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DeFibron - Liquid Methylated SFA For Lab/R&D

  1. 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. Yay! Considering your dosage for gonadin and the androgenic effects people got from it, this might prove to be very very androgenic.
     
  3. Will these retain the uncoupling effects of the parent fatty acids?
     
  4. 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. Ordered. Will keep you all updated with effects.
     
  6. 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. Quick question, are you still having good results Gonadin?
     
  8. 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. 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. Woot! Oh my God, we might really live to 900. :dance
     
  11. Fascintating! Hypothetically speaking, do you think this would be more effective topically or orally?
     
  12. 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. Gonadin and Diamant are good parents. I think they are such a great combo.
     
  14. 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. 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. Are these compounds methyl donors? Could there be any risk with that at these doses?
     
  17. 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. 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. 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. 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.
     
  21. True, have not see much evidence on scar tissue. As far as metabolism - they are still metabolized, just much more slowly. That's why I said "resistant" to metabolism. The studies that looked at them did not find any issues, but feel free to post here anything you may find in that regard.
     
  22. I've seen here and elsewhere that saturated fats can contribute to some endoplasmic reticulum stress. Wonder if the benefit of the MP/MO combination is through a reduction in ER stress with the oleate.

    Oleate protects beta-cells from the toxic effect of palmitate by activating pro-survival pathways of the ER stress response. - PubMed - NCBI

    "Long-term exposure of beta cells to saturated fatty acids impairs insulin secretion and increases apoptosis. In contrast, unsaturated fatty acids protect beta-cells from the long-term negative effects of saturated fatty acids. We aimed to identify the mechanisms underlying this protective action of unsaturated fatty acids. To address the aim, insulin-secreting MIN6 cells were exposed to palmitate in the absence or presence of oleate and analyzed by using nano-LC MS/MS based proteomic approach. Important findings were validated by using alternative approaches. Proteomic analysis identified 34 proteins differentially expressed in the presence of palmitate compared to control samples. These proteins play a role in insulin processing, mitochondrial function, metabolism of biomolecules, calcium homeostasis, exocytosis, receptor signaling, ER protein folding, antioxidant activity and anti-apoptotic function. When oleate was also present during culture, expression of 15 proteins was different from the expression in the presence of palmitate alone. Most of the proteins affected by oleate are targets of the ER stress response and play a pro-survival role in beta cells such as protein folding and antioxidative defence. We conclude that restoration of pro-survival pathways of the ER stress response is a major mechanism underlying the protective effect of unsaturated fatty acids in beta-cells treated with saturated fatty acids."
     
  23. @haidut When the body is unable to maintain glycogen storage for longer periods, what is the mechanism that prevents this? Considering the liver, is it fibrosis and fat levels that block storage? DeFibron seems like some that could help with storage.
     
  24. That's deceiving since it's not necessarily fatty liver that's the issue but liver steaosis, fibrosis and cirrhosis that really create health problems. Right before pathological states the fat starts to dissipate but the individual is in a worse state healthwise. Specifically pointing out fatty liver is not the same as saying here's a severe pathological state. It's the unsaturated fats that deplete apoproteins as well as create peroxide that harm the liver. There's a reason those specific Indians regions Peat mentioned hardly experience these pathologied because of the protective saturated fatty acids of coconut oil. That's what could make this new haidut supplement such a hit.
     
  25. I haven't been keeping up with all the IdeaLabs research chemicals and am trying to catch up now. Comments like this make it seem like some newer products might supersede old ones. @haidut is this the case?
     
  26. A fattened liver does not store glycogen well due to the overload with fat and a fibrotic liver is filled with dead tissue which cannot store anything (glucose or fat). Low metabolism and low ATP levels are usually behind inability to store glycogen, and fat deposits in the liver contribute to that process as well. Saturated fat intake has been shown to help with liver fibrosis and recovery of glycogen storage abilities. The interaction of PUFA with iron as well as PUFA metabolism down the inflammatory pathways is the main driver of fibrosis (and ultimately cancer). The mechanism of protection of saturated fat is mainly prevention of PUFA oxidation and reaction with iron, and some SFA also directly inhibit COX and LOX enzymes, so SFA lowers inflammation as well.
     
