NZer1 wrote:In NZ we can only get Vit D3 in 50,000 ui form, and we cannot import it from suppliers such as IHerb or Vitacost, they won't supply due to regulations.
So pulse is the standard way to supplement in NZ.
BACK TO THE BEGINNING...
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In my continuing spirit of self-guinea-pigdom, I am trying a short burst of big time vitamin D3. This is in order to boost my serum levels up to around 125-150 nmol/l (the level recommended by one of my doctors, who also has MS).
I figured out from the literature, that it was going to take 5 months to get where I am supposed to be, if I stayed on my recent average 4400IU daily.
So, I found out from the drug info centre, how much to take to get a quick jump up about 50 nmol/l. They said they do 50,000IU per day for 10 days, but would usually use that on people that were seriously deficient.
My last level was 72 nmol/l which is only a little bit under the good zone for bone health. Some would argue it is way low for immune system health. So, I am not worried by jumping up another 50 nmol by next week.
I went to my family doc and asked for a prescription for 50000iu for 10 days and 4000 iu per day daily maintenance thereafter.
She said okay but also gave me a lab requisition for baseline testing prior to starting the big dose, another lab req for right after the big doses are over, and a third req for 2 weeks after to see if we're on the right track re: maintenance at 4000 IU/d.
My lab's computer system says that serum D3 levels over 250 are toxic but I relayed the story about the south indian workers with unsupplemented natural levels over 450 [edit: i'm okay with 250 being a safe upper end of the range, and anyway i was not and am not going for over 250!]. I also mentioned that I had a reference from my dietitian that listed a study where 50000IU taken daily for a month resulted in serum levels of 320, so 10 days should be safe in my case, and won't even get near her 250 limit anyway.
So the pharmacy i went to has a compounding license and he had ordered me the smoking highly concentrated D3 after a discussion we had last week. It's 1,000,000IU/gm. So I take 1/20th of a gm per day for 10 days. Instead of having to take 50 d3 pills each day for 10 days, I get to have about 2 drops of this liquid from a graduated oral syringe. SA-WEEEET! so much better than pills!
so, i get the baseline D result back probably on Monday, and will keep u all posted as to the improvement in my levels, and hopefully general condition and symptoms.
it's about time to get back on the supplement regimen again, as the legs have started to go jimmy again and everything.
the following list of results displays
test item;...result; (lab reference range); "lab comment"
serum ferritin;...............82; (51 - 140); "probably not iron deficient"
Uric Acid;.....................194; (150 - 350)
25-OH vitamin d3;..........74; (22.5 - 94.3)
zinc;...............................8.6; (11.5 - 18.5)
uric acid: BOO! stupid ms average, on the dot, AGAIN. food is not doing the trick, apparently.
d3: 22.5 - in the normal range?? that is so not healthy. 74 - BOOOO! i'm going to do that 50,000IU per day for 10 days thing again and kick it up to 150
zinc: interesting. i had not looked carefully through my posts once my legs went squirrelly during this last long layoff from the supplements. i kept having good intentions and then slacking.
the legs started to jimmy out on me again. i remembered an iron connection. i have purchased some within the last week and it worked somewhat. now my bloodwork shows low zinc. i just re-read my posts more thoroughly to note how while in australia i had connected the remaining jimmylegs issues to zinc, to resolve it the rest of the way.
so, i'll take zinc with meals, iron in between, and let you know if the jimmy thing backs off again.
d3 is in. 103 nmol/L.
aiming for 50 higher than that.
therefore am once again on 50,000IU/d for 10d. today is day 5.
as of today have another lab req for zinc, uric acid, copper.
d3, e, and a down the road a bit.
jun 19 labwork is starting to come in.
i actually overdid it with the D3!?!
instead of getting it up to 150 like the first time, this time around it went from 103 to 271 nmol/L!!!
i think this might be because of fixing the zinc deficiency, but i'm not clear on exactly how yet.
more good news re: zinc and uric acid. i'm up to 16.1 with the zinc, and the uric acid has jumped again, right in synch - it's at 278 now!!! only 12 more to go.
MarkW wrote:50,000iu as a pulse dose carries more risks than 5000iu daily. I only recommend such a dose of 50,000 iu under medical supervision. I am happy to recommend 5000 iu/day as a first step to pwMS on their own.
jimmylegs wrote:my understanding is that serum d3 levels are inversely correlated with PTH. i haven't been nose to the grindstone with vit de research over the last few yrs but i would think that correlation would be independent of pulse vs daily doses.
can anyone link to a study examining d3 interrelationships with PTH under different rates of exposure/intake and/or supplementation?
Subjects were randomized to receive oral cholecalciferol, as a single dose of 300 000 IU (group 1) or 800 IU (group 2) daily for 9 months. Both groups received 1250 mg calcium carbonate per day. Serum 25(OH)D and PTH levels were measured at baseline and after 1, 2, 3, 6, and 9 months. Serum 25(OH)D levels in group 1 were significantly higher than in group 2 during the study (P < 0.001). After 1 (P < 0.001) and 2 (P < 0.04) months of treatment, mean serum 25(OH)D levels were higher in group 1. The number of subjects who reached serum 25(OH)D levels >/=20 ng/dl was higher in group 1, after the first (P < 0.001) and third (P = 0.008) months. In the short term, a single 300 000 IU oral dose of vitamin D(3) was more effective than 800 IU per day to increase serum 25(OH)D levels in elderly persons, living in a low-income housing unit, who were taking 500 mg elementary calcium supplement per day.
