Dairy, Yogurt, and Cardiovascular Health

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DAIRY, YOGURT, AND CARDIOVASCULAR HEALTH

27

Christine E. Dugan, Maria Luz Fernandez University of Connecticut, Storrs, CT, United States

27.1 INTRODUCTION It is well established that appropriate nutrition choices become strategic in the maintenance of a healthy body weight and in the promotion of overall health. Numerous dietary interventions have been reported to protect against chronic disease including metabolic syndrome (Andersen and Fernandez, 2013), diabetes (Salas-salvad et al., 2016), heart disease (Mayor, 2016), and others. There is some evidence that the implementation of certain dietary priorities including consumption of dairy products, with a major focus in yogurt, may contribute to healthy lifestyles associated with decreased risk of chronic disease (Mozaffarian, 2016). The association of yogurt with healthy outcomes and general well-being has been known for many years. Recently a scoping review reported that 213 studies have been conducted to determine yogurt health benefits (Glanville et al., 2015) on different aspects of health including bone health, weight management, gastrointestinal health, diabetes, and Parkinson disease to mention just a few. This review confirms for the most part the protective effects of yogurt against different conditions as well as its role in health (Glanville et al., 2015). To further support the role of dairy products in health, it has been reported that if Americans consumed at least 3–4 servings/day of dairy products, the 5-year cumulative savings for health care benefits would be over $200 billion (McCarron and Heaney, 2004). In addition, public health and health economic analysis support the recommendation that the preferred source of calcium for older men and women is dairy products (Ethgen et al., 2015). However, analysis of epidemiological data from the National Health and Nutrition Examination Survey (Mangano et al., 2011) and other sources (Villegas et al., 2010) conclude that Americans consume 70% of recommended calcium intake. Since consumption of dairy products is associated, as mentioned earlier, with decreased risk of a variety of metabolic diseases, the importance of dairy consumption needs to be emphasized. Health effects of yogurt have not been extensively studied. There are numerous benefits in the components of yogurt, which include large quantities of important nutrients in combination with low calories (Glanville et al., 2015). In addition, the beneficial effects of lactic acid bacteria present in yogurt in improving gastrointestinal conditions including constipation, diarrheal diseases, colon cancer, inflammatory bowel disease, and others have been studied (Adolfsson et al., 2004). For the purposes of this chapter, the focus will be on the protective effects of yogurt on (1) metabolic syndrome, (2) heart disease, and (3) diabetes. In the next section, evidence derived from epidemiological studies, clinical interventions as well as mechanistic effects of major nutrients from dairy/yogurt on blood pressure, body weight, plasma glucose, and plasma lipids will be addressed. Yogurt in Health and Disease Prevention. http://dx.doi.org/10.1016/B978-0-12-805134-4.00027-4 Copyright © 2017 Elsevier Inc. All rights reserved.

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27.2 EPIDEMIOLOGICAL STUDIES 27.2.1 METABOLIC SYNDROME Metabolic syndrome (MetS) consists of a constellation of indicators including central obesity, dyslipidemia, hypertension, and hyperglycemia, known to increase the risk for diabetes by fivefold and the risk for heart disease by twofold (Grundy, 2007). Thus dietary interventions that might decrease the development of MetS become very important. Based on the inverse associations reported between calcium (where dairy products are major source) intake and hypertension and glucose intolerance, it has been postulated that calcium deficiency influences the risk of developing metabolic syndrome (Major et al., 2008). The association between dairy consumption and metabolic syndrome has been examined in several cohort studies. For example, the evaluation of a cohort of 16,000 adults from the CARDIA study demonstrated that the highest quintile of dairy consumption decreased the risk of metabolic syndrome by 13% compared to the lowest quintile (Pereira et al., 2002). Similarly, in the DESIR study a higher consumption of dairy products and calcium was associated with a lower 9-year incidence of metabolic syndrome (Fumeron et al., 2011). In contrast to these findings, data from the British Women’s Heart and Health study reported that abstaining from milk reduced the odds for developing MetS by 45% (Lawlor et al., 2005). Further, Snijder et al. (2007) found that dairy intake was associated with lower diastolic blood pressure but not with any other parameter of metabolic syndrome while Beydoun et al. (2008) found a protective effect of yogurt. A more recent study evaluating the effects of dairy consumption on metabolic syndrome in more than 7000 middle-aged Koreans concluded that daily intake of dairy products protected against MetS mainly by an association with decreased central obesity (Shin et al., 2013). In summary, the majority of observational data suggest dairy consumption may protect against the development of MetS. There are also some studies that have specifically investigated the effects of yogurt and the incidence of metabolic syndrome. Babio et al. (2015) evaluated the associations between different types of dairy products in a population from the PREDIMED trial. Their results indicate that high consumption of yogurt, whether low or high fat, was correlated with reduced risk of MetS in these individuals characterized by a high risk for heart disease. In contrast, no significant association was found between yogurt consumption and metabolic syndrome in the 6-year SUN cohort follow-up where 306 cases of MetS were identified (Sayón-Orea et al., 2015). Authors used a 136-item validated food frequency questionnaire and logistic models and reported that only one component of MetS, central adiposity, was found to be inversely related to yogurt consumption. However, when yogurt was combined with fruit, an inverse association with MetS was observed (Sayón-Orea et al., 2015).

27.2.2 CARDIOVASCULAR DISEASE Several reports on diet and cardiovascular health in population studies have established a protective role of yogurt against ischemic heart disease, hypertension, and other cardiovascular problems. For example, a validated food frequency questionnaire was used in 1352 participants from the Observation of Cardiovascular Risk Factors in the Luxembourg survey to determine whether dairy consumption was associated with cardiovascular health (Crichton and Alkerwi, 2014). In this study, cardiovascular health was assessed by seven factors: smoking, body mass index (BMI), physical activity, diet, total cholesterol, blood pressure, and fasting plasma glucose. After controlling for demographics and dietary

27.2  Epidemiological Studies

477

variables, those individuals consuming more than five servings per week of dairy products (including yogurt) were found to have better cardiovascular health scores (Crichton and Alkerwi, 2014). Dietary habits of patients with ischemic stroke (n = 300) were analyzed and compared to controls (n = 300) who only differed from stroke patients in having been diagnosed with ischemic heart disease (RodriguezCampello et al., 2014). One of the differences reported between patients and controls was that control subjects consumed more probiotic yogurt (Rodriguez-Campello et al., 2014). A recent study on Pakistani urban adults, a population at high risk for hypertension (Mittal and Singh, 2010), studied the relationship between diet and hypertension (Safdar et al., 2015). After analyzing 4304 participants aged 15 years or older and using a 33-item food frequency questionnaire, Safdar et al. (2015) demonstrated that a dietary pattern high in seafood and yogurt was less likely to be associated with hypertension. Similarly, 1390 participants from the multiethnic study of atherosclerosis were given a food frequency questionnaire and correlated specific food intake with measurements of pericardial and hepatic fat (Shah et al., 2015). Results indicated that subjects who consumed greater amounts of fruits, vegetables, and yogurt had less regional adiposity suggesting that these foods can protect against cardiovascular risk as well as diabetes (Shah et al., 2015). In the majority of the analyzed studies, for subjects who were at high risk for heart disease (i.e., hypertension or metabolic syndrome) and those that had documented heart disease, yogurt was highlighted as a good dietary option for cardiovascular health.

