DeFibron - Liquid Supplement For R&D

Discussion in 'IdeaLabs' started by haidut, Jun 1, 2017.

  1. haidut

    haidut Member

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    Ever since I read in one of Ray's articles about the ability of saturated fat to reverse even advanced liver fibrosis (cirrhosis) I have been researching the effects of various saturated fatty acids on a number of organs and tissues. A number of studies have been posted on the forum indicating saturated fat can protect from endotoxin, diabetes, heart failure, dementia, cancer, osteoporosis, glucocorticoid excess, etc. While the beneficial effects of saturated fats are numerous and systemic, their benefit is somewhat hampered by the fact that they are quickly metabolized in the mitochondria into Acetyl-CoA and shuttles into the Krebs cycle to be converted into energy (ATP), CO2 and water. Thus, the opportunity to exert their beneficial effects is typically very short-lived. Even Ray mentioned that saturated fats are preferentially oxidized while PUFA is preferentially stored in the fat reserves. This preferential oxidation is probably why the studies showing benefit of saturated fats often use quite high doses (HED 50g+ daily), which for most people would be both inconvenient/impractical, expensive, and maybe even fattening. It would be nice if there was a way to get the benefit of saturated fats for a prolonged period of time without the need to gobble up the stuff like water.
    Fortunately, it looks like there is a solution to this issue. I already posted about the androgenic effects of methyl palmitate, which is now an ingredient in our supplement Gonadin. Well, methyl palmitate as well as other methyl esters of saturated fatty acids are resistant to metabolism and conversion into energy and thus have a much longer opportunity to exert their beneficial effects. In particular, methyl palmitate, methyl stearate and methyl myristate have been shown to have a number of desirable properties including potent anti-fibrotic, anti-inflammatory, anxiolytic, anti-depressant, anti-cancer and anti-pathogen effects. One of the most intriguing effect is the remarkable protection against endotoxin, which methyl palmitate confers to animals upon administration, which renders the animals virtually immune to the effects of endotoxin dose 10-times higher than the LD100. This antagonism of endotoxin undoubtedly plays a role in the anti-fibrotic effects of methyl palmitate in organs such as liver, heart and lungs, where fibrosis is known to be driven primarily by endotoxin and serotonin. Speaking of serotonin, palmitic acid and methyl palmitate have been shown to reduce serotonin formation in the brain and accelerate its degradation. Another very interesting effect is that methyl palmitate is possibly capable of depleting PUFA and inducing an EFA deficiency even in the presence of normal dietary PUFA intake.
    These methylated esters of saturated fatty acids exert their effects mentioned in the studies below at doses an order of magnitude lower than the ones studied for unesterified fatty acids. So, it seems likely that these esters may provide all the benefits of regular saturated fat at a fraction of the calories/amount and thus without the digestive upset that often accompanies intake of spoonfuls of coconut oil. Thus, we decided to release a product with those chemicals as ingredients and in light of the most pronounced property of these acids (anti-fibrotic) we are calling it DeFibron.

    The units listed on the label are just for measurement purposes. They do not indicate suggested or optimal dose. Please note that similar to the products sold by companies like BluePeptides, this product is for lab/research use only. The product can be ordered from the link below:
    www.idealabsdc.com/lab

    *******************************************************************************
    DeFibron is a mixture of the methylated (esterified) saturated fatty acids methyl palmitate, methyl stearate and methyl myristate. These fatty acids are similar in properties to their unesterified equivalents typically found in food sources like coconut oil, butter and dairy products. However, unlike the plain saturated fatty acids the esterified versions are resistant to metabolism and as such have much longer half life, which allows them to exert their effects in much lower concentrations. These esterified saturated fatty acids have been shown to possess a number of beneficial health effects including anti-fibrotic, anti-inflammatory, anti-glucocorticoid, anti-osteoporosis, anti-depressive, anti-estrogenic, anti-diabetic, anti-mutagenic, antimicrobial, anti-cancer, anxiolytic, antidepressant, and generally anti-aging.


