Calcium and Prostate Health

A recent report from 2009 looked at the risk of dying from prostate cancer (PC) compared to the total blood levels of calcium, both ionized (most important) and protein bound. This information came out of the respectable NHANES research study. The analysis revealed increased risk of from 2 to 4 times greater in men at the highest levels, especially of ionized or free calcium ref, compared to those with the lowest levels. ref ref  The 4 times risk was found when these dying from prostate cancer in the first three years were not considered since other influences from before the study began could be involved. The study was a 5-6 year study. And yes, there is a genetic change to a vitamin D receptor that is involved. This information was used to set the calcium supplement level for men in this new criteria. And it is quite low compared to what Nutritionists recommend. Is there anything that can lower the blood level of ionized calcium?  

SIDEBAR: It is the potential for alkaline pH in the blood that can lower ionized calcium levels by increasing calcium protein binding. Eat more vegetables and less sugars, proteins, especially animal source, and simple carbohydrates. It is not that the blood pH will change. It must stay between a very narrow range. It is more about the pH elements that keep this range in check that increase calcium protein binding. To regulate Blood pH, the body can pull calcium compounds out of bone if not enough vegetables are consumed containing potassium, the preferred buffer the body uses to help maintain this vital pH.

Causes are harder to pinpoint as to why higher calcium levels have this increased risk. It could be that higher blood calcium levels turn off the activation of the hormone form of vitamin D plus lower PTH levels might be involved. Or that the non active storage form of vitamin D levels are too low to have a direct influence on protecting prostate tissue by going directly into the prostate and turning into the hormone form. Or that a critical enzyme or mineral, like magnesium, is limited that triggers this conversion. This conversion action was only recently discovered.  Of interest here, several studies show that while dairy foods increase this risk, calcium supplements apparently do not, or at least not at the same rate. Note: Not all studies show a detrimental effect from dietary calcium, dairy or calcium supplements. This fact brought forth another theory recently that since dairy calcium is combined with phosphate, it could be the phosphate levels and not just the calcium levels by themselves that are affecting prostate health. Most calcium supplements are not bound with phosphate, except bonemeal and related hydroxyapatite. But, calcium in bone is combined with phosphate. The damaging effect of colas is due to how much phosphate they add. Remember: Many fast food items contain added phosphate ingredients.

The above mentioned study found that individuals with PC that had lower total calcium blood levels were not at a higher mortality risk level and thus did not require prompt treatment procedures, an important consideration since many prostate cancer treatments have serious side effects.

3 possible SIDEBARS: 

1. There is also the possibility that calcium levels influence Parathyroid hormone (PTH) levels and this could have an effect on prostate cell growth. Again possibly by turning on or off hormone D activation.

2.  A new discovery points to the need for a balance point of vitamin D produced osteocalcin between vitamin K2 carboxylated and non-carboxylated osteocalcin forms. Carboxylated stimulates growth of prostate cells while non-carboxylated inhibits, or balances.

3.  Another new theory from Vanderbilt University School of Medicine; Calcium only gets involved when blood levels or and tissue cell levels of magnesium are also low. ref ref  Plus the ratio of calcium to magnesium might be involved according to new research. Another way to express instead of "ratio" would be to say the balance between the two minerals. They work in tandem with opposite reactions for cell mineral movement gradients. Magnesium inside cells and calcium outside cells until an action energy potential is generated where they are pumped in the other direction, calcium into cell such as muscles to generate contraction potential, and magnesium out of cells and then back in to elicit muscle relaxation.   

This author believes another potential influence is that dairy has a very high ratio of calcium to magnesium, as mentioned above under Calcium and Cardiovascular. Calcium supplements often have magnesium included at a two to one ratio while dairy has a 9 to 1 ratio of calcium to magnesium which could explain why supplemented calcium has a lower risk than dairy. Or it could be any number of other elements in dairy, i.e. saturated fats, IGF-1, etc.

This increased ratio could jeopardize the normal calcium movement in and out of cells. Magnesium is the cell door keeper to control how much calcium goes into cells. These calcium doors are called calcium channels. Remember that calcium channel blocking drugs are given to control blood pressure. Since dietary magnesium amounts are often lower than required, this could be a very real possibility. Some research looking at just adding magnesium to the diet has shown to be of value for proper calcium metabolism.

