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J Neurol Neurosurg Psychiatry 2013;84:e2 doi:10.1136/jnnp-2013-306573.185
Association of British Neurologists (ABN) joint meeting with the Royal College of Physicians (RCP), London, 23–24 October 2013
University of Oxford; Barts and the London School of Medicine and Dentistry
Multiple Sclerosis (MS) is a complex neurological disorder most likely caused by gene–environment interactions. There is a latitudinal gradient of MS prevalence and vitamin D deficiency has been strongly implicated in MS aetiology. Iran is a country of high levels of sunshine which has previously been considered a low–risk MS region. However, Iran has recently observed an 8.3–fold rise in the incidence of MS between 1989–2006.1 Previous studies have indicated a genetic predisposition to MS in the Iranian population but genetic changes are unlikely to account for the substantial rise in MS over the last few decades. Thus, we aimed to develop a novel hypothesis to explain the identification of Iran as a high–risk MS region. We believe that the influence of decreased sunshine exposure and vitamin D levels on MS risk needs to be strongly considered in the context of Iran's history. In 1979 the Iranian Revolution took place and a country previously under great Western influences became an Islamic republic. It became a government requirement for women to wear loose–fitting clothing and the veil in public; it has previously been shown that veiled women have lower vitamin D levels compared to unveiled women. This significant cultural shift would not only potentially explain the observed increase in MS but notably, it would account for the increasing female preponderance of MS in Iran. Given that the average age of MS onset is 30 years old and that MS incidence in Iran just over 30 years following the revolution is the highest so far recorded, an association with the Iranian revolution and reduced subsequent vitamin D levels in particularly pregnant women is likely. Lifestyle changes such as urbanization and use of sunscreen may to some extent have contributed to increased vitamin D deficiency, but these are unlikely to contribute to the particularly high increase in MS observed in Iran as these changes occurred across the developed world and there is no evidence to suggest that they were particularly great in Iran. A similar high incidence of MS has been observed among Iranian immigrants in countries at high latitude such as Sweden where Iranian immigrants have a reported greater prevalence of MS compared to the general population, despite wearing a veil not being a requirement. Instead it is well–known that UVB exposure is lower in countries at high latitude and thus, a similar effect of increased MS incidence due to vitamin D deficiency may be observed among those in Iran wearing the veil and those resident in countries at high latitude, even if they are not wearing the veil. Therefore, vitamin D repletion is a critical public health issue for Iranians both within and outside Iran, and could help prevent an emerging MS epidemic in this population. More generally, this region is highly interesting for MS research and highlights that regions of exception to the latitudinal gradient of MS prevalence are an under–appreciated and very useful resource in evaluating MS aetiology.
Neuroepidemiology 2013;40:68-69 (DOI: 10.1159/000341848) Vol. 40, No. 1, 2013
Amir-Hadi Maghzia, c, f, Mohammad-Ali Sahraiane, Vahid Shaygannejadc, d, Alireza Minagarb
A Department of Neurology, Multiple Sclerosis Center, University of California San Francisco, San Francisco, Calif., and
B Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, La., USA;
C Isfahan Neurosciences Research Center and
D Department of Neurology, Isfahan University of Medical Sciences, Isfahan, and
E Sina MS Research Center, Brain and Spinal Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran;
F Neuroimmunology Unit, Center for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, and London School of Medicine and Dentistry, London, UK
We read with interest the letter by Pakpoor and Ramagopalan , in which they suggest that the reported increase in the prevalence, incidence and sex ratio of multiple sclerosis (MS) is attributed to the occurrence of the Islamic Revolution in Iran, where women were required to wear a veil in public according to the state regulations, and this has resulted in vitamin D deficiency, which is a risk factor for MS.
As the authors also state, MS is a complex disease and a combination of factors are concomitantly needed in order to cause MS. We think that there are many possible explanations for this increase, and vitamin D deficiency – although important – might not fully explain it. During the recent decades, the level of hygiene and health care has increased in Iran. This translates into better diagnostic tools, increased numbers of physicians and increased disease awareness, which might have improved the case ascertainment. However, we believe that this could not be the whole story as the onset of first demyelinating events in both Iranian cohorts from Tehran and Isfahan occurred in the young and during recent years. Therefore, in case of an increase in the number of patients diagnosed, the number of older patient who were missed in the past would also be considerable [2,3,4]. On the other hand, increased hygiene on a population level could delay the exposure of individuals to common viral agents like Epstein-Barr virus translating into infectious mononucleosis, which in turn increases the risk of MS (hygiene hypothesis) . We demonstrated that although smoking was a risk factor for MS in the Iranian population, it was not increasing and might not be responsible for the increased incidence and sex ratio of MS in Iran [6,7]. On the other hand, we have previously proposed the young age structure (age structural shift) of Iran as another possible explanation for the increased crude incidence of MS .
Vitamin D deficiency is currently a health problem in Iran as well as in the rest of the world. However, in Iran there are gender differences in vitamin D levels [8,9,10]. Studies carried out in Isfahan and Tehran suggest that the rate of vitamin D deficiency is high in the general population and significantly more prominent in females and youngsters [8,9,10]. Although it has been shown that wearing a veil and covering is associated with hypovitaminosis D , it should be borne in mind that prior to the occurrence of the Islamic revolution in 1979, most Iranians were still Muslim, and since wearing a hijab by women is required by Islamic rules, most Iranian women used to wear a veil and covering in public even before the revolution. Nevertheless, there have been radical lifestyle changes during the past decades, such as
- living in apartments,
- air pollution,
- insufficient consumption of vitamin-D-rich food,
- widespread use of sun screens,
- avoiding sun exposure for fear of skin cancer and esthetical issues,
all of which are thought to cause vitamin D deficiency, and the latter two are more prevalent among females . Moreover, Iranian women spend less time in the sun compared to men, which could also lead to vitamin D deficiency, but is independent of wearing a hijab or veil and is mostly due to culture and lifestyle [7,9]. These factors combined with the hijab might have caused the gender difference in vitamin D deficiency in Iran. On the other hand, Iranian immigrants to Canada and Sweden have been shown to have similar high rates of MS, and a hijab is not a requirement in those countries [12,13]. Furthermore, the incidence, prevalence and sex ratio of MS are also on the rise in other countries, which seem to be due to the lifestyle changes especially among women, which could have also occurred amongst Iranian women.
