Methylation, Vitamin D intolerance-- biochemical interactions?

[Jimk]

I have a puzzle I'm hoping the biochemically minded folk on this forum may have some insight into. Brief background: I'm 30 years into the CFS journey, having knocked back chronic infections (C. pneumoniae, chronic yeast problems), and working on methylation issues (blood test identified MTHR C677T defect). My two big symptom concerns are fatigue and very significant brain fog. I've been working on methylation, now up to about 3000-4800mcg of folapro a day. I had an energy kick-in when I started to increase the methylcobalamin and dicobenzide. I keep expecting some improvement in the brain fog, but no dice so far. I had no negative reactions to either folapro or B12.

Here's the puzzle piece- I've been low in Vitamin D levels for years, and my CFS doc has been working with me to get them up. I don't have my current levels, but they are likely approaching low normal ranges by now. The difficulty has been that any increase in dosing created reactions: fatigue, muscle and joint pain, gut disturbance. Increasing my D3 very gradually-- 400iu increment for a at least a month-- and I've gotten up to 2000iu a day. This has had a fabulous effect on my immune system, I seem to shrug off viruses and infections, remarkable for a CFS'er. BUT--- the other day I decided I was handling D so well that I decided to double my dose to 4000iu.:Retro redface: Next day I was completely flattened with brain fog and depressed mood. I couldn't think my way out of a paper bag! I'm not entirely certain if this is the D, but I recall this "side effect" from when I first started D, which at that time I attributed to viral/bacterial die-off. I'm thinking of stopping it entirely for a time to see if this is what's flattening me. Since my immune system clearly is better from D I don't want to undercut it, but this much brain fog isn't life. Curiously, I don't seem to get this effect from sunlight exposure, at least that I can recall.

My wish here is to get some speculation by those more knowledgeable than I about the biochemical interactions on potential interactions of methylation problems, Vitamin D and brain chemistry. Could the increased D suppressing available neurotransmitters or interfere with methylation phases? Could I have a defect in metabolizing D3 that might render it toxic, much as I have a defect metabolizing folic acid?

 

[garcia]

My wish here is to get some speculation by those more knowledgeable than I about the biochemical interactions on potential interactions of methylation problems, Vitamin D and brain chemistry. Could the increased D suppressing available neurotransmitters or interfere with methylation phases? Could I have a defect in metabolizing D3 that might render it toxic, much as I have a defect metabolizing folic acid?

Hi jimk, I get the same thing as you, actually worse as I don't seem to be able to tolerate any D3 at all. It sounds to me like the increased D is causing its deleterious effects via inflammation, which is most likely due to the Cpn (and / or other infections). Inflammation alone is going to mess up neurotransmitters (brain fog & depressed mood are classic signs). I don't think we have a defect in metabolising D3. I suspect that the defect lies in the immune system which produces excessive inflammation.

I too don't get any major negative effects from sunlight exposure. Where as I don't seem to be able to tolerate even the smallest amount of D3.

 

[adreno]

I agree with garcia. It's likely the effects of immune system activation you're experiencing.

I would just stay at 2000IU, if you tolerate that. It should be plenty.

I would also recommend that you take the other fat soluble vitamins with D, that is A, E and K, plus magnesium.

 

[Jimk]

Garcia & Adreno- thanks for your thoughts on this. As far as I can tell I don't have any significant sources of infection currently. That's why I'm questioning my previous explanations of die off due to immune activation and seeking some alternative mechanisms that might explain some of this from another angle. That is the difficulty with symptoms like fatigue and brain fog, they can be caused by such a host of things that they don't give you much to discern.

 

[place]

i have yeast allergies and soy also, many substances like b vits. are made with yeast and soy. and my symptoms get crazy when I take stuff with these to substances.

