More than a decade ago, when I was just beginning my exploration of bioenergetics, one of the first indications that Ray’s writings were onto something when it came to SFA vs. PUFA was the fact that while mainstream medicine ruthlessly bashed SFA in general and promoted PUFA, virtually very little bad publicity was directed at dairy fat. In fact, it seemed even back then that medicine had already resigned itself to the existence of the “dairy fat paradox” and periodically published articles about the “surprising” or “paradoxical” benefits of dairy in bastions of medical propaganda such as NEJM, BMJ, Nature, etc that were often given even bigger publicity by mainstream media.
https://pubmed.ncbi.nlm.nih.gov/29951411
That fact that it is dairy fat (and not the protein or calcium in dairy) that has unique beneficial effect is easily surmised from the studies with ice-cream, where the primary ingredient is fat, and mostly of the SFA kind.
https://www.theatlantic.com/magazine/archive/2023/05/ice-cream-bad-for-you-health-study/673487/
https://www.deseret.com/23683767/ice-cream-health-benefits
As part of its studies on dairy, medicine even developed a test for quantifying dairy consumption and that test consists of measuring blood/tissue levels of two odd-chain SFA found primarily in dairy. Namely, pentadecanoic acid (PA, C15:0) and heptadecanoic acid (HA, C17:0). The latter is also known as margaric acid. Their average concentrations in dairy are about 1% and 0.5%, respectively, of total fats in dairy.
https://en.wikipedia.org/wiki/Pentadecylic_acid
https://en.wikipedia.org/wiki/Margaric_acid
After that initial interest in researching dairy fats, I moved onto other research and almost forgot about the existence of PA and HA. Years later, while researching succinic acid as part of the development of our product SolBan, my attention was drawn to a pair of Japanese studies for treating hair loss by topical application of PA. As those studies described, due to its odd-chain, PA is only partially metabolized via the beta-oxidation pathway, through which even-chain fatty acids get metabolized to ultimate form acetyl-CoA and then enter the Krebs Cycle. The terminal metabolism of odd-chain fatty acids, including PA, forms succinic acid, and ultimately succinyl-CoA, which then enters the Krebs Cycle. Since rising levels of acetyl-CoA has an inhibitory effects on pyruvate dehydrogenase (PDH), eating a diet high in fat with mostly even-chain fats would result in reduction of glucose metabolism, even if all the fats are of the SFA type, as per the Randle Cycle. However, if those fats are of the odd-chain species and enter the Krebs Cycle as succinic acid (i.e. without effect on the acetyl-CoA/CoA ratio), then virtually no such reduction of glucose metabolism is expected to occur and, in fact, PA was described in the Japanese studies as stimulating mitochondrial function and ATP production, which ultimately resulted in improved hair growth. The Japanese reseachers even filed a patent for treating hair-loss with PA and in that patent they opined that other odd-chain fatty acids with similar length, especially the C17:0 fat HA mentioned above, would have similarly beneficial effects on hair-growth through increasing mitochondrial function (OXPHOS).
https://doi.org/10.1111/j.1468-2494.1993.tb00592.x
https://www.jstage.jst.go.jp/article/skinresearch1959/37/6/37_6_800/_article/-char/en
Those studies above were performed in the early 1990s and since then there have been quite a few additional studies discovering remarkable benefits of odd-chain SFA, with the bulk of the research focusing on PA and HA. Several studies have compared PA and HA to the “essential” omega-6 fatty acids, as well as to omega-3 fats, and have concluded that PA and HA are much more deserving of the label “essential” than the omega-6, let alone the omega-3. In fact, at least one study demonstrated that the omega-3 are cytotoxic when used in concentrations that are lower than concentrations typically achieved when eating cold-water fatty fish or taking fish oil supplements, while the odd-chain PA and HA were not only not cytotoxic but their cellular benefits were dose-dependent. Such effects are reminiscent of pregnenolone, progesterone, vitamin K, etc for which the body seems to have remarkably high affinity and accumulates them inside cells in concentrations exceeding blood levels by several orders of magnitude.