    Units per container: about 30
    Unit size: 40 drops
    Each unit contains the following ingredients:

    Methyl palmitate: 800mg
    Methyl stearate: 200mg
    Methyl myristate: 200mg


    Other ingredients: tocopherols, MCT
    *******************************************************************************

    References:


    Metabolism/Biochemistry
    Nonpolar lipid methylation. Biosynthesis of fatty acid methyl esters by rat lung membranes using S-adenosylmethionine. - PubMed - NCBI
    Pharmacokinetics and metabolism of the methyl-branched fatty acid (BMIPP) in animals and humans. - PubMed - NCBI (MP)
    Differential oxidation of individual dietary fatty acids in humans. - PubMed - NCBI (MP)
    Metabolism of topically applied fatty acid methyl esters in BALB/C mouse epidermis. - PubMed - NCBI (MP)
    Palmitate and insulin synergistically induce IL-6 expression in human monocytes. - PubMed - NCBI (MP)
    "...Two non-metabolizable analogs of palmitic acid, methyl palmitate and 2-bromopalmitic acid (Figure 2A), were utilized to determine whether intracellular metabolism of palmitate was required for the induction of IL-6 and TNF-α in monocytes. The esterification of palmitate by a methyl group in methyl palmitate prevents activation of this molecule by CoA, and abrogates downstream metabolism of the fatty acid, whereas 2-bromopalmitate can be activated by CoA, but cannot be further metabolized by β-oxidation or esterification with glycerol to form glycerolipids [23]."


    1. Anti-fibrotic and anti-inflammatory
    Methyl palmitate 1431603 (MP)
    "...Methyl palmitate has anti-inflammatory and anti-fibrotic effect. Methyl palmitate prevents bleomycin-induced lung inflammation and fibrosis in rats, by inhibiting NF-κB . Methyl palmitate also prevents CCl4-induced liver fibrosis linked to reduced TGF-β."

    Anti-inflammatory and antifibrotic effects of methyl palmitate. - PubMed - NCBI (MP)
    Insights antifibrotic mechanism of methyl palmitate: impact on nuclear factor kappa B and proinflammatory cytokines. - PubMed - NCBI (MP)
    Modulation of cyclophosphamide-induced cardiotoxicity by methyl palmitate. - PubMed - NCBI (MP)
    Cytoprotective potential of tiron and methyl palmitate against acetaminophen-induced acute liver injury. - PubMed - NCBI (MP)
    The effect of methyl palmitate on treatment of experimental asthma. - PubMed - NCBI (MP)
    Methyl palmitate attenuates lipopolysaccharide-induced acute lung injury in mice. - PubMed - NCBI (MP)
    Protective effects of methyl palmitate against silica-induced pulmonary fibrosis in rats. - PubMed - NCBI (MP)
    Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models. - PubMed - NCBI (MP)
    Methyl palmitate prevents CCl(4)-induced liver fibrosis. - PubMed - NCBI (MP)
    Methyl palmitate inhibits lipopolysaccharide-stimulated phagocytic activity of rat peritoneal macrophages. - PubMed - NCBI (MP)
    Effects of methyl palmitate on cytokine release, liver injury and survival in mice with sepsis. - PubMed - NCBI (MP)
    Methyl palmitate prevents Kupffer cell activation and improves survival after orthotopic liver transplantation in the rat. - PubMed - NCBI (MP)
    Modulation of experimental allergic encephalomyelitis with yeast glucan and methyl palmitate to alter the activity of the reticuloendothelial system. - PubMed - NCBI (MP)
    Evaluation of anti-inflammatory activity and standardisation of hydro-methanol extract of underground tuber of Dioscorea alata. - PubMed - NCBI (MS)


    Endotoxin protection
    Modification of galactosamine-induced liver injury in rats by reticuloendothelial system stimulation or depression. - PubMed - NCBI (MP)
    Influence of endotoxin administration on hepatic function of rats with altered endotoxin sensitivity. - PubMed - NCBI (MP)
    "...Glucan-treated, endotoxin-sensitive rats admin methyl palmitate, a reticuloendothelial depressant which renders rats endotoxin resistant, followed by salmonella enteritidis endotoxin, resulted in enhanced elevation of plasma glutamic oxalacetic transaminase & hypoglycemia."

