Hey Thierry,
Thanks for this lead-in thread. Very timely…
I’ve been conducting a systematic analysis of studies registered on clinicaltrials.gov listing Vitamin D3 (Cholecalciferol) as the intervention since December of last year. The purpose of this analysis is to determine why so few of these studies conclude vitamin D3 results in favorable clinical outcomes and efficacy as a disease modifying therapy (DMT) for a variety of medical conditions.
I extracted data from the clinicaltrials.gov database using the site’s query tools to determine protocol, status, design, dose, dosing interval, duration of dose/exposure, and outcomes for completed registered clinical trials listing vitamin D3 (Cholecalciferol) as the intervention. Studies listing the intervention as vitamin D2 (Ergocalciferol) were excluded from this analysis.
The initial round of queries of the clinicaltrials.gov database determined the population of studies at vitamin D3 doses ranging from 400 IU/day, 1,000 IU/day, 4,000 IU/day, 5,000, IU/day, 10,000 IU/day, 15,000 IU/day, 20,000 IU/day and 40,000 IU/day.
I made additional queries on single oral loading doses of vitamin D3 up to 600.000 IU. Subsequent rounds of queries searched for studies using weekly, fortnight, and monthly bolus dosing. I analyzed selected studies for the same conditions being treated by dose, duration of exposure, outcome measures, and with respect to the guideline rules for individual clinical studies of nutrient effects developed by Dr. Heaney, MD. Additional data used in this analysis were obtained from GrassrootsHealth, Vitamin D Wiki and the Vitamin D Council.
I hope to get this analysis published in a month or two and I’ve already gained the support of two nationally recognized vitamin D3 experts as co-authors.
Here are some of the preliminary results of my analysis:
There have been 760 RCTs, CTs and OS listing vitamin D3, (Cholecalciferol), as the intervention registered in clinicaltrials.gov between 01/01/2000 and 12/07/2015.
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743 of these studies have been registered since January of 2006. 380 of the 760 studies are listed as completed and 60 are listed as having results. 24 of the 740 studies were terminated, 4 were suspended and 18 were withdrawn. Of the 760 registered vitamin D3 studies, 251 (33%) listed vitamin D deficiency (hypovitaminosis D) and 153 (20%) studies listing bone and skeletal as the conditions being treated. That leaves 356 (47%) of the 760 studies investigating non-skeletal medical conditions treated with vitamin D3.
The top ten medical conditions treated with vitamin D3 included: 93 studies for cancer, 71 for osteoporosis, 67 for respiratory disorders, 63 for diabetes, 61 for general infection, 53 for kidney related disorders, 51 for obesity, 36 for autoimmune disorders, 20 for heart related disorders and 16 for hypertension. Of the 760 studies, only 62 (8%) indicated an average daily vitamin D3 dose of 5000 IU or greater.
None of the studies examined met all five of the guideline rules developed by Dr. Heaney for individual clinical studies of nutrient effects and only a handful listed one or more of the vitamin D3 conutrients/co-factors. There were six completed studies using Vitamin D3 as the intervention at doses ≥ 5,000 IU/day and ≤ 40,000 IU/day for Multiple Sclerosis that concluded marked improvements in bio-markers for MS with improved overall clinical outcomes.
My conclusions so far… The majority of RCTs, CTs and OS completed so far have concluded the null hypothesis (it didn’t work), or claimed the results are inconclusive simply because only 62 (8%) of the 760 vitamin D3 studies registered in clinicaltrials.gov used a vitamin D3 dose ≥ 5,000 IU/day and 31 studies listed the vitamin D3 dose ≥ 50,000 IU/week. In simple terms only 93 (12%) of the 760 vitamin D3 studies listed doses of vitamin D3 and dosing intervals capable of generating therapeutic serum concentrations of both cholecalciferol and 25(OH)D. Moreover, of these 93 studies, only 44 (5.7%) of them have been completed since 2000.
