Thyroid Hormones Decrease Plasma 1a,25-Dihydroxyvitamin D Levels

Somewhat ironic that we see this very detailed explanation of why "active" vitamin D is low in HYPERthyroid people, while the most common story here is of HYPOthyroid people having low vitamin D!

As so often, the work was done in mice. Be good to know if the same is true in humans.

Endocrinology. 2013 Jan 10. [Epub ahead of print]

Thyroid Hormones Decrease Plasma 1a,25-Dihydroxyvitamin D Levels Through Transcriptional Repression of the Renal 25-Hydroxyvitamin D3 1a-Hydroxylase Gene (CYP27B1).

Kozai M, Yamamoto H, Ishiguro M, Harada N, Masuda M, Kagawa T, Takei Y, Otani A, Nakahashi O, Ikeda S, Taketani Y, Takeyama KI, Kato S, Takeda E.

Source

Departments of Clinical Nutrition (M.K., H.Y., M.I., M.M., T.K, Y.Takei., A.O., O.N., S.I., Y.Taket., E.T.) and Nutrition and Metabolism (N.H.), Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8503 Japan; and Institute of Molecular and Cellular Biosciences (K.T., S.K.), the University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.

Abstract

The primary determinant of circulating 1a,25-dihydroxyvitamin D (1,25[OH](2)D) levels is the activity of 25-hydroxyvitamin D-1a-hydroxylase (cytochrome P450 27B1 [CYP27B1]) in the kidney. Hyperthyroid patients have been reported to have low levels of plasma 1,25(OH)(2)D. However, the detailed mechanism of thyroid hormone action on vitamin D metabolism is still poorly understood. The present study determined whether renal CYP27B1 gene expression was negatively regulated by thyroid hormones. T(3)-induced hyperthyroid mice showed marked decreases in plasma 1,25(OH)(2)D levels and in renal expression of CYP27B1 mRNA but no changes in plasma concentrations of calcium, PTH, or fibroblast growth factor-23. In addition, we observed that T(3) administration significantly decreased plasma 1,25(OH)(2)D and renal CYP27B1 mRNA levels that were increased by low-calcium or low-phosphorus diets and induced hypocalcemia in mice fed a low-calcium diet. Promoter analysis revealed that T(3) decreases the basal transcriptional activity of the CYP27B1 gene through thyroid hormone receptors (TRa and TRß1) and the retinoid X receptor a (RXRa) in renal proximal tubular cells. Interestingly, we identified an everted repeat negative thyroid hormone response element (1a-nTRE) overlapping the sterol regulatory element (1a-SRE) and the TATA-box -50 to -20 base pairs from the human CYP27B1 gene transcription start site. Finally, we established that CYP27B1 gene transcription is positively regulated by SRE-binding proteins and that a T(3)-bound TRß1/RXRa heterodimer inhibits SRE-binding protein-1c-induced transcriptional activity through the 1a-nTRE. These results suggest that transcriptional repression of the CYP27B1 gene by T(3)-bound TRs/RXRa, acting through the 1a-nTRE, results in decreased renal CYP27B1 expression and plasma 1,25(OH)(2)D levels.

PMID:

23307792

ncbi.nlm.nih.gov/pubmed/233...

Rod

7 Replies

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  • Very interesting indeed.

    My GP reckons everyone this far north is vit D deficient for most of the year, but of course some are more than others.

    I wonder if us thyroidians are more sensitive to being vit D deficient. I must say, taking 5,000 IU daily for a year has done me the world of good, my finger joints are fine again having been very painful. It feels like eating a piece of the sun when you take vit D.

    koala

  • Do you know what your latest Vit D score is?

    My latest score, in Dec, was 99 nmol, I think. The practice manager told me that she'd been told (by the snr GP, whom I've never met) that, as I'm in the optimal Vit D range, I will not be prescribed any more Vit D. The minimum level of the optimal range is 70 nmol. So, unless my Vit D score falls below 70 nmol, they will not accept that I may have insufficient levels of Vit D.

  • But vitamin D3 is dirt cheap on Amazon 365 x 5000iu for only around £8.99

    CityAssays Birmingham NHS path lab do postal vitamin D testing for £25 (less if you bulk buy and share with friends)

    I understand why the doctors are saying what they say but the fact remains that humans living now as human DNA evolved maintain vitamin D levels at 115nmol/l and that level rises during pregnancy and with age.