Science. 2006 Mar 24;311(5768):1770-3. Epub 2006 Feb 23.
Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.
Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL.
Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, CA 90095, USA.
In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.
Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22593-8. doi: 10.1073/pnas.1011624108. Epub 2010 Dec 13.
T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism.
Edfeldt K, Liu PT, Chun R, Fabri M, Schenk M, Wheelwright M, Keegan C, Krutzik SR, Adams JS, Hewison M, Modlin RL.
Division of Dermatology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
We investigated the mechanisms by which T-cell cytokines are able to influence the Toll-like receptor (TLR)-induced, vitamin D-dependent antimicrobial pathway in human monocytes. T-cell cytokines differentially influenced TLR2/1-induced expression of the antimicrobial peptides cathelicidin and DEFB4, being up-regulated by IFN-γ, down-regulated by IL-4, and unaffected by IL-17. The Th1 cytokine IFN-γ up-regulated TLR2/1 induction of 25-hydroxyvitamin D-1α-hydroxylase (i.e., CYP27B1), leading to enhanced bioconversion of 25-hydroxyvitamin D(3) (25D(3)) to its active metabolite 1,25D(3). In contrast, the Th2 cytokine IL-4, by itself and in combination with the TLR2/1 ligand, induced catabolism of 25D(3) to the inactive metabolite 24,25D(3), and was dependent on expression of vitamin D-24-hydroxylase (i.e., CYP24A1). Therefore, the ability of T-cell cytokines to differentially control monocyte vitamin D metabolism represents a mechanism by which cell-mediated immune responses can regulate innate immune mechanisms to defend against microbial pathogens.
PLoS One. 2009 Jun 5;4(6):e5810. doi: 10.1371/journal.pone.0005810.
Convergence of IL-1beta and VDR activation pathways in human TLR2/1-induced antimicrobial responses.
Liu PT, Schenk M, Walker VP, Dempsey PW, Kanchanapoomi M, Wheelwright M, Vazirnia A, Zhang X, Steinmeyer A, Zügel U, Hollis BW, Cheng G, Modlin RL.
Division of Dermatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America. email@example.com
Antimicrobial effector mechanisms are central to the function of the innate immune response in host defense against microbial pathogens. In humans, activation of Toll-like receptor 2/1 (TLR2/1) on monocytes induces a vitamin D dependent antimicrobial activity against intracellular mycobacteria. Here, we report that TLR activation of monocytes triggers induction of the defensin beta 4 gene (DEFB4), requiring convergence of the IL-1beta and vitamin D receptor (VDR) pathways. TLR2/1 activation triggered IL-1beta activity, involving the upregulation of both IL-1beta and IL-1 receptor, and downregulation of the IL-1 receptor antagonist. TLR2/1L induction of IL-1beta was required for upregulation of DEFB4, but not cathelicidin, whereas VDR activation was required for expression of both antimicrobial genes. The differential requirements for induction of DEFB4 and cathelicidin were reflected by differences in their respective promoter regions; the DEFB4 promoter had one vitamin D response element (VDRE) and two NF-kappaB sites, whereas the cathelicidin promoter had three VDREs and no NF-kappaB sites. Transfection of NF-kappaB into primary monocytes synergized with 1,25D3 in the induction of DEFB4 expression. Knockdown of either DEFB4 or cathelicidin in primary monocytes resulted in the loss of TLR2/1-mediated antimicrobial activity against intracellular mycobacteria. Therefore, these data identify a novel mechanism of host defense requiring the induction of IL-1beta in synergy with vitamin D activation, for the TLR-induced antimicrobial pathway against an intracellular pathogen.
And just one more of many, many studies on the role that Vitamin D plays in activating the innate immune system in response to pathogens.Cell Microbiol. 2010 Aug;12(8):1026-35. doi: 10.1111/j.1462-5822.2010.01491.x. Epub 2010 Jun 14.
Innate immunity to mycobacteria: vitamin D and autophagy.
Department of Microbiology, Chungnam National University School of Medicine, Jungku, Daejeon, Korea. firstname.lastname@example.org
Autophagy is an ancient mechanism of protein degradation and a novel antimicrobial strategy. With respect to host defences against mycobacteria, autophagy plays a crucial role in antimycobacterial resistance, and contributes to immune surveillance of intracellular pathogens and vaccine efficacy. Vitamin D3 contributes to host immune responses against Mycobacterium tuberculosis through LL-37/hCAP-18, which is the only cathelicidin identified to date in humans. In this review, we discuss recent advances in our understanding of host immune strategies against mycobacteria, including vitamin D-mediated innate immunity and autophagy activation. This review also addresses our current understanding regarding the autophagy connection to principal innate machinery, such as ubiquitin- or inflammasome-involved pathways. Integrated dialog between autophagy and innate immunity may contribute to adequate host immune defences against mycobacterial infection.
At the very least, we must ensure that every researcher understands the importance of measuring the concentration of the actual transcriptional activator, 1,25 dihydroxy-vitamin-D.
My latest thinking is that vit D3 acts like a regulatory hormone on immune genes which have been turned up/on in an epigenetic manner by EBV/CPn and other things. If D3 is not present at higher blood levels the epigenetic up/on immune switches are not controlled. I also think that BBB porosity is regulated by epigenetics, otherwise why would it change in the relapsing-remitting stages of MS?
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