 

[Lala]

Hi Jim,

I have the exact same experience and I gave up D for some time. Much like you I have had CFS for more than 30 years and suffered from significant brainfog. Cap for cpn did not help with this part of CFS and I was finally diagnosed with bartonella infection. The brainfog actually is mild to moderate encephalitis caused by bartonella according to my doctor. These infections are notoriously difficult to diagnose because bartonella often inhibits production of antibodies either to bartonella or to other infections.

Are you still taking antibiotics with D or not? Perhaps it can strenghten D effect. I am sorry I cannot help with the biochemical interactions as I am not knowledgable in this field at all.

 

[hixxy]

I discussed Vitamin D intolerance with a doctor yesterday, and apparently VDR FOK or VDR TAQ/BSM polymorphisms can cause a lowered tolerance of Vitamin D supplemention. I can't remember which one it was thought!

Likewise, from experience, Vitamin D supplementation exacerbates magnesium deficiency.

 

[Jimk]

Hixxy82- thanks for that tip. VDR polymorphism is one of the things that came across my screen, but I couldn't find anything on whether it might effect D tolerance.
Lala- I'm currently completing a 6 month round of doxycycline & rifampin, the big guns for Cpn. No reactivity any more so my reactions are unlikely to be Cpn.

 

[garcia]

Hixxy82- thanks for that tip. VDR polymorphism is one of the things that came across my screen, but I couldn't find anything on whether it might effect D tolerance.
Lala- I'm currently completing a 6 month round of doxycycline & rifampin, the big guns for Cpn. No reactivity any more so my reactions are unlikely to be Cpn.

VDR polymorphisms are very common, so IMHO I doubt it would affect vit D tolerance. If anything people with polymorphisms may need more Vit D for same effect and so be more tolerant. Also I remember at one point I was able to tolerate 10,000 IU of D3 a day. Now I can't tolerate any! Presumably I have the same genetics (unless I am some kind of weird mutant freak - don't answer that!).

IMHO a lack of reaction to doxy & rifampin (or any other antibiotic combo) doesn't necessarily prove you are free of cpn. I've gone through periods of not reacting, and for me it indicates that the Cpn has adapted (efflux pumps etc.).

I forgot to mention earlier that I found that methyl-folate & vitamin D both potentiated each other greatly.

I would just go back to 2000 IU a day, and carry on incrementing slowly as you were before.

 

[Crux]

I've had this same problem. I tested very low, but was hopeful that vitamin D supplementation would be the answer. Although I averaged 1000-2000 iu daily for a few months, I began to have negative side effects... constipation, insomnia, anxiety, etc... I even became mildly hypercalcemic.

It's been a few years now that I've been concerned about this intolerance because now I have full-blown osteoporosis. But, I may have good news for you.

Zinc is a cofactor for vitamin D absorption. It is involved with the binding of vit. D to its receptors and such. The Vitamin D Council recommends taking Zinc, Magnesium, Vitamin K, and Boron to aid absorption.

 

[rlc]

Hi Crux. You say that you have had a bad reaction to vitamin D, have developed high calcium levels and have osteoporosis, have you been checked for hyperparathyroidism? Because these are classic signs of having it.

People with hyperparathyroidism should not take vitamin D until it is fixed, because in people with this condition it causes calcium levels to rise making them feel very unwell and can lead to a serious worsening of the illness, the osteoporosis is caused by the malfunctioning parathyroid causing calcium to be leached from the bones and put in the blood hence the high blood calcium levels.

Hyperparathyroidism is one of those diseases that most doctors dont know how to diagnose properly, they believe that both Calcium and PTH (parathyroid hormone) have to be above normal range, this is not true some people have high calcium but PTH is in the normal range, if PTH is high normal then the patient has Hyperparathyroidism, because high calcium should suppress PTH levels if someone has healthy parathyroid glands and PTH should be very much at the bottom of the accepted range, this is all explained in this article http://www.parathyroid.com/diagnosis.htm

The symptoms of Hyperparathyroidism are very similar to CFS see http://parathyroid.com/parathyroid-symptoms.htm

There are other diseases that people shouldnt take vitamin D with as it will cause calcium levels to rise as yours have they are Sarcoidosis, lung cancer, non Hodgkins carcinoma and tuberculosis. If there is any chance you have any of these get tested for them, because they will cause calcium levels to rise when only taking relatively small amounts of vitamin D.

