An Update on the Cardiovascular Pleiotropic Effects of Milk and Milk Products

Abstract

Hypertension is a major risk factor in addition to atherosclerosis and type 2 diabetes mellitus for the development of coronary heart disease and strokes. Several prospective clinical studies have demonstrated a possible protective effect of milk and dairy product consumption on these conditions. The putative effects of milk and dairy products are possibly mediated through their mineral content of calcium, magnesium, potassium, and vitamin D. These dairy substances exercise their blood pressure–lowering effect either directly on the arterial wall by these minerals or indirectly through blockade of the angiotensin‐converting enzyme (ACE) by the amino acids contained in the casein and whey of milk. The blockade of ACE results in the inhibition of production of angiotensin II, a potent vasoconstrictive peptide, and the prevention of degradation of bradykinin, a potent vasodilating peptide. For this concise review, a Medline search of the English language literature was conducted from 2006 to September 2012 and 16 pertinent papers were selected. The potential beneficial pleiotropic effects from these studies together with collateral literature will be discussed in this review.

The significance of milk and dairy food consumption on the prevention of coronary heart disease (CHD) and all‐cause mortality has been debated over the years. Earlier studies on the consumption of whole milk indicated an increase in the incidence of CHD, stroke, and all‐cause mortality in persons consuming the highest quantities of milk and dairy products, and was attributed to their high‐fat content.1, 2, 3 This assumption, together with the belief that milk was fattening, led to a widespread conviction that milk and dairy products contribute to obesity and heart disease and should be avoided. However, milk is a complex food that contains fat, calcium, magnesium, potassium, vitamin D, and certain amino acids, which may contribute to the prevention of hypertension, atherosclerosis, type 2 diabetes mellitus (T2DM), and CHD. In addition, milk has been shown to increase satiety and prevent weight gain and fat accumulation in some studies. Based on these facts, the American Heart Association's (AMA's) Nutrition Committee has issued a scientific statement advocating the use of low‐fat milk and dairy products as a dietary supplement.4 Subsequent studies have demonstrated a putative preventive effect of milk and dairy products on the incidence of CHD, hypertension, atherosclerosis, and T2DM. These pleiotropic effects of milk and dairy products will be discussed in this review.

Methods

This review will explore the possible pleiotropic preventive and therapeutic effects of milk and dairy product consumption. For this reason, a Medline search of recent English language literature from 2006 to September 2012 was performed. From this search, 16 pertinent prospective studies and meta‐analyses on the subject matter were selected. These studies together with pertinent collateral literature will be presented and discussed in subsequent sections of this review.

Coronary Heart Disease

Several epidemiologic prospective studies and meta‐analyses of clinical trials have shown that milk and dairy products, especially low‐fat products, may have a preventive effect on CHD. This effect was demonstrated in two recent large prospective cohort studies in Dutch patients. In one investigation of 33,625 Dutch men and women, the effect of the consumption of various dairy products (milk, high‐fat dairy, low‐fat dairy, cheese, and fermented dairy) on the incidence of fatal and nonfatal CHD and stroke were investigated.5 After 13 years of follow‐up, 1648 cases of CHD and 531 cases of stroke were documented. Total dairy intake was not significantly associated with the risk of CHD (hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.94–1.05) or stroke (HR, 0.95; 95% CI, 0.85–1.05), adjusted for lifestyle and dietary factors. However, fermented dairy tended to be associated with a lower risk of stroke (HR, 0.92; 95% CI, 0.83–1.01; P=.07). The presence of hypertension appeared to adversely modify the association of total and low‐fat milk with CHD, in contrast to the absence of hypertension where total (HR, 0.92; 95% CI, 0.85–1.02) and low‐fat milk (HR, 0.94;95% CI, 0.87–1.02) tended to be associated with a lower risk of CHD (P for interaction <.02). Another large study, the Netherlands Cohort Study (NLCS), investigated the effects of various dairy products (milk, cheese, and butter) on 120,852 Dutch men and women aged 25 to 69 years at baseline.6 After 10 years of follow‐up, a nonsignificant increase in the risk of CHF and all‐cause mortality was found only in women with the consumption of dairy fat and butter (HR, 1.04; 95% CI, 1.01–1.06). In contrast, fermented full‐fat milk was inversely associated with all‐cause mortality but not with stroke mortality in both sexes. Another small case control study of 507 Italian patients aged 25 to 79 years showed that the odds ratio (OR) of having a myocardial infarction (MI) was 0.89 for drinking >1 cup of milk per month compared with 0.83 for those drinking ≥7 cups per week of any kind of milk and 0.55 for those drinking ≥7 cups per day of low‐fat milk and milk products.7 Similar findings have been reported from a review by German and colleagues8 and by an overview of studies by Elwood and colleagues.9 Milk consumption (lowest vs highest) was associated with a slightly lower relative risk (RR) in the incidence of CHD (RR, 0.92; 95% CI, 0.80–0.99) and all‐cause mortality (RR, 0.87; 95% CI, 0.77–0.98). A summary of the data from the overview by Elwood and colleagues9 is listed in Table 1. An important factor for the beneficial effects of milk and dairy products on CHD may be the lower incidence of hypertension associated with the consumption of these products.

