by Ian Wishart
A 2006 study tested the vitamin D levels of breast cancer sufferers against a control group and found women with less than 20 ng/ml (50 nmol/L) of vitamin D were three and a half times more likely to develop breast cancer.[7]
Precisely how vitamin D works against breast cancer is still being determined, but a 2010 study reports that when vitamin D was used against breast cancer cells in laboratory experiments, half the cells shrivelled up and died.
“What happens is that Vitamin D enters the cells and triggers the cell death process,” researcher JoEllen Welsh told Good Morning America. “It’s similar to what we see when we treat cells with Tamoxifen.”[8]
Vitamin D status may also determine how vulnerable you are to the nastier breast cancers. There are different types of tumour, and surgeons have to treat them differently. Roughly 75% are known as ER positive, meaning they grow bigger in response to estrogen. Treatment options like Tamoxifen work by helping to block the estrogen receptors (docking bays) that the breast cancer cells feed from.
If your cancer is ER negative, your treatment is more difficult and your prognosis is not as good.
A University of Rochester study has found breast cancer patients with “sub-optimal” vitamin D levels of less than 33 ng/ml in their blood, were more than two and a half times more likely to have a “more aggressive”, ER negative tumour. Worse, if there could be such a thing, they were more than three times more likely to develop what’s known as a “triple negative cancer”, such tumours being unresponsive to drugs like Tamoxifen or Herceptin.[9]
“These cancers generally respond well to adjuvant chemotherapy. Overall, however, they have a poorer prognosis than other types of breast cancer. So far, no targeted therapies like Tamoxifen or Herceptin have been developed to help prevent recurrence in women with triple-negative breast cancer. Cancer experts are studying several promising targeted strategies aimed at triple-negative breast cancer.”[10]
The discovery that vitamin D is manufactured locally in breast cells is a vital clue, because it proves vitamin D is supposed to be found in breasts. There would be no biological reason for vitamin D production in healthy breast cells unless it served a purpose. This discovery makes the protective “effect of vitamin D in breast cancer biologically plausible.”[11]
An intriguing new twist that further establishes vitamin D as central to fighting cancer has emerged from a study of black American women. It has long been known that people with darker skins have a harder time generating vitamin D in the cooler temperate zones, so if vitamin D is involved in cancer you’d expect darker skinned people to be hit harder.
Just as with autism, so with cancer. Not only are African-American women six times more likely to be vitamin D deficient, but they are also more likely to suffer from a faulty gene that interferes with vitamin D production. That leaves them particularly vulnerable to the more aggressive “ER negative” form of breast cancer, which again fits with the study mentioned a moment ago.
Those African-American women who beat the odds and had the highest levels of vitamin D turn out to have a further variation that actually cut their aggressive breast cancer risk by half.
What does this mean? It shows that the rates of the most untreatable breast cancers in dark-skinned women appear to be linked to genetic variations in how they are able to process vitamin D. Once again, this humble, long-forgotten vitamin is at the centre of a revolution in how we understand the rise of cancer in modern times.
Scientists are now beginning to wonder what happens if teenage girls don’t get enough sun or vitamin D while their breasts are developing. Researchers have gone back to a group of 29,480 women interviewed as teenagers way back in 1998 as part of the Nurses’ Health Study.
Of that sample, 682 have since developed what’s known as proliferative benign breast disease. Women with the highest dietary intakes of vitamin D foods in 1998 turn out to have reduced their risk of benign breast disease by 21%, leading the study to conclude, “vitamin D intake during adolescence may be important in the earlier stage of breast carcinogenesis [and offer] new pathways and strategies for breast cancer prevention.”[12]
Another recent study looked at the differences between pre-menopausal and post-menopausal breast cancer sufferers. Again, they found undeniable evidence that lower vitamin D equals a worse outcome. The study covered 2,000 women aged 35 to 69, half diagnosed with breast cancer and half of them in the control group.