As well as lack of the co factors mentioned on the vitamin D council as likely to cause worsening symptoms when taking vitamin D, another cause of a bad reactions to vitamin D is the interaction with certain medications, which are listed here http://www.drugs.com/drug-interactions/cholecalciferol,vitamin-d3.html

All the best

 

[Crux]

Thanks rlc; You've brought up many possibilities that could be applied to my case. My grandmother, (mother's side), died of tuberculosis 10 days after giving birth to my mother. My mother tested positive for TB antibodies up until about 10 yrs. ago. Now she tests negative. I haven't been tested, but it looks like a very good idea to do it.

My father had numerous serious health conditions, but lung cancer, and complications from treatment, were what brought his death.

I did have PTH tested after the hypercalcemic incident and it was low normal. My D levels only got as high as 36.

I'm persuing the possibility that zinc deficiency may be a large part of this vitamin D intolerance, and many other issues that I have, because I have so many symptoms that are associated with it.

I discussed having zinc measured with the endocrinologist, but he repeated the often said fact that serum zinc measures are inaccurate. I might have pressed for it anyway....

For now I'm taking strontium citrate and zinc for the osteoporosis. I'm now better able to tolerate sunlight. (I've read that photophobia may be a symptom of zinc deficiency.) I have some other intolerances that may be related to zinc deficiency, indirectly, so I'll bring them up in case this information might be helpful. I took magnesium for 5 yrs. and found it to be helpful for the most part, but began to have alot of trouble with it about a year ago. I stopped for about 2 months, and then had it measured in a serum blood test. It was highest normal. That can indicate kidney trouble, which I do have, but I've read that this can occur with low zinc as well.

Again, Thank You for bringing to light the possiblities of my vitamin D intolerance, because I do need to move on this.

 

[rlc]

Hi Crux, certainly worth following up on any possibilities for your reactions to vitamin D, Calcium levels rising when only taking smallish amounts of vitamin D is a recognised sign of certain diseases, so worth checking everything out. If youve had TB and lung cancer in your immediate family they certainly should be double checked. Non Hodgkins and Sarcoidosis also causes osteoporosis and can react badly to vitamin D.

Your doctor is right the zinc blood tests are not a very good measure of total body zinc levels but they will show a massive deficiency, I have had treatment for zinc deficiency and found the oral taste tests to be a reasonable measure of how I was responding to treatment. Theres information on all the different kinds of Zinc tests here if youre interested http://www.diabetesexplained.com/zinc-diagnostic-test.html

What kind of Kidney problem do you have? Renal tubular acidosis would explain the osteoporosis and vitamin D deficiency.

A possible explanation for your bad reaction to taking magnesium, is that Calcium and Magnesium are supposed to be in balance in the body, having osteoporosis indicates that your calcium levels are very low, so taking extra magnesium is going to throw the balance out even more and may worsen symptoms, So if you can track down the cause of the osteoporosis then you should be able to treat that and solve the problem. Dont let doctors tell you that Osteoporosis is a disease it isnt it can be a symptom of many other diseases, see http://en.diagnosispro.com/differen...oporosis-osteopenia-causes/11140-154-140.html

Hope things work out for you soon

All the best

 

[Crux]

Hi rlc;
Oh my, you've helped me more in your two posts, than my internist has in 6 yrs....I offer gratitude. I didn't mean to invite attention to myself, but maybe this information applies to this thread (?)

As for the vitamin D intolerance, I don't seem to have the hematological markers of non-hodgkin's lymphoma,(high lymphocytes), or RTA,( disturbed electrolytes). Actually, I've had very low lymphocytes. I only had lowered sodium before I began cortisol replacement. I also had low lymphs. and high neutrophils before cortisol. I've read that cortisol can lower vitamin D,but I don't know how.

