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Phosphate diabetes in patients with chronic fatigue syndrome

natasa778

Senior Member
Messages
1,774
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.
 

natasa778

Senior Member
Messages
1,774
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
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
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
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
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



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

Dolphin

Senior Member
Messages
17,567
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.
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.
 

aquariusgirl

Senior Member
Messages
1,732
surely there are some more sophisticated tests our docs could run other than just a blood phosphate test?
 

liverock

Senior Member
Messages
748
Location
UK
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
 

xchocoholic

Senior Member
Messages
2,947
Location
Florida
http://www.ncbi.nlm.nih.gov/pubmed/11394620



Phosphate, the renal tubule, and the musculoskeletal system.

Laroche M.
Source

Service de rhumatologie, CHU Rangueil, Toulouse, France. laroche.m@chu-toulouse.fr
Abstract

A component of ATP, phosphate is at the hub of the energy-related mechanisms operative in muscle cells. Together with calcium, phosphate is involved in bone tissue mineralization: thus, a chronic alteration in the metabolism of phosphate can induce bone and joint disorders.

Diagnosis of chronic hypophosphatemia. Serum phosphate, calcium, and creatinine should be assayed simultaneously. Serum calcium is increased in hypophosphatemia caused by hyperparathyroidism and decreased in osteomalacia.

Urinary phosphate excretion should be measured in patients with a normal serum calcium level and a serum phosphate level lower than 0.80 mmol/L.

A decrease in urinary phosphate excretion to less than 10 mmol/24 h strongly suggests a gastrointestinal disorder, such as malabsorption, antacid use, or chronic alcohol abuse.

In patients with a urinary phosphate excretion greater than 20 mmol/24 h, the maximal rate of tubular reabsorption of phosphate (TmPO4) and the ratio of TmPO4 over glomerular filtration rate (GFR) should be determined to look for phosphate diabetes.

Manifestations and causes of phosphate diabetes in adults. Moderately severe phosphate diabetes in adults manifests as chronic fatigue, depression, spinal pain, and polyarthralgia, with osteoporosis ascribable to increased bone resorption.

Although many cases are idiopathic, investigations should be done to look for X-linked vitamin D-resistant rickets missed during childhood, a mesenchymatous tumor, or Fanconi's syndrome with renal wasting of phosphate, glucose, and amino acids.

Management of phosphate diabetes. Phosphate supplementation and, in patients with normal urinary calcium excretion, calcitriol produce some improvement in the symptoms and increase the bone mineral density. Whether dipyramidole is clinically effective remains unclear.
 

Deatheye

Senior Member
Messages
161
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

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.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
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

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!
 

nandixon

Senior Member
Messages
1,092
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.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
surely there are some more sophisticated tests our docs could run other than just a blood phosphate test?

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.
 

nandixon

Senior Member
Messages
1,092
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.

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.
 

A.B.

Senior Member
Messages
3,780
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

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.