Another possibility is that the IGF-1 (Insulin-like growth factor) contained in dairy, especially from rBGH (Bovine Growth Hormone given to increase milk production) treated cows might play a role in initiating or stimulating cancer cell growth. This now also has research support. IGF-1 has many positive roles to play in the developing human body plus the maintenance of tissues as one ages, especially muscle mass. It is usually combined with an IGF protein binding 3 molecule. In this form and at normal levels it is protective, but at higher levels and without enough IGF protein binding 3, IGF-1 might participate in turning cells cancerous, stimulating existing cancer cell growth rates, and preventing the destruction of cancer cells through normal cell death mechanisms. ref  Calcium is needed for this process as well and scientist are looking for ways to get cancer cells to uptake more calcium to activate this natural cell death mechanism. 

These facts reveal important considerations for both prostate and cardiovascular disease risk reductions. Watch for follow up research. NOTE: An unexpected result for IGF-1 acting to prevent atherosclerosis... ref 

SIDEBAR: Of course vitamin D levels are associated with calcium levels. Here is study looking into vitamin D levels and prostate. ref

Here is impact from this reference: The optimal range of circulating vitamin D for prostate cancer prevention may be narrow. Supplementation of men (already) with adequate levels may be harmful. Cancer Epidemiol Biomarkers Prev; 23(8); 1494–504. ©2014 AACR.

Here is a study reporting that massive vitamin D just before prostate surgery exhibited positive effects on one cancer marker.

FYI: Now, along comes Vitamin D Binding Protein (DBP) to further complicate factors. DBP controls action levels of vitamin D and thus calcium. High blood DBP and low vitamin D are connected to a decreased risk of PC while low DBP and high vitamin D are related to an increased risk. This appears to say that nature wants to limit vitamin D actions of increasing calcium blood levels and that it is not wise for men to consume vitamin D unless testing low. 

     Below copied from 2009  Medscape cancer news blog

"IONIZED CALCIUM AND PROSTATE CANCER 

Ionized Serum Calcium a Potential Biomarker of Fatal Prostate Cancer

NEW YORK (Reuters Health) Feb 27 - New evidence indicates that elevated serum levels of ionized calcium may predict the risk of death from prostate cancer. If verified in future prospective studies, levels of ionized calcium in serum could assist physicians and patients in making decisions regarding treatment.

In a previous analysis of data from the National Health and Nutrition Examination Survey (NHANES I) study, Dr. Halcyon G. Skinner, at the University of Wisconsin-Madison, and Dr. Gary G. Schwartz at Wake Forest University in Winston-Salem, North Carolina, observed a link between elevated serum calcium and risk of fatal prostate cancer.

For their current report in the February issue of Cancer Epidemiology, Biomarkers & Prevention, the researchers examined associations between total and ionized serum calcium and prostate cancer fatalities among 6710 men examined between 1988 and 1994 for the NHANES III, which was linked to the National Death Index.

During a mean of 5.3 years of follow-up, there were 25 prostate cancer deaths. Average age at death was 78.1 years.

Compared with men in the lowest tertile, men in the highest tertile of total serum calcium had a relative risk for prostate cancer mortality of 2.02, after adjusting for sociodemographics, body mass index, and general health status (1 is neutral no effect, 2 is getting high)

The relative risk associated with ionized serum calcium corrected for serum pH was 3.12. After excluding three cases that died within the first 3 years of follow-up, the relative hazard in the highest tertile was 4.65.

In a Wake Forest press release, Dr. Schwartz comments that many men with prostate cancer are treated unnecessarily. "These new findings, if confirmed, suggest that men in the lower end of the normal distribution of ionized serum calcium are three times less likely than men in the upper distribution to develop fatal disease."

"These men may choose to delay treatment or perhaps defer it

 altogether," Dr. Schwartz added.--

The question researchers have to answer: How does supplemental versus dietary calcium sources influence both ionized free calcium levels and protein bound calcium? What increases this particular protein needed for calcium binding?