I've read case studies of people with low zinc associated with osteoporosis. I've also read cases of people with high copper and osteoporosis. It's estimated that about 30% of zinc in the body is in the bones. I know it's alot to expect from one element, but I'm going to test it these next months to see if it helps to normalize some of my skewed blood test results.

The B12/Folate did bring my MCV,MCH, etc. into the normal range. I guess I'm lucky that way...

I'm wondering, did you experience any discomfort when you began zinc? Like copper or iron dumping? Headaches, nausea, increased fatigue, skin outbreaks.... I'm surprised to have experienced these so strongly. I'm hoping that once these symptoms pass, I'll be able to tolerate vitamin D.

 

[hixxy]

The B12/Folate did bring my MCV,MCH, etc. into the normal range. I guess I'm lucky that way...

What's considered abnormal MCV/MCH for CFS? Is this something that shows up with normal lab ranges or is it a more subtle subclinical interpretation?

 

[Charles555nc]

You should look up the marshal protocol, there are 2 types of vitamin D and vitamin D supplementation only effects the one thats already too high. I would just stick to occasional sun exposure and forget vitamin d supplementation. I get horrible, horrible crashes from oral vitamin d. You could also try methyl folate and see if that helps you out of your crash. Maybe its methylation related.

 

[Crux]

Hi Hixxy;

A complete blood count, CBC, can sometimes indicate a B12/Folate deficiency,but it's vague because so many factors influence the size of red blood cells. For instance, a person may have a concurrent iron deficiency with a B12/Folate def., which could result with a normal sized RBC. Also, in addition to iron deficiency, a B6 deficiency may shrink the size of RBC's.

Many people can have rather horrific symptoms of B12/Folate deficiency, including CFS, and have no abnormalities revealed in a CBC. This is one of the many reasons it's so difficult to diagnose.

 

[Jimk]

Just a note to follow up my original post- since I'm on T3 & T4 for thyroid I thought some of the threads elsewhere noting that increased D might be suppressing natural cortisol, especially if it's low or being used up by thyroid supplementation, and causing a cortisol crash. One intervention is supplementing pregnenolone. As I was measured low a while back when first being treated for CFS/ME it seemed worth trying. So far about 100mg spread over the day does seem to to be increasing energy and reducing brain fog. I'm hesitant to do more than this without some medical monitoring as I've experienced endocrine imbalance before.

Currently, I don't think the methylation has any interaction with this, so I'm continuing on with my own mod of Fredd/Rich methylation programs.

 

[rlc]

Hi Crux, when I was taking zinc supplementation, I was also taking other supplements, so it is hard to give an exact description of the effects of the zinc. I was also taking large amounts of magnesium, prescription strength Multi vitamin and mineral supplements and some herbs to boost the immune system and liquorice for immune and to boost adrenal function. On top of this I was taking 50,000 IUs of vitamin D a week.

What I experienced was for a couple of days after taking the vitamin D there was an increase in chest pain and palpitations and muscles twitching, vitamin D and magnesium are supposed to be in balance in the body, I think this was mainly the cause of the symptoms, increasing the vitamin D faster then I was stocking up on Magnesium was bringing out the symptoms of Magnesium deficiency. After about 4 weeks this stopped I think I had by then raised my magnesium levels to the right levels.

I certainly didnt experience increased fatigue, nausea, headaches or skin outbreaks from increasing zinc levels, the combination of what I was taking lead to a steady improvement.

When you say you began cortisol replacement what do you mean by that? Are you taking something like hydrocortisone? Because that could explain the osteoporosis.

Your test results before taking Cortisol replacement and B12 and folate look interesting (dont see how you ever got a CFS diagnosis with those results) was MCV and MCH high or low? Although taking supplements can help to relieve symptoms, the bad effect of it is that they can normalise some tests results and actually make it very hard to get a proper diagnosis because of this, your pre treatment tests may be very useful in tracking down your proper diagnosis.