  27. I think there are parallels between Diamant and DeFibron, as well as Gonadin but I would not consider one of them superseding the other(s). The adamantane in Diamant is akin to an extremely stable form of saturated fat that cannot be metabolized much and when present in the cell it protects from some of the negative effects of PUFA. It makes the cell more lipophillic, with all of the associated benefits. Adamantane is basically a fully saturated cage of carbon and hydrogen. Saturated fats are a fully saturated chain of carbon and hydrogen, with some extra elements like COOH groups and since our body has enzymes designed to metabolize them they get converted to energy and some byproducts. So, adamantane and saturated fats have similarly stabilizing effects on the cell but adamantane is likely much longer-acting as we have seen in practice. But adamantane has other properties of its own, including increaseing dopamine synthesis, and inhibting reuptake much more potently than saturated fats would. But saturated fats also have some of these. The general principle is the same - delivering saturated carbon/hydrogen compounds is likely to be beneficial but due to their different molecular structure, the focus of benefits may vary. In the case of saturated fats it seems liver, lungs, skin and gonads are the primary targets, while in the cases of adamantanes the brain seems like a preferential target.
    Gonadin has steroidal precursors like squalene and phytol, which neither Diamant nor DeFibron have so the effects on steroid metabolism of Gonadin is likely not shared by neither Diamant nor DeFeibron.
    But good thinking on the parallels. I think is underscores the consistency of everything Peat has been writing about and why I have so many ideas to follow up on for every supplement we release :):
     
  28. Methyl palmitate P5177

    Description
    Packaging
    1, 5, 25 g in glass bottle

    Biochem/physiol Actions
    Methyl palmitate has anti-inflammatory and anti-fibrotic effect. Methyl palmitate prevents bleomycin-induced lung inflammation and fibrosis in rats, by inhibiting NF-κB [2]. Methyl palmitate also prevents CCl4-induced liver fibrosis linked to reduced TGF-β [3].
     
  29. I think that study is in the References section already. Anyways, the study is framed neutrally but the same group of scientists did another study with MP as a vasorelaxant for large blood vessels like aortas and another study showed MP to be protective in ischemic strokes and other ischemic events. It seems to oppose the vasocontriction effects of adrenaline and (very importantly) the mechanism of action is NOT dependent on the release of NO. So, it seems to be a safer vasodilator and may result in lowering of blood pressure, which is also an effect seen with consuming larger amounts coconut oil or isolated palmitic acid.
    Endogenous methyl palmitate modulates nicotinic receptor-mediated transmission in the superior cervical ganglion. - PubMed - NCBI

    Neuroprotection in ischemic stroke:
    The role of fatty acids in the regulation of cerebral vascular function and neuroprotection in ischemia. - PubMed - NCBI
    https://www.ocl-journal.org/articles/ocl/pdf/2016/01/ocl150040-s.pdf
    "...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."
     
  30. As I've been low PufA for over 3 years, I still need 150 grams of total fat to get through the day and sleep well. Would this product have any effect on lowering appetite and improving blood sugar?
     
  31. It did for me, as far as appetite is concerned. Seems to make me more energetic for some reason. Haven't measured blood sugar but mine is not high to start with.
     
  32. Have any other substances compared in lowering appetite?

    For example, at night I generally need a ton of ice cream to get through the night which I know a lot of my fat retention is coming from. Id like to find something that would lower my appetite but keep metabolism high.
     
  33. What other effects did your rats notice during experimentation?
     
  34. :clapping::clapping:
     
  35. More energy, better mood, and fuller/harder muscles combined with increased strength. Much better digestion and resistance to spicy foods, which normally cause IBS-like symptoms depending on how spicy the food is.
     