27.2.3 TYPE 2 DIABETES Diabetic patients are characterized by having insulin resistance, dyslipidemias, increased oxidative stress, and low-grade inflammation as well as increased body weight (Ng, 2013). There is substantial information from clinical trials that lifestyle interventions including diet are effective for primary prevention of type 2 diabetes. However, there is high uncertainty regarding specific dietary factors and diabetes prevention. In the case of diabetic patients, yogurt can be beneficial due to its postulated role in gut health, protection of intestinal barrier, and reduction of inflammation (Pei et al., 2015) as well as its proposed healthy effects in obese patients (Pei et al., 2015). There is accumulating evidence that dairy product intake is associated with decreased risk for diabetes (Elwood et al., 2007; Tong et al., 2011). Data derived from the European Prospective Investigation into Cancer (EPIC) have shown that consumption of certain types of dairy products including yogurt may be more relevant for the protection against diabetes (Forouhi, 2015). The EPIC investigators have come to this conclusion after carrying out a very detailed 7-day food dairy record across eight European countries (Forouhi, 2015). Adolescents (12.5–17.5 years old) from the HELENA study, which involves eight European cities, were examined to determine the relationship between dairy consumption and cardiovascular disease and diabetes risk factors (Moreno et al., 2015). Among the biomarkers that were assessed were: body composition, blood pressure, insulin resistance, plasma lipids, and cardiorespiratory fitness in a subset of 511 subjects. Higher consumption of yogurt and of milk and yogurt-based beverages was associated with lower body fat, lower risk for cardiovascular disease, and better fitness (Moreno et al., 2015). A recent study examined whether yogurt consumption was associated with a better diet quality and metabolic profile (risk factors for diabetes) in 6526 participants from the Framingham cohort (Wang et al., 2013). Yogurt consumption was associated with lower concentrations of circulating triglycerides and glucose as well as lower systolic blood pressure and insulin resistance. Results from these epidemiological studies consistently found protective effects of yogurt with the parameters that define diabetes.

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27.3 CLINICAL TRIALS 27.3.1 METABOLIC SYNDROME Research supports that consumption of dairy products can attenuate many of the clinical biomarkers, which define MetS. Some randomized clinical trials (RCT) specifically have investigated the effect of yogurt intake in subjects having MetS, as defined by the National Cholesterol Education Program Adult Panel III (NCEP ATP III). However, dairy consumption benefits are also shown in RCT with overweight and obese individuals. Other studies also consider the effects of yogurt/dairy products under weight-stable conditions, as weight reduction alone improves MetS components. The literature demonstrates that increased dairy consumption, frequently consumed as a combination of yogurt, milk, or cheese, can attenuate the clinical biomarkers of metabolic syndrome. For example, yogurt or increased dairy consumption of mixed dairy (≥3 servings, compared to ≤1 serving/dairy/day) reduced body weight and fat mass (Zemel et al., 2005), hypertension (van Meijl and Mensink, 2010; Stancliffe et al., 2011; Zemel et al., 2005), and waist circumference (Wennersberg, 2009; Zemel et al., 2005) in weight stable, overweight, or obese adults. Yogurt’s effect on body mass was studied in 34 obese adults (18–50 year) over a 12-week period. Volunteers consumed a calorie-deficient diet (−500 kcal/day) and were randomized to either a control group taking ∼500 mg of a calcium supplement or yogurt, which provided 1100 mg calcium/day (Zemel et al., 2005). The calorie-deficient diet provided ∼35% of fat, ∼49% carbohydrates, and 16% protein in addition to 8–12 g of fiber/day; macronutrients were maintained constant regardless of study group. The yogurt group consumed three 6-ounce servings of commercial fat-free yogurt daily while the control consumed a placebo of three gelatin servings daily. Body weight, body fat, and fat distribution were measured by dual-energy X-ray absorptiometry, and blood pressure, and serum lipids were measured at baseline and at 12 weeks. Serum lipids and systolic blood pressure remained unchanged, but yogurt consumption significantly lowered diastolic blood pressure (−4.27 mmHg, P < .01). All adults lost weight and body fat due to energy restriction. Yet weight and fat losses were significantly increased by yogurt consumption. Yogurt consumption increased fat loss compared to the control group (−4.43 ± 0.47 vs. −2.75 ± 0.73 kg, P < .005). Trunk fat loss was increased by 81% on yogurt versus control diet (P < .001), and thus there was a greater reduction in waist circumference (−3.00 ± 0.48 vs. −0.58 ± 1.04 cm P < .001). Additionally, lean tissue loss was reduced by 31% on the yogurt diet. Thus, yogurt consumption facilitated fat loss while protecting lean muscle during energy restriction. The dietary effect of yogurt and milk, versus carbohydrate control foods, on the metabolic parameters including blood pressure, serum lipids, glucose, and insulin was studied in 35 overweight (BMI > 27 kg/m2) males and females (van Meijl and Mensink, 2011). Overweight or obese adults were randomized to consume low-fat milk (2 cups) and yogurt (2/3 cup) or control foods (600 mL juice and 43 g fruit biscuit) for 8 weeks. Following a 2-week washout period, volunteers consumed the alternate diet. Although systolic blood pressure was unchanged, dairy consumption decreased diastolic blood pressure (−2.9 mmHg, P < .027) compared to the control diet. No changes were found in low-density lipoprotein (LDL), but high-density lipoprotein (HDL) was significantly affected (0.04 mmol/L P < .021), which was lower on dairy versus control (0.024; −5.5 to −0.3 mmHg; P < .027). Other parameters including triglycerides and glucose insulin were unchanged. The effect of increased dairy consumption in diets of those typically consuming a low-dairy diet has also been studied (Crichton et al., 2012; Dugan et al., 2014). In a year-long crossover study

