Mariëlle F. Engberink

Milk and dairy consumption and incidence of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies

BACKGROUND The consumption of dairy products may influence the risk of cardiovascular disease (CVD) and total mortality, but conflicting findings have been reported. OBJECTIVE The objective was to examine the associations of milk, total dairy products, and high- and low-fat dairy intakes with the risk of CVD [including coronary heart disease (CHD) and stroke] and total mortality. DESIGN PubMed, EMBASE, and SCOPUS were searched for articles published up to February 2010. Of > 5000 titles evaluated, 17 met the inclusion criteria, all of which were original prospective cohort studies. Random-effects meta-analyses were performed with summarized dose-response data. Milk as the main dairy product was pooled in these analyses. RESULTS In 17 prospective studies, there were 2283 CVD, 4391 CHD, 15,554 stroke, and 23,949 mortality cases. A modest inverse association was found between milk intake and risk of overall CVD [4 studies; relative risk (RR): 0.94 per 200 mL/d; 95% CI: 0.89, 0.99]. Milk intake was not associated with risk of CHD (6 studies; RR: 1.00; 95% CI: 0.96, 1.04), stroke (6 studies; RR: 0.87; 95% CI: 0.72, 1.05), or total mortality (8 studies; RR per 200 mL/d: 0.99; 95% CI: 0.95, 1.03). Limited studies of the association of total dairy products and of total high-fat and total low-fat dairy products (per 200 g/d) with CHD showed no significant associations. CONCLUSION This dose-response meta-analysis of prospective studies indicates that milk intake is not associated with total mortality but may be inversely associated with overall CVD risk; however, these findings are based on limited numbers.

Dairy Consumption and Incidence of Hypertension A Dose-Response Meta-Analysis of Prospective Cohort Studies

Observational and clinical studies suggest that dairy intake, particularly low-fat dairy, could have a beneficial effect on blood pressure. We performed a dose-response meta-analysis of prospective cohort studies on dairy intake and risk of hypertension in the general population. A systematic literature search for eligible studies was conducted until July 2011, using literature databases and hand search. Study-specific dose-response associations were computed according to the generalized least squares for trend estimation method, and linear and piecewise regression models were created. Random-effects models were performed with summarized dose-response data. We included 9 studies with a sample size of 57 256, a total of 15 367 incident hypertension cases, and a follow-up time between 2 and 15 years. Total dairy (9 studies; range of intake, ≈100–700 g/d), low-fat dairy (6 studies; ≈100–500 g/d), and milk (7 studies; ≈100–500 g/d) were inversely and linearly associated with a lower risk of hypertension. The pooled relative risks per 200 g/d were 0.97 (95% CI, 0.95–0.99) for total dairy, 0.96 (95% CI, 0.93–0.99) for low-fat dairy, and 0.96 (95% CI, 0.94–0.98) for milk. High-fat dairy (6 studies), total fermented dairy (4 studies), yogurt (5 studies), and cheese (8 studies) were not significantly associated with hypertension incidence (pooled relative risks of ≈1). This meta-analysis of prospective cohort studies suggests that low-fat dairy and milk could contribute to the prevention of hypertension, which needs confirmation in randomized controlled trials. # Novelty and Significance {#article-title-50}Observational and clinical studies suggest that dairy intake, particularly low-fat dairy, could have a beneficial effect on blood pressure. We performed a dose-response meta-analysis of prospective cohort studies on dairy intake and risk of hypertension in the general population. A systematic literature search for eligible studies was conducted until July 2011, using literature databases and hand search. Study-specific dose-response associations were computed according to the generalized least squares for trend estimation method, and linear and piecewise regression models were created. Random-effects models were performed with summarized dose-response data. We included 9 studies with a sample size of 57 256, a total of 15 367 incident hypertension cases, and a follow-up time between 2 and 15 years. Total dairy (9 studies; range of intake, ≈100–700 g/d), low-fat dairy (6 studies; ≈100–500 g/d), and milk (7 studies; ≈100–500 g/d) were inversely and linearly associated with a lower risk of hypertension. The pooled relative risks per 200 g/d were 0.97 (95% CI, 0.95–0.99) for total dairy, 0.96 (95% CI, 0.93–0.99) for low-fat dairy, and 0.96 (95% CI, 0.94–0.98) for milk. High-fat dairy (6 studies), total fermented dairy (4 studies), yogurt (5 studies), and cheese (8 studies) were not significantly associated with hypertension incidence (pooled relative risks of ≈1). This meta-analysis of prospective cohort studies suggests that low-fat dairy and milk could contribute to the prevention of hypertension, which needs confirmation in randomized controlled trials.

