I think you meant to write 1 mcg alfacalcidol (rather than 1 mg). In the French study from 2001, the dose was 0.04 mcg/kg per day. For a man weighing 65 kg, that would work out to 2.6 mcg per day. I think you could go up to 2 mcg per day at least, but bloodwork should include testing for hypercalcemia.In the GBM study using the 0.04 mcg/kg dose, there was no evidence of hypercalcemia in any of the patients after months of use.http://www.ncbi.nlm.nih.gov/pubmed/11349882I'll upload a copy of this to the Library.
Thank you Stephen, and yes, I meant 1mcg! Sorry. Actually I think I have already looked at this study previously and came up with 3.6mcg for my husband. This sounded a lot to me, but I think we will go up since there was no evidence of hypercalcemia...
HopeST - Do you mind me asking where you get your alphacalcidol?
Can someone share with me a source for alphacalcidol?
This is approved in Canada but not in the USA. You could get in through any number of Canadian pharmacieshttps://www.canadadrugs.com/products/one-alphahttps://www.universaldrugstore.com/medications/One+Alpha/0.25mcghttps://www.northdrugstore.com/buy-One-Alpha.htmlbut you'd likely need a prescription first.
Also one have to check renal function (estimated GFR using CKD-EPI with blood tests, and ultrasound)!
One advantage of alfacalcidol (which is a calcitriol prodrug) over vitamin D3 is that it doesn't require activation by the kidneys - it is converted into calcitriol directly by the liver. This means alfacalcidol is useful even for people with reduced kidney function.
Granted, the indicated use of alfacalcidol in Canada is "management of hypocalcemia, secondary hyperparathyroidism, and osteodystrophy in patients with chronic renal failure" so using it for patients with normal renal function would be an off-label use.
A new article about vitamin D:2018 https://www.ncbi.nlm.nih.gov/pubmed/29575677"The active form of vitamin D (1α,25-dihydroxyvitamin D) acts as a steroid hormone and binds to the vitamin D receptor.Vitamin D has several functions in the body including effects on brain development, neuroprotection and immunological regulation. It has been shown that vitamin D has antiproliferative activities in different cancer cell lines. Tacalcitol and calcipotriol are synthetic analogues of 1α,25-dihydroxyvitamin D with reduced effect on calcium metabolism. The aim of this study was to analyse the effects of tacalcitol and calcipotriol on cell viability, proliferation and migration in the human glioblastoma cell line T98G."My mom takes 4 months every day 2mkg (0.04mkg / kg) of alfacalcidol.A few days ago, we first made a blood test for the content of 25-hydroxycalciferol - an indicator of the vitamin D content in the body. Surprisingly, we got the value of 25-hydroxycalciferol in the blood within the norm - 61.38 ng / ml. I expected more.(Less than 30.00 ng / ml - vitamin D deficiency. More than 100.00 ng / ml - toxic concentration of vitamin D)Indicators of calcium, phosphorus, magnesium in the blood - normal.Given some reports of the possible benefits of vitamin D in glioblastomas, my question and idea is to do a blood test for vitamin D and regulate the amount of alfacalcidol taken to approach the maximum, but non-toxic values. Your opinion?
Did she have 25-hydroxycholecalciferol in the blood measured at baseline, prior to starting the alfacalcidol? It would be useful to know whether her levels have been increasing over the past four months, or whether they have been stable over that time.61.38 ng/mL = 153 nanomoles/liter (nanomolar). Unit convertor here: http://www.endmemo.com/medical/unitconvert/Vitamin__D.php"sunshine alone can bring 25(OH)D concentrations to210 nmol/L in normal people" [84 ng/mL].It is difficult to get levels higher than this with sunshine alone, so apparently the body naturally wants to restrict levels from going much higher than that. You could potentially increase alfacalcidol dose by small steps until you achieve the target value.information from: https://www.ncbi.nlm.nih.gov/pubmed/10232622
Unfortunately, I find out all too late and the level of 25-hydroxycalciferol has never been measured before.
http://sci-hub.tw/https://doi.org/10.1158/1078-0432.CCR-04-1968"As shown for numerous normal and cancer cell lines, calcitriol is at high concentrations an antiproliferative and prodifferentiating agent that induces apoptosis and inhibits cell migration (8). The antiproliferative properties of calcitriol, as described above, were also shown for central nervous system tumors, including glioblastoma cell lines (9). Beneficial effects of the vitamin D3 metabolite 1α- hydroxyvitamin D3 have been reported for the treatment of glioblastoma multiforme in a small phase II clinical study (10)."So I'm thinking now about replacing alfacalcidol with calcitriol (https://www.drugs.com/mtm/calcitriol.html), which gives a higher level of 1α, 25-dihydroxyvitamin D3 (calcitriol) in the blood.By the way, the risk of hypercalcemia is higher. But this problem is solved by a weekly blood test for calcium and phosphate.The question is a dose of calcitriol, which is significantly stronger than alfacalcidol.
