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Indian endocrinologists warn of vitamin D deficiency

BMJ 2003; 326 doi: (Published 04 January 2003) Cite this as: BMJ 2003;326:12

Rapid Response:

Rheumatic Disease is Th1, Viral Infections are (generally) Th2

One should not confuse our observations about rheumatic
disease with the body's immune response to a viral infection.

Rheumatic disease is associated with a vigorous Th1 immune reaction, almost
certainly fueled by bacterial pathogens [1,2]. The active hormone resulting
from 'Vitamin D' ingestion, 1,25-dihydroxyvitamin-D, is intimately associated
with Th1 immune reactions, being responsible (inter alia) for
differentiation of mast cells into monocytes and differentiation of
monocytes into mature macrophages and dendritic cells [3].

Viral infections, on the other hand, typically elicit a Th2 immune
response. Indeed, many viruses actively suppress the Th1 activity. An
excellent explanation of how the non-infectious surface antigen of
Hepatitis B (HBsAg) works to directly oppose the differentiation activity of
1,25-dihydroxyvitamin-D is expounded by Vanlandschoot, et al [4]. HIV
has also been extensively studied, and found to similarly
directly block the actions of 1,25-dihydroxyvitamin-D.

In other words, bacterial pathogens (rheumatic disease) produce an excess
of 1,25-dihydroxyvitamin-D in the inflamed tissues while viral infections
actively counteract any 1,25-dihydroxyvitamin-D in those tissues.

The concentration of serum 1,25-dihydroxyvitamin-D is also vitally
important in cancers [5,6]. Further, there is a direct association between
the levels of 1,25-dihydroxyvitamin-D and the prognosis of those
cancers [5,6].

It is obvious that we are not dealing with the classical nutrient
activities of a vitamin. 'Vitamin D' is the precursor of a steroid hormone
which fuels an essential component of the body's Th1 immune

Any calcemic activity is of far lesser importance. Indeed, it is the
parathyroid hormone acting in concert with the calcium sensing receptors in
the kidney which primarily determine calcemia in man [7,8].

As Dr Deolankar reminds us [9], there is a wealth of historical clinical
observations which purport to describe the actions of Vitamin D on the human body.
Unfortunately most of these studies are misguided, and many draw incorrect conclusions.
One cannot accurately comprehend of the actions of
'Vitamin D' on the body without a comprehensive understanding of the
(unfortunately complex)
underlying molecular medicine.

If a decision is made to supplement the food chain with 'Vitamin D',
then one group of individuals (those with an under-active Th1 immune
response) will be favored, while another group (those whose rheumatic
disease has led to an overactive Th1 immune response) will be prejudiced. We would submit that public health
officials should stay away from making such decisons until they fully
understand all the implications of their actions.

1. Berger A: Th1 and Th2 responses: what are they? BMJ

Available from URL

2. Marshall TG, Marshall FE: Sarcoidosis succumbs to antibiotics -
implications for autoimmune disease.

Autoimmunity Reviews, in press, doi:10.1016/j.autrev.2003.10.001

Available from URL Accessed
Nov 19, 2003

3. Hewison M, Gacad MA, Lemire J, Adams JS: Vitamin D as a cytokine
and hematopoetic factor.
Rev Endocr Metab Disord 2001, 2(2):217-27 PMID:

4. Vanlandschoot P, Van Houtte F, Roobrouck A, Farhoudi A, Leroux-Roels
G: Hepatitis B virus surface antigen suppresses the activation of
monocytes through interaction with a serum protein and a monocyte-specific
Journal of General Virology (2002), 83, 1281-1289

Available from Last
Accessed 4 April 2004

5. Mawer EB, Walls J, Howell A, Davies M, Ratcliffe WA, Bundred NJ:
Serum 1,25-dihydroxyvitamin D may be related inversely to disease
activity in breast cancer patients with bone metastases.
J Clin
Endocrinol Metab. 1997 Jan;82(1):118-22 PMID: 8989244

6. Lauerova L, Dusek L, Simickova M, Kocak I, Vagundova M, Zaloudik J,
Kovarik J: Malignant melanoma associates with Th1/Th2 imbalance that
coincides with disease progression and immunotherapy response.

Neoplasma. 2002;49(3):159-66 PMID: 12098001

7. Watanabe T, Minagawa M: Familial hypoparathyroidism due to
activating mutations in the calcium-sensing receptor gene.
Rinsho. 2002 Feb;60(2):331-7 PMID: 11857922

8. Thakker RV: Disorders of the calcium-sensing receptor. Biochim
Biophys Acta. 1998 Dec 10;1448(2):166-70 PMID: 9920407

9.Deolankar RP: Vitamin D deficiency may be mediating rotavirus diarrhoea. BMJ
Rapid Response, 2004 March 13; #53146
Available from

Competing interests:
None declared

Competing interests: No competing interests

04 April 2004
Trevor G Marshall
Autoimmunity Research Foundation