To make matters worse, only a handful of these 44 studies meet the gold standard for RCTs, (randomized, blinded, and placebo controlled). Accordingly, the medical evidence mafia relegates the results of the remaining successful vitamin D3 studies as Level III or IV in medical evidence to further diminish their value to physicians.
In addition, there is also evidence of a clear and present bias against treating a wide variety of medical conditions with vitamin D3 at therapeutic doses, i.e., ≥ 5,000 IU/day or ≥ 50,000 IU/week. This bias is widespread frequently taking the form of fear mongering articles warning against the “dangers” of taking pharmacological doses of vitamin D3.
This bias also takes the form of opposition research as evidenced by the number of studies concluding U-shaped, J-shaped and reverse J-shaped mortality curves associated with increasing doses of vitamin D3 and resulting in higher 25(OH)D serum concentrations.
It shouldn’t come as a surprise that Big Pharma is behind most of the fear mongering articles and opposition research in one way or another… All you need to do is follow the money… Big Pharma has $Billions at risk at the bottom line if the truth were to come out in a series of gold standard RCTs that an average of 70 cents per day of vitamin D3 is just as effective and in many cases more so, in treating disorders like multiple sclerosis without adverse side effects than patented pharmaceuticals like Extavia (interferon beta-1b), Gilenya (Fingolimod), or Copaxone (Glatiramer acetate) costing $4400 to $5400 for a months worth of treatments.
As an example of bias… an author of one of these opposition research studies who cited a “Reverse J-Shaped mortality curve” due to higher doses of vitamin D3 had a clear conflict of interest being employed by several large Pharmaceutical firms while writing the study results. This is all very disconcerting when you consider the fact that the FDA Adverse Event Reporting System (FAERS), has yet to report a single death attributed to vitamin D3.
Another classic example of biased reporting and fear mongering can be found on the Wikipedia web page for vitamin D3. Sadly, it appears Big Pharma has taken control of this website…
The operable Wikipedia web page section at the following link concludes:
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“
To Prevent Disease…”
Supplements are not recommended for prevention of cancer as any effects of cholecalciferol are very small. Although significant correlations exist between low levels of blood serum cholecalciferol and higher rates of various cancers, multiple sclerosis, tuberculosis, heart disease, and diabetes, the consensus is that supplementing levels is not beneficial. “
This statement is immediately juxtaposed by:
“
Use as rodenticideRodents are somewhat more susceptible to high doses than other species, and cholecalciferol has been used in poison bait for the control of these pests. It has been claimed that the compound is less toxic to non-target species. However, in practice it has been found that use of cholecalciferol in rodenticides represents a significant hazard to other animals, such as dogs and cats.”
How about that? Tell us vitamin D3 is no good in treating various cancers, multiple sclerosis, tuberculosis, heart disease, and diabetes… then tell us it can be used as a rat poison… WTF Over! What kind of message is that?
While we’re on this topic, let’s run down the rodenticide role of vitamin D3…
The LD50 for oral vitamin D3 for rats, (R. rattus), ( LD50 = the dose of vitamin D3 at which 50% of the rats die) was found to be 42 mg/kg for males and 619 mg/kg for female rats.
The anti-inflammatory regimen we take to prevent our CH calls for an average of 10,000 IU/day and a resulting serum 25(OH)D response around 80 ng/mL. As 10,000 IU of vitamin D3 equals 250 µg, this works out to 250 µg/day. That makes the average dose expressed in kg/day for a Cher weighing between 70 and 100 kg, between 2.5 to 3.5 µg/kg/day. 1 mg = 1000 µg, so 42 mg = 42,000 µg.
Accordingly if we use the male rat LD50 of oral vitamin D3 of 42 mg/kg, we would need to increase our oral vitamin D3 intake/kg/day by a factor of 12,000 to 16,800 or a maximum of 1,680,000 IU/kg which works out to 168,000,000 IU of vitamin D3 per day for a CH’er weighing 100 kg to reach the male rat LD50 dose.
