old Sprague Dawley rats (n = 6 males) dosed orally once with C15:0 at 35 mg/kg body weight had increased C15:0 plasma levels within 30 minutes (Fig. 4). A maximum C15:0 plasma concentration of 4.98 µg/ml (20 µM) was achieved at 1 hour. C15:0 plasma levels were elevated above baseline levels throughout the 24-hour period, with a minimum concentration of 0.7 µg/ml. Thus, a single oral dose of C15:0 at 35 mg/kg succeeded in achieving our targeted active plasma concentrations in this rodent model, between 2.5 to 5 µg/ml (equivalent to 6.7 to 20 µM), from 1 to 8 hours post-dose. Plasma total C17:0 levels also increased, albeit less so than C15:0, following a single oral dose of C15:0; similar, sustained increases were not apparent with C13:0 (Fig. 4). These findings support de novo elongation of C15:0 to C17:0.

Figure 4

figure 4

Plasma deuterated C15:0 (a), C17:0 (b), and C13:0 (c) concentrations achieved over 24 h in male Sprague Dawley rats (n = 6 total, 3 per time point between 15 min and 12 h) dosed orally once with deuterated C15:0 (35 mg/kg body weight). Upper edge of box, maximum; line inside box, median; diamond, mean; lower edge of box, minimum.

Full size image

Daily oral C15:0 maintained safety in vivo at high doses over 14 days

To further evaluate the safety of C15:0 at increasing doses, Sprague Dawley rats (n = 10 per group, 5 females and 5 males, 7 to 8 weeks old) were dosed orally once daily for 14 days with C15:0 at 35, 175 and 350 mg/kg body weight. A non-dosed vehicle control group was included. Safety assessments included clinical observations, body weight, food intake, clinical chemistries, and histology (liver, kidney, heart, and adrenal glands). Additionally, total plasma C15:0 and C17:0 concentrations were measured at Day 14. There were no mortalities or observed abnormal behaviors in animals throughout the 14-day study across all study groups, and there were no significant differences when comparing body weights and organ weight-to-body weight ratios or the prevalence of abnormal clinical chemistry values or histologic observations between C15:0-supplemented and non-supplemented control animals (Suppl Table 3). Following 14 days of daily oral supplementation with C15:0 at three increasing doses, increasing plasma total C15:0 and total C17:0 concentrations were evident (p < 0.0001) (Suppl Fig. 3). Males dosed 35, 175, or 350 mg/kg oral C15:0 had significantly higher total C15:0 and C17:0 plasma concentrations at Day 14 compared to baseline controls (Suppl Table 3). Females dosed 175 or 350 mg/kg oral C15:0 had significantly higher total C15:0 plasma concentrations at Day 14 compared to baseline controls, while only females dosed 350 mg/kg oral C15:0 had significantly higher C17:0 plasma concentrations compared to baseline controls (Suppl Table 3).

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To convert a drug dose from mouse to human, we need to use a method called allometric scaling. This accounts for the differences in metabolism between species. Let’s go through this step-by-step:

Starting dose: 35 mg/kg for mouse
The conversion factor from mouse to human is typically 0.081. This is derived from the body surface area (BSA) normalization method.
Calculate the human equivalent dose (HED): HED = Animal dose × (Animal Km / Human Km)
Where Km is a factor based on body surface area. Mouse to Human conversion:
HED = 35 mg/kg × (3/37) = 35 × 0.081 = 2.835 mg/kg
Now, we need to consider the C:15 notation. This likely refers to a concentration of 1 part drug to 15 parts vehicle or diluent. To account for this, we divide our result by 15: 2.835 mg/kg ÷ 15 = 0.189 mg/kg
Therefore, the human equivalent dose would be approximately 0.189 mg/kg.

(for 350mg mouse=> 1.89mg/kg human, which is 84mg for 44kg human, so maybe 100mg/day is a decent dose).

It’s important to note that this is an estimated starting point for human dosing. Actual safe and effective doses in humans would need to be determined through clinical trials. Also, factors such as the specific drug, its mechanism of action, and the targeted therapeutic effect can influence the final human dose.

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It’s way better than nothing and you may notice a difference. I eat almost all animal products and am going mostly on faith in the studies. My levels are probably pretty high to begin with.
Guidance on this issue would be nice.

Maybe it’s my mood but this phrase (a common one around here I admit) made me laugh out loud. It occurred to me that you need more than a calculator to do that math…you have to add in a huge helping of faith as well.

We think nothing of saying every person is different because of genetics, life history, and microbiome differences, but then look to take an equivalent dose of a chemical that had an effect on a mouse living in a lab…and hope for the best.

I have to think about this more.

At least it’s not worms.

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