Women with 30 ng/ml (75 nmol/L) of vitamin D were found to have only half the risk of developing breast cancer as women with 20 ng/ml (50 nmol/L) – currently regarded as an “adequate” level of vitamin D by health authorities in some countries like New Zealand.
When they looked at the split, pre- and post menopause, they found younger women with good vitamin D cut their risk of developing breast cancer by 40%, while older women enjoyed a 63% risk reduction.[13]
Those are huge numbers in the great scheme of things. And in the great scheme of things, they do actually mean something. It’s true that full randomised, double-blind trials on people to see whether they develop cancer or not are pretty rare. The Women’s Health Initiative RCT was too low-dose to really shine. What’s needed is a study using doses of 4000IU or 5000IU a day. But there have been many studies showing women with high vitamin D levels have a much greater chance of surviving breast cancer, or not developing it at all.
“Prevention of breast cancer is one of the greatest challenges currently facing public health researchers and policymakers,” reported an analysis in 2011.[14]
“Globally, a wide range of epidemiologic studies have shown an inverse relationship between sunlight or UV B (UVB) irradiance (the main source of circulating vitamin D in humans),1-8 oral vitamin D intake,9-14 and serum 25-hydroxyvitamin D [25(OH)D] concentration (the main circulating vitamin D metabolite),15-22 with risk of breast cancer.
“There is also substantial laboratory evidence that vitamin D metabolites exert several powerful anti-carcinogenic effects on breast cancer cells.”
The analysts, in their study funded by the US Navy, also make the point that public health agencies have acted in the past on the basis of evidence staring them in the face, without waiting for randomized trials in every case:
“Epidemiological history has shown that an RCT is not necessary to establish causality or to prevent a disease. For example, it is widely accepted that tobacco smoking causes lung cancer, yet this knowledge was gained as the result of ordinary observational studies.”
Observational studies also found the cause of cholera, and helped in contact tracing for tuberculosis.
“Furthermore, RCT’s take far longer to complete and can cost up to 350 times as much as a nested case-control or ordinary case control study of the same topic when the purpose is testing prevention.
“Study after study, utilizing varying designs in both human populations and the laboratory, has demonstrated that vitamin D substantially reduces the risk of breast cancer. The A.B. Hill criteria have been largely satisfied, providing a compelling case for a causal, inverse relationship between vitamin D status and risk of breast cancer.”
Those arguments are backed up by the conclusions of a 2011 study into the most aggressive breast cancers, which found a 63% reduction in risk for breast cancer overall:
“In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women.[15]
“Because the risk of triple negative breast cancer peaks before menopause, and because vitamin D deficiency can be easily corrected by increasing sun exposure and/or supplement intake, if our findings are confirmed in large prospective studies for temporal causality, vitamin D may be used as a potential cancer preventiv
e agent against triple negative cancers among young women.”
Note that they feel the results are getting strong enough to warrant using vitamin D as a cautionary preventative, much as low dose aspirin has been used for cardiovascular disease.
Another team looking at this issue admits there is a difference in opinion between health policy officials, and specialists working at the coal face:[16]
“25-OH vitamin D is the accepted assessment of vitamin D status and provides a comprehensive measure of vitamin D from all sources (diet, sunlight, and supplementation). Although there is not a ‘standard’ definition of vitamin D status, a widely accepted classification is deficiency at <20 ng/ml, insufficiency at 20–31 ng/ml, and an optimal range of ≥32 ng/ml.[17]
“Despite a number of clinical trials, researchers and clinicians remain divided on the proper supplementation amount to achieve a normal 25-OH vitamin D level. The current recommendation by the Food and Nutrition Board (FNB) of the Institute of Medicine is for 400 IU a day of vitamin D for adults, with 2,000 IU a day as the tolerable upper intake level.
