The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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Can folic acid have a role in mitochondrial disorders?

Discussion in 'Other Health News and Research' started by pattismith, Sep 13, 2017.

  1. pattismith

    pattismith Senior Member

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    Can folic acid have a role in mitochondrial disorders?



    Abstract
    Cellular folate metabolism is highly compartmentalized, with mitochondria folate transport and metabolism being distinct from the well-known cytosolic folate metabolism. There is evidence supporting the association between low folate status and mitochondrial DNA (mtDNA) instability, and cerebral folate deficiency is relatively frequent in mitochondrial disorders. Furthermore, folinic acid supplementation has been reported to be beneficial not only in some patients with mitochondrial disease, but also in patients with relatively common diseases where folate deficiency might be an important pathophysiological factor. In this review, we focus on the evidence that supports the potential involvement of impaired folate metabolism in the pathophysiology of mitochondrial disorders.
    © 2015

    https://www.ncbi.nlm.nih.gov/pubmed/26183769

    Folic acid could suppress Parkinson’s – new study
    Posted by er134 at Jan 21, 2014

    “Our data support the therapeutic potential of folic acid to enhance nucleotide pools, promoting mitochondrial biogenesis and improving mitochondrial function in neurons in neurodegenerative disease and confirm a mechanism by which this acts. Based on our findings, we propose that a high folic acid diet might be beneficial to modulate the pathogenesis of Parkinson’s disease by repressing mitochondrial dysfunction, opening a promising avenue towards exploring the role of folic acid in the prevention and therapy for neurodegenerative diseases such as Parkinson’s as well as other neurodegenerative diseases associated with defective mitochondrial function.”

    http://www2.le.ac.uk/offices/press/...-could-suppress-parkinson2019s-2013-new-study

    Quantitative flux analysis reveals folate-dependent NADPH production
    2014


    "ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway.

    Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP(+) to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP(+) and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress.

    Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power."

    https://lsi.princeton.edu/quantitative-flux-analysis-reveals-folate-dependent-nadph-production

     
    Last edited: Sep 13, 2017
  2. ljimbo423

    ljimbo423 Senior Member

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    United States, New Hampshire
    Hi Patti- I think folate is very important to improve mito function. Here is a few quotes from Robert Naviaux about NADPH in cfs.

    He also says that up to 40% of the cellular supply of NADPH can be made through the folate cycle-

    So it seems that he thinks NADPH is very important in reversing the CDR.

    http://www.pnas.org/content/113/37/E5472.full
     
  3. Hutan

    Hutan Senior Member

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    That's interesting. My daughter has spina bifida occulta - it's the benign and common form of neural tube defect where a vertebrae doesn't close around the spinal cord completely. It doesn't cause her any problems. These days pregnant women take folic acid to prevent spina bifida. I was eating healthily during the pregnancy. So I wonder if I have a genetic tendency to low folate.

    In my first pregnancy, which I was not even aware of until I had a miscarriage at an early stage, I was told the baby had no brain. Anencephaly is an extreme form of neural tube defect and again, folate supplementation seems to substantially lower the risk.

    My paternal grandmother had Parkinson's. With hindsight, we think she had ME for many years before that.

    @charles shepherd, are you aware of any increased incidence of neural tube defects in the babies of women with ME?
     
  4. Helen

    Helen Senior Member

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    Are all readers aware of the fact that one-carbon-metabolism is another expression for methylation? I even met some doctors who weren´t.
     
  5. pattismith

    pattismith Senior Member

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    I didn't know either, and I didn't know this methylation process was occuring in mitochondria as well!

    It looks like the one carbon cycle is a more common appelation than methylation in the medical articles I read, do you know why?

    I am new to methylation, so I need to understand how it works, especially as I feel many side effects from taking folates.

    Another interesting article from 2017 about folates and Autism, it still amazes me to see the similarities between CFS/ME and autism

    The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism
    Spectrum Disorder


    "ASD is a behaviorally defined disorder which now affects ~2% of children [14]. Recent studies
    suggest that ASD is linked to mitochondrial dysfunction [13,15,16], although the exact nature of
    mitochondrial abnormalities in ASD appears to be complicated. For example, classic mitochondrial
    disease is found in 5% of children with ASD [16], yet up to 50% of children with ASD may have
    biomarkers of mitochondrial dysfunction [16,17] and a higher rate of abnormal electron transport
    chain (ETC) activity is found in immune cells [18,19] and post-mortem brain tissue [20]. Perhaps more
    unique is the fact that ETC activity in muscle [21,22], skin [23], buccal cells [11–13] and the brain [20]
    has been documented to be significantly increased, rather than decreased, in individuals with ASD,
    consistent with in vitro data showing elevated mitochondrial respiration in cell lines derived from
    children with ASD [24,25]. More recently, mitochondrial respiration in cell lines has been shown to
    be related to the stereotyped behaviors and restricted interests subscale on the Autism Diagnostic
    Observation Scale (ADOS) with elevated respiratory rates corresponding to worse behavior [26].
    Individuals with ASD are a particularly important group of patients that would benefit from a
    biomarker of mitochondrial dysfunction as well as a marker of the effect of treatments on mitochondrial
    function. First, the great majority of children with ASD do not have genetic mutations to explain their
    mitochondrial dysfunction [16], making diagnosis complicated.
    Second, many children with ASD
    are treated with supplements that potentially target the mitochondrial but it is unclear whether such
    treatments influence mitochondrial function [27]. Understanding which treatments would be most
    helpful and effective for children with ASD, especially on an individual basis, would be tremendously
    helpful for guiding treatment in a personalized medicine fashion.

    if you have time to read it, you will find the full document in the attached file were the study points all the mitochondrial functions improved with the supplementation of the ASD children
     

    Attached Files:

    Last edited: Sep 13, 2017
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  6. Helen

    Helen Senior Member

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    Older, retired doctors use the expression one-carbon-metabolism but very few younger do, if they even know about methylation from what I have experienced. I assume that knowledgeable doctors use the old expression as it´s more related to the actual biochemistry, and used in research as you have noticed.

    Thanks for posting very interesting articles.
     
    Last edited: Sep 14, 2017
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  7. ahmo

    ahmo Senior Member

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    Northcoast NSW, Australia
    Getting my folate levels up, as well as B12, certainly changed my health for the better.
     
    pattismith likes this.

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