27.3  Clinical Trials

479

(Crichton et al., 2012), 36 overweight or obese adults (BMI > 25 kg/m2), 18–71 years old, were randomly assigned to consume diets either high or low in dairy foods for 6 months. Following this period of time, they were crossed over to the alternate diet for an additional 6 months. Initial dairy intake of milk, yogurt, or ice cream was <2 servings/day for all participants. The high-dairy diet included four daily servings of reduced fat milk (250 mL; 1 cup), yogurt (175–200 g), and custard (3/4 cup); and additional dairy intake was limited. On the low-dairy diet volunteers consumed one serving of reducedfat dairy per day and were instructed to consume a normal diet while limiting dairy to not more than one serving/day. All adults were instructed to continue with normal physical activity throughout the study and energy intake was not restricted. Assessment of waist circumference, body weight, BMI, hip circumference, total body fat, and abdominal fat was conducted at baseline and at 6 and 12 months. Most of the cardiometabolic measures tested were unaltered. There were no differences in baseline values for those assigned high or low dairy. There were also no significant changes in blood pressure, fasting glucose, or serum lipids. Additionally, all anthropometric measurements were not different when consuming high or low dairy. However, the mean change in body weight, BMI, and hip circumference was higher in the high dairy compared to the low dairy. The researchers concluded that these results were due to a small increase in energy intake during the high-dairy phase. Surprisingly, their energy intake difference was reported to be an amount that would cause weight gain of ∼1 kg/month and so should have resulted in 6 kg difference over the 6-month time frame on the high-dairy diet. Yet the documented weight increase of 1.8 ± 0.4 kg was much smaller than what the increased caloric intake predicted. Since their body weight and percent fat did not change, the researchers attributed the limited weight increase to the effects of calcium in the decrease of fatty acid absorption, which has been shown by others (Denke et al., 1993). Other researchers aimed to determine the effect of increased dairy intake in typically low-dairy consumers who were classified at having metabolic syndrome (Dugan et al., 2014). Thirty-seven male and female adults, meeting the clinical criteria of MetS (NCEP ATP III), were randomized to incorporate low-fat dairy products (10 oz 1% milk, 6 oz nonfat yogurt, and 4 oz 2% cheese) or control foods (1.5 oz granola bar and 12 oz juice) into their usual diet for 6 weeks. Following a 4-week washout period, subjects consumed the alternate treatment foods for an additional 6 weeks. Subjects received food substitution instruction and were asked to maintain their usual physical activity patterns so that weight was maintained. Anthropometrics, blood pressure, plasma lipids, glucose, and insulin resistance were measured. Metabolic syndrome markers differed by gender with low-fat dairy lowering plasma glucose in men (95.4 ± 9.1 vs. 98.9 ± 10.6 mg/dL, P = .048) compared to control food intake. In women, low-fat dairy intake lowered waist circumference, BMI, and body weight (P < .01 for all) compared to control food consumption. The effect of a functional yogurt product verses a conventional yogurt on MetS characteristics in 101 healthy Koreans was tested (Chang et al., 2011). Volunteers aged 20–65 years were randomized to consume two daily servings of either 300 mL of functional yogurt (with additional microorganisms, soluble fiber, an herbal mixture containing yacca and pine needle extract, and whey protein hydroxylate) or a standard yogurt for 8 weeks. All yogurt products were produced by the same manufacture and contained the same macronutrient profile. MetS marker values of body weight, waist circumference, blood pressure, fasting glucose, glycosylated hemoglobin, and lipids were analyzed at baseline (after a 1-week washout) and at week 8. There was no difference between baseline values for adults assigned to receive the different yogurts. However, functional yogurt intake resulted in

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decreased body weight (−0.24 ± 1.50 kg, P = .006) and BMI (−0.10 ± 0.58 kg/m2, P = .006) compared to the control group. Although LDL decreased in both groups, the lowering effect was greater in the functional group (7.71 ± 14.14 mg/dL; P < .001) from baseline when the control group was also compared to baseline (0.43 ± 15.32 mg/dL; P = .84). This difference in change of LDL between groups was significant (P = .044 by independent t-test). These results highlight a synergistic effect between yogurt consumption with additional added food components. Some of these food components, such as fruits, a good source of soluble fiber, may be added to yogurt thus improving the effects caused by yogurt consumption alone. The question of how much dairy needs to be consumed to observe health benefits and whether these benefits will continue was researched in adults with MetS (Stancliffe et al., 2011). Adults meeting NCEPT ATP III MetS classification (n = 40) were randomly assigned to consume diets containing either an adequate dairy intake (3.5 daily servings of milk and yogurt) or low-dairy intake (<0.5 servings) with nondairy food substitutions (fruit cups, granola bars) foods with a weight-maintenance diet. Markers of inflammation and oxidative stress were measured during baseline, at day 7 and weeks 1, 4, and 12. The higher dairy intake lowered oxidative markers following 1 week of intake with a 35% decrease in malondialdehyde and 11% in oxidized LDL (P < .01). This effect continued with 25% decrease in oxidized LDL by 4 weeks, however, no differences were found in oxidative markers on the low-dairy intake. Similarly, higher dairy intake reduced systemic inflammation following 4 weeks of intake with decreases in tumor necrosis factor (TNF)α (35%, P < .05), interleukin-6 (IL-6) (21%; P, .02), and monocyte chemoattractant protein-1 (MCP-1) (14% P < .05). These benefits also continued at 12 weeks with further decreases in MCP-I (24%, P < .05) and circulating C-reactive protein (CRP) (47%, P < .005). Additional MetS markers were also positively affected with higher dairy intake. There was no effect on fasting glucose but higher dairy significantly lowered insulin starting at day 7 and continuing throughout the study (lowered −0.83 mmol/L day 7, −0.28 at day 84; P < .05). HOMA-IR also improved (lowered −0.59 P < .05). Neither diet affected body weight; however, higher dairy reduced waist circumference and trunk fat (P, .01 for both).