    Relationship of reticuloendothelial functional activity to endotoxin lethality. - PubMed - NCBI (MP)
    "...The administration of methyl palmitate 100 mg/100 g, iv to rats caused an increase in survival at endotoxin doses of 0.75 to 3.0 mg/100 g. although a mean 38% mortality was caused by salmonella enteritidis entoxin 0.5 mg/100 g, iv in normal rats , a 6-fold increase of this dose did not cause mortality in the methyl palmitate group. Methyl palmitate, when admin to glucan-treated rats, caused normal phagocytic activity in the presence of reticuloendothelial system hypertrophy."


    CVD, hypertension, ischemia
    Role of perivascular adipose tissue-derived methyl palmitate in vascular tone regulation and pathogenesis of hypertension. - PubMed - NCBI (MP)
    Methyl palmitate: a potent vasodilator released in the retina. - PubMed - NCBI (MP)
    Endogenous methyl palmitate modulates nicotinic receptor-mediated transmission in the superior cervical ganglion. - PubMed - NCBI (MP)
    The role of fatty acids in the regulation of cerebral vascular function and neuroprotection in ischemia. - PubMed - NCBI (MP, MS)
    Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and global cerebral ischemia. - PubMed - NCBI (MP, MS)
    https://www.ocl-journal.org/articles/ocl/pdf/2016/01/ocl150040-s.pdf (MP, MS)
    "...Lin et al., 2008, 2014 reported that PAME but not SAME is a vasoactive substance causing vasodilation while SAME is not a vasoactive substance but can provide neuroprotection against ischemia along with PAME in both animal models of global and focal ischemia. It is interesting to note that the synthesis of PA/SA is well-known but the methyl esterification of PA/SA to form PAME/SAME is not prevalent in nature and therefore, not well-understood (Lin and Perez-Pinzon, 2013)."

    "...Only recently has PAME and SAME been presented as a novel component in neuroprotection during cerebral ischemia (Lin and Perez-Pinzon, 2013; Lin et al., 2014). PAME and SAME are simultaneously released from the sympathetic nervous system (Lin et al., 2008). More specifically, PAME has been shown to induce aortic vasodilation and neuroprotection, while SAME causes neuroprotection in cardiac arrest and middle cerebral artery occlusion (MCAO) models of ischemia. More specifically, PAME/SAME was first discovered to be released from the superior cervical ganglion (SCG) upon electrical/chemical depolarization. Endogenous application of PAME induced aortic vasodilation and was found to be 3000 times more potent than other known nitric oxide (NO) donors (Lin et al., 2008). With proper timing and dosage, administration of PAME and SAME can be a successful therapy against cerebral ischemia."
    "...Furthermore, exogenous application of palmitic acid (PA) failed to induce aortic vasodilation (Blondeau et al., 2007; Lin et al., 2008) indicating that the methylation of PA is essential for vasodilation and PAME’s bioactivity."