https://doi.org/10.3945/an.115.011387
“…The robust inverse association of 15:0 and/or 17:0 concentrations in plasma phospholipids or RBCs with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) risk is quite impressive. The latter is observed in various European populations with different dietary backgrounds (5). This review brings forward hypotheses about the possible sources of 15:0 and 17:0 and their potential involvement in metabolic pathways. They may be used for synthesis of odd-numbered VLCFAs, provide anaplerotic intermediates for the CAC, or store away excess propionic acid. ”
https://pubmed.ncbi.nlm.nih.gov/32424181/
“…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 disease7–9. As such, there is a need re-evaluate potential health risks versus benefits of dietary dairy fats10.”
“…While dietary ECFAs have been associated with increased risk of inflammation, heart disease, and type 2 diabetes in humans12–15, higher dietary intake and circulating levels of OCFAs have been associated with lower risks of adiposity, chronic inflammation, cardiovascular disease, metabolic syndrome, type 2 diabetes, nonalcoholic steatohepatitis (NASH), chronic obstructive pulmonary disease, pancreatic cancer and other conditions14–27. In a prospective cohort involving over 14,000 people followed for an average of 14 years, increased dietary intake of OCFAs was associated with lower mortality in both men and women, while higher ECFA intake was associated with higher mortality in women28.”
“…Since fatty acids can affect mitochondrial function45, the effects of OCFAs and ECFAs on repairing mitochondrial function and reducing mitochondrial ROS were evaluated in serum starved HepG2 cells. Here, C15:0 had a dose-response u-curve effect on mitochondrial function, including lower mitochondrial ROS production in cell systems supplemented at 10 µM (17.8 ± 2.7%, P = 0.04), 20 µM (12.9 ± 3.2%, P = 0.005) and 50 µM (15.4 ± 2.6%, P = 0.007) compared to non-supplemented control cell systems (23.4 ± 4.3%) (Fig. 1). There were no differences in ROS production when comparing cells supplemented at higher C15:0 concentrations (100 and 200 µM) compared to non-supplemented controls. Among a variety of other OCFAs and ECFAs evaluated (C13:0 through C18:0), C15:0 through C18:0 (20 µM) had lower mitochondrial ROS compared to the non-supplemented control group, while C13:0 and C14:0 did not significantly lower mitochondrial ROS (Suppl Fig. 2).”
“…Based on a definition of cytotoxicity in which more than 50% of total protein in the cell system was reduced, C15:0 did not induce cytotoxicity in any of the 12 cell systems (Suppl Table 2).”
“…Here, C15:0 had dose-dependent, annotated anti-inflammatory activities, including reduced monocyte chemoattractant protein 1 (MCP-1) and secreted immunoglobulin G (IgG) (Fig. 2). C15:0 also had antifibrotic activities, including reduced Collagen I, plasminogen activation inhibitor 1 (PAI-1), and 72-hour fibroblast proliferation (Fig. 2). Anti-inflammatory and antifibrotic activities were present at both 6.7 and 20 µM. C15:0 cell-based anti-inflammatory and antifibrotic activities at 20 µM were better than C17:0 at the same concentration; other saturated fatty acids (C13:0, C14:0 and C16:0) had no anti-inflammatory or antifibrotic activities (Fig. 3). Because C14:0, C15:0, and C16:0 all had similar dual PPARα/δ agonist activities (reported above), results from our human cell phenotypic screening support that C15:0 activities go beyond C15:0’s role as a natural PPARα/δ fatty acid ligand. This study also supports that a relatively minor increase in C15:0 concentrations (e.g. from 2.2 µM to 6.7 µM) can positively impact its anti-inflammatory and antifibrotic activities.”
“…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.”
