1. Registering for the Forum

    We require a human profile pic upon registration on this forum.

    After registration is submitted, you will receive a confirmation email, which should contain a link to confirm your intent to register for the forum. At this point, you will not yet be registered on the forum.

    Our Support staff will manually approve your account within 24 hours, and you will get a notification. This is to prevent the many spam account signups which we receive on a daily basis.

    If you have any problems completing this registration, please email support@jackkruse.com and we will assist you.

Free Fatty Acids and Mitochondrial Respiration

Discussion in 'The Epi-Paleo Diet' started by QiGuy1997, Jan 17, 2014.

  1. QiGuy1997

    QiGuy1997 New Member

    Dr. Kruse has convinced me that mitochondria really are the keys to health and longevity and for that reason, I've delved full force into studying the bioenergetics of mitochondria. I've been trying to find how mitochondrial bioenergetics react to different substrates like free fatty acids and glucose. Considering Dr. Kruse's epi-paleo, ketotic diet would result in a substantial rise in blood free fatty acids, I thought I'd post some of my thoughts/questions here. I hope I can get a Kruse-ian interpretation of these studies I've been looking in to.

    First, this study http://www.ncbi.nlm.nih.gov/pubmed/6279918 seems to suggest the opposite of what we would desire from free fatty acid metabolism. Mitochondrial repsiration appered to decrease in response to increase free fatty acid content in the blood. Nicotonic acid was used to reverse these effects and reactivated proper mitochondrial respiration by supressing the rise of free fatty acids in the blood. The author states that "These results suggest that high plasma FFA itself, whether it may be exogenous or endogenous, may impair the oxidative phosphorylation of the mitochondria isolated from normal and ischemic hearts." This worries me as I want fully functioning, high mitochondrial respiration.

    Another study I found analyzes how free fatty acid beta-oxidation affects heart function, http://cardiovascres.oxfordjournals.org/content/59/1/143.abstract Essentially, it shows that inhibiting free fatty aicd utilization by heart cells increased glucose oxidation, decreased lactate production (good, bad? I'm not fully sure here.), decreased glycogen depletion and resulted in stronger and more efficient regional contractile power in the heart. This suggests that fatty acid oxidation is not the substrate that provides the optimal bioenergetic state for the heart and glucose seems to make hearts stronger/more efficient. Do you guys have any thoughts in this regard? Similarly, this study http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071466/ concluded that a high fat diet causes greater oxygen consumption in heart cells, seemingly due to the increase of uncoupling proteins in the heart's mitochondria reducing the efficiency of ATP generation (uncoupling caused by the fatty acids makes the mitochondria burn more fuel to produce the same amount of energy). I'm not sure of the implications here so your thoughts would be greatly appreciated.

    Last but not least, this study http://www.ncbi.nlm.nih.gov/pubmed/6867023 claims that "oxidation of fat is one of the fundamental responses to stress" and free fatty acids are released in response to stress. FFAs seem to supress full glucose oxidation and abort the process at lactate instead of full oxidation to carbon dioxide. Does this mean FFAs are necessarily stressful? Not necessrily, but compounds released in synchrony with FFAs during stress, like cortisol and adrenaline, are things we do not want to have in high concentrations during our non-stressed state.

    I'm not trying to make any claims here, I'm just genuinely trying to understand the maze of bioenergetics that surround mitochondria function. I really do hope somebody can explain these findings!
    Last edited: Jan 17, 2014
  2. Jack Kruse

    Jack Kruse Administrator

    You need to review the Volek video I posted and read up on how complex 1 can be affected by drugs that block it. Complex I dysfunction leads to intracellular lipid accumulation in the tissues whose mitochondria are damaged. .For example......metformin, rotenone, bisphenyl A,isoniazid, flunarizine, and atrazine are all complex 1 blockers but only metformin works on weight loss because it affects the DIRECTION of the current of flow electrons in and out of ETC. Metformin is unusual because it does not actively block ROS production on a chronic basis. It can under a shorter time frame but this drug is never given acutely. It is given long term to T2D who have a trashed complex one. So in T2D with chronic reverse flow of electrons metformin signals itself from the pack of complex one blockers. In all the links you post not one looks that details of QED effects. Have a look here at one that does.

    The story is always in the details......and when you begin to realize quantum actions tie to specifics of atomic structure you begin to see why the literature is useless in many cases. They never control for these small changes that appear to make huge differences in how mitochondria are designed to work.
  3. QiGuy1997

    QiGuy1997 New Member

    Wait, wait, wait, I'm a bit confused now. You seem to suggest that reverse electron flow is bad and that metformin inhibits this, thereby being beneficial. But according to Peter over at hyperlipid, we need superoxide generated by reverse electron flow in order to generate physiological insulin resistance and spare glucose for our brains. In fact, high fat diets are extremely good at generating reverse electron flow and physiological insulin resistance. If metformin inhibits this reverse electron flow, wouldn't it increase insulin sensitivity? Isn't this something we want to avoid on a high fat diet? What causes this disparity between your position and Peter's?
  4. QiGuy1997

    QiGuy1997 New Member

    I have a feeling I'm totally misunderstanding this reverse electron flow in the mitochondria. Oh well, I have a no school on Monday so this will be a perfect weekend to read through your blog posts on the topic and Peter's at hyperlipid. Any particular posts you recommend? Also, any books at go into the deep biochemistry of mitochondria that you suggest? I started Power, Sex, Suicide tonight but I don't think it goes quite this deep into everything.

Share This Page