Table 1.

Milk and Dairy Product Consumption and Incidence of Ischemic Heart Disease

Author	Patients, No.	Follow‐Up, y	Events, No.	Product	Adjustments	RR (95% CI)
Snowdon and colleagues10	8725 men	20	758	Milk (2 glasses vs 0)	(age, smoking, weight)	0.94 (NA)
	15,048 women	20	841	Milk (2 glasses vs 0)	(age, smok, weight)	1.11 (NA)
van der Vijver and colleagues11	1340 men	NA	366	Diet Ca (high vs low)	(age, smok, BMI, cholesterol)	0.77 (0.53–11.11)
van der Vijver and colleagues11	1265 women	NA	178	Diet Ca (high vs low)	(age, smoking, BMI, cholesterol)	0.91 (0.55–1.50)
Kelemen and colleagues12	29,017	15	739	Composite milk, cream, cheese	(age, smoking, BMI)	1.41 (1.07–1.87)
Nettleton and colleagues13	14,153	13	1140	HF dairy (milk, cheese)	(age, sex, smoking)	1.08 (1.01–1.16)
Shaper and colleagues14	7735	9.5	608	Milk (drink, cereal vs 0)	(age, smoking, cholesterol, BP)	0.88 (0.55–1.40)
Mann and colleagues15	10,802	13.3	63	Milk (≥0.5 pt vs <0.5)	(age, sex, smoking)	1.50 (0.81–2.78)
Bostick and colleagues16	34,486	8	387	Milk (top vs bottom quartile)	(age, BMI, WHR, DM)	0.94 (0.66–1.35)
Hu and colleagues3	80,082 women	14	939	Milk (>2 glass/d vs <1/wk)	(age, BMI, smoking, HTN)	1.67–0.78 (1.14–85)
Ness and colleagues17	5765	25	892	Milk (>1 pt/d vs <1 pt/d)	(age, SC, health habits)	0.68 (0.40–1.13)
Elmwood18	2512	20–25	493	Milk (≥1 pt/d vs little 0)	(age, smoking, BMI, cholesterol)	0.71 (0.40–1.26)
Al Delaimy and colleagues19	39,800	12	1458	Dairy Ca (high vs low)	(age, BMI, smoking, cholesterol, DM)	1.01 (0.83–0.93)
Trichopoulou and colleagues20	1013	4.5	46	Dairy products (150 g + 1 SD)	(age, sex, BMI, WHR)	0.95 (0.68–1.31)
Umesawa and colleagues21	21,068 men	10	135	Dairy Ca (high vs low quintile)	(age, sex, BMI, smoking DM)	0.80 (0.45–1.44)
Umesawa and colleagues21	32,319 women	10	99	Dairy Ca (top vs bottom quintile)	(age, sex, BMI smoking DM)	1.06 (0.50–2.25)
Umesawa and colleagues22	41,526	13	322	Dairy Ca (top vs bottom quintile)	(age, sex, BMI, smoking, DM)	1.09 (0.74–1.61)