In this study https://clinicaltrials.gov/ct2/show/NCT01293682 for breast cancer, a mega dose of calcitriol is used - 45 mg once a week for 12 weeks.Medication name: Rocatrol
http://sci-hub.tw/https://doi.org/10.1007/s00520-018-4094-4"Participants assigned to one of the calcitriol arms took 45 micrograms (mcg) of calcitriol once weekly. This dose was selected based on previous research that showed reduced hypercalcemia by using a weekly dosing strategy [5, 6, 8].Participants were advised to increase their water intake by 3–4 cups on the day they took the calcitriol and on the following Support Care Cancer day. Because a 45-mcg dose of calcitriol was not commerciallyavailable, bulk calcitriol was purchased from ChromaDex (Irvine, CA)..."https://www.ncbi.nlm.nih.gov/pubmed/17066293"DN-101 is a new, high-dose, oral formulation of calcitriol under investigation for the treatment of cancer...Repeat doses of DN-101 at 45 microg weekly are well tolerated and this dose is suitable for studies of weekly DN-101 in cancer patients."
Calcitriol is 1,25-dihydroxycholecalciferolAlfacalcidol is 1-hydroxycholecalciferolAlfacalcidol is a prodrug for calcitriol, and is rapidly converted to calcitriol in the liver. I've actually seen studies where taking alfacalcidol produced higher blood levels of calcitriol than taking calcitriol itself (both were taken orally if I recall correctly).
It is strange, but I can not find any studies on the effect of doses of alfacalcidol on calcitriol levels. Although I'm already looking for this week!)Conversely, these studies report that there is no increase in the levels of 25 OH D3 (calcidol) and 1a, 25 (OH) 2D3 (calcitriol) after the administration of alfacalcidol!http://sci-hub.tw/https://doi.org/10.1055/s-0042-103932https://academic.oup.com/ndt/article/19/4/870/1810359At clinicaltrials.gov, I see active trials in cancer with calcitriol, but not with alfacalcidol.Perhaps, since 2001, when alfacalcidol was tested for glioblastoma, did the paradigm change?Synthetic calcitriol "Rocaltrol" is on sale. 1 capsule - 0.25 mkg. However, in these studies, mega-doses are used!https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749360/table/T2/?report=objectonlyThus, mega-doses of Rocaltrol can give completely different levels of calcitriol than 2-2.5 μg of alfacalcidol in studies of 2001 with glioblastoma.Interesting Facts:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749360/"...the inhibition of CYP3A4 may lead to reduced ability of the enzyme to oxidize calcitriol in the liver and thus sparing calcitriol catabolism to yield higher intracellular levels. Therefore, the metabolism of calcitriol in the intestine and liver could contribute more to calcitriol bioavailability and tissue levels than CYP24A189. The combination of calcitriol with CYP3A4 inhibitors, therefore, could allow for the use of lower doses of calcitriol and still achieve significant anticancer effects......Calcitriol biosynthesis and metabolism pathways are catalyzed by multiple CYP enzymes. This provides the opportunity to the researchers and clinicians to either stimulate calcitriol biosynthesis or inhibit its metabolism in an organ-specific manner, leading to higher exposure to endogenous or exogenously administered calcitriol."
Vitamin D3 has to undergo an intermediate step, first to 25 OH D3 (calcidiol) and then to calcitriol. Alfacalcidol doesn't undergo that intermediate step, it is converted directly into calcitriol. So alfacalcidol wouldn't be expected to increase blood calcidiol concentrations, only calcitriol concentrations. If alfacalcidol didn't increase blood calcitriol, there would be no point taking it.
See Table 4 in this study:http://www.jptcp.com/articles/oral-calcitriol-versus-oral-alfacalcidol-for-the-treatment-of-secondary-hyperparathyroidism-in-patients-receiving-hemodialysis-a-r.pdfBlood calcitriol was tested at 6 weeks following oral calcitriol versus oral alfacalcidol administration. Oral alfacalcidol was more effective at increasing plasma calcitriol levels than oral calcitriol, which is very interesting.Alfacalcidol isn't approved for use in the USA, which might explain the relative rarity of clinical trials compared to calcitriol.
I presume by "mega dose" you're talking about the study that combined 0.5 microgram per kg Rocaltrol WEEKLY with docetaxel. Keep in mind the 2001 GBM trial used 0.04 microgram/kg per DAY, so that would be 0.28 microgram/kg per WEEK.The weekly dose of Rocaltrol was therefore about twice the weekly dose of alfacalcidol in the 2001 GBM trial. At least we know that the dose in the GBM trial didn't lead to any significant hypercalcemia. Monitoring the blood for signs of hypercalcemia may be required for any significantly high dose of alfacalcidol or calcitriol/Rocaltrol.
Stephen, thank you very much for the detailed explanations!By the way, as I understood, 45 mcg of calcitriol was an impulse dose for 1 day a week.