  36. @haidut. . Is there Any reason why we can't combine a bottle of Gonadin and a bottle of Defibron to get the best of both worlds in One supplement.. for experimental use on rats
     
  37. @haidut What is the iu amount of the tocopherols with a full unit size dose?
     
  38. Sure, I don't see an issue with combining them. But the doses will get mixed up as they are very different in bottle and dropper size.
     
  39. About 100 IU per 40 drops, maybe even less. I tried to keep the tocopherol dose as low as possible as per requests from the MitoLipin thread.
     
  40. When I've tried tocopherol products in the past, I've had poor reactions to Unique E, mitolipin, and tocovit; all reactions were th exact same. However, Progest e has never given me poor reactions only good ones. Is the make up of this product possibly different?
     
  41. Haidut, is DeFibron suitable for women, or are there some caveats? I like the idea of a hepatoprotective product.

    Thanks.
     
  42. I think this is unlikely to be an issue. The body produces palmitate naturally, even if you don't consume it/its precursors. It also is not a claim of the article that palmitate is the only fatty acid that can be used this way. Also, the quantity of palmitate needed for signaling enzymes is miniscule. So it seems likely this process could happen even in the absence of palmitate and that avoidance of palmitate would be entirely insufficient for inhibiting it.
     
  43. I think it may be a dose issue, so the lower dose in DeFibron should be less problematic.
     
  44. I think the research on Palmitic acid and cancer is biased and possibly flawed. The fact that cancer cells take palmitate in can be adaptive and an attempt to restore normal functioning. Other studies show that palmitate inhbits other cancer, like liver cancer for example.
    Functional lipidomics: palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. - PubMed - NCBI
     
  45. My rat is currently taking niacinamide and aspirin. If he took Defribron, could he continue taking the previously mentioned supplements?
     
  46. As I mentioned in my other post I think the studies trying to show palmitic acid in a bad light are driven by the same idea of "saturated fat = bad for health" dogma we have been seeing for decades. Other studies show cancer-inhibiting effect by palmitate and specifically inhibition of the enzyme fatty acid synthase (FAS), which is one of the most promosing target for cancer and Peat has spoken about it too. Palmitic acid also activates PDH and inhibits PDK, which is how the drug DCA works.
    Functional lipidomics: palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. - PubMed - NCBI
     
  47. I don't think there is any contraindication for women. I have not seen reports of women turning into men even when taking much more potent androgens like androsterone and in doses of 150mg+ daily. DeFibron is basically a long-acting lower-calorie analog of saturated fats like coconut oil, and it should be able to do what coconut oil does without the extra calories from ingesting 50g - 60g coconut oil (to achieve the same effects as DeFibron).
     
  48. I don't see why not. The vitamin E amount is pretty low so it should not increase bleeding risk more than the aspirin on its own would.
     
  49. So my DeFibron arrived today. Ordered on Friday and arrived on Monday so that's good. It comes in a MitoLipin-sized bottle but is more liquidy. It actually kind of looks like apple juice. It has a very mild smell, can barely notice it.

    I applied 21 drops to the torso, and for a few seconds there was a pleasant rush or tingle on the skin around the torso. It has a definite nootropic effect like methylene blue or inhaled CO2 but stronger.

    Subject is currently taking Cyproheptadine, thyroid, fat solubles, B1, B3, 1T salt, topical magnesium chloride.

    Just an initial test, just thought I'd check in! I'm excited to try this because I react poorly to steroids and many other substances, and my stools are quite pale, so I suspect that my liver is heavily compromised. So far, none of the suggestions have worked even high dose caffeine. Maybe this has promise for someone with a condition like mine, but further testing will make that clear.
     
  50. Nootropic effect stronger than MB? Can't wait till mine comes in.
     
  51. It's the kind of thing that could be placebo but hopefully your experiments will confirm.
     
  52. I'm hoping. A nootropic effect does seem to be well in the realm of possibilities for such a supplement. I'll try to avoid confirmation bias though.
     