27.3.2 CARDIOVASCULAR HEALTH Yogurt was tested as part of a low-glycemic preload snack food on the effect of various cardiovascular risk factors (Azadbakht et al., 2013). The preload snack consisted of a combination of foods with a low-glycemic index snack (yogurt and vegetable salad) on cardiovascular disease risk factors and anthropometrics. Sixty-five adults (25 men and 35 women) consumed a prepared hypocaloric diet for 3 months and were randomized to consume the preload either 15 min before the meal or to consume the low-glycemic test foods with the meal directly. Meals for both groups contained the same macronutrients. There was a greater reduction of cardiovascular risk factor in those consuming the preload compared to those consuming the low-glycemic foods directly with the meal. Specifically, preload consumption decreased waist circumference (−7.8 cm ± 0.5%), body weight (−2.7 kg ± 0.2%), systolic blood pressure (−2.7 mmHg ± 0.2%), and serum lipids triglycerides and HDL-cholesterol (−3.1 mg/dL ± 0.53%, −4.4 mg/dL ± 0.4%; P < .05 for all), compared to consuming them with a meal. Additionally, only those consuming a preload experienced a reduction in fasting glucose and LDL cholesterol. Consumption of yogurt with other low-glycemic foods as a preload snack furthered combined weight loss benefits in reducing heart disease risk factors.

27.3  Clinical Trials

481

Dairy products contain high amounts of saturated fatty acids thus their intake has been discouraged as a dietary treatment for cardiovascular disease prevention. However, current research indicates that total dairy products are not associated with increased artery thickening (Ivey et al., 2011). Specifically, yogurt consumption has shown to be protective of the carotid artery intima thickness, thus attenuating heart disease risk. Dietary analysis was conducted in 1080 women (70 years) in Australia with a validated food frequency questionnaire (Ivey et al., 2011). Dairy food intake including milk, yogurt, and cheese was determined. Carotid artery intima thickness was examined 3 years later with ultrasound. Serum lipids and blood pressure were evaluated at baseline. No association was found between total dairy consumption and carotid artery intima thickness (P = .05). However, yogurt consumption, but not that of other dairy foods, was negatively associated with artery intima thickness (Ivey et al., 2011). Yogurt intake was then evaluated by quantity consumed with intake categorized as low (100 g/day), moderate (100–200 g/day), or high (200 g/day). Those consuming increased yogurt consumption (>100 g yogurt/day) had a significantly lower artery intima thickness than those with lower yogurt consumption (<100 g/day; P = .002). This association remained significant after adjusting for dietary and lifestyle factors including age, BMI, type 2 diabetes, never smoking, history of vascular disease, macronutrient intake, and physical activity (Ivey et al., 2011).

27.3.3 DIABETES van Meijl and Mensink (2010) determined the effect of dairy on inflammation in obese (BMI 31.1 men, 32.4 women) subjects (n = 35; aged 18–70). Subjects were randomized to consume dairy foods (500 mL low-fat milk and 150 g low-fat yogurt; ∼3 servings dairy/day) or control foods (600 mL fruit juice and 43 g fruit biscuits) in a crossover fashion with 8 weeks of intervention separated by a two-week washout. Body weight was not different at the end of each intervention. Energy content of products was similar (360 kcal dairy vs. 405 kcal control). Dairy consumption significantly (P = .027) decreased systolic blood pressure by 2.9 mmHg (P = .027) and trended toward decreasing (P = .09) diastolic blood pressure by 2.9 ± 5.2 mmHg, but did not alter other components of MetS. Inflammatory markers C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were not changed. There was a trend for TNFα to be lower following dairy consumption (P = .070). It is not clear if the subjects ate dairy other than what was provided to them. In fact, researchers state that “subjects drank more milk during the control periods.” Additionally, comparing the mean daily intake of calcium, excluding calcium from the intervention foods, shows that subjects had greater calcium intakes on the control diet than while on the dairy diet. Thus there may not have been a large enough difference between calcium intakes to capture differences in inflammatory compounds. Increased insulin secretion is especially important in those with T2DM as they typically experience a decreased insulin response to carbohydrate (CHO). This beneficial effect of combining the insulin-stimulating effects of whey with CHO intake was demonstrated by Manders et al. (2005). These authors provided CHO alone or with a protein hydrolysate/amino acid mixture to 10 volunteers with type 2 diabetes and measured the plasma insulin response from CHO with and without the protein/amino acid mixture. Consuming protein/amino acids with CHO resulted in higher (299 ± 64% vs. 132 ± 63%; P < .001) plasma insulin and reduced plasma glucose (28 ± 6% vs. 33 ± 3%), compared to those consuming CHO alone. Further, isotope tracers ([6,6-2H2] glucose)

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used to measure glucose disposal found that diabetics consuming protein with CHO experienced a significant increase (13 ± 3%; P < .01) in glucose disposal compared to those consuming CHO alone. Seventy first-time pregnant women in their third trimester were randomly allocated to consume either regular yogurt or a probiotic-enhanced yogurt (Asemi et al., 2013). All women consumed 200 g of their assigned yogurt for 9 weeks. They continued their usual physical activity and were instructed to avoid all other fermented or probiotic-containing foods. Probiotic-enhanced yogurt contained additional Lactobacillus acidophilus and Bifidobacterium animalis, providing a total count of at least 1 × 107 cfu. Fasting plasma glucose and serum insulin was measured at study baseline and at the 9-week end point. Insulin was unaffected by both yogurts, but there was greater change from baseline in serum insulin in those consuming probiotic yogurt +1.2 ± 1.2 compared to those with conventional yogurt (+5.0 ± 1.1 μIU/mL, P = .02). These results were similarly reflected in the change from baseline for the homeostatic assessment–insulin resistance score in probiotic yogurt (−0.2 ± 0.3) and regular yogurt intakes (0.7 ± 0.2, P = .01). The effect of yogurt and probiotic-enhanced yogurt was also examined in diabetic patients. Sixty (30–60 years) adults diagnosed with type 2 diabetes and who did not consume probiotic yogurt or probiotic products were randomized to consume 300 mL regular yogurt or probiotic-enhanced yogurt for 6 weeks (Ejtahed et al., 2012). Probiotic-enhanced yogurt contained added L. acidophilus La5 and Bifidobacterium lactis Bb12. Volunteers maintained their usual physical activity and avoided other yogurt foods. Compared with those consuming the regular yogurt, those eating probiotic yogurt had decreased fasting glucose (P < .01) and glycosylated hemoglobin (P < .05). Antioxidant status was also improved in the probiotic yogurt group, with increased activities in glutathione peroxidase and superoxide dismutase activities and total antioxidant status (P < .05). In accordance with increased antioxidant capacity serum malondialdehyde also significantly decreased (P < .05). Importantly, this decreased oxidant marker was found in both yogurt groups. Thus while probiotic yogurt protects serum glucose and insulin more than regular yogurt, benefit is still seen by increased regular yogurt intake. Collectively, these data support a beneficial role of yogurt and other dairy products in the attenuation of inflammatory markers, oxidative stress, and glucose control in healthy or overweight and obese individuals with components of MetS and the resultant comorbidities CVD and T2DM. In addition, it has been reported that that obese subjects provided either a hypocaloric diet with yogurt (providing 100 mg calcium/day) or a eucaloric diet with high dairy (1200 mg calcium/day with three servings of dairy) had lower serum CRP (P < .05) and higher adiponectin (P < .05), regardless of weight loss status (Zemel and Sun, 2008). The main randomized clinical trials with yogurt/dairy and the health outcomes are presented in Table 27.1.

