By Andy Ho
THERE is a story making the rounds that many Singaporeans are deficient in vitamin D, so we had better be popping supplements of it.
A Tan Tock Seng Hospital (TTSH) study published in Clinical Chemistry in 2009 examined the blood levels of vitamin D of locals in the form called 25(OH)D3, or simply 25-D.
Without scientific consensus on the issue, two cut-off points to determine deficiency were used.
The report said that 'the prevalence of vitamin D deficiency... varies from 0-12.5 per cent (at the first cut-off) to 70-100 per cent (at the other cut-off) according to the sub-group examined'.
For example, in the latter instance, 70 to 100 per cent of Malay and Indian females were supposedly deficient in vitamin D.
But up to 100 per cent of Malay and Indian women cannot be deficient in a vitamin that the skin makes in sunlight.
Note that vitamin D deficiency, whichever the cut-off, is always diagnosed using the blood levels of 25-D, the inactive form of vitamin D. Doctors everywhere routinely use its levels as the biomarker of vitamin D deficiency.
But this might be a mistake.
Occurring in a family of related molecular forms, the one made in the skin in the sunlight is called D3. This is transported to the liver, where it changes into 25-D, the inactive intermediate form.
This is then changed in the kidneys into the active form called 1,25-D. Thus, D3 made in the skin becomes 25-D in the liver and 1,25-D in the kidneys.
Importantly, vitamin D is less of a vitamin - vitamins act as helpers of enzymes - and more of a steroid. Though the active form called 1,25-D has powerful steroidal effects, its levels are not measured.
To repeat, only 25-D levels are routinely measured. For example, the Wikipedia entry is typical in baldly asserting that blood 25-D levels are 'the accepted way to determine vitamin D nutritional status'. No reason is offered for this.
It is assumed that the two levels - the inactive 25-D and the active 1,25-D - move in lock-step. That is, a high level of 25-D supposedly means a high level of 1,25-D.
But if this is not so in real life, then low blood levels of the inactive form may not always mean low blood levels of the active steroidal form as well.
In fact, some scientists now argue that if there is a lot of an active end-product - (1,25-D) - in a metabolic pathway, there could be less of its inactive precursor (25-D) in the same pathway.
Here is one way this might come about in the case of vitamin D. In many illnesses, the body produces lots of interferon gamma, an immune substance that helps fight things ranging from bacterial infections to cancers.
Interferon gamma can activate those big white blood cells called macrophages that gobble up germs. Macrophages that have been activated by this interferon are known to produce 1,25-D itself.
Remember this is the activated form of vitamin D and it is a steroid that can have an impact on the body's immune functions.
But while 1,25-D levels may be raised by this mechanism, blood levels of 25-D, the inactive form, are known to be lowered across a whole gamut of different illnesses, from infections to cancers.
This means that there are some circumstances in which low blood levels of the inactive form of vitamin D (25-D) which are routinely measured could co-exist with elevated blood levels of the active form of the vitamin (1,25-D), which are not usually measured.
If so, the TTSH finding that 70 to 100 per cent of some of us may be deficient in (the inactive form of) vitamin D could actually mean that many in this sub-group may well have sufficient levels of (the active form of) vitamin D.
This inference seems far more reasonable, given that the skin makes the vitamin in sunlight, which Singapore has in abundance.
In sum, measuring only one form of the vitamin while ignoring the other form may lead to an erroneous diagnosis of deficiency.
Here is why all this matters: Today, vitamin D supplements are widely advocated as a way to avert a multitude of illnesses. This is because innumerable epidemiological studies have reported 'vitamin D deficiency' across a wide range of conditions, especially auto-immune ones, from diabetes to rheumatoid arthritis.
This 'deficiency' is also supposedly associated with kidney diseases, breast, prostate and colon cancers, as well as heightened risks of infections, from viruses to TB.
Yet this advice to take vitamin D supplements in these illnesses or to prevent them is based on such epidemiological studies that typically look only at the 25-D levels alone and almost never the 1,25-D levels.
What if most conditions associated with 'vitamin D deficiency' were actually correlated with sufficient or a surplus of the active steroidal form instead?
If so, could taking vitamin D supplements as advised raise your blood levels of this steroid? Might this be why people tend to report feeling better with vitamin D pills since steroids can cause some euphoria?
But too much of any steroid might eventually suppress the immune system. If so, could vitamin D supplements be actually harmful in the long run?
This is not scare-mongering either. Instead, this is a wake-up call for doctors who have patients on vitamin D supplements to check their blood levels of the active steroidal form of vitamin D as well.
Better safe than sorry.
[A story to remind us that when using proxy measures, we must remind ourselves that they are only proxies.]