Let me put that in a visual perspective. A 300-count bottle of Nature’s Bounty 5,000 IU liquid softgel capsules totals 1,500,000 IU of vitamin D3. Accordingly, we would need to consume 112 bottles of this brand of vitamin D3 all in one sitting… to reach the male rat LD50…
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So much for the LD50 of vitamin D3 as a toxin... Remember, vitamin D3 intoxication or toxicity refers to a condition where too much of the hormonal form of vitamin D3 in the blood stream pulls too much calcium from the gut and pushes it into the bloodstream causing serum calcium concentrations to exceed it's normal reference range.
Remember the movie Cool Hand Luke and "I can eat 50 eggs?" My guess is if anyone is dumb enough to try this stunt as a suicide method, would suffer severe abdominal pain from GI tract blockage caused by all the gelatin in the gel coats long before reaching the LD50 dose of vitamin D3.
Getting back to the title of this thread “Can Too Much Vitamin D Be Toxic?” The short answer is yes… but you need to define “Too Much” and you also need to define the treatment protocol.
For example, Dr. Cicero Coimbra, MD, PhD, Associate Professor, Department of Neurology and Neurosurgery, Federal University of Sao Paulo, Brazil, has been treating multiple sclerosis (MS) patients since 2011 with a vitamin D3 protocol calling for 1000 IU of vitamin D3 per kg of body weight per day… He also treats his MS patients with vitamin B2... He now has several thousand MS patients on this treatment protocol.
For a sleek rascal like me weighing up to 100 kg… at times… following Dr. Coimbra's protocol would have me taking 100,000 IU/day of vitamin D3. That’s ten times more vitamin D3 than suggested as a CH preventative.
What’s important about Dr. Coimbra’s MS treatment protocol is the complete avoidance of food types high in calcium and no calcium supplements. MS patients on this protocol also take vitamin B2 and drink 2.5 liters of water a day to help flush any calcium buildup from their kidneys.
In many cases Dr. Coimbra's MS patients cannot monitor their actual 25(OH)D serum concentration because the assay methods used only go up to a maximum of 150 ng/mL or 200 ng/mL. What Dr. Coimbra’s MS patients monitor closely is their serum calcium, serum PTH and serum phosphorus.
I’ve shared results of the anti-inflammatory regimen treatment protocol to prevent CH with Dr. Coimbra, and he’s been kind enough to share some insights on his MS treatment protocol with me. He indicated he started his treatment of MS patients in 2002 with a similar protocol using 10,000 IU/day of vitamin D3. It was effective for a few of his MS patients in reducing the number of relapses, but it didn’t result in an MS remission so he started titrating their vitamin D3 doses up and finally settled on 1000 IU of vitamin D3 per kg of body weight per day around 2011 to 2012.
I’ve also had the opportunity to exchange email with one of Dr. Coimbra’s MS patients. She lives in the US and travels to Sao Paulo, Brazil once a year for follow-up meetings and lab tests with Dr. Coimbra. She takes 50,000 IU/day vitamin D3 and indicated it took a few months for Dr. Coimbra’s protocol to take effect, but she is now free of MS symptoms and has been in complete remission since then. The key words she used were, “I live a very normal life free of any MS symptoms…” and “Before meeting Dr. Coimbra and starting his protocol, my future with MS was very bleak.”
You can find more information on Dr. Coimbra’s MS protocol and physicians trained by Dr. Coimbra in the use of this protocol at the following links:
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Before I go any further, DO NOT, I REPEAT, DO NOT, ATTEMPT THIS PROTOCOL WITHOUT DIRECT SUPERVISION BY DR. COIMBRA OR A PHYSICIAN TRAINED BY HIM!
My rationale for bringing up Dr. Coimbra’s MS treatment protocol is simple… If any of you think 10,000 IU/day vitamin D3 is too high a dose or toxic… read through the above links then think again…
Take care,
V/R, Batch