vitamin D and CLL

I wrote about vitamin D in January this year, but I am prompted to write about it again by the recent announcement by the Institute of Medicine that older people should take a bigger dose, and the identification of low vitamin D levels as a poor prognostic factor in CLL by the Mayo Group. A further prompt was the suggestion by my oncologist that my steroid-induced proximal myopathy might benefit from some vitamin D, and why didn't I go outside and bear my skin to the sunlight? At minus 17 degrees Centigrade?

None of this changes what I wrote about vitamin D back in January; the idea that it can prevent or ameliorate cancer is still to be formally tested.

The level of vitamin D supplement required by most people was set at 200 iu in 1997. The new recommendation is 600 iu or 800 if you are over 70.

Although we know that apart from controlling calcium metabolism, vitamin D controls over 2000 genes and interferes with the functioning of many tissues, the Institute of Medicine, an arm of the National Academy of Sciences that sets US governmental nutrient levels, said there wasn't enough evidence to prove that low vitamin D causes chronic diseases; it based its new recommendations on the levels needed to maintain strong bones alone. The panel also raised the acceptable upper limit of daily intake to 4,000 IUs for adults, from 2,000 previously.

The panel dismissed concerns that many Americans and Canadians are vitamin D deficient, noting that there is no scientifically validated level that's considered optimum. Even so, the panel concluded that for 97% of the population, a blood level of 20 nanograms of vitamin D per milliliter is sufficient. However, several major medical groups, including the Endocrine Society and the International Osteoporosis Foundation, have concluded that a level of 30 ng/ml is necessary for optimal bone health. Others have set far higher levels.

The panel was also concerned about emerging evidence of concern about possible ill effects of too much vitamin D. Besides a risk of kidney and heart damage noted with vitamin D levels of 10,000 iu per day. They said that they had seen higher death rates from pancreatic cancer, prostate cancer and other causes in men whose blood levels were above 50 ng/ml. The link is still tentative and may never be proven.

But the real concern is about serum calcium levels, which constitute a risk for everybody. High levels of calcium cause thirst, constipation, dehydration, sleepiness and coma. In diseases like myeloma and breast cancer they are recognized as medical emergencies which could prove fatal in a day or so. Other less dramatic features of a high serum calcium are deposits of calcium in soft tissues including the prostate gland and kidney. Kidney stones are a painful complication.

A high calcium can be caused by increased resorption from the bones or increased absorption from the bowel. Vitamin D controls the absorption and parathormone the resorption. The commonest abnormal finding on blood test screening is a high serum calcium, almost invariable due to secretion of parathormone by a parathyroid adenoma. I have one of these and a consequent high calcium. One of the ways that parathormone works is by converting vitamin D into its active form of vitamin D3. So some patients are walking around with high vitamin D3 levels because their bodies are mistakenly manufacturing it.

Before embarking on a megadose regime for vitamin D, always check serum calcium first.

Now, how about the Mayo paper.

They found that low levels of serum vitamin D3 were an adverse prognostic factor in CLL. In a multivariate analysis it was independent of most of the usual adverse prognostic factors for time to treatment, though not for overall survival. The study was perhaps insufficiently powered to show that.

Several reports have suggested that low serum vitamin D3 levels may be associated with increased incidence of colorectal, breast, and other cancers. One population based, double-blind, randomized placebo-controlled trial found women who increased their daily vitamin D intake by 1100 IU reduced their risk of cancer by 60-77%.

Recent data suggest low vitamin D3 levels at diagnosis may be associated with poorer prognosis in colorectal, breast, melanoma, and lung cancer, although these data have not yet been replicated in independent cohorts.

Sounds an open and shut case, doesn't it?

The problem is that association does not prove causation.

Here is another example of an association being unrelated to causation: A low Hb is a poor prognostic factor in CLL. If you correct the Hb does it make the prognosis better? Of course not! the problem is that the CLL is destroying the bone marrow; raising the Hb artificially by blood transfusion or erythropoietin won't affect that.

One possible reason for a low vitamin D3 being a poor prognostic factor is that D3 is protective against CLL and if you have low levels it roars away. But equally it may be that aggressive CLL consumes vitamin D3 and that's why the level is low. If you give more D3 you might be feeding the flames.

Generally there seems no downside to giving megadoses of D3 as long as you keep the serum calcium in check, but so far no-one has shown any benefit in CLL. The Mayo group are right to call for clinical trials