by Ian Wishart
“Another large, NCI-sponsored randomized, placebo-controlled trial explored the effects of calcium supplementation and blood levels of vitamin D on adenoma recurrence. Calcium supplementation reduced the risk of adenoma recurrence only in individuals with vitamin D blood levels above 73 nmol/L. Among individuals with vitamin D levels at or below this level, calcium supplementation was not associated with a reduced risk.”[7]
There are many other factors that help you avoid or survive cancers of course – diet being one of them – but the point here is that vitamin D is operating over and above that. Clearly, some people with high levels die regardless (otherwise the risk reduction would be 100%), but doubling your odds of survival with the Big C is not something to be sneezed at.
Given bowel cancer’s high mortality rate, however, there is evidence that people can’t be too complacent. Like breast cancer, if your vitamin D levels are not already high at the point of diagnosis, it may be too late for vitamin D to play much of a role in keeping you alive. Waiting until you get cancer, before reaching for the mega supplement, could be a deadly oversight.
A study published 2011, involving patients with Stage IV bowel cancer that had metastasised through the body, found two things. Firstly, that only 10% of their patient sample still had vitamin D levels high enough to be useful, and secondly, that the cancers had taken most of the victims beyond the point of no return.
The researchers led by Kimmie Ng provided a thoughtful analysis:[8]
“In the United States, colorectal cancer mortality follows a latitudinal gradient, with higher mortality rates seen in individuals who reside at higher latitudes. A large observational study in Norway found that 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.[9] We previously showed that higher prediagnosis plasma levels of 25(OH)D and higher postdiagnostic 25(OH)D scores are associated with significant reductions in mortality among patients with established colorectal cancer, although, in those studies, a substantially greater proportion of the population had plasma 25(OH)D levels higher than 33 ng/mL.
“In this study, we did not detect an association between higher plasma 25(OH)D and patient outcome. It is possible that vitamin D may have limited impact on the natural history of colorectal cancer once it has metastasized. Preclinical data indicate that VDR expression is decreased in late stages of neoplasia,[10] perhaps leading to loss of response of colon tumor cells to vitamin D. Yet another potential explanation for the discrepant results is that our study had limited statistical power, with only a small number of patients with plasma 25(OH)D levels sufficient for a protective effect on cancer outcome.”
Other studies, likewise, have found that high vitamin D levels of 30 ng/ml (75 nmol/L) or more going into a cancer episode play an important role in survival:
“The majority of epidemiologic studies consistently support an approximately 20–30% reduction in risk of colorectal cancer and adenomas comparing high to low intake categories of both calcium and vitamin D, although independent effects may not be adequately separated. Less consistency exists on the dose–response relation for both nutrients. Intake of calcium of not more than 1000 mg/d and intake of vitamin D of 1000–2000 IU/d, achieving a level of at least 30 ng/mL, appear important for colorectal cancer prevention.”[11]
CANCER, PROSTATE
Vitamin D’s links to prostate cancer are mixed. Blood samples taken from 14,000 American doctors in what’s known as the Physicians Health Study reveal those with vitamin D levels below 25 ng/ml (62.5 nmol/L) had more than double the risk of developing an aggressive, often lethal, form of prostate cancer.[12]
The researchers found some men had a genetic variation that made them even more susceptible – two and a half times more likely to be struck with aggressive prostate cancer – in combination with low vitamin D, but that if men with that same gene fault had high vitamin D they actually enjoyed a drop in their risk – not a rise – of between 60 and 70%.
Staggering stuff, that vitamin D could work that hard to out-muscle a gene fault.
What’s more sobering is that 51% of male doctors were suffering vitamin D ‘insufficiency’ or ‘deficiency’ even during summer time (possibly a direct result of following the sun avoidance advice), rising to 77% who were insufficient or deficient during winter and spring. With those low levels, clearly more than half the men were at a much higher risk of aggressive prostate cancer.
“Our data suggest that a large proportion of the US men had suboptimal vitamin D status (especially during the winter/spring season), and both 25(OH)D and 1,25(OH)2D may play an important role in preventing prostate cancer progression,” the study authors concluded.
