Calcium – Prostate Cancer

/Calcium – Prostate Cancer
Calcium – Prostate Cancer2017-10-19T10:43:00+00:00

A.  Take Home Message.

Prostate cancer

[PCa] research overwhelmingly suggests that a high calcium intake, whether from dairy or supplements, is associated with more aggressive PCa.

The likely reason is that excess calcium inhibits the conversion of circulating inactive vitamin D to its active hormonal form.  This is very important, since PCa loses the ability to make that conversion from within the cell.

Osteoporosis is often not due to calcium insufficiency, but to a deficiency of vitamin K (preferrably obtained in the K2-7 form), which is required for the transportation of calcium to bone.  Without adequate vitamin K, calcium will be deposited on arterial walls or excreted. 

I do not use a calcium supplement, but I would never go above 500 mg / day.

Milk should be avoided, except perhaps for a small amount in tea & coffee.  If cheese has to be eaten, ignore the low-fat varieties.  The high-fat, such as the triple cremes, have far less calcium, & one is not likely to over-indulge.  

If osteoporosis is a concern, the following co-factors should be taken with calcium: magnesium, zinc, boron, vitamin D, vitamin K2.  (Be wary of lists that include copper.)

If the osteoporosis is due to androgen therapy, a low-dose estrogen patch can bring estradiol up to the level required for bone health (12 pg/mL)

B.  Introduction.

In the days before farming, hunter-gatherer societies obtained all the calcium they needed from plant sources – no dairy; no supplements.

Vegetable sources include greens, which also come with the vitamin K needed for transportation to bone.

In 2013, the U.S. Preventive Services Task Force came out against calcium being effective against avoiding fractures in men & women.

Also in 2013, the large NIH / AARP Diet and Health Study reported that [Ba]:

“… high intake of supplemental calcium is associated with an excess risk of CVD death in men …”  I suspect that an unfavorable calcium:magnesium ratio might be involved.

(Men with PCa are noted for already having increased CVD risk.)

There are many factors involved in bone health, & calcium is not a quick fix – but that’s a separate topic.

Note that small levels of calcium do get used-up in the body. However, under normal circumstances, bone remodeling associated with maintaining circulating calcium homeostasis does not result in significant loss of calcium. The healthy body conserves calcium. It’s not natural for significant amounts of calcium to leach from bones into urine.

Humans are the only mammals where milk (& from a different species) is considered essential to the bone health of infants weaned from human milk. In some parts of the world, there is no dairy tradition, & the children do just fine. But U.S. children enter adulthood with the idea that it is difficult to obtain adequate calcium. “Got milk?” (Blame the advertising agency Goodby Silverstein & Partners for that one.)

Meanwhile, the dairy industry finds more outlets for its products. In 1970, a person in America ate, on average, eight pounds of cheese in a year. Now it’s 23. Twenty-three pounds of cheese a year! [Bb] That was in 2010 & the trend is upward. When you add in ice cream & yogurt, that’s a lot of calcium, even without factoring in milk.

There is only so much salt, sugar & fat a restaurateur can add to a meal, but one can never add too much cheese. LOL

The association between calcium and aggressive PCa is complicated by phosphorus.  Both minerals are often found together & both inhibit the generation of active vitamin D.  When the kidneys are busy excreting excess calcium &/or phosphorus, they cannot convert inactive vitamin D to its hormonal form.

C.   Edward Giovannucci research.  Physicians’ Health Study, Health Professionals Follow-up Study, etc.

[Ca]  In 2001, Giovannucci reported that:

“Dairy product intake increased risk of metastatic prostate cancer {by 40%} for top vs. bottom quintile comparison, but no association remained after controlling for calcium …”  i.e. the association is due to calcium.

[Cb]  Again with Giovannucci, 2001:

“At baseline, men who consumed >600 mg {calcium/day} from skim milk had lower plasma {hormonal vitamin D} concentrations than did those consuming {150 mg calcium/day or less}”

Interest in vitamin D was just warming up 15 years ago, but Edward G. had made the connection: calcium lowered hormonal vitamin D. From this point on, researchers included calcium in PCa-dairy studies.

[Cc]  In 2002, Giovannucci sat in on another study:

“Our results support the hypothesis that very high calcium intake, above the recommended intake for men, may modestly increase risk of prostate cancer.”

[Cd]  In a 2005 U,S, study:

” Low-fat milk was associated with {50%} increased risk {third compared to first tertile}”

“Dairy consumption may increase prostate cancer risk through a calcium-related pathway.”

Interestingly, whole fat milk was not associated with PCa.  Skim has more calcium.