  53. Excellent, thanks for sharing! Just keep an eye out for lower blood pressure as the studies showed MP is a powerful vasodilator, even at very low doses.
     
  54. This is a challenge, especially for those of us late to the party. And every one of these things is like, "Whoa, I don't even want to think about trying to keep myself on the sunny side of the grass without that!"

    Maybe the solution for the lazy and biochemically inept (which would include at least me and every member of the AMA) is to just order one of everything and take one drop of each daily. I'll have to consider that further. In the meantime, my order's in.

    (Hmmm, that might make an interesting study. "One hundred SAD-addled mortals were randomized into either Group A, take a drop of each, or Group B, follow doctor's orders." Anyone know how to write a grant proposal?)
     
  55. These days a grant proposal should resemble a prayer of worship in style and prose.

    I would recommend your plan on said supplements,low dose and a notebook.
     
  56. Sadly, in the absence of a highly desirable and potentially accessible female, which in my current state of decrepitude is as mythical as a unicorn (which is why a merciful God made dreams), a worshipful style is not in my repertoire.

    But of course my modest proposal – just take a drop of everything – is absurd anyway. And yet it is a measure of both my respect for Haidut and my contempt for the medical profession that I actually do believe:

    Drop of each > Do nothing > Follow doc’s orders :)
     
  57. Ordered 2 days ago, arrived today, and it's in a fancy new bottle :) Experiment to commence in 3... 2... 1...
     
  58. Wow, topical application of DeFibron is sweet! Didn’t turn brown, orange, yellow, OR blue, and it’s neither sticky nor greasy. In fact it makes my skin feel soft and smooth. Seriously, it might become first choice for a cold weather hand cream. Now to wait for results.
     
  59. Great, thanks! Please keep us posted.
     
  60. Arrived today in The Netherlands (ordered june 2th), , I was wondering, how can it be so liquid if it is saturated?
     
  61. For a long time I thought that saturated fats are always solid at room temperature, and if a fat is liquid at room temperature then it has to be mono or poly unsaturated. But, turns out, that is not the case. For example, MCT oils from coconut (Caprylic, Capric, and Lauric acids) are fully saturated, but liquid and clear at room temperature.
     
  62. Although it is calming it also has a stimulatory effect. Took it before bed and was wired all night.
     
  63. Defibron+Gonadin+Diamant+30mgPregnenolone=Nirvana.
    I think I had 360 degree peripheral vision on my walk today. I think I was also about 10 feet tall with amazing posture.
    I'm okay with this delusion. :ss2
     
  64. Wow, this is impressive speed of shipping! I hope all of the packages take so little time to arrive internationally.
    Anyways, myristic acid and some other saturated acids like @skominac said are liquid at room temp.
     
  65. I think the wired feeling is due to the dopaminergic effects of methyl palmitate. That's why I prefer to take DeFibron in the morning.
     
  66. I just got mine today, and stupidly added to a cold glass of milk, and it promptly solidified on top.
     
  67. Wow, nice! How much had you taken of the first three? Full doses?
     
  68. 20 drops Defibron+5 drops gonadin+6 drops diamant with a 30mg pregnenolone capsule. This was all oral.
    I also had some strong coffee and fresh squeezed OJ and a couple of cheese sticks. About 20 minutes later, I walked the dog along the lake.
    My body felt empty of discomfort or worry; but the expansive vision is really beautiful. :thumbsup:
     
  69. Lol, at least you know it contains saturated fatty acids as it claims :): Wish there was a way to verify all other products so easily...
     
  70. First evening, I didnt notice stimulating effect that kept me awake. I slept very deep. Not sure if it had to do with defibron. Felt very calm.

    First office day. More organised than normal. More big picture. Very little stress. Very calm and happy. No superpowers, didnt do anything last two hours of the day, except playing with stuff I liked myself. Maybe felt more playful and rebellious?

    Not any reactions to food. No reaction to commercial bread and commercial filet american. I dont always react, but it is remarkable still.
     
