Vitamin D

Property	Information
Drug Name	Vitamin D
FDA Approval	No
Used for	Glioblastoma Multiforme (GBM), various types of cancer
Clinical Trial Phase	Various studies, including recent meta-analyses and reviews
Clinical Trial Explanation	Not specified
Common Side Effects	Hypercalcemia at high doses of calcitriol; other forms generally safe
OS without	Not explicitly detailed in recent reviews
OS with	Recent meta-analyses suggest potential for improving cancer treatment outcomes
PFS without	Not specified
PFS with	Not specified
Usefulness Rating	4
Usefulness Explanation	Not specified
Toxicity Level	2
Toxicity Explanation	A toxicity level of 2 for this treatment implies that it has a low toxicity level, meaning the common side effects observed are generally mild and tolerable. The main known side effect is a condition called Hypercalcemia, which is an excessive level of calcium in your blood, that occurs only at high doses of one type of Vitamin D variant. But, it's essential to follow recommended dosage and supplementation strategies for the best therapeutic benefits. The treatment lacks FDA approval currently, hence, it's important to have a conversation with your healthcare provider before starting any new supplement or treatment.

Notes: Recent reviews underscore Vitamin D's potential in cancer prevention and treatment, emphasizing its impact on biological mechanisms related to cancer regulation and its possible synergistic effects with chemo/immunotherapeutic drugs. The dosage and supplementation strategies are critical for optimizing its therapeutic benefits.

Links: * [The impact of vitamin D on cancer: A mini review - PubMed](https://pubmed.ncbi.nlm.nih.gov/37054849/)

• [Vitamin D supplementation and total cancer incidence and mortality - British Journal of Cancer](https://www.nature.com/articles/s41416-020-01188-1)

From Ben Williams Book: Numerous laboratory studies have shown that Vitamin D is highly cytotoxic to cancer cells, due to several different mechanisms (although labeled as a vitamin it more properly should be considered a hormone). While most research has focused on its ability to activate genes that cause cancer cells to differentiate into mature cells, other effects have also been identified, including cell cycle regulation, inhibition of the insulin-like growth factor, and the inhibition of angiogenesis (246). However, the calcitriol form of Vitamin Dis not readily usable for cancer treatments because the dosages producing anti-cancer effects also cause hypercalcemia, which can be life threatening (the major function of Vitamin D is to regulate calcium absorption and resorption from the bones and teeth). But like many vitamins/hormones, the generic designation refers not to a specific chemical structure but to a family of related molecules that may have different properties of various sorts. For Vitamin D several of these variants (commonly referred to as analogues) have been shown to effectively inhibit cancer cell growth but without the same degree of toxic hypercalcemia. In a 2002 paper in the Journal of Neuro-oncology (247), 10 patients with glioblastoma and one with a grade III AA tumor received a form of Vitamin D called alfacalcidol in a dosage of .o4 micrograms/kg each day, a dosage that produced no significant hypercalcemia. The median survival was 21 months, and three of the eleven were long-term survivors (greater than 5 years). Although the percentage of patients who responded to the treatment was not high, the fact that any relatively non-toxic treatment can produce any number of long-term survivors is remarkable. There is also strong reason to believe that Vitamin D is synergistic with retinoids such as accutane (248). Its effectiveness is also increased in the presence of dexamethasone (249) and a variety of anti-oxidants, notably carnosic acid, but also lycopene, curcumin, silibinin, and selenium (250).

Alfacalcidol is not available in the USA, but is available in Europe and Canada. For those in the USA it is possible obtain it from various online marketers. It also should be noted that several other Vitamin D analogues are available, which also have much reduced hypercalcemic effects. One of these, paricalcitol, was developed for treatment of a disorder of the parathyroid gland, and recently has been the subject of several experimental studies (251, 252, 253) that have shown it to be highly cytotoxic to 34

many different types of cancer. Given that other forms of Vitamin D have been shown to be highly cytotoxic to for glioblastoma cells, and that glioma cells are known to have receptors for Vitamin D, it seems likely that paricalcitol should have efficacy for glioblastoma as well. Unfortunately, its routine use is complicated by the fact it is available only in a form that requires intravenous injection.

The most common version of Vitamin D3 found in health food stores is cholecalciferol, which is the precursor of calcitriol, the form of Vitamin D utilized by the body. A recent study of cholecalciferol with prostate cancer patients who had progressed after standard therapy (254) suggests that this common form of Vitamin D3 may be clinically beneficial. Fifteen patients who had failed standard treatments were given 2000 I.U. daily. PSA levels were reduced or stayed the same for nine patients, and there was a reliable decrease in the rate of PSA increase for the remainder. No side effects of the treatment were reported by any of the patients.