“…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”
“…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). ”
“…Mice supplemented with oral C15:0 for 90 days at low doses (5 mg/kg) had lower circulating levels of the proinflammatory chemokine, monocyte chemoattractant protein 1 (MCP-1), and the proinflammatory cytokine, interleukin 6 (IL-6) compared to non-supplemented controls (Fig. 5). The C15:0-supplemented group also had lower glucose, lower cholesterol, and lower percent body weight gain on the high fat diet compared to non-supplemented controls (Fig. 5, Suppl Table 4). In contrast, mice supplemented with daily low dose C17:0 (5 mg/kg) had no significant differences in clinical chemistry values compared to non-supplemented, diseased controls, while high dose C17:0 (50 mg/kg) supplemented mice had lower serum MCP-1 compared to controls (Suppl Table 4). ”
“…Specifically, C15:0 supplementation raised hemoglobin, hematocrit, and red blood cell count, and lowered nucleated red blood cells, red blood cell distribution width, and reticulocytes. In this model, these changes are consistent with decreased loss of fragile red blood cells and lowered need for new red blood cell production46. Further, C15:0-supplemented animals had lower cholesterol, triglycerides, globulins, and platelets compared to non-supplemented diseased controls (Fig. 7). Additionally, multiple liver health indices in C15:0-supplemented animals, including bilirubin and icterus were lower than non-supplemented diseased controls, matching that of healthy controls (Supplement Table 6). Histologically, C15:0-supplemented animals also had less severe liver fibrosis and liver iron staining scores within Kupffer cells compared to non-supplemented diseased controls. Unlike the non-supplemented diseased controls, C15:0-supplemented animals did not progress from Stage 2 to Stage 3 (bridging) fibrosis (Suppl Table 6).”
“…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.”
https://pubmed.ncbi.nlm.nih.gov/35617322
“…Beyond population-based studies, experimental research has shown that C15:0 is an active and beneficial fatty acid with direct pleiotropic activities relevant to stemming chronic conditions, especially with age [26–29]. Specifically, C15:0 is a dual partial peroxisome proliferator-activated receptor α/δ agonist, AMP-activated protein kinase activator, and histone deacetylase 6 inhibitor [26–28]. Further, C15:0 has been shown to repair mitochondrial function, improve the stability of red blood cells, regulate glucose metabolism, and decrease proliferation of cancer cells [26–29].”
“…In addition to MCP-1, C15:0 and EPA effectively lowered CD40 and T cell proliferation in a single system relevant to T-cell driven inflammatory conditions. This cell system is used to discover potential therapeutics for autoimmune diseases, including rheumatoid arthritis, psoriasis, and Crohn’s disease, as well as for hematological oncology applications. Although use of EPA has been proposed as a method to manage autoimmune diseases, supportive studies have been primarily limited to fish oil that did not discriminate between the effects of EPA versus other fatty acids [32–36]. Our study is the first to report the potential for C15:0 to manage autoimmune diseases. ”
“…While C15:0 and EPA shared 12 common activities, our studies also demonstrated 35 differences between these two fatty acids, including substantially broader anti-inflammatory, immunomodulatory and antifibrotic activities caused by C15:0 that were not present with EPA. Of the 11 cell systems in which C15:0 had disease-attenuating properties that were not present with EPA, three were relevant to atherosclerosis, vascular inflammation, and restenosis, as well as two others relevant to asthma, allergies, and metabolic diseases. Examples of biomarkers lowered by C15:0 and not EPA in these systems included sIL-10, CD69, HLA-DR, TNF-α, IL-17F, IL-17A, and IL-1α. Given these findings, further studies are warranted to evaluate if C15:0’s broader therapeutic activities at the cellular level translate to broader health benefits to individuals and populations compared to EPA and other omega-3s fatty acids.”
“…Demonstrated mechanisms of actions for C15:0 and EPA may help explain both their shared and differentiated activities. C15:0 and EPA are endogenous peroxisome proliferator activated receptor (PPAR) agonists, including PPAR alpha and delta; their roles as PPAR agonists can explain their shared anti-inflammatory and antifibrotic activities [28, 39]. Additionally, C15:0 and EPA have been shown to target the AMP-activated protein kinase (AMPK) pathway, which modulates glucose metabolism [23, 40, 41], as well as inhibit histone deacetylase (HDAC), a proposed means of treating cancer by stemming cancer cell proliferation [26, 42]. While C15:0 and EPA share several key mechanisms of action, they appear to have opposing effects related to MAPK and JAK-STAT signaling, which use oxidative stress to elicit cytokine and inflammatory processes. Specifically, polyunsaturated fatty acids, like EPA, induce MAP and JAK-STAT signaling, while C15:0 inhibits these pro-inflammatory pathways [29, 43, 44]. JAK-STAT inhibitors have been proposed as promising therapeutics to inhibit cytokines and treat numerous inflammatory and autoimmune diseases, and this key mechanism of C15:0 may explain why it had broader anti-inflammatory effects in our study compared to EPA [45].”
