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Palmitic Acid (palmitate) Strongly Increases Oxidative Metabolism

Discussion in 'Scientific Studies' started by haidut, Jun 16, 2017.

  1. haidut

    haidut Member

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    This is yet another thread as a follow up on the recent posts about plamitic acid inhibiting fatty acid oxidation and having therapeutic roles in cancer, diabetes and all other disease characterized by elevated/abnormal fatty acid metabolism.
    Palmitic Acid (palmitate) Is A Fatty Acid Oxidation Inhibitor More Powerful Than Mildronate
    Palmitic Acid (palmitate) Dramatically Inhibits Liver Cancer Progression

    The study below shows that a physiological concentration (HED: ~3g) of palmitate basically doubled oxygen consumption/metabolism. The increase in respiration was NOT due to palmitate serving as the fuel, and fatty acid oxidation was not increased by palmitate either (something also suggested by the other threads on FAO inhibition).

    Palmitate-induced activation of mitochondrial metabolism promotes oxidative stress and apoptosis in H4IIEC3 rat hepatocytes. - PubMed - NCBI
    http://vanderbilt.edu/younglab/pdf/egnatchik14.pdf

    "...ROS can be produced due to accelerated flux of electrons through the ETC as a result of increased mitochondrial activity. We measured the oxygen consumption of H4IIEC3 cells treated with 400 μmol/L PA to determine if ROS accumulation was associated with elevated mitochondrial metabolism. PA-treated cells were characterized by increased oxygen consumption (Fig. 2). Cells treated with 400 μmol/L OA had similar oxygen consumption rates as vehicle-treated cells. This result confirms that the elevated oxidative phenotype is unique to cells treated with SFA and that an equal load of MUFA is not sufficient to alter mitochondrial function."

    "...Therefore, we analyzed ion fragments of citrate and malate for enrichment of M + 2 mass isotopomers (Fig. 6A). However, we found little to no incorporation of 13C, suggesting that a negligible flux of palmitate carbon was directed into the CAC for complete oxidation."

    "...For example, ROS accumulation is a critical event leading to apoptosis of palmitate-treated CHO cells [30], while palmitate-treated neonatal cardiomyocytes undergo apoptosis independently of oxidative stress [31]. In our experiments, we measured a burst of ROS at approximately 6 h following palmitate administration, which was 25%–50% higher than cells treated with vehicle (BSA) alone."

    "...Since mitochondria require oxygen to carry out oxidative phosphorylation, increased oxygen consumption is a direct measure of increased mitochondrial metabolism. Palmitate-treated cells exhibited a 2-fold increase in oxygen consumption rate and in most mitochondrial fluxes prior to ROS accumulation. However, NAC co-treatment did not affect palmitate-induced metabolic alterations, indicating that neither elevated ROS nor downstream apoptotic events contributed to mitochondrial activation. Instead, elevated mitochondrial metabolism appears to be an inherent consequence of palmitate overload that is independent of subsequent ROS accumulation and apoptosis initiation."

    "...
     
  2. Peat Tong

    Peat Tong Member

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  3. OP
    haidut

    haidut Member

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    What do you mean by opposite conclusions? Did they find oleic acid to stimulate metabolism and palmitic to suppress it? The studies I posted also claim that decreased FAO may contribute to insulin resistance. I don't think that is true, so the study you posted actually confirms the one I posted. Most studies consider increased FAO to be a good thing, a concept that Peta has challenged for decades and is now finally being acknowledged in the clinics.
     
  4. Peat Tong

    Peat Tong Member

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    "We recently demonstrated that saturated fatty acids and, more specifically, palmitic acid cause brain insulin resistance (10). CNS resistance to leptin and insulin compromises the ability of both hormones to regulate food intake and body weight in the presence of diets high in saturated fat/palmitic acid, subsequently resulting in obesity. Additionally, we found that palmitic acid impairs the ability of insulin to activate its intracellular signaling pathways (10). Importantly, these effects of palmitic acid are unique for this the type of fatty acid. Oleic acid, for example, has been demonstrated to act as a central insulin mimetic and to have beneficial effects on hepatic glucose homeostasis and body weight regulation (11). Consistently, it has been demonstrated that diets high in monounsaturated fatty acids (oleic acid) prevent dietary fat–induced insulin resistance (11, 12), whereas diets high in palmitic acid accelerate obesity (10). Potential mechanisms by which these fatty acids differentially influence insulin signaling as well as body weight regulation have been posited. Here, we focus on the CNS and provide data suggesting what we believe to be a novel mechanism by which specific fatty acids impair central insulin (and leptin) signaling by activating a novel family member of PKC."