Abbreviations: WHR, waist‐to‐hip ratio; DM, diabetes mellitus; NA, not applicable; SC, social class; SD, standard deviation. Adapted with permission from Elwood and colleagues.9

Hypertension

Several clinical trials have indicated that in the management of hypertension, besides pharmacologic treatment, the adoption of healthy lifestyle and a diet that contains fruits, vegetables, and low‐fat dairy products are very important. The potential benefits of dairy foods on blood pressure (BP) have been ascribed to the high content of calcium, potassium, magnesium, and vitamin D in these products.23 An analysis of dietary data from 10,000 patients in the first National Health and Nutrition Examination Survey (NHANES I) disclosed an inverse relationship between calcium intake and BP level. A calcium intake >1000 mg/d was associated with a 40% to 50% reduction in the prevalence of hypertension.24 The association between the intake of dairy products and the risk of developing hypertension has been extensively investigated by Kris‐Etherton and colleagues25 (Table 2. In a prospective cohort study of 28,886 US women from the Women's Health Study (WHS), aged 45 years and older, the effects of dairy products on the incidence of hypertension were investigated after 10 years of follow‐up.42 In this study, the RR association of the lowest compared with the higher quintile of low‐fat dairy product consumption in developing hypertension were 1.00 (reference), 0.98, 0.97, 0.95, and 0.89 (P=.001 for trend). In another cross‐sectional study of the National Heart, Lung, and Blood Institute's (NHLBI's) Family Heart Study cohort of 4797 patients, mean age 52.2±13.7 years, with either a normal or a high risk for CHD, the OR of developing hypertension across categories of dairy food consumption were estimated.31 In this study, there was an inverse association between the lowest quartile of 0.4 dairy servings per day to the highest quartile of 3.1 servings of milk per day, and the incidence of hypertension adjusted for age, sex, and other variables was as follows: OR, 0.82; 95% CI, 0.64–1.05 and OR, 0.62; 95% CI, 0.45–0.86, respectively. The result was a 2.6‐mm Hg reduction in systolic BP (SBP) (P=.003 for trend) and 0.9 mm Hg reduction in diastolic BP (DBP) (P=.09 for trend). In another longitudinal study of 2290 patients aged 55 to 80 years at high cardiovascular risk, the consumption of low‐fat dairy products on hypertension incidence was assessed after 12 months of observation.41 The patients were divided into quintiles based on the consumption of dairy products. In the longitudinal analysis, the adjusted SBP and DBP were significantly lower in the highest quintile of low‐fat dairy product intake by 4.2 mm Hg (95% CI, −6.9 to −1.4) and −1.8 mm Hg (95% CI, −3.2 to −0.4), respectively. The inverse association between low‐fat dairy product consumption was significant for SBP (P=.01 for trend) but not for DBP. No significant trends for either SBP or DBP reduction were observed with the consumption of whole‐fat dairy products.41 Similar results have also been reported in 912 men from the French Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) cohort study.37 In contrast, some other studies have shown an equivocal association between the consumption of dairy products and BP reduction. In a prospective study from the Nurses Health Cohort involving 41,541 middle‐aged and older women followed for 4 years, high‐fat and low‐fat dairy foods were not associated with a change in either SBP or DBP, whereas the intake of fruits, vegetables, and high‐fiber foods was associated with a decrease in SBP and DBP.28 Similar results have been reported from the Dietary Approaches to Stop Hypertension (DASH) trial of 459 patients with a baseline BP of 131/85 mm Hg.43 In this study, high intake of fruits and vegetables was associated with a decrease in SBP and DBP of 2.8 mm Hg and 1.1 mm Hg, respectively. However, the group who consumed a combination of fruits, vegetables, and low‐fat dairy products showed a greater reduction in SBP and DBP of 5.5 mm Hg and 3.0 mm Hg, respectively, which was twice as low as in patients who consumed only fruits and vegetables. In a subgroup of patients with elevated BP, the consumption of fruits and vegetables resulted in reductions of SBP and DBP by 7.2 mm Hg and 2.8 mm Hg more than in the control group, whereas those who consumed a combination of fruits, vegetables, and low‐fat dairy products demonstrated the greatest decrease in SBP and DBP of 11.4 mm Hg and 5.5 mm Hg, respectively.43 In a recent 1‐year review of published studies, additional information has been provided on the BP‐lowering effects of micronutrients (calcium, potassium, and bioactive peptides) contained in milk and dairy products.44 The lactopeptides that are contained in the casein and whey parts of milk have an angiotensin‐converting enzyme (ACE) inhibitory and bradykinin antidegratory effect, as demonstrated in Figure 1. The blockade of ACE leads to a decrease in the formation of angiotensin II and an increase in the levels of bradykinin, resulting in peripheral vasodilation, a reduction in systemic vascular resistance, and a decrease in BP.45 The lactopeptides that have been mostly studied for the treatment of hypertension are the lactotripeptides, isoleucine‐proline‐proline (IPP), and valine‐proline‐proline (VPP). In a multicenter trial of 91 naïve hypertensive patients, the treatment with a lactotripeptide product (AmealPeptide; Calpis, Tokyo, Japan) resulted in a mean daytime ambulatory SBP reduction of 7.6±9.99 mm Hg compared with a reduction of 3.6±6.51 mm Hg with placebo (P<.005) and a 24‐hour mean SBP reduction of 4.9±6.97mm Hg compared with a −1.4±5.82 mm Hg reduction with placebo (P<.014). No significant reductions in DBP were noted.46