    See

    Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l.

    ncbi.nlm.nih.gov/pubmed/222...

    It's only around 50ng/ml 125 nmol/l we see the optimal anti inflammatory action of vitamin d and it's actions as a natural antibiotic.

    I wasted far too long with a 25(OH)D at 100nmol/l thinking that was adequate. Increasing to 125nmol/l enabled me to stop using antibiotics to treat repeat UTI's.

    This link leads to a chart showing the EXTRA (in addition to your current vitamin D intake) you need 25 iu per KG to move from 100nmol/l to 125nmol/l

    So 60kg weight x 25 = 1500 extra daily or 10500iu a week. So 2 x 5000iu capsules extra each week should raise your 25(OH)D so you have that stored reserve of vitamin D that enables your immune function to respond more effectively when challenged.

  • HyperT as well as HypoT? Well It's in the news a lot lately - hope folks take notice!

    Still wondering about the chicken and egg thing, Vitamin D & Thyroid probs, meanwhile it works for me - as Koala says eating, but drinking sunshine helps me - only in the morning mind, as taking it later keeps me awake! J :D

    and gov advice

    dh.gov.uk/health/2012/02/vi...

  • You may also be interested to know that both MAGNESIUM and the Omega 3 fatty acid DHA and Curcumin and the Vitamin E form gamma-tocotrienol help activation of the circulating form of Vitamin D switch to the active hormonal form.

    Calcidiol the circulating form has a half life of around 30 days whereas the Active hormonal form Calcitriol has a half life measured in hours. Because the active hormone is so powerful and you can have too much of a good thing it's best if when it's needed it can be upregulated efficiently and then switched off effectively when the jobs done.

    Most of us don't actually consume the current RDA for magnesium (it's partly to do with modern fertiliser use and plant breeding so there is less in food now than previously) Most of us could do with extra magnesium with each meal and before bedtime particularly if you are raising your vitamin d to higher levels. More Vitamin D enables more calcium to be absorbed BUT calcium requires counterbalancing with magnesium.

    To make a muscle fibre tense calcium is used to relax it requires magnesium

    To excite a neurone requires calcium but to calm that neurone requires magnesium.

    It's a ying yang arrangement but most of us have adequate calcium from milk, cheese yoghurt veggies but too little magnesium from nuts. Hence if we increase our calcium via increased vitamin D we should also top up our magnesium. There are calcium and magnesium calculators online to help you work out how much your currently getting. Don't forget if you're in a hard water area that will provide some (not enough but some) calcium and magnesium.

    The problem with omega 3 arises because we consume too much omega 6. They have a counterbalancing effect and if your diet is providing far too much omega 6 (these oils weren't available when human dna evolved and we had omega 3 omega 6 ratios about 1<>1 now it's 1 omega 3 <> 15 omega 6 so the poor omega 3 gets overwhelmed. Reducing the omega 6 (corn, sunflower, soy, cottonseed etc oils and intensively raised chicken/port or FEEDLOT beef if in USA) are our major sources (unless you are still eating margarine type spreads.

    You may find that using a fish oil supplement (high in DHA) would help.

    Be careful with the vitamin 3 not all have gamma-tocotrienol most are tocopherals.

    There is a blog here explaining what to look for in a Curcumin supplement.

    Best Curcumin Supplement?

    healthyfellow.com/1406/best...

  • That should have read Vitamin E not Vitamin 3

    You should be looking for a form with gamma-tocotrienol as well as mixed tocopherols.

    One of the things that goes wrong is scientific medical nutrition research is that they like to change one thing at a time so they know the effect is from that single ingredient or change.

    But Vitamin D3, Curcumin, omega 3, and Vitamin E are all anti inflammatory agents in their own right BUT TOGETHER their action is greater than each individual element.

    So you won't see the benefit of Vitamin D3 unless it's fully activated as and when required and the response will be greater when each of (or a combination of) the other players is also present.

    It's a bit like testing your car's fuel consumption in relation to tyre pressures.

    To get optimum fuel economy all the tyres have to be at makers specifications. It's no good just inflating the tyre called vitamin D3 without also ensuring you have the magnesium tyre optimal. and balanced by a good omega 3 omega 6 balance and other natural anti inflammatory agents available.

  • Hi there,

    I have hashis and have now been told very low on Vit D and need mega boost once a week. Endocrinologist says that is why I have been having life changing bone pain and feeling really poorly for such a long time. We shall see what happens when I start taking it.

    Cassie

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