“…When assessing clinically relevant and dose-dependent activities of C15:0 and over 4,500 additional compounds, our study demonstrated common cell-based phenotypic profiles between C15:0 and therapeutics for mood disorders, infections, and cancer, based on concentration. At lower concentrations (1.9 and 5.6 μM), C15:0 human cell-based activities closely matched those of bupropion at 10 and 30 μM, respectively. Bupropion, sold as Wellbutrin®, is a dopamine-norepinephrine reuptake inhibitor and commonly used antidepressant that is considered safe, well tolerated, and does not result in weight gain [51]. Specific conditions managed by bupropion include major depressive disorder and seasonal affective disorder, and it has shown promise as a non-nicotine agent that promotes smoking cessation in clinical trials [51]. Bupropion is a pill that is typically taken 2–3 times a day in doses ranging from 100–150 milligrams. Based on human pharmacokinetic data with pure free fatty acid C15:0, approximate doses of 19 to 56 mg is expected to achieve circulating C15:0 concentrations with activities similar to bupropion [52].”
“…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.”
Now, if something has such a broad beneficial effects on health as the studies above describe, one would expect said substance to have an anti-aging and lifespan extending effects as well. While we still don’t have direct in-vivo evidence for such effects of PA and/or HA, in-vitro evidence already exists. As the study below demonstrated, PA has anti-aging effects matching, and even exceeding, those of the standard drug for anti-aging research, rapamycin, the most widely used antagonist of the eponymous pathway mTOR.
https://doi.org/10.3390/nu15214607
“…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.”
“…First, as anticipated for a healthspan and longevity-enhancing compound, C15:0 directly targets multiple hallmarks of aging, including mitochondrial dysfunction, cellular senescence, impaired cellular signaling, and inflammaging. Pure C15:0 rescues mitochondrial function at complex II of the mitochondrial respiratory pathway via increased production of succinate and has a dose–response effect on repairing mitochondrial function [2,83,84]. Consistent with the cell membrane pacemaker theory of aging, C15:0, as a stable, odd-chain saturated fatty acid that is readily incorporated in cell membranes, stems premature cellular senescence and lowers the risk of lipid peroxidation [23,35,36,37,38,85,86]. Beyond the role of C15:0 as an mTOR inhibitor and AMPK activator, C15:0 supports healthy cellular signaling as a dual partial PPAR α/δ agonist, JAK-STAT inhibitor, and HDAC6 inhibitor, which are well-established moderators of metabolism, lipids, inflammation, and cancer [2,22,24,26,87,88,89]. As shown in the current study, C15:0 has broad anti-inflammatory activities expected to directly address inflammaging, a chronic, low-level inflammatory state that contributes to the onset and exacerbation of many aging-associated diseases [90].”
“…Beyond evidence that C15:0 lowers the risk of conditions that are leading causes of mortality, higher C15:0 has been linked to lower risks of a number of other aging-associated conditions, including anemia, chronic obstructive pulmonary disease, hair loss, and Alzheimer’s disease. Specifically, children with higher erythrocyte cell membrane C15:0 levels have less severe iron deficiency anemia [37], and daily oral C15:0 supplementation successfully attenuates anemia in vivo [2]. Regarding lung disease, dietary C15:0 intake is linearly correlated with improved lung function (FEV1/FVC) in people with COPD [100]. A double-blinded clinical trial demonstrated the efficacy of topical pentadecanoic acid glyceride in treating male pattern alopecia [82,101]. Further, higher free fatty acid C15:0 in cerebrospinal fluid is associated with a lower risk of Alzheimer’s disease [102]. These studies support C15:0 as a healthspan and longevity-enhancing nutrient that can delay the onset and progression of multiple chronic age-related diseases.”