  71. Great, thanks for sharing.
    Btw, if anybody does any blood tests related to inflammation (ESR, CRP, TNFa, NK-kB, LDH, WBC) before/after please share in this thread.
     
  72. First dose was yesterday morning, 10 drops transdermal, underneath side of forearms. Had smooth energy and moderate antidepressant effect <I still deal with dysthymia> throughout the whole day. Took me a long time to eventually fall asleep last night, which is not uncommen for me taking anything dopaminergic.

    I like the effect of it and should compliment Gonadin well, which I did not take yesterday, so I could gauge the effect of DeFibron on it's own. I'll have to see if the disruption of sleep continues, and if so, will have to lower dose further.
     
  73. I added 10 drops DeFibron to my usual 5 drops Gonadin and 6 drops Diamant this morning. After eating breakfast, I was walking back to my desk from the cafeteria and noticed both the expanded vision and the amazing posture you mentioned. Gonadin has always made my abdominal girdle more activated, but this was even different from that. My posture's never been so good (and with so little effort).
     
  74. :feelsgoodman
     
  75. About the expanded vision thing, yes I feel like defibron opens up my eyes, huge time. Similar what I had with diamant. But more intense.

    I think someone said it lowers appetite? I feel like I have to eat more. Much more carbs. I actually eat more starch now, beause I don't seem to have any bad reaction with it if I take defibron, and it is easy cheap and less liquid. I already drank 3L of OJ, 1000 ml skyr yoghurt (100 gram protein, 60 gram carb). 2 portion of icecream. Gulping another liter of orange juice seems to much.

    If I don't eat enough, stuff seems to intense for me. I feel over alert, like if I can see and feel anything. What the guy on the left is eating, what the girl on the right is worrying about. This is a new experience for me. Normally my worries are more inwards, it seem to be now more outwards. If there was an terror attack on the train today, I'm sure I would be the first to react.
     
  76. Just received my bottle and going it a go :). Took 5 drops orally and ten drops topically. Anything that is dopaminergic has my heart so looking forward to it!
     
  77. That's it, I have to spend more money.
     
  78. Would this have potential benefit for pulmonary fibrosis. I'm assuming if so it would be a downstream affect from it working against endotoxin and thus creating less serotonin in the body rather than a direct method of action. Is there any evidence that these substances directly lower serotonin?
     
  79. Haha the 360 vision makes me think my basketball prowess is about to go through the roof!!
     
  80. :emoji_basketball: Woot!
     
  81. I'm wondering if it would be worth a try putting this on the hairline (for regrowing hair on the hairline). Wasn't MPB associated with fibrose?
     
  82. Hate to say it, but my hair is longer, thicker and more attractive to my girlfriend since eating a ***t tonne more fat. Especially fat from chocolate. My hair was like a dead womans on a very low fat, high carb diet. It literally did not grow for five months. Scary ***t.
     
  83. Why do you hate to say it, lots of people report that going very low fat was detrimental to their health, the treshold of feeling good seems to vary between individuals.

    As for fibrosis, as discussed in the earlier posts, the mechanisms against fibrosis do not suggest that the product would be effective against fibrosis in such cases .DeFibron - Liquid Supplement For R&D
    Of course the systemic effects could be beneficial anyway.
     
  84. Update on my test! Usually I do not finish complete tests of supplements because some kind of side effect deters me, but this compound has been extremely interesting. I've been keeping notes on it.

    The night of 6/5, after my 21 drop dose, I started to see symptoms of inflammation. I notice all these: bloated, painful joints in the knees (might be the vit. E as I'm very sensitive to AIs of all kinds), aching all over, green phlegm, sour stomach, loss of appetite, nausea, loose stools. These were very minor.