    "The fatty acid composition of the HFS [ high fat, saturated ] diet was 10% myristate/27% palmitate/12% stearate/25% oleate. The composition of the oleic acid diet was 11% palmitate/ 70% oleate/13% linoleate. "
     
  5. OP
    haidut

    haidut Member

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    In that reference [10] they simply state that palmitate is "known to induce insulin resistance" and cite 2 studies.
    "...Because palmitate readily induces insulin resistance in peripheral tissues (15, 35) and because HF feeding increases hypothalamic palmitoyl-CoA levels (Fig. 3A), we asked whether intracerebroventricular infusion of palmitate in rats maintained on a standard chow diet mimics the effect of HF feeding on hypothalamic insulin signaling, palmitoyl-CoA accumulation, and IKKβ activity. "

    However, if you look at those studies (ref 15, 35 above) you will see that one of them does not even mention palmitate, while the other one used a mixture of palmitate and oleate to induce insulin resistance. So, the evidence against palmitate is non-existent or at least based on what the study has cited. In most cases I have seen the narrative is the same as for EFA - i.e. "it is well-known that palmitate causes insulin resistance because it is a saturated fat and SFA are bad". But when you look at the reference cited they usually point to each other in a circular fashion and at the end there is no evidence against palmitate.
     
  6. yerrag

    yerrag Member

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    Can these studies do that? Great for you Haidut to catch it. Another set of fake studies exposed!
     
  7. mujuro

    mujuro Member

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    I don't think I've ever encountered someone with insulin resistance and obesity who wasn't ingesting a whole spectrum of fatty acids, way more than 20% of total caloric intake. Is it really of consequence that SFAs are more insulin desensitizing than UFAs when we are ingesting <10% total caloric intake?
     
  8. yerrag

    yerrag Member

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    Is 20% the upper limit for fats as far as caloric intake goes? I've been making a formula for my mom where coconut oil is 40% of caloric intake (carbs at 40, protein at 20). Seems to be doing well. My blend is very arbitrary though.
     
  9. Mufasa

    Mufasa Member

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    40% is way too much, thats like 9 tablespoons of coconut oil
     
  10. yerrag

    yerrag Member

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    30-50-20 for fat/sugar/protein, or 20-60-20?
     
  11. raypeatclips

    raypeatclips Member

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    Peat has said up to 50 percent of the diet can be from fat sources and has spoken about eating pints of ice cream at a time. If your mum is improving health wise on a ratio of macros, I wouldn't change them simply from a single post on the forum.
     
  12. Mufasa

    Mufasa Member

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    He had lowered his fat intake though. And his later suggestions are too limit fat much more.

    Also he doesnt recommand much more than a couple of teaspoons of coconut oil a day IIRC. He eats more fat from dairy I think.
     
  13. raypeatclips

    raypeatclips Member

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    Oh yeah don't think I've ever seen him suggest having coconut oil as the sole source of fat he's mentioned 1tsp per day as having beneficial effects.
     
  14. mujuro

    mujuro Member

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    I should have prefaced this with an "IME". This is just my experience. I do best on minimal fats. I was eating lots of ice cream in recent months, but since replacing it with sorbet I feel so much better and my hair and skin are better too. Of the people in my personal life who are overweight and insulin resistant, they tend to eat a lot of fat, misled by the entire "carbs are the problem" myth.
     
  15. yerrag

    yerrag Member

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    I haven't heard this said from Peat, but I'm still going through many interviews of his, and if he has said this I would think it is a matter of context on how much fat one could use. I couldn't tell at all if my mom is doing well on that blend, but I could be overdoing it given that I understand coconut oil to be good for old people, as it prevents the onset of Alzheimer, from what I've been reading. Also, Ray has said many good things about coconut oil, such as it having sterols (or steroid, not sure) that could be used for steroids and hormones, has vitamin E (although it was not expounded upon), and is one of the protective substances he mentions of often enough. It also has shorter chain fatty acids that bypass the liver and is used directly for energy.

    I heard him recommend such amounts, but I didn't get the impression he was using that figure as an upper limit for daily consumption. I felt he was saying that amount would be enough. I find it hard to swallow any oil, and I would not tell anyone to take more than the minimum because it might turn them away from it. Taking in oil has the yukky feel, and just thinking of taking it straight up just makes me put it off until I don't do it. In my mom's case, I would always give her a milk blend of different ingredients, coconut oil being one, so she doesn't feel like it's torture each time.

    I understand coconut oil to be a different kind of fat, and it's been recommended by many people for weight loss, given that its quickly metabolized and not stored as fat in the body.

    Also, fats contains many calories and it helps because I can't give my mom much volume but I want her to meet her calorie needs. Using sugar instead of rice, for example, is one way. It becomes a toss-up between using sugar and coconut oil, and I could adjust it one way favoring more coconut oil, or the other way favoring sugar. Knowing sugar isn't bad, and knowing my mom has no blood sugar problem, adding more sugar wouldn't be a bad idea. Moreover, sugar also gets converted to saturated fats or mead acid also.

    So, I may play around my ratio of macronutrients and will try to observe the effects of different blends.
     
  16. paymanz

    paymanz Member

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    Maybe he just meant that's OK to have half your calorie from good fat, but he probably prefers sugar, for more co2 for example...
     
  17. raypeatclips

    raypeatclips Member

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    Oh yes he definitely prefers sugars no debate about that.
     
  18. OP
    haidut

    haidut Member

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    Well, I think the real message is "if you eat too much fat you will inhibit sugar metabolism". But not all fats are equal, so I would like to see a study with glucose/sucrose and pure palmitic acid. Until then nothing really can be concluded from these biased studies.
     
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