Table 2.

Association of Dairy Food Intake and BP Changes

Author	Patients, No.	Age, y	Design	Follow‐Up, y	Foods	Adjustments	Outcome
Ackley and colleagues26	541 men	30–79	Cross‐sectional	NA	Dairy Ca Milk Ca	Age, obesity, alcohol	DBP, SBP, inverse association (P<.05)
Alonso and colleagues27	5880	37	Prospective	2.25	HF, LF dairy	Age, sex, smoking	HR (95% CI) LF 0.46 (0.26–0.84) HF 1.37 (0.77–2.42)
Ascherio and colleagues28	41,541 women	38–63	Prospective	NA	Dairy foods	Age, BMI, energy	No association
Azadbahkt and colleagues29	827	18–74	Cross‐sectional	NA	Dairy foods	Age, BMI, estrogen, BP	OR (95% CI) 0.83 (0.69–0.99) P<.05
Beydoun and colleagues30	14,464	≥18	Cross‐sectional	NA	Dairy foods	Age, sex, activity	Inverse association SBP/DBP <.05
Djousse and colleagues31	5525	52	Cross‐sectional	NA	Milk 0.4–3.1 servings/d	Age, sex, BMI, diabetes	OR (95% CI) 0.64 (0.46–0.90) SBP P<.01 DBP P<.09
Elmwood and colleagues18	2512 men	45–59	Prospective	20–24	Milk 1 pt/d vs none	Activity	SBP P=.02 DBP P=.11
Iso and colleagues32	1928 men	40–69	Cross‐sectional	NA	Dairy Ca	Age, BMI, alcohol, Na	SBP P<.001 DBP P=ns
Joffres and colleagues33	1379 men	NA	Cross‐sectional	NA	Milk	Age, BMI	SBP P<.01
Jorde and Bonaa34	15,596	25–69	Cross‐sectional	NA	Dairy foods	Age, sex, activity	DBP P<.001 SBP P=ns
Pereira and colleagues35	3157	18–30	Prospective	10	Dairy intake	Age, sex, activity	HTN P<.001
Reed and colleagues36	6496 men	NA	Cross‐sectional	NA	Milk (oz/d)	Age, BMI, activity	SBP P<.001 DBP P<.01
Ruidavets and colleagues37	912 men	45–64	Cross‐sectional	NA	Dairy intake (93–335 g/d)	Age, BMI, smoking, activity	SBP P<.02 DBP P=ns
Snijder and colleagues38	1896	50–75	Cross‐sectional	NA	Dairy foods	Age, race sex, activity	DBP P<.01 SBP P=ns
Steffen and colleagues39	4304	18–30	Prospective	15	All dairy, Milk (0.3≥2.1 times per d)	Age, sex, BMI, ex	No association BP P<.03
Takashima and colleagues40	473 men	40–49	Cohort study	NA	Dairy intake (1≥5 times/wk)	Age, BMI, work	SBP P=.003 DBP P<.0001
Toledo and colleagues41	2290	55–80	Longitudinal	1.0	LF 3.1–632 g/d HF 34.9–261.1 g/d	Age, BMI, Age, BMI, smoking, diabetes	SBP P<.01 DBP P<.09 HF No association with BP
Wang and colleagues42	28,886 women	≥45	Prospective	10	LF 0.13–2.71 servings/d HF 0.13–1.49 servings/d	Age, race, smoking, BMI	LF, BP P<.001 HF, BP=ns