The studies above mostly focus on PA, and one would be tempted to conclude that most of the benefits of dairy fat stem from the presence of PA. However, the much less discussed HA has been the subject of several intervention studies that strongly suggest it is at least as beneficial as HA and not only contributes to the beneficial effects of dairy fat but is synergistic with PA. One particularly interesting study found that dolphins, our closest relatives in the animal world in terms of intelligence and metabolism, readily develop diabetes when fed the crappy processed food diet full of PUFA, but that diabetes can be prevented and even quickly reversed when the dolphins are fed the human equivalent of 50mg-100mg HA daily for about 6 moths.
https://pubmed.ncbi.nlm.nih.gov/26200116/
https://www.sciencedaily.com/releases/2015/07/150722144627.htm
“…”We were surprised to find that among the 55 fatty acids studied, the saturated fat heptadecanoic acid appeared to have had the most beneficial impact on dolphin metabolism,” said Venn-Watson. “Dolphins with higher levels of heptadecanoic acid in their blood had lower insulin and triglycerides.” The study also showed that while some fish have high levels of heptadecanoic acid, other fish types had none. Six dolphins with low heptadecanoic acid were then fed fish high in this fatty acid. Within six months on the new diet, indicators of metabolic syndrome in dolphins, including elevated insulin, glucose, and triglycerides normalized. Key to this surprising outcome was reversal of high ferritin, an underlying precursor to metabolic syndrome. “We saw blood ferritin levels decrease in all six dolphins within three weeks on the new diet,” said Venn-Watson. Heptadecanoic acid, also called margaric acid or C17:0, is a saturated fat found in dairy fat, rye, and some fish.”
Another interesting finding from the dolphin study above was that high ferritin was causally associated with the (pre)diabetes seen in the animals and HA was able to alleviate this iron toxicity, which provides another plausible mechanism of why these odd-chain SFA are beneficial and suggests other diseases for which they may also be therapeutic – i.e. above all, cancer. Iron overload is a well-known feature of cancer and iron chelators such as desferoxamine have shown great promise in pre-clinical studies for the treatment of many types of cancer. Low and behold, HA (in the forum of ship tail fat), in a human equivalent dose (HED) of just 0.5mg/kg daily was effective in restricting growth of a human lung cancer (xenograft model), as effectively as the so-called standard-of-care drug.
https://pubmed.ncbi.nlm.nih.gov/36034869
“…We previously reported that the odd-chain saturated fatty acid (OCSFA), heptadecanoic acid (C17:0), profoundly inhibits non-small-cell lung cancer (NSCLC) cell proliferation. However, the antitumor potential of edible lipids rich in C17:0 remains unclear. Here, we determined that sheep tail fat (STF) is a dietary lipid rich in C17:0 and exhibited the greatest inhibitory effect against three NSCLC cell lines (A549, PC-9, and PC-9/GR) among common dietary lipids. Cell migration experiments demonstrated that STF could significantly inhibit the wound healing capacity of three NSCLC cell lines by promoting the generation of reactive oxygen species (ROS) and subsequent cell death. Mechanistic studies showed that STF suppressed NSCLC cell growth by downregulating the Akt/S6K signaling pathway. Furthermore, administration of STF reduced tumor growth, weight, and expression of the proliferative marker Ki-67 in nude mice bearing A549 xenografts. Collectively, our data show that STF has antitumor activity against NSCLC, implying that dietary intake of C17:0-rich STF may be a potential adjuvant therapy for lung cancer (NSCLC).”