[Ce]  In 2007, we get the scary Giovannucci study:

“Higher calcium intake was not appreciably associated with total or nonadvanced prostate cancer but was associated with a higher risk of advanced and fatal prostate cancer [for fatal prostate cancer, compared with men whose long-term calcium intake was 500-749 mg/d (excluding supplement use of <5 years); those with intakes of 1,500-1,999 mg/d had a {risk factor of} 1.87 ..; and those with > or = 2,000 mg/d had a {risk factor of} 2.43 …]. ”

“Dietary calcium and supplementary calcium were independently associated with an increased risk. For high-grade prostate cancer (Gleason > or = 7), an association was observed for high versus low calcium intake {risk factor of 1.89}, but a nonsignificant, inverse association was observed for organ-confined, low-grade prostate cancer {risk factor of 0.79}.”

“In a sample of this cohort, higher calcium intake was associated with lower circulating {hormonal} vitamin D levels. Our findings suggest that calcium intakes exceeding 1,500 mg/d may be associated with a decrease in differentiation in prostate cancer and ultimately with a higher risk of advanced and fatal prostate cancer but not with well-differentiated, organ-confined cancers.”

[Cf]  A 2007 U.S. study in the in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, differed from the above, but studies don’t always neatly agree:

“In this large prospective study in a prostate cancer screening trial, greater dietary intake of calcium and dairy products, particularly low-fat types, may be modestly associated with increased risks for nonaggressive prostate cancer, but was unrelated to aggressive disease. Furthermore, we found no relationship between calcium intake and circulating vitamin D.”

[Cg]  In 2009, in another U.S. study:

“Our findings, in a sample including a large proportion of black participants, do not confirm previous findings showing an inverse association between calcium intake and {hormonal vitamin D} levels. As such, they suggest that future work should explore other mechanisms by which dairy foods and calcium might increase prostate cancer risk.”

“Black participants were more likely to have low vitamin D levels than were non-black participants (61% vs. 20%).”  Low levels of circulating vitamin D might imply low levels of the hormonal form even without high calcium intake.  

[Ch]  Giovannucci in 2012: 

This study was different, in that it looked at post-diagnostic intakes.

“Men with the highest versus lowest intake of whole milk were at an increased risk of progression (HR = 2.15 …)” whereas: “Men in the highest versus lowest quintile of low-fat dairy intake were at a decreased risk of progression (HR = 0.62 …)”

That seems to turn things upside-down.  However, one must be careful of post-diagnosis diets.  Many men make dietary changes after diagnosis.  A man who continues to drink a significant amount of whole milk has possibly made no dietary concessions, whereas low-fat milk consumption might suggest that a range of dietary changes have also been made.  It is improbable that one can actually inhibit PCa progression by drinking high amounts of skim milk.

[Ci]  In 2015, Giovannucci introduces a confounding factor: phosphorus. 

Dairy products contain phosphorus, although it is found in meat & fish in significant amounts too. Phosphorus/phosphates have been associated with PCa progression risk. One should avoid deli meats & soft drinks with phosphates. As with excess calcium, excess phosphorus will inhibit the conversion of vitamin D to its hormonal form. (Excess phosphorus causes the hormone FGF-23 to be secreted. Not only does it inhibit the production of hormonal vitamin D, but it accelerates its degradation. None of this is mentioned in the paper, though.)

“Calcium intakes >2000 mg/d were associated with greater risk of total prostate cancer and lethal and high-grade cancers. These associations were attenuated … when phosphorus intake was adjusted for.”

“Phosphorus intake was associated with greater risk of total, lethal, and high-grade cancers, independent of calcium and intakes of red meat, white meat, dairy, and fish.”

“Calcium intake was associated with an increased risk of advanced-stage and high-grade disease 12–16 y after exposure, whereas high phosphorus was associated with increased risk of advanced-stage and high-grade disease 0–8 y after exposure.”

“Given the high correlation between calcium and phosphorus intake, because dairy is the major contributor of both minerals in this population, it is difficult to truly separate their effects.”

After 15 years I would have expected more clarity. Anyway, dairy has other issues (that I will get to), & the NIH/AARP study is a strong warning against supplemental calcium.

[D]  Other studies.

[Da]  (2017 – France)

Animal study suggests that calcium risk is modified by vitamin D intake.

In the studies that used older data, vitamin D supplementation would probably mean 400 IU.  Nowadays, there are numerous supplements that offer 4,000 IU & higher.  Such levels might make it more difficult to demonstrate calcium risk in future studies.

 

[Ba] http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1568523

[Bb] https://www.theatlantic.com/health/archive/2013/09/now-is-the-time-of-cheese/279933/

[Ca]  https://www.ncbi.nlm.nih.gov/pubmed/11519764

[Cb]  http://ajcn.nutrition.org/content/74/4/549.long

[Cc]  http://cebp.aacrjournals.org/content/12/7/597.long

[Cd]  http://ajcn.nutrition.org/content/81/5/1147.long

[Ce]  http://cebp.aacrjournals.org/content/15/2/203.long

[Cf]  http://cebp.aacrjournals.org/content/16/12/2623.long

[Cg]  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895954/

[Ch]  http://cebp.aacrjournals.org/content/21/3/428.long

[Ci]  http://ajcn.nutrition.org/content/101/1/173.long

[Da]  https://www.ncbi.nlm.nih.gov/pubmed/27879271