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Phosphate diabetes in patients with chronic fatigue syndrome

Discussion in 'Latest ME/CFS Research' started by natasa778, Jun 10, 2010.

  1. natasa778

    natasa778 Senior Member

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    London UK
    not new but...

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360873/?tool=pubmed

    Phosphate depletion is associated with neuromuscular dysfunction due to changes in mitochondrial respiration that result in a defect of intracellular oxidative metabolism. Phosphate diabetes causes phosphate depletion due to abnormal renal re-absorption of phosphate be the proximal renal tubule. Most of the symptoms presented by patients with phosphate diabetes such as myalgia, fatigue and mild depression, are also common in patients with chronic fatigue syndrome, but this differential diagnosis has not been considered. We investigated the possible association between chronic fatigue syndrome and phosphate diabetes in 87 patients who fulfilled the criteria for chronic fatigue syndrome. Control subjects were 37 volunteers, who explicitly denied fatigue and chronic illness on a screening questionnaire. Re-absorption of phosphate by the proximal renal tubule, phosphate clearance and renal threshold phosphate concentration were the main outcome measures in both groups. Of the 87 patients with chronic fatigue syndrome, nine also fulfilled the diagnostic criteria for phosphate diabetes. In conclusion, we report a previously undefined relationship between chronic fatigue syndrome and phosphate diabetes. Phosphate diabetes should be considered in differential diagnosis with chronic fatigue syndrome; further studies are needed to investigate the incidence of phosphate diabetes in patients with chronic fatigue syndrome and the possible beneficial effect of vitamin D and oral phosphate supplements.
  2. natasa778

    natasa778 Senior Member

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    Neuromuscul Disord. 1993 May;3(3):223-5.
    Oral phosphate supplements reverse skeletal muscle abnormalities in a case of chronic fatigue with idiopathic renal hypophosphatemia.

    Land JM, Kemp GJ, Taylor DJ, Standing SJ, Radda GK, Rajagopalan B.

    Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford, U.K.

    A 57-yr-old man presented with a long history of undiagnosed fatigue but no evidence of bone disease. He was noted to have hypophosphatemia due to an idiopathic phosphaturia. Marked abnormalities of exercising skeletal muscle detected by phosphorus magnetic resonance spectroscopy and by plasma metabolite measurements were consistent with mitochondrial dysfunction. Oral phosphate supplements restored plasma phosphate concentration and muscle biochemistry to normal and produced considerable improvement in symptoms and exercise tolerance, although the phosphate concentration in muscle was only marginally low and increased little by treatment. We conclude that hypophosphatemia should be excluded in unexplained fatigue.
    PMID: 8400863
  3. alex3619

    alex3619 Senior Member

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    Hi natasa778

    There were actually two very small studies on this, and I have been trying to raise awareness of this for a decade now. If it is right (and so far as I know their results were never validated) then about ten percent of CFS patients have this. Take ten percent away and the rest of the patients would be in the range of the biomarker percentages.

    It is also very easy to treat, which is the key to quick testing as I have said over the last ten years. There is a downside however. First, take a vitamin D supplement with a lot of phosphate. I would talk to someone very knowledgeable about nutritional therapy before even considering this, however. Then if there were no severe effects, continue on a daily basis. You should be almost recovered in a week.

    Now the downside. Many patients with CFS who take vitamin D like this feel very very sick. I know I did. It may cause a full crash.

    Blood tests should show phosphate is in the near normal or normal range before even considering this approach, but it has to be at the very low end of normal. If phosphate is mid-range or high, taking more phosphate will only cause problems. If the phosphate is below normal I would be looking for other causes, because this disorder tends to present as normal (but low) blood phosphate with low tissue phosphate levels.

    Bye
    Alex
  4. natasa778

    natasa778 Senior Member

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    Thanks Alex. Any theories as to why some crash on VitD?
  5. alex3619

    alex3619 Senior Member

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    Hi natasa778

    There are many theories as to why, but none I find very compelling. Vit D3 can damage immune function, and vitamin D will alter calcium regulation. Since calcium is one of the most critical intracellular signalling factors (Ca++ actually, the other is cAMP) this could be having an impact. Sadly we don't know, just as we don't know why some CFS patients seem to do well on vitamin D. The Marshal protocol, if I recall correctly, also has patients avoid D. There is no shortage of theories, but a serious shortage of hard evidence.