Because serum Vitamin D levels have recently been shown to be inversely related to cancer incidence, there recently has been considerable discussion about the dosage that is toxic. Doses as high as 5000-10,000 I.U. per day appear to be safe. Recently, it has become common for women suffering from osteoporosis with low Vitamin D levels to be given as much as 50,000, I.U./day for short time periods. Nevertheless, it is important to note that all forms of Vitamin D can occasionally produce dangerous serum calcium levels, in part because there is a great deal of variability in their effects across individuals. It is thus important that blood calcium levels be monitored, especially while a nontoxic dosage is being established.Property "Has original text" (as page type) with input value "Numerous laboratory studies have shown that Vitamin D is highly cytotoxic to cancer</br>cells, due to several different mechanisms (although labeled as a vitamin it more properly</br>should be considered a hormone). While most research has focused on its ability to</br>activate genes that cause cancer cells to differentiate into mature cells, other effects have</br>also been identified, including cell cycle regulation, inhibition of the insulin-like growth</br>factor, and the inhibition of angiogenesis (246). However, the calcitriol form of Vitamin</br>Dis not readily usable for cancer treatments because the dosages producing anti-cancer</br>effects also cause hypercalcemia, which can be life threatening (the major function of</br>Vitamin D is to regulate calcium absorption and resorption from the bones and teeth).</br>But like many vitamins/hormones, the generic designation refers not to a specific</br>chemical structure but to a family of related molecules that may have different properties</br>of various sorts. For Vitamin D several of these variants (commonly referred to as</br>analogues) have been shown to effectively inhibit cancer cell growth but without the</br>same degree of toxic hypercalcemia. In a 2002 paper in the Journal of Neuro-oncology</br>(247), 10 patients with glioblastoma and one with a grade III AA tumor received a form</br>of Vitamin D called alfacalcidol in a dosage of .o4 micrograms/kg each day, a dosage</br>that produced no significant hypercalcemia. The median survival was 21 months, and</br>three of the eleven were long-term survivors (greater than 5 years). Although the</br>percentage of patients who responded to the treatment was not high, the fact that any</br>relatively non-toxic treatment can produce any number of long-term survivors is</br>remarkable. There is also strong reason to believe that Vitamin D is synergistic with</br>retinoids such as accutane (248). Its effectiveness is also increased in the presence of</br>dexamethasone (249) and a variety of anti-oxidants, notably carnosic acid, but also</br>lycopene, curcumin, silibinin, and selenium (250).</br></br>Alfacalcidol is not available in the USA, but is available in Europe and Canada. For those</br>in the USA it is possible obtain it from various online marketers. It also should be noted</br>that several other Vitamin D analogues are available, which also have much reduced</br>hypercalcemic effects. One of these, paricalcitol, was developed for treatment of a</br>disorder of the parathyroid gland, and recently has been the subject of several</br>experimental studies (251, 252, 253) that have shown it to be highly cytotoxic to</br>34</br></br>many different types of cancer. Given that other forms of Vitamin D have been shown to</br>be highly cytotoxic to for glioblastoma cells, and that glioma cells are known to have</br>receptors for Vitamin D, it seems likely that paricalcitol should have efficacy for</br>glioblastoma as well. Unfortunately, its routine use is complicated by the fact it is</br>available only in a form that requires intravenous injection.</br></br>The most common version of Vitamin D3 found in health food stores is cholecalciferol,</br>which is the precursor of calcitriol, the form of Vitamin D utilized by the body. A recent</br>study of cholecalciferol with prostate cancer patients who had progressed after standard</br>therapy (254) suggests that this common form of Vitamin D3 may be clinically</br>beneficial. Fifteen patients who had failed standard treatments were given 2000 I.U.</br>daily. PSA levels were reduced or stayed the same for nine patients, and there was a</br>reliable decrease in the rate of PSA increase for the remainder. No side effects of the</br>treatment were reported by any of the patients.</br></br>Because serum Vitamin D levels have recently been shown to be inversely related to</br>cancer incidence, there recently has been considerable discussion about the dosage that is</br>toxic. Doses as high as 5000-10,000 I.U. per day appear to be safe. Recently, it has</br>become common for women suffering from osteoporosis with low Vitamin D levels to be</br>given as much as 50,000, I.U./day for short time periods. Nevertheless, it is important to</br>note that all forms of Vitamin D can occasionally produce dangerous serum calcium</br>levels, in part because there is a great deal of variability in their effects across individuals.</br>It is thus important that blood calcium levels be monitored, especially while a nontoxic</br>dosage is being established." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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