You are very right that changes in blood results are a very late sign of B12 and folate deficiencies its called Macrocytosis, symptoms of B12 and folate deficiencies start at a level way higher than is required for Macrosytosis to start and doctors who rely on WBC to diagnose B12 and Folate deficiencies are doing it wrong, also the reference ranges are wrong, everybody should have their B12 and folate levels above the middle of the normal range to make sure that they are not deficient. An iron deficiency at the same time as having a B12 deficiency will stop Macrocytsosis happening and the diagnosis will be missed if WBC is relied on.

My feeling is that you need to start by getting all the diseases that react badly to vitamin D ruled out first hopefully this will provide the answer, if not then get minerals like zinc checked and see if that helps.

I think this information is very relevant to the tread because it is very abnormal to have bad reactions to vitamin D and is an indicator of certain diseases, lack of co factors and drug interactions, the only way anyone can come to an understanding of whether increasing vitamin D is affecting methylation and causing symptoms, is if all the other possibilities for increased symptoms from taking vitamin D have been ruled out first. Unfortunately most doctors do not have good knowledge of what causes an increase in symptoms from taking vitamin D and because of this opportunities to help the patient get missed.

All the best

 

[Crux]

Hi rlc;

My attempts to get any sort of diagnosis have been due in part to my own denial and fear. I mostly avoided doctors because I found it difficult to develop a rapport. I remember using the words, malaise and fatigue, to describe how I felt 27 or so yrs. ago, and I was quickly ushered away from the office. I've not sought a diagnosis for CFS.

In 1998, an internist noted that I had macrocytosis, an elevated MCV. Instead of discussing it with her, I did some research and somehow came upon the possibility that it could be due to low B12,and liver dysfunction. I assumed that the condition was dietary, as I had a history of vegetarianism/veganism. I began subs. of cyanocobalamin and did feel better. But I did not take them daily,and I began to go long periods of time without them. I was eating meat fairly regularly, so I wrongly assumed that diet alone would suffice.

I continued to have symptoms of B12/ Folate def., but I can only recognize that now.

Then in 2004, my health deteriorated rapidly. I remember intense pain and fatigue. I was an artist and painting contractor, and I began to turn down jobs. I became very confused.

During late 04 to early '05, I began to have daily vomiting and diarrhea, with daily migraines. I lost alot of weight. I was hyperpigmented. I have a long history of low BP and fainting.

During that time, I did see that internist, but our relationship had deteriorated. We were both accountable for that. I looked to be a textbook addisonian, but very few docs. can recognize the symptoms.

I again gave up on the medical industry, and began to haunt book stores and natural foods stores. Since I'd had a long history of amenorrhea,and I was approaching menopause, I thought that was a possible cause of my condition. I began Otc progesterone. But, I found I needed pharmalogical amounts to aleviate symptoms. I also began HCL,and many other supps. As I read about progesterone, I also learned about cortisol. The progesterone did stop my vomiting,along with HCL. The hyperpigmentation also decreased alot.

I met with a couple of naturopaths later in '05 and began cortisol during that time. I had a salivary test and a serum test that showed it was low.

Unfortunately, I found those two ND's to be rather unprofessional and inexperienced with my condition. I moved on to an endocrinologist. At first, he was impatient with me, in part because he "hates naturopaths", and that I no longer looked the part of an addisonian. He had me stop HC for 24 hrs., then he tested ACTH and cortisol. They were both subnormal. Some time later, he repeated the procedure. The results were much the same, cortisol was <1.

So, he's been dubious of the etiology of my condition...I understand. But even though I may no longer produce cortisol now, it doesn't explain my symptoms prior to HC replacement. Actually, I had a crisis last year, and he became more understanding.

Yes, even folks who need HC may develop osteoporosis. I suspect that I was a candidate anyway as I have been a skinny white female most of my life.

The Endo was the first to measure vit D. He also seems to have alot of knowledge about other vitamins. I feel fortunate in that way.