27.4 MECHANISMS OF ACTION BY COMPONENTS OF DAIRY/YOGURT 27.4.1 DAIRY AND CALCIUM EFFECTS ON ADIPOSITY Calcium is a component of yogurt (dairy) that has been postulated to promote weight reduction through the tightly regulated modulation of plasma1, 25-hydroxyvitamin D concentrations via parathyroid hormone (PTH). PTH increases renal calcium reabsorption and activates bone resorption and the kidney

Table 27.1  Randomized Clinical Trials With Yogurt/Dairy and Health Outcomes Study

Population

Dairy Type and Intake

Health Outcome

Zemel et al. (2005)

RCT—parallel design N = 34—trial 1 N = 29—trial 2

van Meijl and Mensink (2010)

RCT-crossover study N = 35 overweight or obese, male/female

Three dairy servings/day—one milk; low calcium vs. high calcium; trial 2—same dairy but also calorie restriction Low-fat milk (2 cup) and low-fat yogurt (2/3 cup) or fruit juice (600 mL) and fruit biscuit for 8 weeks 4 serv./day reduced fat dairy vs. low dairy ≤1 serv./day

HD group decrease in body fat, trunk fat, insulin, BP; lean mass was increased; there were no changes in low-dairy group Dairy consumption decreased systolic blood pressure by 2.9 mmHg No change in other MetS markers

Crichton et al. (2012)

RCT-crossover study N = 36 overweight or obese adults Dugan et al. RCT-crossover study (2014) N = 37 male/female adults with MetS Chang et al. RCT-parallel design (2011) N = 35 healthy adults Stancliffe et al. RCT, parallel (2011) N = 40 with MetS

Zemel and Sun N = 29 (2008) Parallel design obese adults van Meijl RCT and Mensink N = 35, overweight (2010) adults Manders et al. RCT (2005) N = 10 adults with T2DM

Asemi et al. (2013)

RCT N = 70 third trimester pregnant women

Ejtahed et al. (2012)

RCT—parallel design N = 64 adults with T2DM

Azadbakht et al. (2013)

RCT N = 65 adults

3 serv./day: 1% milk, 6 oz nonfat yogurt, 4 oz 2% cheese; or control: 1.5 oz granola bar and 12 oz juice Consumed functional yogurt (300 mL) or placebo yogurt 2×/day Weight maintenance diets Low dairy (<0.5 serv./day and <600 mg Ca) Adequate-dairy (>3.5 serv./day and ≥600 mg calcium) Three dairy servings/day—one milk Milk, yogurt, and cheese Low-fat milk and low-fat yogurt or fruit juice and fruit biscuit for 8 weeks Provided CHO alone or with a protein hydrolysate/amino acid mixture

No difference in WC, BW, fat mass Study did not restrict energy intake Dairy decreased systolic BP Low-fat dairy decreased plasma glucose in men and WC, BMI, and BW in women Functional yogurt reduced body weight, BMI, and LDL cholesterol AD—decreased MNDA and oxidized LDL; decreased TNFα, IL-6, MCP1; reduced wc and trunk fat, reduced plasma insulin and insulin sensitivity LD—no change Dairy and hypocaloric diet decreased CRP

Decreased TNFα No effect on CRP, PAI-1, IL-6, MCP-1, or VCAM-1 Consuming protein/amino acids with CHO resulted in higher plasma insulin Reduced plasma glucose (28 ± 6% vs. 33 ± 3%), vs. consuming CHO alone Provided 200 g of probioticThere was no change in serum insuenhanced yogurt or regular yogurt lin, HOMA at 6-week vs. baseline following enhanced yogurt Serum insulin levels, HOMA were lower following PB yogurt vs. regular yogurt Intervention: 300 g/day of probiotic Fasting glucose, HbA1C were yogurt decreased and erythrocyte SOD, Control: 300 g/day of conventional glutathione peroxidase, and total yogurt for 6 weeks antioxidant activity were increased following probiotic yogurt compared to control Preload with yogurt, and vegetable BW, WC, TG, TC, and SBP were salad with hypocaloric diet lower in preload group vs. control Fasting glucose and LDL-cholesterol decreased only in the preload group

AD, adequate dairy; BP, blood pressure; BW, body weight; CHO, carbohydrate; CRP, C-reactive protein; HbA1C, glycosylated hemoglobin; HD, high dairy; HOMA, homeostatic model assessment; IL-6, interleukin 6; LD, low dairy; MCP-1, monocyte chemoattractant protein-1; MetS, metabolic syndrome; RCT, randomized clinical trial; SBP, systolic blood pressure; SOD, superoxide dismutase; T2DM, type 2 diabetes mellitus; TC, total cholesterol; TG, triglycerides; WC, waist circumference.   

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hydroxylase enzyme, which converts inactive vitamin D into its active form. Thus, lower plasma calcium triggers an increase in the synthesis of 1, 25-OH2-vitD, which causes an influx of calcium ions into adipocytes resulting in increased intracellular calcium. Intracellular calcium activates gene transcription of fatty acid synthase (FAS) within the adipocyte and inhibits lipolysis through activation of phosphodiesterases and inhibition of hormone-sensitive lipase (Zemel, 2003). Thus a theory has been proposed that when dietary calcium is increased, intracellular calcium is lowered therefore there is mitigation of adiposity via decreases of de novo lipogenesis and direct stimulation of lipolysis (Zemel, 2003). This proposed mechanism was demonstrated in a transgenic mouse model for diet-induced obesity (Shi et al., 2001). Mice were fed diets containing either low calcium, supplemental calcium, medium dairy, or high dairy for 6 weeks. Fat pads were harvested to quantify fat mass and to determine fatty acid synthase expression and activity levels in adipocytes. Mice fed low-calcium diets had higher body weight gain and fat mass compared to those fed supplemental calcium or dairy. Both supplemental calcium and high dairy decreased FAS activity by 35% and 65%, respectively (Shi et al., 2001). Treatment of human adipocytes with 1, 25-OH2-vitD has also resulted in increases in fatty acid synthase and inhibition of lipolysis (Shi et al., 2002). However, this theory has not been fully supported by human studies (Shockravi et al., 2008; Dugan et al., 2014). Furthermore, the previous mechanism is incongruent with epidemiological data that demonstrate lower levels of vitamin D in overweight and obese populations (Parikh et al., 2004; Ganji et al., 2011).