“However, numerous clinical trials administering low-dose vitamin D supplementation (≤800 IU/day) to participants with sub-optimal vitamin D levels failed to achieve optimal 25-OH vitamin D levels.[18] A recent study of breast cancer patients receiving treatment found supplementation with almost 2,000 IU a day of vitamin D failed to normalize 25-OH levels in 50% of participants.[19] Vitamin D deficient individuals often require a short course (4–16 weeks) of high-dose vitamin D supplementation (≥40,000 IU/week) to achieve an optimal 25-OH vitamin D level, although experimental evidence is severely limited.[20] While the FNB defines 2,000 IU a day of vitamin D as the upper intake level, high-dose vitamin D supplementation is well tolerated among a variety of participant populations, including those with cancer.”[21]
It seems pretty clear then that small doses of vitamin D are not enough to help cancer patients, and that some fairly serious prescribed supplements of up to 40,000IU a week may be necessary to compensate for initial vitamin D deficiency.
[1] “Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer,” Chlebowski et al, J Natl Cancer Inst
Volume 100, Issue 22:1581-1591
[2] “Calcium plus vitamin D supplementation and the risk of colorectal cancer,” Wactawski-Wende et al, N Engl J Med. 2006 Feb 16;354(7):684-96
[3] “Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women’s Health Initiative (WHI) limited-access data set,” Bolland et al, Am J Clin Nutr October 2011 vol. 94 no. 4 1144-1149
[4] “Vitamin D status at breast cancer diagnosis: correlation with tumor characteristics, disease outcome and genetic determinants of vitamin D insufficiency,” Hatse et al, Carcinogenesis. 2012 May 24. [Epub ahead of print]
[5] “Vitamin D status at breast cancer diagnosis,” Hatse et al, Carcinogenesis 2012, published online 23 May, doi: 10.1093/carcin/bgs187
[6] It’s also a direct example of how different studies can be. The 2008 Women’s Health Initiative study found 400IU daily of vitamin D made no difference, while nearly three times that dose in the 2007 study clearly did. See “Vitamin D and calcium supplementation reduces cancer risk,” Lappe et al, American Journal of Clinical Nutrition, 2007, 85(6):1586-91, http://img2.tapuz.co.il/forums/1_153137280.pdf
[7] “Vitamin D status and breast cancer risk,” Colston et al, Anticancer Res. 2006 Jul-Aug;26(4A):2573-80
[8] “In tests, vitamin D shrinks breast cancer cells,” by Suzan Clarke, ABC News, 22 Feb 2010
[9] “The association between breast cancer prognostic indicators and serum 25-OH vitamin D levels,” Peppone et al, Annals of Surgical Oncology 2012, doi: 10.1245/s10434-012-2297-3
[10]http://www.webmd.com/breast-cancer/breast-cancer-types-er-positive-her2-positive
[11] “Vitamin D and breast cancer,” Shao et al, The Oncologist, January 2012; Vol 17(1):36-45
[12] “Adolescent intakes of vitamin D and calcium and incidence of proliferative benign breast disease”, Su et al, Breast Cancer Research & Treatment 2012, doi: 10.1007/s10549-012-2091-8
[13] “Serum 25-hydroxyvitamin D and risk of breast cancer: results of a large population-based case-control study in Mexican women,” Fedirko et al, Cancer Causes And Control, 2012, Vol 23(7):1149-1162
[14] “Does the evidence for an inverse relationship between serum vitamin D status and breast cancer risk satisfy the Hill criteria?”, Mohr et al, Dermato-Endocrinology, Volume 4, Issue 2, April/May/June 2012, http://www.es.landesbioscience.com/journals/dermatoendocrinology/2012DE0186.pdf
[15] “Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study,” Yao et al, PLoS ONE 6(2): e17251. doi:10.1371/journal.pone.0017251, http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017251
[16] “The effect of various vitamin D supplementation regimens in breast cancer patients”, Peppone et al, Breast Cancer Research & Treatment, Volume 127, Number 1 (2011), 171-177, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085185/
[17] “Vitamin D insufficiency in North America,” Hanley et al, J Nutr. 2005;135:332–337 See also:
“Redefining vitamin D insufficiency,” Malabanan et al, Lancet. 1998;351:805–806. See also: “Estimates of optimal vitamin D status”, Dawson-Hughes et al, Osteoporos Int. 2005;16:713–716