Abbreviations: BMI, body mass index; Ca, calcium; CI, confidence interval; DBP, diastolic blood pressure; ex, exercise; HF, high‐fat; HR, hazard ratio; HTN, hypertension; LF, low‐fat; Na, sodium; NA, not applicable; ns, not significant; OR, odds ratio; SBP, systolic blood pressure. Adapted with permission from Kris‐Etherton and colleagues.25

Figure 1.

The effect of angiotensin‐converting enzyme (ACE) inhibition on the conversion of angiotensin (Ang) I to Ang II, and the prevention of degradation of bradykinin to inactive products. Adapted with permission from Chrysant and colleagues.45

Atherosclerosis

Diets containing dairy fats have been blamed in the past for contributing to CHD, primarily as a result of an increase in saturated fat intake. Because of this assumption, the AMA's Nutrition Committee has issued a scientific statement recommending the consumption of low‐fat dairy foods.4 The rationale for these recommendations is that full‐fat milk contains saturated fats that increase serum cholesterol levels,47 which, in turn, increases the incidence of cardiovascular disease (CVD), as has been clinically demonstrated.48 However, there are conflicting data regarding the association of dairy product consumption and CVD due to complex composition of fatty acids, and the evidence from the WHS, which did not show any clear association between the consumption of high‐fat dairy foods and incidence of CHD.28 In a cross‐sectional study of Swedish patients, of 444 cases and 55 were investigated.49 The adjusted OR of having an MI were 0.74 (95% CI, 0.58–0.94) for women and 0.91 (95% CI, 0.77–1.10) for men.49 However, cross‐sectional studies have failed to demonstrate a clear relationship between the consumption of certain fatty acids and the plasma levels of low‐density lipoprotein cholesterol (LDL‐C). One study has demonstrated an inverse relationship between LDL‐C and apolipoprotein B (ApoB) levels with the consumption of fatty acids of 4 to 15 carbon atoms in adolescent boys and girls,50 while another study showed that ingestion of high‐fat dairy products resulted in modification of LDL‐C particles to a larger size, which are more favorable from the perspective of CAD, since these particles are less atherogenic.51 This favorable association was demonstrated for saturated fatty acids of 4:0 to 10:0 and 14:0 carbon atoms in the diet, and 15:0 and 17:0 carbon atoms in the serum phospholipids. In addition, another favorable effect of milk, in contrast to polyunsaturated oils, is the increase in serum high‐density lipoprotein cholesterol (HDL‐C), which is associated with a decrease in the incidence of CHD.52 Also, in a sample of 587 patients from the Main‐Syracuse Longitudinal Study (MSLS), the effects of various quantities of milk and dairy products on age‐adjusted carotid to femoral pulse wave velocity (cfPWV), pulse pressure (PP), and SBP were examined.53 These items are considered important surrogate markers for arteriosclerosis. In this study, there was a progressive linear inverse relationship between dairy food intake and cfPWV, PP, and SBP values, after adjusting for demographic, cardiovascular, and dietary factors. The values for cfPWV, PP, and SBP from this study are depicted in Figure 2A, B, and C. The findings of this study are consistent with those of previous studies showing the effects of different milk‐derived proteins on BP and arterial stiffness.52 In a recent meta‐analysis, it was estimated that for every 1‐m/s increase in cfPWV, there were increases of 14%, 15%, and 15% in CVD events, CVD mortality, and all‐cause death, respectively, adjusted for age, sex, and other risk factors.54

Figure 2.