Why do I say “mixed”? Because studies so far have not shown a link between vitamin D levels and the less-aggressive, more general and gentle prostate cancer. One recent report followed up the health outcomes of 1,260 men who’d been diagnosed with prostate cancer at some point after providing blood samples way back in 1993-1995. Of that sample, 114 men had “lethal outcomes” by March 2011.
Researchers found strong links between high vitamin D levels in the blood, and a 57% lower chance of contracting the most aggressive prostate cancers. However, they “found no statistically significant association” between vitamin D levels and “overall prostate cancer”. From that, they concluded “vitamin D is relevant for lethal prostate cancer”.[13]
Adding to the “mixed” is a strange study from Finland, known as the Alpha Tocopherol, Beta Carotene (or ATBC) trial, where higher vitamin D levels in the blood were linked to an increased risk of aggressive prostate cancer.[14] The fly in the ointment with this study is that the sample were entirely men who actively smoked, aged from 50-69. That same sample was also used in a study showing an increased risk of pancreatic cancer.[15] So is the lesson we take from this supposed to be that smoking and vitamin D don’t mix? Vitamin D expert William Grant suspects so.
“The best hypothesis for why Finnish smokers have higher incidence of pancreatic cancer with higher serum 25(OH)D levels is that the vitamin D-pancreatic cancer relation is different for smokers and nonsmokers.”[16]
He makes the point that there may be other environmental factors muddying the trial, or even a genetic variation peculiar to Scandinavia, similar to the genetic variations discovered in other races. There’s also the problem that baseline vitamin D levels were very low in the Finnish men anyway, prompting this comment on one prostate cancer forum:
“These Scandinavian vitamin D studies drive me nuts. When half the men are deficient and most of the others have insufficiency, what is the definition of “High”?”[17]
The answer, possibly, Finnish men caught smoking vitamin D supplements.
In all seriousness, however, researchers do wonder whether starting with a really low vitamin D average has made a difference:
“As recently summarized by Li et al,[18] the Nordic study populations[19] were distinguished by the large proportion of men deficient for serum vitamin D (ie, with serum levels <50 nmol/L – approximately 50% of the men were deficient, compared with only 20% for the US study populations).”[20]
Another example of racial variations affecting vitamin D’s impact on prostate cancer comes from a study by the US National Institutes of Health of African-American men, which found a genetic variation that may account for some of the disproportionate prostate cancer in that community.
One of the theories behind prostate cancer is that it is stimulated by a high calcium intake. Although most of the men they studied (82%) consumed less than the recommended daily intake of 1200 mg of calcium in the diet, nonetheless men with the highest calcium intake (>1059 mg/day) were more than twice as likely to develop prostate cancer as men with the lowest intake (<488 mg/day).
Vitamin D is, of course, a key regulator of calcium absorption.
African-Americans were found to carry a gene making them much more susceptible to cal
cium intake. The same gene is found in European and Hispanic populations to a lesser degree. Where it has appeared in European men, it has also shown an increased risk for prostate cancer in conjunction with higher vitamin D levels.[21]
However, the US researchers say the amount of calcium involved exceeds what vitamin D would normally process in a day, so the risk pathway for calcium is likely to be another as yet undiscovered mechanism. They suspect this genetic anomaly may lie behind conflicting results in vitamin D/prostate studies.
“A positive effect of serum calcium on prostate cancer risk may confound the relationship between 25(OH)D and prostate cancer risk in some studies, which may account for some discrepant results in the literature.”