27.4.2 DAIRY INTAKE AND BLOOD PRESSURE Different mechanisms have been suggested to account for the blood pressure–lowering effect of dairy products. The most accepted mechanism involves inhibition of the angiotensin-converting enzyme (ACE), which plays a major role in the activation of angiotensin (Ma et al., 2010). Several proteins in food have been identified as ACE inhibitors including those from dairy (Majumder and Wu, 2014). Peptide sequences believed to be responsible for ACE inhibition include the lactotripeptide amino acid sequences isoleucine-proline-proline and valine-proline-proline (Phelan and Kerins, 2011). Data from clinical interventions support a blood pressure–lowering effect of dairy, specifically from low-fat dairy and from the whey fraction (Pal and Ellis, 2010).

27.4.3 EFFECT OF DAIRY INTAKE ON SERUM GLUCOSE LEVELS The high–amino acid content, specifically the branch chain amino acids in dairy, may modulate glucose levels by increasing postprandial insulin secretion. Increased dairy intake has been shown to lower serum glucose through several potential mechanisms, which may include protein-induced increases in serum insulin and increasing hepatic regulatory control of glucose production. Whey protein, for example, has been shown to increase glucose-dependent insulinotropic polypeptide, which triggers insulin release by pancreatic β cells (Graf et al., 2011), a mechanism that might be beneficial for diabetic patients. For example, Frid et al. (2005) demonstrated that whey increased insulin and decreased postprandial response in diabetic patients when provided at breakfast in combination with high-glycemic foods. Further, when isotope tracers were used to measure glucose disposal

27.5  Conclusion

485

[(6,6-2H2) glucose], consumption of protein with carbohydrate resulted in an increase (P < .01) in glucose disposal compared to intake of carbohydrate alone (Manders et al., 2005). Layman et al. (2003) have also postulated that when carbohydrates are replaced with protein, the branched-chain amino acids, specifically leucine, will “shift” the regulatory control of glucose homeostatic away from the pancreas and insulin secretion toward hepatic control through gluconeogenesis. After feeding a 400 kcal breakfast with either high protein or high carbohydrate to 24 women for breakfast, insulin increased more than 2-fold and was >40% higher in the high-carbohydrate group and plasma branched-chain amino acids were lower compared to the high-protein group (Layman et al., 2003). Leucine has also been shown to exert a protective effect against insulin resistance and weight gain in mice fed a high-fat diet (Macotela et al., 2011), although more studies on the specific effects of leucine are still needed.

27.4.4 CALCIUM, DAIRY AND PLASMA LIPIDS, LIPOPROTEINS, AND APOLIPOPROTEINS High-calcium content and the lipid fractions present in dairy products may positively alter the serum lipid profile. The postulated mechanisms are intestinal binding of calcium to saturated fatty acids, which forms insoluble soaps that are excreted in the feces or calcium binding to bile acids, which leads to the interruption of the enterohepatic circulation and the removal of circulating cholesterol via upregulation of hepatic LDL receptors (Abedini et al., 2015). In a randomized trial, healthy men with moderately high plasma cholesterol received either high or low calcium (Denke et al., 1993). Higher calcium intake resulted in greater excretion of palmitic, stearic, and oleic acids as well as lower total and LDL cholesterol and apolipoprotein B (Denke et al., 1993). Results from a meta-analysis aimed at determining the effect of calcium on fetal fat excretion concluded that an increase in 1240 mg of dairy calcium per day corresponds to 5.2 g/day increase in fat in the feces (Christensen et al., 2009). These cholesterol-lowering effects of calcium may attenuate the potential cholesterol-raising effects of palmitic, myristic, and lauric acids found in dairy foods. Specific fatty acids provided by dairy may also modulate lipoprotein metabolism. Other lipid components in milk including phospholipids and sphingolipids have been reported to decrease cholesterol absorption in animals (Kamili et al., 2010).

27.5 CONCLUSION It is clear from all the evidence derived from studies described in this chapter that dairy and yogurt have protective effects against MetS by decreasing blood pressure (Shockravi et al., 2008) and fasting glucose (Elwood et al., 2007) and by helping in the maintenance of a healthy body weight (Snijder et al., 2007; Shin et al., 2013). In terms of beneficial effects on cardiovascular health, it has been shown that yogurt may decrease inflammation (Dugan et al., 2016), oxidative stress (Ejtahed et al., 2012), and improve dyslipidemias (Ganji et al., 2011). Finally, yogurt has been shown to decrease insulin resistance (Sayón-Orea et al., 2015; Wang et al., 2013) and glycosylated hemoglobin (Mohamadshahi et al., 2014) in patients diagnosed with diabetes. A summary of the effects of yogurt in all these conditions is depicted in Fig. 27.1.

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Cardiovascular Disease

WC Blood pressure Triglycerides Fasting glucose

Metabolic Syndrome

Inflammation Oxidative stress Dyslipidemias Blood pressure

Yogurt

Central fat Body Weight

Diabetes

Insulin resistance HBGc1 Plasma glucose

Obesity

FIGURE 27.1 Yogurt has been found to have effects on: Cardiovascular disease by decreasing inflammation, oxidative stress, dyslipidemias, and blood pressure; on Diabetes by lowering insulin resistance, glycosylated hemoglobin, and plasma glucose; on Obesity by decreasing central fat and body weight; and on Metabolic Syndrome by decreasing waist circumference (WC), blood pressure, plasma triglycerides, and fasting glucose.

REFERENCES Abedini, M., Ebrahim, F., Sajjad, R., 2015. Dairy product consumption and the metabolic syndrome. Diabetes Metab. Syndr. Clin. Res. Rev. 9 (1), 34–37. Adolfsson, O., Meydani, S.N., Russel, R.M., 2004. Yogurt and gut function. Am. J. Clin. Nutr. 80, 254–256. Andersen, C.J., Fernandez, M.L., 2013. Dietary strategies to reduce metabolic syndrome. Rev. Endocr. Metab. Disord. 14 (3), 241–254. Asemi, Z., et al., 2013. Effect of daily consumption of probiotic yoghurt on insulin resistance in pregnant women: a randomized controlled trial. Eur. J. Clin. Nutr. 67 (1), 71–74. Azadbakht, L., Haghighatdoost, F., Karimi, G., Esmaillzadeh, A., 2013. Effect of consuming salad and yogurt as preload on body weight management and cardiovascular risk factors: a randomized clinical trial. Int. J. Food Sci. Nut. 64 (4), 392–399. Babio, N., et al., 2015. Consumption of yogurt, low-fat milk, and other low-fat dairy products is associated with lower risk of metabolic syndrome incidence in an elderly Mediterranean population. J. Nutr. 145 (10), 2308–2316.