    6/6 I noticed a strength increase working out. There was a 10% gain in push-ups done before failure with an increase in explosive force. It was not comparable to PanSterone or caffeine, but noticeable. Performance on the balance beam was especially noticeable, in terms of quickness and stability. This increase in balance is something I've seen with PanSterone. Similarities to adamantane were noticed: clear singing voice, a little emotional, pleasurable rushing sensation on the skin. 10 more drops were administered that night, and there was some twitching of the eyebrow. It was constant for the next 24 hours but eventually stopped.

    6/7 The eyelids seem like they might be drooping less, but that could be the vit. E or I might be imagining things.

    6/8 I started to see much more noticeable increase in libido and arousal. I look for signs of suppression as I have seen most dopaminergics or AIs like Lisuride, PanQuinone, vit. E, etc. These can cause a rebound impotence or erectile dysfunction. I haven't seen anything like that yet with DeFibron. Inflammatory symptoms have abated as I expected might happen. No more loose stools or runny nose, a little bloating but a little drier at other times. That night I administered 21 drops again (up from 10 before)

    6/9 I started administering in the morning to get the proper circadian effect and started with 10 this morning (on top of 21 last night). Noticed a relaxation consistent with lowered cortisol like from magnesium, holy basil, Lapodin, sodium thiosulfate, etc. Too much can be fatiguing. Edit: I wanna make clear that the inflammatory symptoms returned after this larger dose but not as bad as before, then abated again by the 10th.

    My conclusion is that this is dopaminergic and has many similar properties to adamantane, maybe due to its effects on water. Sorry for the long post, but I thought other experimenters might want a more in-depth look at some of the effects.

    Very interesting compound. I'm especially curious of the inflammation symptoms as they seem like they could be caused by endotoxin, yet I'm hoping this will solve a lot of problems with endotoxin. Do you have any thoughts or studies on how this might affect the immune system? This study says it should be anti-inflammatory but I'm wondering why I saw these effects flare up when I started or increased my dose?
     
  85. I started applying a small amount to the scalp topically yesterday. I will report back if I see any changes.
     
  86. My findings are consistent with yours, including the initial loose stools.
     
  87. @Pointless since you want to target the liver why not try to use it orally? (not sure you did from what you report, thanks for the detailed report btw)
     
  88. Applied topically to the torso in every dose. Vitamin E causes digestive issues so oral is unlikely to be a good choice.
     
  89. Would defibron have similar effects to saturating cardiolipin as mitolipin does?
     
  90. Because high consumption of sugar is not turning into cholesterol for me, or making my hair amazing. Fat on the other hand, seems to do the trick, in quantities much greater than the 65g of sat fat that Ray eats reportedly.
     
  91. He said a few times that 33/33/33 could be close to the ideal macro nutrient ratio, not sure if he still thinks it is.
     
  92. I think that the suggestion makes no sense. Each of the macronutrients have a different calorie quantity. Even ethanol has approx 6 calories per gram despite being considered a carbohydrate. Why divide the calorie load so arbitrarily into equivalents?

    Not very scientific.
     
  93. I have noticed extra teeth sensitivity and sorenesss in gums from taking this, and only taking 10 drops daily. I can't put my finger on it if its from anything else that I'm doing. Anyone else having these symptoms, or have a clue as to why I'm experiencing this? I took a 325mg aspirin tab last night and felt better not long afterwards.

    Extra inflammation? Sounds contradictory since methyl palmitate is anti-inflammatory.
     
  94. Yes, I've noticed this, but for me it's not really a sensitivity. I can drink cold and hot liquids without pain. It's more of a soreness or stinging. On the other hand, I was noticing last night that my teeth seem to fit together better when I bite, and I wasn't thinking that DeFibron could've caused it, so I think this deserves more testing.
     
  95. So you have also noticed gum soreness? I've had teeth sensitivity before but without the gum soreness. I'm going to give it a rest for now, and re-visit later with even a smaller dose.
     
  96. I'm going to drop down to 1 drop and increase the dose by 1 drop twice a week as I just think that's wise with most dopaminergics. They just seem to cause less problems when gradually increasing dose. Memantine, caffeine, Bromocriptine, etc.