INTRODUCTION. Overweight and obesity are defined as abnormal or excessive fat accumulation that

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1 INTRODUCTION 1.1 Obesity Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health (WHO 2012). A crude population measure of obesity is the body mass index, a person s weight (in kilograms) divided by the square of his or her height (in meters). A person with a body mass index equal to or more than 25 is considered overweight, whereas body mass index of 30 or more is generally considered obese. Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes, cardiovascular diseases and cancer. Obesity is today s most blatantly visible yet most neglected public health problem. Once considered a problem only in high income countries, overweight and obesity are now drastically on the rise in low- and middle-income countries, particularly in urban settings. Paradoxically coexisting with undernutrition, an escalating global epidemic of overweight and obesity- globosity is taking over many parts of the world. Obesity is a complex condition, one with serious social and psychological dimensions, that affects virtually all ages and socio-economic groups and threatens to overwhelm both developed and developing countries. According to WHO, overweight and obesity are the fifth leading risks for global deaths. At least 2.8 million adults die each year as a result of being overweight or obese. In addition, 44 per cent of the diabetes burden, 23 per cent of the ischemic heart disease burden and between 7 per cent and 41 per cent of certain cancer burdens are attributable to overweight and obesity.

2 Some facts about the prevalence of obesity given by WHO are: 1.5 billion adults, 20 years of age and older, were overweight. Of these 1.5 billion overweight adults, over 200 million men and nearly 300 million women were obese. Overall, more than one in ten of the world s adult population was obese (WHO Fact Sheet N*311). Obesity has reached epidemic proportions in India in the 21st century, with morbid obesity affecting 5 per cent of the country's population. India is following a trend of other developing countries that are steadily becoming more obese. Unhealthy, processed food has become much more accessible following India's continued integration in global food markets. New data released by the International Diabetes Federation shows that every sixth diabetic in the world is an Indian - earning India the title "the world's diabetes capital." Research over the past decade shows that genetically, Indians store more body fat per kilogram than Europeans, making them more prone to obesity. 1.2 Causes of Obesity and Overweight The fundamental cause of obesity and overweight is an energy imbalance between calories consumed and calories expended. Globally, there has been: An increased intake of energy-dense foods which are high in fat, salt and sugars but low in vitamins, minerals and other micronutrients. A decrease in physical activity due to the increasingly sedentary nature of many forms of work, changing modes of transportation, and increasing urbanization. Changes in dietary and physical activity patterns are often the result of environmental and societal changes associated with development and lack of supportive policies in

3 sectors such as health, agriculture, transport, urban planning, environment, food processing, distribution, marketing and education. Overweight and obesity, as well as their related non-communicable diseases, are largely preventable. Supportive environments and communities are fundamental in shaping people s choices, healthier choice of food and regular physical activity is the easiest choice and therefore helps to prevent obesity. At the individual level, people can: Limit energy intake from total fats. Nuts, oil seeds & fried foods should be avoided. Increase consumption of fruit and vegetables, as well as legumes, whole grains and nuts. Limit the intake of sugars to about 15g/day. Engage in regular physical activity. Achieve energy balance and a healthy weight. Individual responsibility can only have its full effect where people have access to a healthy lifestyle. Therefore, at the societal level it is important to: Support individuals in following the above recommendations, through sustained political commitment and the collaboration of many public and private stakeholders; Make regular physical activity and healthier dietary patterns affordable and easily accessible too all - especially the poorest individuals. The food industry can play a significant role in promoting healthy diets by: Reducing the fat, sugar and salt content of processed foods; Ensuring that healthy and nutritious choices are available and affordable to all consumers. Practicing responsible marketing; Ensuring the availability of healthy food choices and supporting regular physical activity practice in the workplace.

4 The identification of factors that influence energy balance is an important issue in the research field of nutrition and becomes a growing necessity in the context of obesity epidemic throughout the world. It is a risk factor for chronic diseases such as heart disease, cancer, stroke and diabetes and weight loss is known to reduce the risk for some of these diseases. Although much of effort has been devoted to studying the effects of macronutrients on weight control, the role of micronutrients has not been well studied. It is well understood that thermodynamics and energy balance are core factors involved in the obesity epidemic, with small increase in energy intake coupled with declining physical activity resulting in a net positive energy balance and progressive weight gain. It has consequently become axiomatic to reduce the obesity epidemic to a simple question of energy balance and to invoke various strategies to induce negative energy balance to address the problem. However, it is equally well understood that obesity is a complex genetic trait, with multiple genes interacting to confer relative resistance or susceptibility to positive energy balance. Similarly, specific micro or macronutrients, dietary patterns or both may modulate the same metabolic pathways affected by these genetic factors and thereby alter nutrient and energy partitioning. Whereas there can be a little doubt that it is of prime importance to address issue of energy intake and energy expenditure. It has also become critical to address nutritional strategies and dietary patterns that may alter energy partitioning and thereby reduce energy balance and the risk of overweight and obesity. This approach, if viable, becomes increasingly important as the frequent failures of individual person and population to adhere to strategies designed to produce negative energy balance is recognized. Indeed, it is known from the previous experiences the value of promoting positive behaviors rather than using a prohibitive approach to accomplish a given health outcome. For example, although, there is a well-established relation between salt intake