References

487

Beydoun, M.A., et al., 2008. Ethnic differences in dairy and related nutrient consumption among US adults and their association with obesity, central obesity, and the metabolic syndrome. Am. J. Clin. Nutr. 87 (6), 1914–1925. Chang, B.J., et al., 2011. Effect of functional yogurt NY-YP901 in improving the trait of metabolic syndrome. Eur. J. Clin. Nutr. 65 (11), 1250–1255. Christensen, R., et al., 2009. Effect of calcium from dairy and dietary supplements on faecal fat excretion: a metaanalysis of randomized controlled trials. Obes. Rev. 10 (4), 475–486. Crichton, G.E., Alkerwi, A., 2014. Dairy food intake is positively associated with cardiovascular health: findings from Observation of Cardiovascular Risk Factors in Luxembourg Study. Nutr. Res. 34 (12), 1036–1044. Crichton, G.E., Howe, P.R.C., Buckley, J.D., Coates, A.M., Murphy, K.J., 2012. Dairy consumption and cardiometabolic health: outcomes of a 12-month crossover trial. Nutr. Metab. 9 (1), 19. Denke, M.A., Fox, M.M., Schulte, M.C., January 1993. Short-term dietary calcium fortification increases fecal saturated fat content and reduces serum lipids in men. J. Nutr. 123, 1047–1053. Dugan, C.E., Aguilar, D., Park, Y.-K., Lee, J.-Y., Fernandez, M.L., 2016. Dairy consumption lowers systemic inflammation and liver enzymes in typically low-dairy consumers with clinical characteristics of metabolic syndrome. J. Am. Coll. Nutr. 35 (3), 255–261. Dugan, C.E., Barona, J., Fernandez, M.L., 2014. Increased dairy consumption differentially improves metabolic syndrome markers in male and female adults. Metab. Syndr. Relat. Disord. 12 (1), 62–69. Ejtahed, H.S., et al., 2012. Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition 28 (5), 539–543. Elwood, P.C., Pickering, J.E., Fehily, A.M., 2007. Milk and dairy consumption, diabetes and the metabolic syndrome: the Caerphilly Prospective Study. J. Epidemiol. Community Health 61 (8), 695–698. Ethgen, O., Hiligsmann, M., Burlet, N., Reginster, J.Y., 2015. Cost-effectiveness of personalized supplementation with vitamin D-rich dairy products in the prevention of osteoporotic fractures. Osteoporos. Int. 1–7. Forouhi, N.G., 2015. Association between consumption of dairy products and incident type 2 diabetes–insights from the European Prospective Investigation into Cancer Study. Nutr. Rev. 73 (Suppl. 1), 15–22. Frid, A.H., Nilsson, M., Holst, J.J., Björck, I.M.E., 2005. Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am. J. Clin. Nutr. 82 (1), 69–75. Fumeron, F., et al., 2011. Dairy consumption and the incidence of hyperglycemia and the metabolic syndrome: results from a french prospective study, Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 34 (4), 813–817. Ganji, V., et al., 2011. Serum 25-hydroxyvitamin D concentrations are associated with prevalence of metabolic syndrome and various cardiometabolic risk factors in US children and adolescents based on assay-adjusted serum. Am. J. Clin. Nutr. 25 (1), 225–233. Glanville, J.M., Brown, S., Shamir, R., Szajewska, H., Eales, J.F., October 2015. The scale of the evidence base on the health effects of conventional yogurt consumption: findings of a scoping review. Front. Pharmacol. 6, 1–12. Graf, S., Egert, S., Heer, M., 2011. Effects of whey protein supplements on metabolism: evidence from human intervention studies. Curr. Opin. Clin. Nutr. Metab. Care 14 (6), 569–580. Grundy, S.M., 2007. Metabolic syndrome: a multiplex cardiovascular risk factor. J. Clin. Endocrinol. Metab. 92 (2), 399–404. Ivey, K.L., Lewis, J.R., Hodgson, J.M., 2011. Association between yogurt, milk, and cheese consumption and common carotid artery intima-media thickness and cardiovascular disease risk factors in elderly. Am. J. Clin. Nutr. 6, 234–239. Kamili, A., et al., 2010. Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids. Nutr. Metab. 7 (1), 90. Lawlor, D.A., Ebrahim, S., Timpson, N., Davey Smith, G., 2005. Avoiding milk is associated with a reduced risk of insulin resistance and the metabolic syndrome: findings from the British Women’s Heart and Health Study, 808–811 Layman, D.K., Shiue, H., Sather, C., Erickson, D.J., Baum, J., 2003. Increased dietary protein modifies glucose and insulin homeostasis in adult women during weight loss. J. Nutr. 133 (2), 405–410.