Inverse association between dairy intake and hypertension: the Rotterdam Study

BACKGROUND Little is known about the effect of different types of dairy food products on the development of hypertension. OBJECTIVE The objective was to determine whether the incidence of hypertension in older Dutch subjects is associated with intake of dairy products. DESIGN We examined the relation between dairy intake and incident hypertension in 2245 participants of the Rotterdam Study aged > or =55 y with complete dietary and blood pressure data, who were free of hypertension at baseline (1990-1993). Blood pressure was reexamined in 1993-1995 and in 1997-1999. Hazard ratios (HRs) with 95% CIs for 2- and 6-y incidence of hypertension were obtained in quartiles of energy-adjusted dairy intake, with adjustment for age, sex, BMI, smoking, educational level, dietary factors, and intake of alcohol and total energy. RESULTS Risk of hypertension after 2 y of follow-up (664 incident cases) was inversely associated with dairy product intake. After adjustment for confounders, HRs (95% CIs) were 1.00, 0.82 (0.67, 1.02), 0.67 (0.54, 0.84), and 0.76 (0.61, 0.95) in consecutive quartiles of total dairy product intake (P for trend = 0.008). Corresponding HRs for low-fat dairy products were 1.00, 0.75 (0.60, 0.92), 0.77 (0.63, 0.96), and 0.69 (0.56, 0.86) (P for trend = 0.003). Analysis of specific types of dairy products showed an inverse association with milk and milk products (P for trend = 0.07) and no association with high-fat dairy or cheese (P > 0.6). After 6 y of follow-up (984 incident cases), the associations with hypertension were attenuated to risk reductions of approximately 20% for both total and low-fat dairy products between the extreme quartiles of intake (P for trend = 0.07 and 0.09, respectively). CONCLUSION Intake of low-fat dairy products may contribute to the prevention of hypertension at an older age.

Dietary Protein and Blood Pressure: A Systematic Review

Background Elevated blood pressure (BP), which is a major risk factor for cardiovascular disease, is highly prevalent worldwide. Recently, interest has grown in the role of dietary protein in human BP. We performed a systematic review of all published scientific literature on dietary protein, including protein from various sources, in relation to human BP. Methodology/Principal Findings We performed a MEDLINE search and a manual search to identify English language studies on the association between protein and blood pressure, published before June 2010. A total of 46 papers met the inclusion criteria. Most observational studies showed no association or an inverse association between total dietary protein and BP or incident hypertension. Results of biomarker studies and randomized controlled trials indicated a beneficial effect of protein on BP. This beneficial effect may be mainly driven by plant protein, according to results in observational studies. Data on protein from specific sources (e.g. from fish, dairy, grain, soy, and nut) were scarce. There was some evidence that BP in people with elevated BP and/or older age could be more sensitive to dietary protein. Conclusions/Significance In conclusion, evidence suggests a small beneficial effect of protein on BP, especially for plant protein. A blood pressure lowering effect of protein may have important public health implications. However, this warrants further investigation in randomized controlled trials. Furthermore, more data are needed on protein from specific sources in relation to BP, and on the protein-BP relation in population subgroups.