5 and blood pressure control, but most people are unable to adhere to energy-restricted weight-control diets for extended periods of time. In contrast, the Dietary Approach to Stop Hypertension (DASH) diet presents the positive approach of increasing fruit, vegetable and dairy intake to lower blood pressure. Notably, recent evidence now indicate that these same diet play a significant role in the partitioning of dietary energy and helpful in the prevention and management of obesity. 1.3 Micronutrients and Obesity Micronutrients are a key part of nutrition, and while they are not directly related to weight loss, they play a vital role in keeping body healthy. Some micro nutrients are closely involved in specific body functions related to weight management. For example, Vitamins B1, B5, and B6 aid in metabolism, while chromium aid in insulin action and selenium and iodine contribute to thyroid hormone function. Metabolism, insulin and thyroid hormones can all have an effect on body weight and appetite. Lack of micronutrients or small portions of vitamins and minerals in diet has been linked to an increased risk of obesity (Calton, 2010). Micronutrients work in specific ways to enhance the loss of body fat, preserve muscle mass, and regulate levels of blood sugar and insulin. Calcium may be the newest weight-loss secret. Recent studies provide more evidence that calcium can fight body fat and help to keep weight under control. Calcium and weight loss have been positively associated. It has been shown that more dietary calcium intake may help to facilitate fat loss, prevent fat storage, help raise metabolism and reverse gradual weight gain. Although energy balance is the most critical factor in weight regulation, recent studies suggest that Ca contribute to shifting the energy balance and thus play a vital role in weight regulation (Teegarden, 2003).

6 1.4 Dietary Calcium, Adiposity and Obesity Risk Although this concept of calcium modulating energy metabolism and obesity risk is new and has been developed over only during the past few years, much evidence from observational, clinical intervention and mechanistic studies now support this concept. This antiobesity effect was first observed accidentally, during a study in the 1980s while investigating the antihypertensive effect of dairy products in obese African American men. Increasing dietary calcium produced expected decrease in blood pressure that was accompanied by an unexpected reduction in body fat (Shi et al., 2001). Similarly, it was noted that there is a significant inverse relation between dietary calcium and body weight in an early study of the relation between dietary calcium and blood pressure in the first NHANES l database (McCarron, 1983). 1.5 Effect of Intracellular Ca 2+ and Calcitrophic Hormones on Adipocyte Metabolism Parathyroid hormone and 1,25-dihydroxyvitamin D [1,25(OH) 2 D], which respond to low-calcium diets, exert coordinated regulatory effects on human adipocyte lipogenic and lipolytic systems, that results in increased lipid storage during low-calcium diets, whereas the suppression of these hormones during high-calcium diets inhibits adiposity. Intracellular calcium ion ([Ca 2+ ]i) is a key regulator of adipocyte lipid metabolism, which serves to increase lipogenic gene expression and de novo lipogenesis and to inhibit lipolysis, that results in increased lipid storage. The suppression of parathyroid hormone and 1,25(OH) 2 D via increase in dietary calcium facilitates repartitioning of dietary energy from lipid storage to lipid oxidation and thermogenesis. 1,25(OH) 2 D plays a pivotal role in the modulation of lipid metabolism, human adipocytes possess membrane (nongenomic) vitamin D receptors that transduce a rapid [Ca 2+ ]i response to 1,25(OH) 2 D 3 ; consequently, the treatment of human adipocytes with

7 1,25(OH) 2 D 3 results in the coordinated activation of fatty acid synthase expression and activity and the suppression of lipolysis, leading to an expansion of adipocyte lipid storage. Various data provide a plausible mechanism of action based on in vitro studies in human adipocytes, the direct effect of calcitrophic hormones on human adipocyte metabolism has not yet been assessed with the use of in vivo techniques such as microdialysis. Nonetheless, a potential role of 1α,25(OH) 2 D 3 in human obesity has been suggested. Polymorphisms in the nuclear vitamin D receptor (nvdr) gene are associated with the susceptibility to obesity in humans with early onset type 2 diabetes. Human body weight and body mass index (BMI; in kg/m 2 ) is associated with a BsmI restriction site polymorphism in the nvdr gene (Barger et al, 1995) whereas much evidence indicates increase in circulating concentrations of 1α,25(OH) 2 D 3 in obese humans. High-calcium diets may also affect energy partitioning by suppressing the 1,25(OH) 2 D 3 -mediated inhibition of adipocyte UCP2 expression. However, the role of UCP2 in thermogenesis is not clear and the observed thermogenic effect may accordingly be mediated by other, as of yet unidentified mechanisms. Moreover, thermogenic effects of dietary calcium have not yet been shown in humans. Nonetheless, in addition to inducing a mitochondrial proton leak, UCP2 serves to mediate mitochondrial fatty acid transport and oxidation, which suggests that the 1,25(OH) 2 D 3 suppression of UCP2 expression may still contribute to decreased fat oxidation and increased lipid accumulation with low-calcium diets (Shi et al., 2002)