488

CHAPTER 27  YOGURT AND HEALTH BENEFITS

Ma, T.K.W., Kam, K.K.H., Yan, B.P., Lam, Y.Y., 2010. Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: current status. Br. J. Pharmacol. 160 (6), 1273–1292. Macotela, Y., et al., 2011. Dietary leucine – an environmental modifier of insulin resistance acting on multiple levels of metabolism. PLoS One 6 (6). Major, G.C., et al., 2008. Recent developments in calcium-related obesity research. Obes. Rev. 9 (5), 428–445. Majumder, K., Wu, J., 2014. Molecular targets of antihypertensive peptides: understanding the mechanisms of action based on the pathophysiology of hypertension. Int. J. Mol. Sci. 16 (1), 256–283. Manders, R.J., et al., 2005. Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes. Am. J. Clin. Nutr. 82 (1), 76–83. Mangano, K.M., Walsh, S.J., Insogna, K.L., Kenny, A.M., Kerstetter, J.E., 2011. Calcium intake in the United States from dietary and supplemental sources across adult age groups: new estimates from the National Health and Nutrition Examination Survey 2003-2006. J. Am. Diet. Assoc. 111 (5), 687–695. Mayor, S., April 2016. Mediterranean diet reduces cardiovascular events in people with heart disease, study shows. Br. Med. J. 2348, i2348. McCarron, D.A., Heaney, R.P., 2004. Estimated healthcare savings associated with adequate dairy food intake. Am. J. Hypertens. 17 (1), 88–97. van Meijl, L.E.C., Mensink, R.P., 2011. Low-fat dairy consumption reduces systolic blood pressure, but does not improve other metabolic risk parameters in overweight and obese subjects. Nutr. Metab. Cardiovasc. Dis. 21 (5), 355–361. van Meijl, L.E.C., Mensink, R.P., 2010. Effects of low-fat dairy consumption on markers of low-grade systemic inflammation and endothelial function in overweight and obese subjects: an intervention study. Br. J. Nutr. 104 (10), 1523–1527. Mittal, B.V., Singh, A.K., 2010. Hypertension in the developing world: challenges and opportunities. Am. J. Kidney Dis. 55 (3), 590–598. Mohamadshahi, M., et al., 2014. Effects of probiotic yogurt consumption on inflammatory biomarkers in patients with type 2 diabetes. BioImpacts 4 (2), 83–88. Moreno, L.A., Bel-Serrat, S., Santaliestra-Pasías, A., Bueno, G., 2015. Dairy products, yogurt consumption, and cardiometabolic risk in children and adolescents. Nutr. Rev. 73 (Suppl. 1), 8–14. Mozaffarian, D., 2016. Dietary and policy priorities for cardiovascular disease, diabetes, and obesity: a comprehensive review. Circulation. http://dx.doi.org/10.1161/CIRCULATIONAHA.115.018585. Ng, D.S., 2013. Diabetic dyslipidemia: from evolving pathophysiological insight to emerging therapeutic targets. Can. J. Diabetes 37 (5), 319–326. Pal, S., Ellis, V., 2010. The chronic effects of whey proteins on blood pressure, vascular function, and inflammatory markers in overweight individuals. Obesity (Silver Spring Md.) 18 (7), 1354–1359. Parikh, S.J., et al., 2004. The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J. Clin. Endocrinol. Metab. 89 (3), 1196–1199. Pei, R., Martin, D.A., DiMarco, D.M., Bolling, B.L.W., May 2015. Evidence for the effects of yogurt on gut health and obesity. Crit. Rev. Food Sci. Nutr. 8398, 0. Pereira, M.A., et al., 2002. Dairy consumption, obesity, and the insulin resistance syndrome in young adults: the CARDIA study. J. Am. Med. Assoc. 287 (16), 2081–2089. Phelan, M., Kerins, D., 2011. The potential role of milk-derived peptides in cardiovascular disease. Food Funct. 2 (3–4), 153–167. Rodriguez-Campello, A., et al., 2014. Dietary habits in patients with ischemic stroke: a case-control study. PLoS One 9 (12), 1–14. Safdar, N.F., Bertone-Johnson, E.R., Cordeiro, L., Jafar, T.H., Cohen, N.L., 2015. Dietary patterns and their association with hypertension among Pakistani urban adults. Asia Pac. J. Clin. Nutr. 24 (4), 710–719. Salas-salvad, J., Guasch-ferr, M., Ros, E., 2016. Protective effects of the Mediterranean diet on type 2 diabetes and metabolic syndrome. J. Nutr. 146, 920S–927S.

References

489

Sayón-Orea, C., et al., 2015. Association between yogurt consumption and the risk of Metabolic Syndrome over 6 years in the SUN study. BMC Public Health 15 (1), 170. Shah, R.V., et al., 2015. Diet and Adipose tissue distributions: The Multi-Ethnic Study of Atherosclerosis. Nutr. Metab. Cardiovasc. Dis. 26 (3), 185–193. Shi, H., Dirienzo, D., Zemel, M.B., 2001. Effects of dietary calcium on adipocyte lipid metabolism and body weight regulation in energy-restricted aP2-agouti transgenic mice. FASEB J. 15 (2), 291–293. Shi, H., Norman, A.W., Okamura, W.H., Sen, A., Zemel, M.B., 2002. 1alpha,25-dihydroxyvitamin D3 inhibits uncoupling protein 2 expression in human adipocytes. FASEB J. 16 (13), 1808–1810. Shin, H., Yoon, Y.S., Lee, Y., Kim, C.I., Oh, S.W., 2013. Dairy product intake is inversely associated with metabolic syndrome in Korean adults: Anseong and Ansan Cohort of the Korean Genome and Epidemiology Study. J. Korean Med. Sci. 28 (10), 1482–1488. Shockravi, S., Jalali, M.T., Rokn, M., Karandish, M., 2008. Effect of calcium supplementation on blood pressure in overweight or obese women. J. Biol. Sci. 8, 773–778. Snijder, M.B., et al., 2007. Is higher dairy consumption associated with lower body weight and fewer metabolic disturbances? The Hoorn Study. Am. J. Clin. Nutr. 85 (4), 989–995. Stancliffe, R.A., Thorpe, T., Zemel, M.B., 2011. Dairy attentuates oxidative and inflammatory stress in metabolic syndrome. Am. J. Clin. Nutr. 94 (2), 422–430. Tong, X., Dong, J.Y., Wu, Z.W., Li, W., Qin, L.Q., 2011. Dairy consumption and risk of type 2 diabetes mellitus: a meta-analysis of cohort studies. Eur. J. Clin. Nutr. 65 (9), 1027–1031. Villegas, R., et al., 2010. Dietary patterns are associated with lower incidence of type 2 diabetes in MiddLe-aged women: The Shanghai Women’s Health Study. Int. J. Epidemiol. 39 (3), 889–899. Wang, H., Livingston, K.A., Fox, C.S., Meigs, J.B., Jacques, P.F., 2013. Yogurt consumption is associated with better diet quality and metabolic profile in American men and women. Nutr. Res. 33 (1), 18–26. Wennersberg, M.H., 2009. Dairy products and metabolic effects in overweight men and women: results from a 6-mo intervention study. Am. J. Clin. Nutr. 90 (4), 960–968. Zemel, M.B., et al., 2005. Dairy augmentation of total and central fat loss in obese subjects. Int. J. Obes. 29 (4), 91–97. Zemel, M.B., 2003. Symposium: dairy product components and weight regulation mechanisms of dairy modulation of adiposity1. J. Nutr. 133, 252–256. Zemel, M.B., Sun, X., 2008. Dietary calcium and dairy products modulate oxidative and inflammatory stress in mice and humans. J. Nutr. 138, 1047–1052.