Clin Chem Lab Med 2009;47(3):334–338  2009 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2009.074 2007/535 Article in press - uncorrected proof Vitamin B12 deficiency is associated with coronary artery disease in an Indian population Jitender Kumar 1 , Gaurav Garg 1 , Elayanambi Sundaramoorthy 1 , P. Veerendra Prasad 2 , Ganesan Karthikeyan 3 , Lakshmy Ramakrishnan 3 , Saurabh Ghosh 2 and Shantanu Sengupta 1, * 1 Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, Delhi, India 2 Human Genetics Unit, Indian Statistical Institute, B.T. Road, Kolkata, India 3 Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India Abstract Background: The incidence of coronary artery disease (CAD) is increasing at an alarming rate, especially in developing countries, such as India. It is often advo- cated that a vegetarian lifestyle could reduce the bur- den of CAD. However, in spite of a majority of Indians being vegetarians, the incidence of CAD is highest in this population. This may be due to deficiency of vita- min B12, a micronutrient, sourced only from animal products. Methods: Herein, we assessed the effect of vitamin B12 with respect to CAD in 816 individuals (368 CAD patients and 448 controls) recruited from a tertiary care center in New Delhi, India. Results: We found that vitamin B12 levels were significantly lower in CAD patients than in controls (p-0.0001). Also, vegetarians were found to have significantly lower vitamin B12 concentrations (ps0.0001) and higher incidence of CAD (ps0.01). Interestingly, elevated homocysteine levels, a hall- mark of vitamin B12 deficiency, was not associated with CAD. In contrast, cysteine levels were signifi- cantly higher in CAD patients than in controls (ps0.004). Conclusions: We believe that, when vitamin B12 is deficient, homocysteine is rapidly metabolized via the transsulfuration pathway leading to increased cyste- ine levels. Clin Chem Lab Med 2009;47:334–8. Keywords: coronary artery disease; cysteine; homo- cysteine; vegetarian diet; vitamin B12. Introduction Coronary artery disease (CAD) is probably the largest cause of mortality and morbidity worldwide and is *Corresponding author: Shantanu Sengupta, Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007 Phone: q91-11-27666156, Fax: q91-11-27667471, E-mail: shantanus@igib.res.in Received October 30, 2008; accepted December 18, 2008; previously published online February 4, 2009 reaching epidemic proportions in developing coun- tries. In India, mortality due to coronary heart dis- eases increased from 1.17 million to 1.59 million from 1990 to 2000 and is expected to rise to 2.03 million by 2010 (1). It has been predicted that deaths due to CAD are likely to be more than any other disease in India (2). Furthermore, in Indians, CAD tends to occur much earlier than any other ethnic groups (3). Risk of fatalities due to heart diseases has been shown to be reduced up to 24% by switching to a vegetarian diet (4). If this is indeed the case, it could be expected that in a country such as India where a majority of the population is taught to adhere to a vegetarian diet due to family conventions or religious doctrines, the incidence of heart diseases would be relatively lower. However, in reality, the incidence of CAD is much higher in India compared to the rest of the world (5, 6). Although a vegetarian diet might con- tain low levels of some of the classical risk factors for CAD, it lacks important micronutrients, prominent among which is vitamin B12. Vitamin B12 is an important micronutrient sourced only from animal and animal products. Most vegetar- ians in India have never consumed animal products except in the form of milk or milk products. Thus, it is expected that these individuals have chronic vita- min B12 deficiency. Earlier studies in such popula- tions have reported high prevalence of vitamin B12 deficiency (7, 8). Cross-sectional studies carried out four decades earlier have pointed to the fact that veg- etarianism and the types therein had varying grades of vitamin B12 deficiency (9, 10). Recent studies by Herrmann et al. have validated these findings (11). We thus hypothesized that since a majority of Indi- ans lead a vegetarian lifestyle, they might be deficient in vitamin B12 and this might lead to an increase in concentrations of homocysteine and cysteine, the two thiol amino acids that have been associated with CAD. In the current study, we evaluated the effect of vita- min B12 concentrations with respect to CAD in a case- control setup recruited at a tertiary care center situated in New Delhi, India. Materials and methods Study population The study population (ns816, mainly from the northern part of India) with a median age of 50 years was recruited con- secutively, between September 2004 and March 2007, from the Department of Cardiology, All India Institute of Medical Sciences (AIIMS), New Delhi, India. Out of these 816 individ- uals, 368 had CAD as confirmed by coronary angiography, while 448 individuals with a negative treadmill test were con- sidered as controls. The treadmill test negative controls had Brought to you by | Tokyo Daigaku Authenticated Download Date | 5/25/15 11:09 PM