The effects of milk and dairy products on carotid to femoral pulse wave velocity (cfPWV), pulse pressure (PP), and systolic blood pressure (SBP). There was a progressive decrease with their intake on cfPWV (A), PP (B), and SBP (C). Adapted with permission from Crichton and colleagues.53

Diabetes Mellitus

T2DM is a common condition and its incidence increases with the increase of body weight and the advancement of age. Because T2DM and its complications, including CVD, hypertension, renal failure, blindness, and limb amputation, impose an enormous economic and social burden, its primary prevention is very critical. Recent studies have shown that dietary modifications, with the inclusion of dairy products, might decrease the incidence of T2DM.55, 56, 57, 58, 59, 60 The findings from the studies reported by Elwood and colleagues58 are listed in Table 3. From these studies, the estimated overall risk reduction in the incidence of T2DM was 15% (RR, 0.85; 95% CI, 0.75–0.96). In concordance with the findings from these studies, a review of observational studies indicated that the prevalence of T2DM and the metabolic syndrome were 64% (OR, 0.36; 95% CI, 0.16–0.80) and 24% (OR, 0.76; 95% CI, 0.59–0.89) lower among persons with the highest intake of 25‐hydroxyvitamin D, compared with those with the lowest intake.61 Dairy foods provide a high supply of calcium and vitamin D and are associated with a decrease in obesity and the metabolic syndrome, conditions predisposing to prediabetes or overt T2DM. The replacement of starchy carbohydrates with low‐fat dairy foods enhances satiety and thereby facilitates weight loss.62 In addition, there is evidence that dairy calcium promotes weight loss, although the mechanism for its action is not clearly understood at present.63 It has been shown that high intake of dairy food calcium attenuates body fat accumulation and weight gain during periods of high‐caloric intake, increases fat breakdown, and preserves the metabolism during caloric restriction, thereby accelerating weight and fat loss.64 Also, in a research study, the group with the high‐calcium intake (1100 mg/d) lost more trunk fat (3.16 vs 1.74 kg) compared with the low‐calcium group.65

Table 3.

Effects of Milk and Dairy Product Consumption on the Incidence of New Diabetes

Authors	Patients	Follow‐Up, y	New Diabetes	Food Factor	Adjusted RR (95% CI)
Choi and colleagues55	41,254 men	12	1243	Increase 1 serving/y	0.91 (0.85–0.97)
Liu and colleagues56	37,183 women	10	1603	Top‐bottom quintile	0.79 (0.67–0.94)
Van Dam and colleagues57	41,186	8	1964	Highest vs lowest quintile	0.93 (0.75–1.15)
Elwood and colleagues58	2375 men	20	342	Highest vs lowest quintile	0.38 (0.18–0.78)
Villegas and colleagues60	64,191 women	6.9	2270	Milk >200 mL/d vs none	0.60 (0.41–0.88)

Abbreviations: CI, confidence interval; RR, relative risk. Adapted and modified from Elwood and colleagues.9 Adjustments were made for age, social class, smoking, alcohol intake, body mass index, activity, and hypertension.