Dietary Acid Load and Metabolic Acidosis in Renal Transplant Recipients

BACKGROUND AND OBJECTIVES Acidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs. This study examined the association of metabolic acid load with acidosis and with cardiovascular risk factors in RTRs and aimed to identify dietary factors associated with acidosis. DESIGN, PARTICIPANTS, SETTING, & MEASUREMENTS: 707 RTRs were included. Metabolic acid load was assessed by measuring 24-hour urinary net acid excretion (NAE; i.e., titratable acid + ammonium - bicarbonate). Acidosis was defined as serum [HCO(3)(-)] < 24 mmol/L. BP and insulin resistance, reflected by hemoglobin A1c, were among cardiovascular risk factors. Diet was assessed with food-frequency questionnaires. Linear regression analysis was applied to investigate association between NAE and acidosis and between dietary factors and acidosis. RESULTS Mean age ± SD was 53 ± 13 years; 57% of patients were male. Acidosis was present in 31% of RTRs. NAE was associated with acidosis (serum HCO(3)(-): β=-0.61; serum pH: β=-0.010; both P<0.001). Patients with high intake of animal protein (i.e., from meat, cheese, and fish) and low intake of fruits and vegetables had significantly lower serum HCO(3)(-) and serum pH. No associations were observed between NAE and cardiovascular risk factors, such as hypertension and insulin resistance. CONCLUSIONS In addition to conventional factors contributing to acidosis, diet might influence acid-base homeostasis in RTRs. Higher intake of fruits and vegetables and lower animal protein intake is associated with less acidosis in RTRs.

Intake of total protein, plant protein and animal protein in relation to blood pressure: a meta-analysis of observational and intervention studies

There is growing evidence from epidemiological studies that dietary protein may beneficially influence blood pressure (BP), but findings are inconclusive. We performed a meta-analysis of 29 observational studies and randomized controlled trials (RCTs) of dietary protein and types of protein in relation to BP or incident hypertension, published until January 2012. The analysis included eight cross-sectional studies (n=48 985), four prospective studies (n=11 761) and 17 RCTs (n=1449). A modest inverse association between total protein intake and BP (−0.20 mm Hg systolic (95% CI: −0.39, −0.01) per 25 g (∼1 s.d.)) was found in cross-sectional studies, but not in prospective studies (relative risk of 0.99 (95% CI: 0.96, 1.02)). For RCTs that used carbohydrate as a control treatment, the pooled BP effect was −2.11 mm Hg systolic (95% CI: −2.86, −1.37) for a weighed mean contrast in protein intake of 41 g per day. A non-significant inverse association of −0.52 mm Hg systolic (95% CI: −1.10, +0.05) per 11 g (∼1 s.d.) was found for plant protein in cross-sectional studies, whereas animal protein was not associated with BP. In prospective studies and RCTs, however, the associations of plant protein and animal protein with BP were broadly similar. These findings suggest that increasing the intake of protein at the expense of carbohydrates may have a beneficial effect on BP. The BP effect of specific types of protein remains to be established.

Lactopeptides and human blood pressure.

Purpose of review Since the mid-1990s, a number of randomized controlled trials have been published that showed an antihypertensive effect of peptides derived from milk. Research has mainly focused on isoleucine-proline-proline and valine-proline-proline (IPP + VPP), two lactotripeptides that can inhibit the angiotensin-converting enzyme (ACE) in vitro. In Finnish and Japanese subjects with (mild) hypertension, systolic blood pressure (SBP) reductions of approximately 5 mmHg were reported during 4–12 weeks of IPP + VPP supplementation. This review was performed to summarize new data from human intervention studies. Recent findings The effect of lactotripeptides on blood pressure has recently been examined in six double-blind, placebo-controlled trials that involved a total of 780 subjects with high-normal blood pressure or untreated hypertension from the UK and The Netherlands. Intervention periods lasted 4–8 weeks, and IPP + VPP intake ranged from 2 to 10 mg/day. Contrary to earlier trials, there was little evidence for an antihypertensive effect of IPP + VPP. Furthermore, no ACE inhibition was observed in vivo. Summary Recent data do not support a role for lactotripeptides in blood pressure regulation. However, we cannot exclude a beneficial effect in hypertensive subjects from specific populations (e.g. Finland, Japan). Should this be confirmed, more research is needed on mechanisms other than the renin-angiotensin-aldosterone system that could be involved.

Dietary protein and risk of hypertension in a Dutch older population: the Rotterdam study.