8 * Source: Zemel MB (2004) Fig 1.1: Mechanism of dietary calcium and dairy modulation of adiposity. 1,25(OH) 2 D 3 is a potent inhibitor of both murine and human adipocyte apoptosis. This effect is mediated via the inhibition of UCP2 expression and a consequent increase in mitochondrial potential and in part via the 1,25(OH) 2 D 3 regulation of cytosolic and mitochondrial Ca 2+ and results in marked increase in adipocyte apoptosis in mice fed diets high in calcium or high in dairy products. 1.6 Mechanism Vitamin D acts as both a vitamin and chemical messenger, and one of its jobs is to stimulate calcium uptake into the cells of the body when blood calcium levels are low. However, when blood calcium levels are high (for example on a high-calcium diet), levels of a particular metabolite of vitamin D (1,25-dihydroxyvitamin D) fall, and this

9 in turn reduces the rate at which calcium is transferred into cells, including fat cells and pancreatic cells. *Source: Fig 1.2: Link between calcium and fat reduction A reduced calcium level in fat cells decreases the activity of a fat storage enzyme called fatty acid synthase (FAS), which in turn leads to reduced fat synthesis and subsequent storage. Reduced FAS activity also leads to increased lipolysis (the breakdown of fat for energy). At the same time, reduced calcium concentrations in pancreatic cells lead to lower insulin output which, in turn, results in reduced fat synthesis and enhanced fat breakdown in fat cells. 1.7 Sources of Calcium Calcium is the main component of bones and teeth. It is essential for the growth in children and helps to ensure efficient muscle contraction and blood clotting. It also helps in lowering blood pressure. Our bodies use calcium to help our heart, muscles and nerves to work properly. Our bodies cannot make calcium itself so, when calcium rich

10 food is eaten the calcium enters our blood and is carried to the organs to perform the work that is needed. The extra calcium is stored in our bones and when there is deficiency of calcium from food, the body will take the calcium from our bones to meet its needs. Milk and dairy products are among the major sources of calcium. Table 1.1 Calcium Content of Some Common Indian Foods FOOD PORTION SIZE CALCIUM CONTENT (milligrams) Ragi 100 g 344 mg Whole Wheat Flour 100 g 48 mg Bajra 100 g 42 mg Whole Bengal Gram 100 g 202 mg Black Gram 100 g 154 mg Whole Green Gram 100 g 124 mg Lentil 100 g 69 mg Rajmah 100 g 260 mg Red Gram (dhal) 100 g 73 mg Soyabean 100 g 240 mg Beet Green 100 g 380 mg Broad Bean Leaves 100 g 111 mg Carrot Leaves 100 g 340 mg Cauliflower Green 100 g 626 mg Colocasia Leaves 100 g 570 mg Radish Leaves 100 g 265 mg Lotus Stem (dry) 100 g 405 mg Milk (Buffalo s) 100 ml 210 mg Curd (Cow s Milk) 100 g 149 mg Chena (Cow s Milk) 100 g 208 mg Cheese 100 g 480 mg * Source- Gopalan et al. (2004) Nutritive Value of Indian Foods

11 Milk is one of the best providers of calcium in the diet. A 200ml glass of milk provides 55 per cent of the calcium to a six-year-old child. Cheeses and yogurts are also good sources of calcium and according to The Dairy Council - three dairy products a day are recommended to meet the daily requirement. People in the age group of are recommended to consume about 1 g of calcium per day, while for people in 50s, it should be approximately about 1.2 g per day. Other than milk and dairy products there are several other types of non-dairy sources of calcium that can be taken to ensure daily calcium intake. The soft bones of fish provide us with valuable calcium. Other useful sources include Soya bean products, such as tofu, as well as sesame seeds, nuts, white bread, dried fruit, pulses and green leafy vegetables. Soya milk alternatives, bottled water, breakfast cereals and orange juice are also fortified with extra calcium. The present research work Role of Calcium in Modulating Obesity was conducted with the following objectives: To compare the effect of different sources of calcium (dairy, non-dairy sources and Ca supplement) in modulating obesity. To examine the effect of calcium intake on serum calcium level, lipid profile and fecal fat excretion. To assess the effect of high calcium diet on weight.