“…Edible oils extracted from plants and deep-sea fish are thought to be beneficial for human health because of their high content of UFAs (Wang et al., 2016). In contrast, common animal lipids are considered unhealthy due to their abundance of SFAs. Excessive intake of SFAs is considered to drive the occurrence and development of several health conditions, including obesity, hypertension, and cardiovascular diseases (Eckel et al., 2014; Kromhout et al., 2016; Binns et al., 2017). However, other studies have found that SFAs are not the underlying cause of these conditions (Malhotra, 2013; Chowdhury et al., 2014; Li et al., 2015; Dehghan et al., 2017; Malhotra et al., 2017; Veum et al., 2017). It was recently reported that SFAs also play important roles in various diseases. For instance, intake of SFAs can reduce the severity of pancreatitis in humans (Khatua et al., 2021). C16:0 decreases the metastatic capacity of hepatocellular carcinoma cells (Lin et al., 2017). These reports suggest that animal lipids rich in certain SFAs may enhance the efficacy of clinical therapies for various diseases. As a functional OCSFA, C17:0 intake has been inversely correlated with multiple diseases (Holman et al., 1989; Khaw et al., 2012; Meikle et al., 2013). Here, we found that, among the common dietary lipids, C17: 0 is abundant in STF. Interestingly, our results show that STF is unique in its ability to inhibit NSCLC cell proliferation compared to other common dietary lipids.”
“…Although C17:0 increases with animal age in sheep (Watkins and Frank, 2019), the concentration of C17:0 is still much lower in STF than that of other fatty acids, such as C18:0. To assess the role of high levels of C17:0, fatty acid mixtures with different ratios were generated. The results shown in Supplementary Figure S7 indicate that enrichment of C17:0 may result in a more significant antitumor effect of fatty acid mixtures. However, little is known about C17:0 enrichment in ruminant lipids. Therefore, optimization of C17:0 in lipids and its antitumor potential against lung cancer cells require further investigation.”
Interestingly enough, anemia, which is almost always present in cancer patients, is apparently preventable and preventable and treatable by PA (as per the studies above), at least in amimals. Most substances that improve one of these biomarkers usually exacerbate the other – i.e. aspirin is well-known to lower body stores of iron (i.e. ferritin, iron saturation index, etc), however it can readily cause anemia if it is taken in high doses for a few weeks or months, and the high doses are often needed for conditions such as diabetes, CVD, cancer, etc. Thus, the combination of PA and HA seems to have the, possibly unique, property of ameliorating anemia while also preventing/treating iron toxicity. Needless to say, given the effects of PA and HA describes so far, those fatty acids may be synergistic with aspirin and other pro-metabolic and anti-inflammatory chemicals like it.
On an somewhat related and very interesting note, a pair of studies demonstrated that PA and HA can be extracted from algal and fish oils. This suggests that the numerous studies on the benefits of fish/algal oil consumption may be legitimate findings but ascribing the benefits to the wrong constituents – i.e. omega-3 fatty acids instead of odd-chain SFA such as PA and HA.
https://pubmed.ncbi.nlm.nih.gov/13269382/
https://pubmed.ncbi.nlm.nih.gov/34332011/
In summary, given the extensive evidence of health benefits from consuming dairy fat, as well as the studies narrowing down the effects to specific SFA found in dairy – specifically PA and HA – we decided to release a product – named LipOdd, after the odd-chain lipids – containing both of those lipids in the ratio at which they are found in dairy fat. The suggested daily serving provides sufficient amounts of PA and HA to match the design of most studies mentioned above and below (references). Of course, with PA and HA being simply lipids with apparently non-toxic effects even in high doses (as per the publicly available toxicity data), one could take higher daily doses to determine if there is dose-dependent benefit increase. It is also possible that even lower daily doses than the suggested serving may be needed to observe benefits. Namely, the studies listed above and the reference section below almost invariably studied the effects of either PA or HA, but not a combination of both. The amounts provided by LipOdd in a single serving are based on those studies with the individual fats. At the same time, both PA and HA are present in dairy (in a ratio of roughly 2:1) and we have extensive evidence for the health benefits of consuming even low amounts of dairy fat daily, which suggests a synergistic effect of PA and HA and thus the possibility that lower doses than the suggested daily serving of LipOdd would do.