Background Several observational studies suggest an inverse association of protein with blood pressure (BP). However, little is known about the role of dietary protein from specific sources in BP. Method We examined the relation between several types of dietary protein (total, plant, animal, dairy, meat, grain, fish, soy, and nut) and incident hypertension in 2241 participants from the Rotterdam Study, aged at least 55 years, who were free of hypertension at baseline. Hazard ratios, with 95% confidence intervals (CIs), for incident hypertension during 6 years of follow-up were obtained per standard deviation (SD) of energy-adjusted intake of protein. Hazard ratios were adjusted for age, sex, body mass index (BMI), baseline systolic blood pressure (SBP) smoking, educational level, alcohol, intake of carbohydrates, other nutrients, and other types of protein (if applicable). We conducted stratified analyses by age (cut-off 70 years), sex, and BMI (cut-off 25 kg/m2). Results The risk of hypertension in the total cohort (1113 cases) was not related to intake of total protein or types of protein (all hazard ratios ∼1.00 per SD). Sex and BMI did not significantly modify the associations of dietary protein with hypertension. In 559 participants aged at least 70 years, the intake of animal protein was positively related to risk of hypertension (hazard ratio 1.37 per SD, 95% CI 1.09–1.72). For participants aged below 70 years no association was found (hazard ratio 0.92, 95% CI 0.81–1.06). Conclusion Total dietary protein or types of protein are not related to incident hypertension in this older population. In the more aged, however, high intake of animal protein may increase the risk of hypertension, which warrants further investigation.

Dietary amino acids and the risk of hypertension in a Dutch older population: the Rotterdam Study

BACKGROUND Inverse associations between dietary protein and hypertension have been reported, which may be attributed to specific amino acids. OBJECTIVE We examined whether the intake of glutamic acid, arginine, cysteine, lysine, or tyrosine was associated with blood pressure (BP) levels (n = 3086) and incident hypertension (n = 1810) in the Rotterdam Study. DESIGN We calculated BP levels in quartiles of amino acid intake as a percentage of total protein intake (% of protein) with adjustment for age, sex, BMI, smoking, alcohol intake, education, and dietary factors. Subsequently, we used Cox proportional models that included the same confounders to evaluate the associations between specific amino acid intake and hypertension incidence. RESULTS Glutamic acid contributed most to protein intake (21% of protein), whereas lysine provided 7%, arginine 5%, tyrosine 4%, and cysteine 1.5%. A higher intake of tyrosine (∼0.3% of protein) was significantly related to a 2.4-mm Hg lower systolic BP (P-trend = 0.05) but not to diastolic BP (P = 0.35). The other amino acids were not significantly associated with BP levels in a cross-sectional analysis. During 6 y of follow-up (7292 person-years), 873 cases of hypertension developed. None of the amino acids were significantly associated with incident hypertension (HR: 0.81-1.18; P-trend > 0.2). CONCLUSION Our data do not suggest a major role for glutamic acid, arginine, lysine, tyrosine, or cysteine intake (as % of protein intake) in determining population BP or risk of hypertension.

Dietary acid load and rapid progression to end-stage renal disease of diabetic nephropathy in Westernized South Asian people.

Diabetic nephropathy is now the most common cause of end-stage renal failure in many countries of the world. Despite increasing implementation of preventive treatment, the chance that an individual diabetic patient will reach end-stage renal failure has been increasing rather than decreasing during recent decades. Current dietary habits in The Netherlands and the rest of the Western world are slowly shifting from relatively alkalinizing (e.g., potatoes and vegetables) toward more acidifying (e.g., rice and meat). Moreover, immigrants who consumed traditional diets in their homelands, usually adapt to Western dietary habits. This phenomenon of diet acculturation could, for instance, be involved in the up to 40 times higher chance of development of end-stage renal failure in association with diabetes in South-Asian immigrants compared with whites, in Western countries. High ingestion of nonvolatile acids with food increases susceptibility for progression to end-stage renal failure. These high dietary acid loads lead to compensatory increases in renal acid excretion and ammoniagenesis. The price paid for maintenance of acid-base homeostasis is renal tubulointerstitial injury, with subsequent decline in renal function and induction of hypertension. The tendency for metabolic acidosis that results from the changing dietary habits could be corrected by a shift toward more alkalinizing food. We hypothesize that promoting such a shift can prevent the epidemic of end-stage renal failure in diabetes.