Vitamin D: The Active Form, And The Role Of Calcium

Active vitamin D, the molecule that acts as a steroid hormone in our bodies, is not the same as the vitamin D we eat in food, the vitamin D that we take in a pill, or the vitamin D that is manufactured in our skin. All of those less active forms of vitamin D are precursors. They're stored more easily in the body, and for longer, than active vitamin D.

Active vitamin D, also called calcitriol, is a high-energy, twice-hydroxylated¹ compound with a very short half-life (about 5 hours) - such that levels of active vitamin D are tightly controlled by the body. It is primarily calcitriol that is responsible for the benefits we're discovering about this vitamin, e.g. mineral balance and bone mineralization, immunity, blood pressure control, reduction in cancer cell proliferation, and insulin secretion. You can have adequate stores of vitamin D, but unless you're converting it to its most active form, your benefits are limited.²

The body expends energy to make the most active form of vitamin D. A specific enzyme controls its manufacture.^{3, 4} The activity of that enzyme, 1-hydroxylase, is influenced by a variety of factors.

The following inhibit the activity of 1-hydroxylase, resulting in lower concentrations of active vitamin D (calcitriol):

1. High concentrations of calcitriol - A negative feedback mechanism is in play, meaning, the more active vitamin D you have circulating, the less active the enzyme.
   
2. Decreasing levels of parathyroid hormone (PTH) - PTH stimulates 1-hydroxylase.
   
3. High calcium intake/high blood calcium - High calcium levels cause PTH to decline.
   
4. High phosphorus intake/high blood phosphorus. (An aside: Fructose we eat gets phosphorylated, grabbing phosphorus and holding it in the liver. So fructose (fruit) consumption can counter high phosphorus (dairy, fish, meat, soda) intake.)

The following stimulate the activity of 1-hydroxylase, resulting in higher concentrations of active vitamin D (calcitriol):

1. Low concentrations of calcitriol.
   
2. Increasing levels of parathyroid hormone (PTH).
   
3. Low calcium intake/low blood calcium.
   
4. Low phosphorus intake/low blood phosphorus.

Serum concentrations of active vitamin D (calcitriol) are not typically correlated with vitamin D intake, or vitamin D stored as 25(OH)D3. So, taking more vitamin D will not necessarily lead to increased activity of the vitamin.

Another controlling factor: As levels of calcitriol rise, the body makes relatively more of a form of D3 that is thought to be involved in the breakdown of calcitriol, or at least results in lower calcitriol levels.⁵ This is another type of negative feedback loop. It may indicate an Upper Intake Level (UL) for vitamin D since, in contrast to calcitriol, the production of 24,25(OH)₂D3 is correlated with vitamin D intake.

Of course, you need working receptors for that active vitamin D. The manufacture of those receptors, the cells where they're located, and their affinity for circulating calcitriol, are additional variables in the effective function of this hormone. I'll discuss later.

Studies

You can see these mechanisms played out in studies. Looking around I found this one:
Calcium and Fructose Intake in Relation to Risk of Prostate Cancer, Cancer Research, 1998

In 47,781 men from the Health Professionals Follow-Up Study, those who had a high intake of calcium had a higher risk for prostate cancer (recall: the manufacture of calcitriol is inhibited by high calcium intakes):

"Higher consumption of calcium was related to advanced prostate cancer (RR: 2.97) and metastatic prostate cancer (RR: 4.57)."

That's a three-fold increased risk for advanced cancer, and a 4.6 times increased risk for metastatic cancer.

"Our findings provide indirect evidence for a protective influence of high 1,25(OH)2D levels on prostate cancer and support increased fruit consumption and avoidance of high calcium intake to reduce the risk of advanced prostate cancer."

These findings are in line with other blogs I posted:
Dairy Food And Prostate Cancer
More Evidence That Dairy Foods Increase Risk For Prostate Cancer

Which support:

"[Consumption of dairy products] is one of the most consistent dietary predictors for prostate cancer in the published literature."

Dairy foods are good sources of both calcium and phosphorus, two minerals that have been shown to decrease levels of active vitamin D in the body.

There are lots of other studies, especially cancer-related ones (colon, breast) which interest me, but I'm out of time.

In Sum:

To encourage beneficial levels of active vitamin D in the body, it may be helpful to:

• Watch calcium intake.
  
• Watch phosphorus intake.

________¹ On carbons 1 and 25, thus called 1,25-dihydroxycholecalciferol or 1,25(OH)₂D3.
² Stored vitamin D is usually measured as hydroxylated cholecalciferol, that is, 25(OH)D3.
³ 25(OH)D3-1-hydroxylase, or just 1-hydroxylase. This enzyme places an OH group onto carbon 1.
⁴ Since this enzyme is most active in the kidney, actually in the mitochondria of the kidney, people who are on dialysis or who have limited kidney function (many diabetics) may have the hormone calcitriol injected directly.
⁵ 24,25(OH)₂D3.

Photo of vitamin D: Bix