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Calcium, Magnesium, and Vitamin D

Discussion in 'General Treatment' started by Changexpert, Oct 26, 2015.

  1. Changexpert

    Changexpert Senior Member

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    I think many people may know this topic on vitamin D already, but I think a very important connection to an immune response initiated inflammation needs to be addressed.

    There are two forms of vitamin D, 25-OH, which is a storage form. Most supplements we take are in is in this storage form (cholecalciferol). Once cholecalciferol is ingested, our liver converts it into the active form calcitriol, aka vitamin D 1,25. I have had multiple lab tests for both of these readings and many my storage form is constantly on the low side while my active form is constantly elevated, above the reference range. Even after standing in the sun for at least 40 minutes daily for 3 months, I could not get my storage level up. In hindsight, I think these contrary levels were due to supplementation of magnesium for a long time as magnesium is a necessary component that gets used up for the conversion process of storage vit D to active vit D.

    One big problem with high active level and low storage level is immune system dysfunction. The storage form is associated with immune system regulation, making sure that the immune system does not go haywire to attack our own cell (autoimmune response). On the contrary, active form makes sure that our immune system stays active enough to combat pathogens/infection. This perfectly matches with a thought I have had from JAK/STAT connection, where overstimulation of immune system is one of primary causes of hair loss.

    The best way to raise vitamin D level up is sun exposure, especially for people with a congested liver. If supplemental route is pursued, Vitamin D should not be taken alone. Storage vitamin D intake would convert more active form by nature (enhanced by magnesium intake, whether from food or supplement), and increased active D level leads to increased calcium absorption in the intestine. So vitamin D and calcium are synergistic. If calcium is not taken with vit D, then active D just floats around and do not get consumed to absorb calcium. This creates another issue where parathyroid hormone (PTH) is released in response to low calcium serum level, resulting in breaking down of a bone (osteoclast) to pull calcium away from bone to the serum (blood). So vitamin D consumption will create an endless cycle without an adequate calcium intake (http://courses.washington.edu/conj/bess/calcium/PTH-action.png).

    In addition, magnesium is used up to convert storage D into active D, so magnesium is also important assuming your active D level is not elevated. However, I would think that many hair loss sufferers have high, if not elevated level of active D form because I have seen too many posts about itchy scalp, a perfect example of inflammation from immune system overreaction.

    So many of people on PR (including myself) focus heavily on magnesium intake and pay close attention to details. What are magnesium agonists? What are magnesium antagonists that I should avoid? What are other minerals that need to be in balance with magnesium? What forms of magnesium should I take? Is transdermal better? What dosage is the most appropriate? Should it be taken before/after meals or away from meals? So much magnesium love here. I do not think it is coincidental that a lot of people (again, including myself) have elevated active D level while having low storage D level.

    Looking back, I have stopped drinking milk completely for 2.5 years because I realized I am lactose sensitive (not intolerant). Also, I have stayed away from dairy as much as possible, which means my calcium intake has been significantly lower for past 2.5 years. The time frame coincides perfectly with the onset of aggressive hair loss. If my guess is right, restoring calcium level (not through osteoclast - this is not ideal) along with storage vit D level should lower the active D level, both of which would lower inflammation greatly.

    Please share your thoughts/comments on this approach. Thank you so much.

    https://www.vitamindcouncil.org/blog/activated-vitamin-d-vs-25ohd-levels-what-should-you-measure/

    PS - There are multiple posts/articles claiming magnesium is needed for vitamin D conversion, but they do not cite any scientific studies. Upon research, I have found that vitamin D conversion is dependent on several CYP genes in the liver, which are all dependent on heme (metabolized iron). FAD (one of active forms of B2) is needed for heme synthesis. Magnesium is a cofactor for FAD synthesis. It is a very roundabout explanation, but it does its job ;)

    PS2 - The above reference only shows magnesium as a cofactor, which means magnesium is not used up in the process. Taking a stab from a different perspective, NADPH is used in the kidney to convert storage D into active D. Maybe, it is the conversion of NADP+ to NADPH and pentose phosphate pathway that use up the magnesium (1, 2, 3).

    http://www.uniprot.org/uniprot/Q8NFF5

    @Gondwanaland @Beyond @heapsreal @MeSci @snowathlete @adreno @Sushi @Hip
     
    Last edited: Oct 26, 2015
  2. Hutan

    Hutan Senior Member

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    It's interesting what you say about Mg being needed for the conversion of Vitamin D to an active form - and that active form of Vit D ramping up the immune system.