    Bye
    Alex



  6. Dolphin

    Dolphin Senior Member

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    Yes, the Marshall Protocol is either good for us or, it would appear, possibly quite bad for us. I wish there was more research progress so we could know one way or another on this and other issues.
  7. aquariusgirl

    aquariusgirl Senior Member

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    surely there are some more sophisticated tests our docs could run other than just a blood phosphate test?
  8. liverock

    liverock Senior Member

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    Another problem for some people with Vitamin D is it increases glutathione levels and particularly in the brain. This may be good news for some people as Glutathione binds to mercury and some people can detox mercury readily. It might not be so good for people with a high body mercury level and poor detox enzymes, otherwise you could be just moving it around the body.

    http://www.sciencedirect.com/scienc...serid=10&md5=36fe7df09fbacd4b33fe816072a1793d
  9. xchocoholic

    xchocoholic Senior Member

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    http://www.ncbi.nlm.nih.gov/pubmed/11394620



  10. Deatheye

    Deatheye Senior Member

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    I tought I once read something about an Explanation why People get more ilness in the winter.
    It sad that the Problem isn't actually the cold but the shortage of sun rays, which are a good source for Vitamin D.
    Vitman D they sad functions kinda like a go to work Signal for some cells in the immune system. If tehre isn't enough Vitamin D a lot of those cells remain inactive till they can connect to Vitamin D. They explained which cells and If I remember correctly they showed that higher Vitman D Levels makes those cells more active.

    Sadly I don' remember where I've read that. I guess going by that it's no wonder that it influences People with immune system Problems.
  11. Tristen

    Tristen Senior Member

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    I would suggest labs looking at Phosphorus levels before supplementation. My Phosphorus levels were always high.
  12. Ema

    Ema Senior Member

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    Stupid question of the day...I'm looking for a phosphate test on the Labcorp menu but only find phosphorus. Is this the one to test?

    Thanks!
  13. nandixon

    nandixon Senior Member

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    I started researching this a few days ago, looking for underlying genetic issues that could explain the "phosphate diabetes" (renal phosphate wasting) seen in 10% of the 87 patients with CFS/ ME in the 1998 study given in the original post:

    "Phosphate diabetes in patients with chronic fatigue syndrome"
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360873/

    If you've done 23andMe testing, you can check some of the genes related to phosphate metabolism that can cause hypophosphatemia (in the presence of normal parathyroid hormone levels - I'm needing to have my PTH rechecked) including:

    FGF23
    SLC34A1 ("NPT2a")
    SLC34A3 ("NPT2c")
    KL ("Klotho")
    PHEX
    DMP1
    SLC9A3R1 ("NHERF1")

    (Note: The FGF23 gene wasn't discovered until 2000, I believe. There are other potentially relevant genes as well.)

    [If you have a chance @Valentijn, would you mind looking at these? It seems worthwhile, since if the study is correct, phosphate wasting could be responsible for up to 10% of cases. Thanks!]

    In my own case for example, I'm heterozygous (AG) for rs7955866 in FGF23, which is a missence mutation, and although not super rare, is bad enough that it can cause childhood rickets in some people due to hypophosphatemia. (I'm also homozygous for rs6420094 in SLC34A1, but not sure how important that is.)

    As a first effort to try to raise my phosphate levels, I'm going to switch to calcium phosphate type supplements (e.g., calcium glycerophosphate or hydroxyapatite) instead of the calcium carbonate or citrate I've been using. (I can't use milk products as these are a migraine trigger.)

    Btw, I started investigating this while trying to find an explanation for my high 1,25-dihydroxy vitamin D (calcitriol) levels in the presence of low 25-hydroxy levels:

    25-Hydroxy = 30.6 ng/mL (ref 30-100)
    1,25-Dihydroxy = 75.4 pg/mL (ref 10-75)

    The full-text of the 1998 study doesn't indicate what the calcitriol levels are for the patients, unfortunately.
    Sidereal and Valentijn like this.
  14. alex3619

    alex3619 Senior Member

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    Blood phosphate is homestatically regulated. So measuring it will fail to diagnose phosphate diabetes unless so very much is lost the patient is in crisis. Its intracellular phosphate that is important, and this is not typically measured, and even then only for blood cells.
    Valentijn and nandixon like this.
  15. nandixon

    nandixon Senior Member

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    That's sort of what I'm assuming too. My recent serum phosphorus (phosphate) came back well within range at 3.3 mg/dL (ref 2.5-4.5).

    I'd been supplementing 5000 iu of vitamin D3 per day for a couple weeks. I'm not sure if this may have affected the measurement or not, given the interrelationship between phosphate, calcitriol and FGF-23.

    I'm hoping it's possible that some people with ME/ CFS may need greater phosphate levels than what their routine labs would indicate.
  16. A.B.

    A.B. Senior Member

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    Vitamin D can increase calcium levels, and calcium and magnesium play against each other (sorry I don't know the correct English word). CFS patients seem to benefit from magnesium supplementation (http://forums.phoenixrising.me/inde...magnesium-and-chronic-fatigue-syndrome.27439/) so increased calcium levels may counter-productive.

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