    Diabetes, metabolism
    Identification of fatty acid methyl ester as naturally occurring transcriptional regulators of the members of the peroxisome proliferator-activated... - PubMed - NCBI (MP)
    Assessment of anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan induced diabetes in mice. - PubMed - NCBI (MS)


    Abtimicrobial, antiparasitic
    Methyl palmitate, an acaricidal compound occurring in green walnut husks. - PubMed - NCBI (MP)
    Identification of ant repellent allomone produced by social waspPolistes fuscatus (Hymenoptera: Vespidae). - PubMed - NCBI (MP)
    In vitro study of biological activity of four strains of Burkholderia gladioli pv. agaricicola and identification of their bioactive metabolites us... - PubMed - NCBI (MS)
    Isolation and characterization of chemical constituents of Stoechospermum marginatum (Dictyotales, Phaeophyta) and their antimicrobial activity. - PubMed - NCBI (MM)


    PUFA depletion
    Effect of methyl 2-hexadecynoate on hepatic fatty acid metabolism. - PubMed - NCBI (MP)


    Anti-cancer
    Saturated fatty acid-induced apoptosis in MDA-MB-231 breast cancer cells. A role for cardiolipin. - PubMed - NCBI (MP)
    Functional lipidomics: palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism (MP)
    Palmitic acid is the major fatty acid responsible for significant anti-N-methyl-N'-nitro-N-nitroguanidine (MNNG) activity in yogurt. - PubMed - NCBI (MP)
    Anticancer Activity of Branched-chain Derivatives of Oleic Acid (MO)
    Cytotoxic effect of Alpinia scabra (Blume) Náves extracts on human breast and ovarian cancer cells. - PubMed - NCBI
    "...This may be due to the presence of methyl palmitate and methyl stearate in the extract. Furthermore, this finding on cytotoxicity of methyl esters is supported by Takeara et al. [19] which reported that methyl palmitate showed cytotoxic effect on T-cell leukemia cell line (Molt-4) with IC50 value of 2.28 μg/ml while methyl stearate was cytotoxic to acute promyeloblastic leukemia cell line (HL-60) and Molt-4 cell line with IC50 values of 3.08 and 4.65 μg/ml, respectively."
    Antileukemic effects of Didemnum psammatodes (Tunicata: Ascidiacea) constituents. - PubMed - NCBI
    "...Amongst the different fractions and compounds isolated from D. psammatodes outgone the initial screening on the 4 lines of leukemia cells, the methyl esters mixture showed the strongest antiproliferative activity...The methyl myristate (1) is the minor compound of the activity fraction with 14% of the total relative area. The major compounds are methyl palmitate (2) and methyl stearate (3) with 49% and 36% respectively. As seen in Table 1, this mixture has the lowest IC50 in every cell line tested after 72h incubation (IC50 values ranged from 2.43mcg/mL on Molt-4 cels to 9.96 mcg/mL on K-562 cells)."


    Inhbition of fatty acid synthase (FAS)
    Inhibition of fatty acid synthesis in bovine mammary homogenate by palmitic acid is not a detergent effect. - PubMed - NCBI (MP)


    Anti-serotonin / pro-dopamine, anxiolytic
    Myristic acid produces anxiolytic-like effects in Wistar rats in the elevated plus maze. - PubMed - NCBI (MP)
    Serotonin- and Dopamine-Related Gene Expression in db/db Mice Islets and in MIN6 β-Cells Treated with Palmitate and Oleate. - PubMed - NCBI (MP)
    "...We confirmed that Maob expression was lower in islets from db/db versus wild-type mice and decreased in MIN6 β-cells exposed to palmitate and oleate compared to control, accompanied by decreased 5HT content and impaired GSIS. Our results suggest that impaired GSIS in β-cells in response to palmitate and oleate might be partly explained by decreased Maob expression, which in turn would lead to increased dopamine content, release, and signaling through specific receptors."
    The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice. - PubMed - NCBI (MP)
    "...Table 1 shows that 24 hrs after palmitic acid administration mice had a 33% increase in 5-HIAA in the amygdala. Table 2 demonstrates that 24 hrs after palmitic acid administration there was a 25% decrease in the 5-HT:5-HIAA ratio in the amygdala and a 42% increase in the DA:DOPC ratio in the hippocampus."
     
  2. Constatine

    Constatine Member

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    Yay! Considering your dosage for gonadin and the androgenic effects people got from it, this might prove to be very very androgenic.
     
