In a remarkable paper from Stanford University, Dr Swami and company, working under senior author Professor David Feldman, discovered that vitamin D has a treatment effect in mice that have surgically implanted inflammatory breast tumors. This is the same famous Dr Feldman who edits the textbook, Vitamin D.
Swami S, Krishnan AV, Wang JY, Jensen K, Horst R, Albertelli MA, Feldman D. Dietary vitamin D₃ and 1,25-dihydroxyvitamin D₃ (calcitriol) exhibit equivalent anticancer activity in mouse xenograft models of breast and prostate cancer. Endocrinology. 2012 Jun;153(6):2576-87.
The authors discovered that the effect of higher doses of vitamin D were equal to the anticancer effects of activated vitamin D (calcitriol) in these mice. Calcitriol’s anti-cancer effect in mice has been known for many years. In humans, resulting high blood calcium has limited the usefulness of calcitriol or similar analogues in treating cancer.
The researchers divided the mice into many groups, to either induce cancer into some of them, use some of the mice as healthy controls and to administer different amounts of vitamin D or calcitriol. For vitamin D groups, they administered it through their diet (chow). For calcitriol, they administered it through injections. Again, while there were many groups, here are the four most important groups to compare:
- One group with breast cancer received 5,000 IU of vitamin D per kg of chow
- One group with breast cancer received 1,000 IU of vitamin D per kg of chow. This was the first control group.
- One group with breast cancer received calcitriol at injections of .05 µg/week. They also received 1,000 IU of vitamin D per kg of chow.
- One group without breast cancer received 5,000 IU of vitamin D per kg of chow. This was a second control group.
Amazingly, the mice receiving 5,000 IU of vitamin D/kg of chow showed greater than 50% tumor shrinkage in four weeks compared to the 1,000 IU/kg of chow group. Unfortunately, the actual dose of vitamin D in an IU/kg/day format was not available. It takes mice months to consume a kg of chow.
In the mice with cancer on the 5,000 IU of vitamin D/kg of chow, 25(OH)D was only 38 ng/ml, but calcitriol was elevated in these mice at 117 pg/ml. Interestingly, when the researchers gave mice without cancer 5,000 IU of vitamin D/kg of chow, their levels of calcitriol did not spike nearly as high and were only at 72 pg/ml, possibly suggesting that the breast tumor was making the extra calcitriol.
However, there was evidence of another mechanism. In the cancerous mice taking 5,000 IU/kg of chow, the enzyme that makes calcitriol was elevated in the intestine (intestinal wall specifically), as well as in and around the tumor. No such elevation was seen in the non-cancerous control mice taking the same amount, suggesting the tumor, or the immune system’s response to the tumor, was somehow increasing systemic calcitriol increases.
We do know that in the test tube, calcitriol inhibits inflammatory breast cancer cells but has little effect on non-inflammatory breast cancer cells.
Hillyer RL, Sirinvasin P, Joglekar M, Sikes RA, van Golen KL, Nohe A. Differential effects of vitamin D treatment on inflammatory and non-inflammatory breast cancer cell lines. Clin Exp Metastasis. 2012 May 20. [Epub ahead of print]
In the Swami et al study, 5,000 IU/kg of chow also suppressed estrogen levels by 75% and aromatase (an enzyme that makes estrogen) by a similar amount in cancerous postmenopausal mice. In postmenopausal breast cancer, estrogen in tumor and surrounding fat tissue is thought to drive the tumor’s progression, raising the possibility that vitamin D will decrease aromatase activity and estrogen levels in human females with breast cancer.
However, the vitamin D physiology and pharmacology of mice and humans are quite different, so we have no idea of what dose might be effective in having a treatment effect in women with breast cancer. It does appear the dose must be high enough to raise calcitriol levels in breast cancer patients, as the authors found evidence that the elevated calcitriol levels were contributing to vitamin D’s anti-cancer effects.
In normal humans, the dose of D3 needed to raise calcitriol levels appears to be in the highly toxic range. In the study of 11 vitamin D toxic patients below, all with very high blood calcium, only three had elevated levels of calcitriol. If researchers have measured calcitriol levels in women with inflammatory breast cancer on adequate doses of vitamin D, I am not aware of that study.
Remember, the dose used in this study was not 5,000 IU/kg of body weight, rather 5,000 IU per kg of chow; please keep that in mind. 5,000 IU/kg of body weight would be 250,000 IU per day for a 110-pound woman. Such doses would always lead to toxicity and probably death if taken for several months.
Swami et al’s study is so interesting that I hardly know what to say, other than quote the authors, who concluded:
“At the supplement levels that we tested, our data support the hypothesis that dietary vitamin D3 is useful in the chemoprevention and treatment of breast cancer since it is an economical and easily available nutritional agent that is as active as calcitriol in inhibiting tumor growth with minimal hypercalcemic side effects. However, the use of very high doses of dietary vitamin D3 in the presence of cancers will require careful monitoring for hypercalcemia.”
However, given the fact that even toxic doses of vitamin D do not consistently raise calcitriol levels in normal humans, we do not know how much of this animal study can be transferred to women with breast cancer. We continue to recommend that anyone with cancer keep their 25(OH)D in the high range of normal, not in toxic ranges.