Discussion

From the data presented earlier, it appears that low‐fat milk and dairy product consumption may have beneficial preventing effects on hypertension, atherosclerosis, T2DM, and CHD. However, the data in most studies were collected with dietary recalls, and there are obvious problems with such data collection. Despite these limitations, these studies have shown putative beneficial effects of milk and dairy foods on CHD, hypertension, atherosclerosis, and T2DM. Therefore, these new findings have changed the old held public belief that milk and dairy products are bad foods because they contain fat, which increases blood cholesterol and body weight and leads to an increase in the incidence of CHD.1, 2, 3 In addition, recent studies have shown that the consumption of low‐fat milk and dairy products could decrease the incidence of hypertension, atherosclerosis, T2DM, and CHD. Based on these observations, the AMA's Nutrition Committee has recommended the inclusion of low‐fat milk and dairy products as a dietary supplement.4 In addition, some studies have shown that milk consumption increases HDL‐C levels and modifies the LDL‐C particle to a larger size, which is less atherogenic because it does not penetrate the arterial wall,51 whereas others have shown that milk‐derived fatty acids of various carbon atom sizes decrease the ratio of total cholesterol:HDL‐C52 or show an inverse association with the serum concentrations of cholesterol and ApoB.50 In concordance with these findings, a recent study has reported a decrease in cfPWV, PP, and SBP.53 The BP‐lowering effects of milk and dairy products could be due, in addition to the prevention arteriosclerosis, to their ACE‐inhibitory effect contained in the casein and whey proteins of milk.25, 66

Regarding the effects of calcium on BP, a review of 25 epidemiologic studies relating the intake of calcium or calcium‐rich foods to BP, found that the majority of these studies showed an inverse relationship between milk intake and BP.67 Similarly, a meta‐analysis of 19 published papers has associated a high calcium intake with lower SBP and DBP.68 Supporting data have been reported by other studies. Follow‐up data from NHANES I of more than 6600 adults found that patients who reported high‐calcium intake were less likely to develop hypertension 10 years later.69 Similar data also were reported from the Dietary Intervention Study in Children (DISC) of 600 children in whom high‐calcium intake was associated with lower DBP.70 On the same subject, the AMA has issued a position paper stating that increasing dietary calcium may, preferentially, reduce BP in individuals with salt‐sensitive hypertension, especially in individuals with low‐calcium intake.71

With respect to the magnesium content of milk and dairy products, the experience on its BP‐lowering effects is limited, although some clinical studies have reported a significant inverse relationship between serum magnesium levels and BP.33, 72, 73 In addition, experimental studies have shown that magnesium deficiency is associated with an increase in BP.74, 75 Due to these putative beneficial pleiotropic effects, especially of low‐fat milk, the 2010 Dietary Guidelines Advisory Committee has recommended the use of milk as a food supplement because it was shown to reduce BP.44 It is estimated that a cup of bovine milk provides about 300 mg of calcium, which represents 30% of the daily value (DV), and dairy products contribute approximately 80% of the total calcium intake in the American diet.44 In addition, fortified milk is the main source of vitamin D, providing 200 IU of vitamin D per cup (30% of DV). Due to these putative BP‐lowering effects of milk, especially through its ACE‐inhibitory effect contained in the proteins in the casein and whey of the milk,76, 77 several companies are developing commercial products with an ACE‐inhibitory effect. These synthetic products are listed in Table 4.

Table 4.

Milk Peptides With ACE Inhibitory Properties

Product	Amino acid Sequence	Company
Ameal S	VPPIPP	Calpis Co, Tokyo, Japan
Biozate	ND	Davisco Co, Le Sueur, MN
Caseine DP	FFVAPFEVFGK	Kaneko Ltd, Tokyo, Japan
C 12 Peptide	FFVAPFEVFGK	DMV International, Veghel, The Netherlands
Danetan	ND	Danone, Paris, France
Evolus	VPPIP	Valio, Helsinki, Finland

Abbreviations: ACE, angiotensin‐converting enzyme; ND, not disclosed. Adapted with permission from Phelan and colleagues.77

Conclusions

The data presented in this review provide putative clinical and experimental evidence that low‐fat milk and dairy products possess several pleiotropic effects, which could help prevent the development of atherosclerosis, CHD, hypertension, stroke, and T2DM. Because milk and dairy products are food staples, are easier to take, and have no adverse effects, they should be encouraged to be incorporated into peoples' diets, especially in children and young adults, as recommended by National Committee guidelines.

J Clin Hypertens (Greenwich). 2013;15:503–510. © 2013 Wiley Periodicals, Inc.23815539