As Muslim women can expose their face and hands in public, sun exposure to these parts for a certain daily period could help supplying vitamin D levels. Taken together, dietary and lifestyle changes could help improve vitamin D deficiency in Iran. Moreover, as we have previously suggested , and as rightfully suggested by Pakpoor and Ramagopalan , vitamin D supplementation for Iranian women could be a good strategy to control the rising incidence and sex ratio of MS in Iran.
1. Pakpoor J, Ramagopalan SV: Multiple sclerosis and the Iranian revolution. Neuroepidemiology 2012;38:122.
2. Etemadifar M, Maghzi AH: Sharp increase in the incidence and prevalence of multiple sclerosis in Isfahan, Iran. Mult Scler 2011;17:1022–1027.
3. Saadatnia M, Etemadifar M, Maghzi AH: Multiple sclerosis in Isfahan, Iran. Int Rev Neurobiol 2007;79:357–375.
4. Sahraian MA, Khorramnia S, Ebrahim MM, Moinfar Z, Lotfi J, Pakdaman H: Multiple sclerosis in Iran: a demographic study of 8,000 patients and changes over time. Eur Neurol 2010;64:331–336.
5. Maghzi AH, Marta M, Bosca I, Etemadifar M, Dobson R, Maggiore C, Giovannoni G, Meier UC: Viral pathophysiology of multiple sclerosis: a role for Epstein-Barr virus infection? Pathophysiology 2011;18:13–20.
6. Maghzi AH, Etemadifar M, Heshmat-Ghahdarijani K, Moradi V, Nonahal S, Ghorbani A, Minagar A: Cigarette smoking and the risk of multiple sclerosis: a sibling case-control study in Isfahan, Iran. Neuroepidemiology 2011;37:238–242.
7. Alonso A, Cook SD, Maghzi AH, Divani AA: A case-control study of risk factors for multiple sclerosis in Iran. Mult Scler 2011;17:550–555.
8. Hovsepian S, Amini M, Aminorroaya A, Amini P, Iraj B: Prevalence of vitamin D deficiency among adult population of Isfahan City, Iran. J Health Popul Nutr 2011;29:149–155.
9. Moussavi M, Heidarpour R, Aminorroaya A, Pournaghshband Z, Amini M: Prevalence of vitamin D deficiency in Isfahani high school students in 2004. Horm Res 2005;64:144–148.
10. Rabbani A, Alavian SM, Motlagh ME, Ashtiani MT, Ardalan G, Salavati A, Rabbani B, Shams S, Parvaneh N: Vitamin D insufficiency among children and adolescents living in Tehran, Iran. J Trop Pediatr 2009;55:189–191.
11. Guzel R, Kozanoglu E, Guler-Uysal F, Soyupak S, Sarpel T: Vitamin D status and bone mineral density of veiled and unveiled Turkish women. J Womens Health Gend Based Med 2001;10:765–770.
12. Guimond C, Dyment DA, Ramagopalan SV, Giovannoni G, Criscuoli M, Yee IM, Ebers GC, Sadovnick AD: Prevalence of MS in Iranian immigrants to British Columbia, Canada. J Neurol 2010;257:667–668.
13. Ahlgren C, Oden A, Lycke J: A nationwide survey of the prevalence of multiple sclerosis in immigrant populations of Sweden. Mult Scler 2011.
14. Maghzi AH, Ghazavi H, Ahsan M, Etemadifar M, Mousavi S, Khorvash F, Minagar A: Increasing female preponderance of multiple sclerosis in Isfahan, Iran: a population-based study. Mult Scler 2010;16:359–361.
Amir-Hadi Maghzi, MD
Department of Neurology, Multiple Sclerosis Center
UCSF, 675 Nelson Rising Lane
2nd floor, Room 221E, Box 3206, San Francisco, CA 94158 (USA)
Tel. +1 415 502 7226, E-Mail firstname.lastname@example.org
Received: July 4, 2012; Accepted: July 12, 2012; Published online: October 11, 2012
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- Muslim women wore hijabs before and after the Iran revolution (and have dark skins)
- Changes in the past few decades have further reduced the vitamin D which they get
- Probably need to supplement with vitamin D
- Missed many reasons for vitamin D deficiency, such as
air conditioning, less cholesterol in diet, more drugs which consume of block vitamin D
increased consumption of polyunsaturated fats, Less magnesium in foods
- They seem to go out of their way to ignore dark skin
- Overview Middle East and vitamin D
- Overview MS and vitamin D
- Google Search for "+"Multiple sclerosis" +african-american difference" got more than 2 million hits Oct 2012
There are probably a similar number of hits for dark skin and MS
- Overview Dark Skin and Vitamin D
- Dark skin births are much riskier due to lack of vitamin D
Something not yet discussed in the Middle East
- More hijab clothing may have resulted in 6X increase in Multiple Sclerosis in Tehran – May 2013