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LipOdd is a liquid (but very viscous) product containing the odd-chain SFA known as pentadecanoic acid (PA, C15:0) and heptadecanoic acid (HA, C17:0). Those odd-chain SFA are found primarily in dairy, but also in lipids of marine origin. The latter may explain the much-touted benefit of eating fatty fish, which has unfortunately been ascribed to omega-3, which are anything but beneficial. PA and HA have been the subject of an extensive list of studies in regards to obesity, diabetes, inflammation, fibrosis, cancer, depression, neurodegenerative conditions, anemia, ferrotoxicity , mitochondrial function, metabolism, aging and lifespan. It can be bought from the www.idealabsdc.com link.
Serving size: 20 drops
Servings per container: about 30
Each serving contains the following ingredients:
Pentadecanoic acid (C15:0): 100mg
Heptadecanoic acid (C17:0): 50mg
Other ingredients: add product to shopping cart to see info
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References:
1. Studies with both PA (C15:0) and HA (C17:0)
https://doi.org/10.1016/S2213-8587(14)70146-9
https://pubmed.ncbi.nlm.nih.gov/36699724
https://pubmed.ncbi.nlm.nih.gov/25647578/
https://pubmed.ncbi.nlm.nih.gov/29540275/
https://pubmed.ncbi.nlm.nih.gov/28465289/
https://pubmed.ncbi.nlm.nih.gov/21779090/
https://pubmed.ncbi.nlm.nih.gov/29244873/
https://pubmed.ncbi.nlm.nih.gov/28552966/
https://pubmed.ncbi.nlm.nih.gov/20484449/
https://pubmed.ncbi.nlm.nih.gov/34547017/
https://pubmed.ncbi.nlm.nih.gov/30887402/
https://pubmed.ncbi.nlm.nih.gov/18042359/
https://pubmed.ncbi.nlm.nih.gov/15035691/
https://pubmed.ncbi.nlm.nih.gov/33650014/
2. Studies with PA (C15:0)
https://pubmed.ncbi.nlm.nih.gov/14841191/
https://pubmed.ncbi.nlm.nih.gov/18469284/
https://doi.org/10.1111/acel.13645
https://doi.org/10.1021/np50103a002
https://doi.org/10.1016/j.bmcl.2022.128881
http://dx.doi.org/10.1111/j.1468-2494.1993.tb00592.x
https://www.koreamed.org/SearchBasic.php?RID=2014463
https://pubmed.ncbi.nlm.nih.gov/26840268
https://pubmed.ncbi.nlm.nih.gov/37386075/
https://pubmed.ncbi.nlm.nih.gov/36232636/
https://pubmed.ncbi.nlm.nih.gov/32503225/
https://pubmed.ncbi.nlm.nih.gov/30698031/
https://pubmed.ncbi.nlm.nih.gov/33965456/
https://pubmed.ncbi.nlm.nih.gov/33613155/
https://pubmed.ncbi.nlm.nih.gov/36699724/
https://pubmed.ncbi.nlm.nih.gov/34563667/
https://pubmed.ncbi.nlm.nih.gov/33399331/
https://pubmed.ncbi.nlm.nih.gov/227923/
https://pubmed.ncbi.nlm.nih.gov/25411288/
https://pubmed.ncbi.nlm.nih.gov/8730747/
https://pubmed.ncbi.nlm.nih.gov/9925119/
https://pubmed.ncbi.nlm.nih.gov/21796302/
https://pubmed.ncbi.nlm.nih.gov/23704475/
https://pubmed.ncbi.nlm.nih.gov/33631767/
https://pubmed.ncbi.nlm.nih.gov/36771436/
3. Studies with HA (C17:0)
https://pubmed.ncbi.nlm.nih.gov/31002344/
https://pubmed.ncbi.nlm.nih.gov/37466104/
https://pubmed.ncbi.nlm.nih.gov/30110135/
https://pubmed.ncbi.nlm.nih.gov/36716276/
https://pubmed.ncbi.nlm.nih.gov/30007304/
https://pubmed.ncbi.nlm.nih.gov/35616739/