One of those results was a 2008 study – also involving scientist Demetrius Albanes, that found a higher risk of aggressive prostate cancer among men with higher vitamin D levels, but it is noteworthy that the study authors did not consider calcium intake was relevant to the result: “Factors that were found not to confound the associations of interest included the following: … vitamin D (<200, 200 – 399, 400 – 599, 600 – 799, 800 – 999, ≥ 1000 IU/d), and calcium (<750, 750 – 999, 1000 – 1499, 1500 – 1999, ≥ 2000 mg/d) intake.”[22]
US cancer biologist Gary Schwartz has gone so far as to place in the scientific record his evidence indicating “that the recent association between prostate cancer and serum 25-OHD by Albanes et al. [the Finnish study] is due to confounding or interaction with serum calcium.”[23]
African-Americans who didn’t have the gene variation and were not as susceptible to calcium had a reduced risk of prostate cancer, further strengthening the suspicion that the often-used Finnish data may be flawed because it’s being skewed by genetics. Adding to the scientific confusion further, a study of Caucasian American men included those who had the genetic variant but found they were unaffected by it: “Conversely, in a U.S. study of non-Hispanic white men, we found no significant association between VDR Cdx2 genotype and advanced prostate cancer risk, regardless of sun exposure.”[24]
Moral of the story? Talk to your doctor.
[1] “Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis,” Gorham et al, American Journal of Preventive Medicine 2007; 32(3):210-16
[2] “Circulating 25-Hydroxyvitamin D Levels and Survival in Patients With Colorectal Cancer,” Ng et al, Journal of Clinical Oncology June 20, 2008 vol. 26 no. 18 2984-2991. See also, “Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer,” Ng et al, British Journal of Cancer, 2009 Sep 15;101(6):916-23
[3] “Prospective study of serum vitamin D and cancer mortality in the United States”, Freedman et al, Journal of the National Cancer Institute 2007; 99(21):1594–1602
[4] “The association of calcium and vitamin D with risk of colorectal adenomas,” Hartman et al, Journal of Nutrition 2005; 135(2):252–259
[5] “Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals,” Lieberman et al, Journal of the American Medical Association 2003; 290(22):2959–2967
[6] “Vitamin D and prevention of colorectal adenoma: A meta-analysis,” Wei et al, Cancer Epidemiology, Biomarkers, and Prevention 2008; 17(11):2958–2969
[7] “Vitamin D, calcium supplementation, and colorectal adenomas: Results of a randomized trial,” Grau et al, Journal of the National Cancer Institute 2003; 95(23):1765–1771
[8] “Vitamin D Status in Patients With Stage IV Colorectal Cancer: Findings From Intergroup Trial N9741,” Ng et al, Journal of Clinical Oncology, April 20, 2011 vol. 29 no. 12 1599-1606
[9] “Solar radiation, vitamin D and survival rate of colon cancer in Norway,” Moan et al, Journal of Photochemistry & Photobiology, 2005 Mar 1;78(3):189-93. See also “Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway),” Robsahm et al, Cancer Causes Control. 2004 Mar;15(2):149-58
[10] “1,25-Dihydroxyvitamin D3 Receptor as a Marker of Human Colon Carcinoma Cell Line Differentiation and Growth Inhibition,” Shabahang et al, Cancer Res August 15, 1993 53; 3712
[11] “Calcium, vitamin D and colorectal cancer chemoprevention,” Zhang and Giovannucci, Best Practice & Research Clinical Gastroenterology, Volume 25, Issue 4 , Pages 485-494, August 2011
[12] “A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer,” Li et al, PLoS Med. 2007 Mar;4(3):e103, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1831738/?tool=pubmed
[13] “Vitamin D related genetic variation, plasma vitamin D, and risk of lethal prostate cancer etc,” Shui et al, Journal of the National Cancer Institute, 2012, 104(9):690-699
[14] “Serum 25-Hydroxyvitamin D and Prostate Cancer Risk in a Large Nested Case-Control Study,” Albanes et al, Cancer Epidemiology, Biomarkers and Prevention, July 22, 2011; doi: 10.1158/1055-9965.EPI-11-0403
[15] “A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers,” Stolzenberg-Solomon et al, Cancer Research 2006; 66(20):10213–10219
[16] “Critique of the U-shaped serum 25-hydroxyvitamin D level-disease response relation,” William Grant, Dermato-Endocrinology 1:6, 289-293; November/December 2009;
[17]http://health.groups.yahoo.com/group/natural_prostate_treatments/message/22796
[18] “A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer,” Li et al PLoS Med . 2007 ; 4 ( 3 ): e103
[19] “Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland),” Ahonen et al, Cancer Causes Control . 2000 ; 11 ( 9 ): 847 – 852. See also “Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries,” Tuohimaa et al, Int J Cancer 2004 ; 108 ( 1 ): 104 – 108
[20] “Serum Vitamin D Concentration and Prostate Cancer Risk: A Nested Case – Control Study,” Ahn, Albanes et al, Journal of the National Cancer Institute, 2008 Vol. 100, Issue 11 | June 4, 2008
[21] “Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to
prostate cancer” Bodiwala et al, Environ Mol Mutagen. 2004. 43(2):121-127.