[18] “Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis,” Hiremath et al. Mult Scler. 2009;15:735–740, See also “Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial,” Lips et al, Ann Intern Med. 1996;124:400–406. See also “Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial,” Meyer et al, J Bone Miner Res. 2002;17:709–715. See also “High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy,” Crew et al. J Clin Oncol. 2009;27:2151–2156
[19] “Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study.Prieto-Alhambra D, Javaid MK, Servitja S, Arden NK, Martinez-Garcia M, Diez-Perez A, Albanell J, Tusquets I, Nogues X. Breast Cancer Res Treat. 2011;125:869–878
[20] “Diagnosis and treatment of vitamin D deficiency,” Cannell et al, Expert Opin Pharmacother. 2008;9:107–118
[21] “A phase 2 trial exploring the effects of high-dose (10, 000 IU/day) vitamin D(3) in breast cancer patients with bone metastases,” Amir et al, Cancer 2010;116:284–291. See also “High-dose oral vitamin D3 supplementation in the elderly,” Bacon et al, Osteoporos Int. 2009;20:1407–1415. See also “A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis,” Burton et al, Neurology. 2010;74:1852–1859. See also “No significant effect on bone mineral density by high doses of vitamin D3 given to overweight subjects for one year,” Jorde et al, Nutr J. 2010;9:1
CHAPTER 6
CANCER, COLON & PROSTATE
“People diagnosed with colorectal cancer in the summer and autumn, when 25(OH)D concentrations are highest, had significantly better survival than those diagnosed in the winter”
– Dr Kimmie Ng, Harvard, 2011
COLORECTAL CANCER
Like breast cancer, the science on bowel cancer, as it is commonly known, is being written every day. There’s a lot riding on it. In 2008, an estimated 1.23 million people developed colorectal cancer, and more than 600,000 died from it, making it a bigger and more efficient killer than breast cancer.
In 2007, a review of published medical studies (known as a ‘meta analysis’) found that estimated blood levels of vitamin D of 33 ng/ml (82.5 nmol/L) were associated with a 50% lower risk of colon cancer.[1]
A 2008 study of bowel cancer patients found those with the highest vitamin D levels in their blood when they were first diagnosed with cancer cut their risk of dying by 48% – these we
re patients who already had the disease. Once again, the higher the vitamin D, the better chance you have of beating bowel cancer.[2]
The US National Cancer Institute’s main information page on vitamin D acknowledges that studies are showing benefits:
“At least one epidemiologic study has reported an association between vitamin D and reduced mortality from colorectal cancer. Among the 16,818 participants in the Third National Health and Nutrition Examination Survey,[3] those with higher vitamin D blood levels (≥80 nmol/L or 32ng/ml) had a 72 percent lower risk of colorectal cancer death than those with lower vitamin D blood levels (< 50 nmol/L or 20 ng/ml).”
The National Cancer Institute points out that most bowel cancers begin with benign tumours known as adenomas, and that higher levels of vitamin D in the blood appear to lower the risk of adenomas developing.
An NCI-sponsored study into the effect of diet on adenomas recurring after a colonoscopy was also able to monitor dietary intake for vitamin D – both through food and through supplements. The NCI reports the study found vitamin D gained solely from food appeared too trivial to have a beneficial effect, but that “individuals who used any amount of vitamin D supplements had a lower risk of adenoma recurrence.”[4]
“In another study, the vitamin D intakes of 3,000 people from several Veterans Affairs medical centers were examined to determine whether there was an association between intake and advanced colorectal neoplasia (an outcome that included high-risk adenomas as well as colon cancer). Individuals with the highest vitamin D intakes (more than 16 μg, or 645 IU, per day) had a lower risk of developing advanced neoplasia than those with lower intakes.[5]
“A pooled analysis of data from these and a number of other observational studies found that higher circulating levels of vitamin D and higher vitamin D intakes were associated with lower risks of colorectal adenoma.”[6]
The National Cancer Institute also notes that circulating blood levels of vitamin D might actually need to be quite high for protective purposes: