Data from this study show that an increase in dairy intake from suboptimal to adequate levels (≈3.5 servings/d) significantly attenuates both oxidative and inflammatory stress in metabolic syndrome. Notably, although these effects may result, in part, from reductions in adiposity on higher dairy diets (17
), the rapid onset (within the first 7 d of dietary change) suggest that there is an adiposity-independent effect as well. This is further supported by our previous evidence that showed direct effects of dairy components on adipocyte cytokine expression and secretion (23
Our results are at variance with the recent report by Wennersberg et al (15
), because they showed no effect of a 6-mo dairy intervention on body composition or oxidative or inflammatory biomarkers in Scandinavian subjects with metabolic syndrome, although they did find an improvement in the HOMA index of comparable magnitude to that reported here. However, there are some key design differences between the 2 trials. The Wennersberg (15
) study did not control macronutrient and energy intake, and the dairy intervention group exhibited increases in energy and fat intakes that were not shown in the present study. In addition, subjects recruited for the present study were not habitual consumers of dairy products, and those in the control (low-dairy) group maintained their dairy intake at <0.5 serving/d and their calcium intake at <600 mg/d. In contrast, the baseline calcium intake of the milk intervention group in the Wennersberg (15
) study was 815 mg/d, possibly too high to observe an effect of additional dairy foods. Similarly, van Meijl et al (26
) observed only a reduction of TNF-α and an increase in soluble TNF-α receptor, but no effects on other inflammatory biomarkers in overweight and obese subjects fed a low-fat dairy diet for 8 wk. However, the estimated calcium intake of their control subjects was 931 mg/d, which suggests that they were already consuming sufficient levels of calcium, leaving little opportunity for dairy to exert significant effects. Notably, a post hoc analysis of subjects below and above a habitual calcium intake of 700 mg/d showed a significant effect of the dairy intervention on waist circumference and sagittal abdominal diameter only in those with habitually low calcium intakes, but no effect on oxidative or inflammatory markers. It is possible that a lower threshold exists for dairy effects on these biomarkers, but data to evaluate this concept are not available.
We showed previously that calcitriol stimulates inflammatory cytokine production in adipocytes (23
) and that dietary calcium–induced suppression of calcitriol attenuates adiposity-induced inflammatory cytokines in a mouse model of obesity (16
). We have also shown comparable effects of dairy foods in humans, because dairy significantly reduced circulating biomarkers of oxidative and inflammatory stress in otherwise healthy overweight and obese adults (16
We observed few significant differences between overweight and obese subjects. Although increased adiposity is generally associated with increased oxidative and inflammatory stress, the effects of BMI have been studied previously in the absence of complicating factors. Thus, the additional inflammatory stress that results from metabolic syndrome appears to exert a greater effect than the adiposity differences between overweight and obese subjects. However, the oxidative biomarkers (malondialdehyde and oxidized LDL) were both higher in the obese than in the overweight individuals, and the adequate-dairy diet exerted significantly greater effects on both oxidative biomarkers in the obese subjects compared with the overweight subjects.
These data also indicate that other components of metabolic syndrome are significantly improved by an increase in dairy food intake to an adequate level. Numerous studies have shown an inverse relation between dietary calcium and blood pressure (27
), and an increase in dairy intake to adequate levels is a key component of the DASH diet for blood pressure control (30
). Whereas these effects are attributable, in part, to dietary calcium, food sources of calcium have consistently exerted greater effects (30
). In addition to calcium, dairy contains bioactive components, including angiotensin-converting enzyme inhibitory peptides (31
), that also appear to contribute to these effects. We showed the adequate-dairy diet to significantly reduce systolic pressure in both overweight and obese participants and to reduce diastolic pressure in obese, but not overweight, subjects. These data confirm that the achievement of adequate levels of dairy consumption attenuates the elevated blood pressure that is typically characteristic of metabolic syndrome.
Previous studies have suggested that milk proteins, particularly the whey fraction, possess insulinotropic effects in healthy individuals (32
), whereas data from the CARDIA study show a strong inverse association between dairy consumption and abnormal glucose homeostasis, as well as the development of the insulin resistance syndrome (33
). Furthermore, a higher intake of low-fat dairy appears to reduce the risk of type 2 diabetes (34
). However, the underlying mechanism of this protective effect is not well understood. Numerous studies have indicated a relation between calcium and vitamin D insufficiency and type 2 diabetes (35
), and calcium has been proposed to exert a direct role (34
). However, other dairy components, such as angiotensin-converting enzyme inhibitory peptides, may play a significant role (33
). Consistent with these observations, data from the present study suggest that an increase in dairy food intake from suboptimal to adequate levels results in an improvement in insulin sensitivity, because circulating insulin and HOMA-IR were markedly improved by the adequate-dairy diet.
Key strengths of this study include the randomized controlled design, the maintenance of the macronutrient composition in the diets, and the assessment of early and sustained time points to isolate the effects of dairy-induced changes in adiposity. Our findings are limited by the relatively short duration of the intervention (12 wk), the use of self-report diet records to assess compliance, and the inability to blind subjects to the use of test (dairy) compared with control foods. In addition, the design of this study may have suffered additional confounding because of the use of readily available foods as control products, some of which may have contributed constituents that exerted potential positive (soy, fruit) or negative (luncheon meats, trans fatty acids in peanut butter crackers) independent effects that were not controlled for. Finally, although our selection criteria of subjects with very low habitual dairy and calcium intakes strengthens our design by increasing the likelihood that all subjects started below anticipated calcium and dairy thresholds for treatment effects, it also limits the external validity of our findings, because we cannot extrapolate these findings to individuals with more moderate levels of habitual dairy intake.
Nonetheless, the data from this study support our previous cellular and mouse data, as well as clinical trial data from overweight and obese individuals without metabolic syndrome. Notably, the effects in metabolic syndrome, which is characterized by a higher level of oxidative and inflammatory stress, are greater in magnitude than we recently reported in otherwise healthy overweight and obese individuals (18
). The rapid onset of these improvements indicates that they are likely independent of any changes in adiposity that may result from dairy-rich diets. Moreover, these data also suggest that other key components of metabolic syndrome are significantly improved by an increase of dairy food intake to an adequate level.