    Looking at my diary, around a week ago, I had foot and hand cramps and took magnesium over a couple of days to try to stop the cramps. Immediately after that, I had sweats, not a usual symptom for me. My morning temperature had been in the 36.2 to 36.3 degrees C range prior to the magnesium. After the magnesium, my morning temperature has increased to a range of 36.5 to 36.8. And, at that time, considerable hair loss started and has been going on until now, again not something that happens usually.

    It all could be a coincidence of course. Maybe others have found something similar?
     
    Gondwanaland likes this.
  3. Hutan

    Hutan Senior Member

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    I just googled magnesium deficiency and found among the symptoms this:

    In this week since taking the magnesium, along with changes noted in my post above, my weight has dropped 1.4 kg (roughly 2% of my body weight), with incremental loss each day. Prior to that, my weight had been slowly, inexorably increasing so this fairly rapid weight loss is quite remarkable for me and I had been wondering about the cause. (And I don't think all of the weight loss is a result of the hair loss :))

    Thanks @Changexpert for prompting this insight. Sorry if all this has been boring anecdotes but I'm a bit excited to find a theory that hangs together to possibly explain the quite significant changes of the past week.
     
  4. alicec

    alicec Senior Member

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    The other thing we need to take into account is that 1,25 diOH vit D (calcitriol) can have an extra-renal source, namely immune cells such as monocytes and macrophages. These are not subject to the controls described above which can lead to elevated levels independently of calcium or magnesium intake or any of the other things that normally regulate the interconversion of cholecalciferol and calcitrol. Elevated calcitriol in turn drives down cholecalciferol.

    Extra-renal production is very characteristic of certain inflammatory disease such as sarcoidosis, some auto-immune conditions and it seems very likely ME/CFS. At least the pattern you describe of high calcitriol and low cholecalciferol seems to be common. There is a thread which discusses it here.
     
  5. maryb

    maryb iherb code TAK122

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    @Changexpert
    Ditto on massive hair loss after going dairy free, I never connected it before though.
     
  6. Changexpert

    Changexpert Senior Member

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    @Hutan
    I can definitely relate. I have taken magnesium almost daily for almost 10 months straight. In the course of the time, my temperature fluctuated somewhat, but had an upward trend. My body temperature started at 96.5 F and gradually increased to 97.3, and finally to 97.8 F. However, recently, I have stopped taking magnesium altogether because I was suspecting that something was off. I had a physical check up last week and my temperature was back down to 97.3 F. Maybe it is just a coincidence, since my body temperature always fluctuated somewhat. I have not been able to hit 98.6 F since my CFS worsened. Fortunately enough, my fasting glucose level is optimal and fasting insulin level is very low. Perhaps 10 months of magnesium supplementation helped me optimizing glucose metabolism.

    @alicec
    Thank you for a great post. Can you explain what drives extra-renal production in more details please? I suppose extra mineral consumption would cause this, but I do not know much about this topic.

    @maryb
    Osteoclast results in extra hydrogen ion (H+) in the body, resulting in increased "acidity" (1). Hydrogen ion activates TRPV1 pathway, which brings a wide range of problems. These problems include decreased growth of hair shaft, apoptosis induction, increased endogenous hair growth inhibitors (interleukin-1beta, transforming growth factor-beta(2)), and decreased hair growth promoters (hepatocyte growth factor, insulin-like growth factor-I, stem cell factor).

    Source: http://www.ncbi.nlm.nih.gov/pubmed/15793280

    I am not suggesting take megadose of calcium. What I am suggesting is take adequate amount to the point osteoclast does not occur.I personally think cycling between calcium and magnesium supplements would be a good way to alleviate high active vit D, low storage vit D issue.
     
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  7. alicec

    alicec Senior Member

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    No it has nothing to do with mineral consumption, nor is it a normal occurrence. I don't know if the exact triggering mechanism is understood but it occurs in particular circumstances which are usually pathological. The only non-pathological circumstance I know of is during pregnancy.

    As you note, Vit D modulates the immune response and it seems as if immune cells like macrophages draw on their own capacity to produce calcitriol to help deal with certain immune crises. The enzyme in macrophages is not subject to the same negative feedback as in the kidney and so if the immune crisis becomes chronic there is the possibility that uncontrolled calcitriol production will continue.
     
    picante likes this.
  8. Gondwanaland

    Gondwanaland Senior Member

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    Can anyone envision why I get hypothyroid symptoms when I supplement with D3? Consequently, my anti-TG antibodies skyrocket. (could it be iodine deficiency?)

    The only time I checked both my D 25OH was 43.1 ng/mL and D 1,25 49 pg/mL

    Last time I checked D 25OH was 38.9 ng/mL. I notice it raises without supplementation when I eat plenty of eggs and butter, so I don't consider supplementing any time soon due to the thyroid issues.

    (@picante )
     
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