Yet Another Study Calls For Inhibiting Fat Oxidation As A Treatment For Cancer

Discussion in 'Scientific Studies' started by haidut, Oct 17, 2017.

  1. haidut

    haidut Member

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    I have posted a number of threads on the role of fatty acid oxidation (FAO) and fatty acid synthase (FAS) in cancer growth and progression.
    Inhibiting Lipolysis May Treat / Cure Cancer
    For more than 100 years FAO and FAS were thought of pathways irrelevant for cancer and also as ones that are largely mutually exclusive. Peat has said numerous time that this is not true and that both FAO and FAS are upregulated in cancer cells. This is why they appear glucose hungry - i.e. they waste glucose through the FAS pathway to enter the FAO pathway and also they produce a lot of lactic acid due to downregulation of Krebs cycle and ETC. Not much different from diabetes and simple (central) hypothyroidism.
    After more than 80 years of denial that metabolism plays a role diseases, the medical profession has finally started to wake up to the role of metabolism in cancer and this has even entered the popular culture due to articles in the popular press (NYT, WP, PopularMechanics, etc). Unfortunately, mainstream medicine is still misguided as it has now focused on inhibiting glycolysis (and sugar deprivation) as a treatment.
    The study below finally recognizes the mistake in this approach and elucidates the importance of both FAO and FAS as therapeutic targets. Hopefully, we will see something practical come out of this soon.

    Cancer metabolism: fatty acid oxidation in the limelight. - PubMed - NCBI
    "...The data suggesting a greater requirement of FAO in undifferentiated cells also raise an interesting possibility. It is plausible that in quiescent and undifferentiated cells the competition between FAS and FAO may be less prominent (as these cells display a lower membrane synthesis rate), thus indicating that these cells might derive a full survival benefit from FAO activation and its biological output. In turn, their dependence on FAO could make them vulnerable, providing a unique therapeutic opportunity from the pharmacological manipulation of this metabolic pathway. For all the reasons stated above, there is an exciting therapeutic potential for the pharmacological blockade of FAO in cancer. Two key enzymes in the FAO pathway are particularly interesting as potential targets for pharmacological intervention. CPT1 is considered the rate-limiting enzyme in FAO and can be pharmacologically targeted. Drugs that target 3-ketoacylthiolase (3-KAT), which catalyses the final step in FAO, are also available (TABLE 1)."

    "...In summary, the study of FAO in the context of cancer metabolism has unveiled new and exciting therapeutic opportunities, together with a more profound comprehension of the metabolic wiring of cancer cells. We have learned over the past few decades that targeting single enzymes or pathways rarely results in cures for cancer, so it is likely that agents that target FAO will need to be combined with chemotherapies or with other targeting agents to be successful. Clearly, further knowledge of the dependence of cancer cells on FAO will be necessary to refine rational approaches to combination therapies that target fatty acid catabolism."
     
  2. charlie

    charlie The Law & Order Admin

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  3. Ania

    Ania Member

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    What would be the most effective supplentation to support the above ?
     
  4. Risingfire

    Risingfire Member

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    Are you coming out with a mildronate type supplement?
     
  5. johnwester130

    johnwester130 Member

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    niacinamide ?

    biotin ?

    thiamine ?

    simply eating more sugar than fat ?

    they will make sure you burn sugar instead of fat
     
  6. OP
    haidut

    haidut Member

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    Visit the link on line 2 of my post. It lists a a few other posts and talks about supplements.
     
  7. OP
    haidut

    haidut Member

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    Yes, probably before the end of the year. It has a ton of other beneficial effects that Mildronate does not and is about 10-fold more potent than Mildronate as FAO inhibitor.
     
  8. OP
    haidut

    haidut Member

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    Yes, all of these. Also, thyroid, MB (NO inhbition also inhibits FAO), emodin, aspirin, palmitate, vitamin E, progesterone, etc.
     
  9. Regina

    Regina Member

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    :thumbup:
     
  10. Fractality

    Fractality Member

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    I don't intend to hijack this thread but it's my understanding that FAO inhibitors would lead to weight gain unless the diet is sugar/carb and the fat used is MCT. Correct?
     
  11. OP
    haidut

    haidut Member

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    Not necessarily, depends on many other factors. They may lead to increased lipid storage on high fat diets but on normal calorie diets they should either keep weigh unchanged or even drop it. Inhibiting FAO seems to improve steroid profile by lowering cortisol/adrenaline/insulin and increasing synthesis of pregnenolone/DHEA/progesterone and androgens (mostly in men). That steroid balance change can also lead to weight loss even if FAO is inhibited. The liver can still excrete unmetabolized fats by glucuronidation (even with FAO inhibitor use), which is how Peat suggests is best to get rid of PUFA instead of oxidizing it.
     
  12. jb116

    jb116 Member

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    Sugar also helps build/spare lean tissue which is metabolically active. At res,t muscles feast safely on fats.
    It's a net effect. Sugar keeps metabolism going, it sees no end. Fat burning eventually hits a wall; diminishing returns.
     
  13. dand

    dand Member

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    Since adding high dose niacinaamkde these last few weeks I can totally corroborate @hadiut’s points. I’ve never felt a complete abscess of stress like this and have been at thing from Peat perspective for a while. Even seem to have had some fat loss.
     
  14. grenade

    grenade Member

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    Haidut, just to confirm, is glucuronidation the ine possible method of slowly shedding bodyfat whilst not tapping into the stress hormones? Also, is there any available literature that discusses the liver’s max potential of fatty acid glucuronidation?
     
  15. Peater

    Peater Member

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    How high is high dand?
     
  16. OP
    haidut

    haidut Member

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    The GI tract seems to be able to do it as well.
    Glucuronidation of the dietary fatty acids, phytanic acid and docosahexaenoic acid, by human UDP-glucuronosyltransferases. - PubMed - NCBI

    Based on the study, there is a limit for glucuronidation of DHA, which can be maxed with about 3g dose of DHA. But that is in vitro. I don't know what is the total glucuronidation capacity of all human organs that can do it. It would depend on both organ health, substrate availability (how much fat is present) and availability of glucuronic acid (which depends on sugar intake and liver health).
    It would be a great question for Peat IMO.
     
  17. dand

    dand Member

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    Really not that high, but at minimum 500mg up to 2 grams total throughout the day. Just go by how I feel.
     
  18. Peater

    Peater Member

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    Thanks, I'll try taking 2 capsules and see how I feel. (NOW Brand)
     
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