[22] “Serum Vitamin D Concentration and Prostate Cancer Risk: A Nested Case – Control Study,” Ahn, Albanes et al, Journal of the National Cancer Institute, 2008 Vol. 100, Issue 11 | June 4, 2008
[23] “Circulating Vitamin D and Risk of Prostate Cancer – Letter,” Gary Schwartz, Cancer Epidemiology, Biomarkers & Prevention, January 2012 21; 247; doi: 10.1158/1055-9965.EPI-11-091
[24] “Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer,” John et al, Cancer Res. 2005. 65(12):5470-5479.
CHAPTER 7
THE HEART OF THE MATTER
“Researchers found those with the lowest vitamin D levels were three times more likely to die of heart disease, and two and a half times more likely to die of any cause”
– results of NHANES III study
Heart disease is the world’s biggest natural killer. Each year it accounts for between one in three and one in four deaths. In the US, roughly one in every 300 people suffers a heart attack each year.[1] We’ve been invited to try the so-called Mediterranean diet rich in olive oil and red wine, but researchers are now beginning to suspect the real secret ingredient in the Mediterranean diet was actually sunlight.
In 2012, a major study of ‘metabolic syndrome’ heart patients in Europe which tracked their health for nearly eight years has found people with the highest levels of vitamin D reduced their risk of sudden death by a massive 85%. There’s not a drug on the planet that can deliver those kinds of odds.[2]
Ninety-two percent of those taking part had what research teams called “sub-optimal” levels of vitamin D: below 75 nmol/L (30 ng/ml), and a total of 22% of the sample fell into the “severely deficient” category of less than 25 nmol/L
(10 ng/ml).
Of the 1,801 patients being tracked, 462 died within the trial period. Those with the highest levels of vitamin D were 75% less likely to die of any cause (heart failure, road crash, meteorite strike, any cause of death at all) and 85% less likely to suffer a “sudden death”. For people with ‘optimal’ vitamin D, there was a 76% reduction in the risk of dying from congestive heart disease during the 7.7 year follow-up period. The reduction in death rate followed a sliding scale depending on vitamin D levels.
Fifteen percent of all European adults are believed to have ‘metabolic syndrome’, which is linked with obesity, hypertension and faulty glucose and insulin metabolism. It is a known precursor to both type-2 diabetes and cardiovascular disease. Up to one in three Americans suffer from it. The significance of this 2012 heart mortality study is thus fairly obvious.
Precisely how vitamin D works on the cardiovascular system is still under investigation – given that medical researchers have really only cottoned on to the vitamin’s multiple benefits over the past fifteen years. However, one recent study shows a possible pathway. There’s a chemical known as plasma renin which has been linked to higher mortality in heart disease.
Now, a Serbian study of 101 heart patients in a double blind trial of 2000IU vitamin D supplements daily has found a big impact of vitamin D on renin production.
The results, presented to a cardiovascular conference this year, show that after six weeks, patients given the 2000IU of D daily saw their blood levels rise from an average of only 48 nmol/L (19.2 ng/ml) to 80 nmol/L (32 ng/ml). In contrast, the vitamin D levels of heart patients on the placebo dropped from 47 nmol/L average to 44 nmol/L (17.6 ng/ml) over the six week trial.
“Six weeks of [vitamin D] supplementation dropped plasma renin activity by 1.3 nmol/L per hour, while control patients saw a 2.4 nmol/L/hr rise over the same period,” said study leader Rudolf de Boer.[3]
In terms of the big picture, harmful plasma renin levels dropped from 65 ng/L to 55 ng/L in vitamin D patients, while they rose from 56 to 72 ng/L in the placebo group.