  3. Such_Saturation

    Such_Saturation Member

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    Will these retain the uncoupling effects of the parent fatty acids?
     
  4. OP
    haidut

    haidut Member

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    That's my hope as well, but the methyl oleate in Gonadin is also important for the effects of that supplement. The study in the Gonadin thread showed that methyl palmitate on its own only had androgenic effects but did not raise T levels. Only the combination of MP and MO both raised T levels and had androgenic effects on prostate and seminal vesicles. But I'll settle for the androgenic, anti-serototin, pro-dopamine and anti-endotoxin effects :)
     
  5. Constatine

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    Ordered. Will keep you all updated with effects.
     
  6. OP
    haidut

    haidut Member

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    Yes, the only difference between the methylated versions and the plain ones seems to be that 1) the methylated esters have much longer half life due to resistance to metabolism and 2) the presence of a methyl group at position 16 allows it to bind the androgen receptor as an agonist. Other than that they seem to share all other properties of the SFA including activating the UCP family.
     
  7. aarfai

    aarfai Member

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    Quick question, are you still having good results Gonadin?
     
  8. Constatine

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    Yes, I'm most excited about the anti-endotoxin effects as endotoxin is such a huge problem for many on this forum including myself.
     
  9. Constatine

    Constatine Member

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    Yes I am still getting good results with Gonadin. The only thing I notice is larger muscles but that's probably because my mood and general healthy is already good. I have the old version without methylated saturated fatty acids.
     
  10. Regina

    Regina Member

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    Woot! Oh my God, we might really live to 900. :dance
     
  11. bradley

    bradley Member

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    Fascintating! Hypothetically speaking, do you think this would be more effective topically or orally?
     
  12. TubZy

    TubZy Member

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    Cool, seems very interesting. Looks like a gonadin and diamant had a baby and this is it. Is this any way similar to monolaurin (like in coconut oil) and how it acts like a strong anti pathogen?
     
  13. Regina

    Regina Member

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    Gonadin and Diamant are good parents. I think they are such a great combo.
     
  14. OP
    haidut

    haidut Member

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    All the studies were with oral use, but as I posted a few day ago topically administered SFA reach systemic circulation and affect fatty acid balance in blood. So, topical use should also work especially given the presence of tocopherol which enhances the absorption.
     
  15. OP
    haidut

    haidut Member

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    Yes, I think all SFA are anti-pathogen and the monolaurin is also resistant so metabolism and that is what it has more noticeable anti-bacterial effects. Applying coconut oil or ghee to wounds is a powerful antiseptic so we know other SFA have these properties too.
     
  16. Pointless

    Pointless Member

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    Are these compounds methyl donors? Could there be any risk with that at these doses?
     
  17. Tarmander

    Tarmander Member

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    Sweet supplement. Endotoxin blocking seems really interesting. I have a pretty good line on what endotoxins feel like. Theoretically, I could take this, and then I would not get a usual Endotoxin result? Have you tried an experiment like this Haidut? Meaning, eating something you know will raise Endotoxin while on this...
     
  18. Wagner83

    Wagner83 Member

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    Is the fact they are not metabolized not a bad sign?
    From what you say and what I see in the studies it could help with liver injuries and endotoxin related issues but not sure what effects it could have topically on scar tissue (e.g. peyronie's disease, so scar tissue below the skin).
     
  19. OP
    haidut

    haidut Member

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    I think, similar to caffeine, even though they contain methyl groups that does not make them methyl donors. None of the studies on the metabolism of these fatty acids showed increase in methylation but if somebody finds evidence please post here.
     
  20. OP
    haidut

    haidut Member

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    They make me very calm and stress-resistant. Also seem to calm my irritated gut when I eat very spicy food but I don't think this has much to do with endotoxin. I think it would be an interesting experiment if there is a known food/event that triggers endotoxin. Running is one such activity that will significantly raise it.
     
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