Further questioning the vitamin D ratio test.

[Guest guest]

Ken Lassesen has well argued the lack of scientific basis for using

the ratio of 1,25-D3 to 25-D3 as a means of determining TH1 production

of 1,25-D3. The following study shows yet another example of that:

J Clin Endocrinol Metab. 1995 Jul;80(7):2227-32.

Calcium-regulating hormones across the menstrual cycle: evidence of a

secondary hyperparathyroidism in women with PMS.

This study confirms another study that was previously mentioned here,

which is that vitamin D levels can significantly vary during the

menstrual cycle. However, more interestingly is that in PMS patients,

1,25-D3 was significantly increased, and 25-D3 was significantly

decreased.

When this occurs, doctors will test PTH levels, as PTH can increase

renal production of 1,25-D3. This can occur due to a calcium

deficiency. However, PTH levels also vary significantly during the

menstrual cycle, and only during certain days were PTH levels

significantly increased in PMS patients, compared to controls. On

many days, PTH levels were normal, so that one could easily test such

people, and on the basis of the vitamin D ratio, claim that they had

TH1 production of vitamin D. In fact, in half of the PMS patients,

PTH levels looked quite normal during almost the whole cycle. This

anomoly is likely due to estrogen, which can directly influence

1,25-D3 levels.

This is just one of many possible factors which influence 1,25-D3 levels.

It's one of the reasons why 25-D3 is mainly used to test for a vitamin

D deficiency, as too many factors influence 1,25-D3 levels.

In the above study, one of the PMS patients was treated with calcium

and vitamin D supplementation, and this corrected the high 1,25-D3 and

low 25-D3 levels.

Calcium is known to suppress normal renal production of vitamin D.

Calcium supplementation, or loading, is a common and much more valid

way of determining whether increased 1,25-D3 levels is due to either

non-renal or extra-renal production. In fact, this was suggested in

the following study:

J Clin Invest. 1993 Apr;91(4):1396-8.

Increased calcium intake does not suppress circulating

1,25-dihydroxyvitamin D in normocalcemic patients with sarcoidosis.

To determine if increased Ca intake suppresses serum 1,25(OH)2D in

normocalcemic patients and to identify those at risk, 17 normal

subjects and 11 patients were studied on a metabolic ward for two

and one-half days while receiving first 400 and then 1,000 mg/d of Ca.

On the low Ca intake, serum angiotensin-converting enzyme (ACE), an

index of disease activity, was higher in only three of the patients

than in the controls, mean serum 1,25(OH)2D was higher in the

patients, and mean serum total Ca, serum Ca++, and urinary Ca weren't

different in the two groups. On the higher Ca intake, mean urinary Ca

increased in both groups, but mean serum 1,25(OH)2D was suppressed

only in the normal subjects. Thus, 1,25(OH)2D production is

abnormally regulated, indicating that (a) normocalcemic patients with

sarcoidosis are at risk for developing abnormal Ca metabolism, and (

a better index of disease activity is provided by the oral Ca

suppression test than by serum ACE.

As for people who claim that using an ARB like Benicar can reduce

vitamin D levels, and that that is proof of TH1 vitamin D production,

that is not so clear either. For example, here's an interesting study

on angiotensin II's effects on calcium metabolism and vitamin D levels:

Am J Hypertens. 2003 Jun;16(6):453-9.

Effect of quinapril, quinapril-hydrochlorothiazide, and enalapril on

the bone mass of hypertensive subjects: relationship with

angiotensin converting enzyme polymorphisms.

Few studies have been conducted on the relationship between

angiotensin II and its effects on calcium metabolism. I could not

find a study that used ARBs, but in the above study which used ACE

inhibitors on people with hypertension, they found that these drugs

caused a decrease in 1,25-D3 levels. They concluded:

" This therapeutic group acts by blocking angiotensin II synthesis.

Consequently, it has a beneficial effect on the skeleton because there

is a decrease in angiotensin concentration. It has been hypothesized

that angiotensin can indirectly act on bone cells by regulating the

flow of bone marrow capillaries or directly by binding to AT1

receptors located on osteoblasts, thus promoting the mediator release

that would activate the osteoclasts. " " The reduction of angiotensin

II levels has a beneficial effect of inhibiting bone resorption and

promoting mineralization.

Angiotensin II can interfere with calcium metabolism. The

administration of this peptide in a group of healthy volunteers caused

a decrease in ionic calcium levels and an increase in PTHi levels.

The decrease of calcemia was not related to an increase in calciuria,

but it could be caused by an increase in calcium uptake by vascular

smooth muscle cells. In our patients, ACE inhibitors increased the

level of calcium, although the concentration of PTHi was not modified.

These data suggest a beneficial effect on the blockage of the

synthesis of angiotensin in calcium metabolism. "

If AT1 receptors are responsible for this effect, then one could

easily speculate that ARBs should have at least a strong, if not much

stronger effect, on calcium metabolism, than ACE inhibitors. So even

if it was determined that ACE inhibitors do not exhibit a similar

effect on non-hypertensives, an ARB with a much stronger ability to

block angiotensin II, might still be able to have an significant effect.

Therefore, even if Benicar actually could lower vitamin D levels, it

still would not be positive proof of TH1 vitamin D production. Other

testing methods would need to be used, such as calcium loading, which

have been shown by studies to be useful in detecting TH1 vitamin D

production.

Mark