Article

Effects of Dairy Products on Intracellular Calcium and Blood Pressure in Adults with Essential Hypertension

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Abstract

Consumption of dairy foods has been associated with lower blood pressure in certain populations. This study examined the effects of dairy foods on blood pressure (BP) and intracellular calcium ((Ca)(i)) and the dependence of BP changes on changes in (Ca)(i). Twenty-three stage 1 hypertensive adults were fed the following 3 experimental diets (5 wk each) in a randomized cross-over design study; a dairy-rich, high fruits and vegetables diet (D-FandV; 30% fat, 7% saturated fat (SFA), 3.4 servings/d dairy), a high fruits and vegetables diet (FandV; 30% fat, 7% SFA, 0.4 servings/d dairy), and an average Western diet (control; 36% fat, 15% SFA, 0.4 servings/d dairy). Systolic (SBP) and diastolic (DBP) BP, calcium regulatory hormones, and erythrocyte (Ca)(i) were determined. SBP and DBP were significantly reduced by approximately 2 mm Hg following both D-F&V and F&V diets vs. the control (P < 0.05). The D-F&V diet significantly lowered 1,25-dihydroxyvitaminD compared with the F&V and control diets (P < 0.01). Serum calcium, parathyroid hormone, calcitonin, and renin activity were unchanged. The D-F&V diet lowered (Ca)(i) vs. the other two diets (P < 0.01), and this change correlated with the fall in DBP (r = 0.52, P < 0.05). Subjects who responded to the D-F&V diet by significantly reducing (Ca)(i) exhibited significantly greater net decreases in DBP on the D-F&V vs. the F&V (-2.8 +/- 1.0 mm Hg) and control diets (-5.4 +/-1.0 mm Hg; diet x group interaction, P < 0.02). Consumption of dairy foods beneficially affects (Ca)(i), resulting in improved BP in a subgroup defined by (Ca)(i) response.

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... Of these 538 were duplicates and 2337 were abstracts, leaving 77 full text citations. Out of these, only 13 (Smilowitz et al. 2011;Khaw et al. 2018;Kris-Etherton et al. 1993;Park et al. 1996;Drouin-Chartier et al. 2015;Sørensen et al. 2014;Thorning et al. 2015;Abdullah et al. 2015;Crichton et al. 2012;Demmer et al. 2016;Hilpert et al. 2009;Nguo et al. 2018;Wennersberg et al. 2009) Randomized Clinical Trials (RCT) meeting our eligibility criteria were included in the systematic review ( Figure 1). Two articles were parallel RCT (Khaw et al. 2018;Wennersberg et al. 2009) and 11 (Smilowitz et al. 2011;Kris-Etherton et al. 1993;Park et al. 1996;Drouin-Chartier et al. 2015;Sørensen et al. 2014;Thorning et al. 2015;Abdullah et al. 2015;Crichton et al. 2012;Demmer et al. 2016;Hilpert et al. 2009;Nguo et al. 2018) had crossover design with washout period. ...
... Out of these, only 13 (Smilowitz et al. 2011;Khaw et al. 2018;Kris-Etherton et al. 1993;Park et al. 1996;Drouin-Chartier et al. 2015;Sørensen et al. 2014;Thorning et al. 2015;Abdullah et al. 2015;Crichton et al. 2012;Demmer et al. 2016;Hilpert et al. 2009;Nguo et al. 2018;Wennersberg et al. 2009) Randomized Clinical Trials (RCT) meeting our eligibility criteria were included in the systematic review ( Figure 1). Two articles were parallel RCT (Khaw et al. 2018;Wennersberg et al. 2009) and 11 (Smilowitz et al. 2011;Kris-Etherton et al. 1993;Park et al. 1996;Drouin-Chartier et al. 2015;Sørensen et al. 2014;Thorning et al. 2015;Abdullah et al. 2015;Crichton et al. 2012;Demmer et al. 2016;Hilpert et al. 2009;Nguo et al. 2018) had crossover design with washout period. ...
... In total, eight studies evaluated the association between dairy intake and blood pressure or glycemia are described in Table 4 ( Khaw et al. 2018;Drouin-Chartier et al. 2015;Sørensen et al. 2014;Abdullah et al. 2015;Crichton et al. 2012;Hilpert et al. 2009;Wennersberg et al. 2009). These studies shown a decreasing trend in blood pressure with dairy intake, and in some studies this associations was linked to the calcium intake increase (Hilpert et al. 2009). ...
Article
To analyze the effects of dairy intake on cardiometabolic risk markers compared to other dietary fat sources in adults. Literature database and gray literature were searched for studies published up to October 2018. Two independent authors selected and extracted data from articles. Summary tables were constructed to present data for all outcomes. The intake of dairy appears to have a protective effect on some cardiovascular risk factors, or it is not worse than other SFA sources. The higher intake of dairy can decrease total cholesterol and reduce waist circumference and increase HDL cholesterol. However, it can also increase LDL and triglycerides, although those were small changes. It was observed that the effect of dairy on several serum lipids varied according to the type dairy product used on intervention. Dairy products seem to present a different effect on cardiometabolic risk factors than other fat sources, with evidence of improvement on metabolic parameters compared to another animal source of SFA.
... This randomized, crossover, controlled feeding study evaluated the impacts of consuming 1% fat milk or regular cheddar cheese, compared with a dairy-free diet, on daytime ambulatory BP and cardiometabolic risk factors. These data add to a body of knowledge from 13 randomized controlled trials (RCTs) (23,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), of which only 2 (37, 40) were full-feeding studies and only 1 measured ambulatory BP (23). Our results showed that consuming 3 daily servings of 1% fat milk or 50 g 31% fat cheese providing 10.1 mg GABA had no effect on SBP and DBP, both ambulatory and resting measurements, compared with a dairy-free diet. ...
... Because data from the DASH study have shown that BP lowering was more pronounced among subjects with a more deteriorated BP profile at baseline (50), the observed reduction in DBP among subjects with lower values at baseline is counterintuitive. In another RCT, dairy products have been shown to reduce intracellular calcium concentrations and increase intracellular magnesium concentrations in many but not all subjects (39). Interestingly, they found that a hypotensive effect, especially for DBP, of dairy products was evident only in subjects most responsive to changes in intracellular ion concentrations (39). ...
... In another RCT, dairy products have been shown to reduce intracellular calcium concentrations and increase intracellular magnesium concentrations in many but not all subjects (39). Interestingly, they found that a hypotensive effect, especially for DBP, of dairy products was evident only in subjects most responsive to changes in intracellular ion concentrations (39). These data suggest that there may be responders and nonresponders to the potential hypotensive effects of dairy products and emphasize the need for further interventional studies to better understand this heterogeneity. ...
Article
Background: The extent to which dairy products and their fat content influence cardiovascular health remains uncertain. Objective: This study aimed to assess how consumption of low-fat milk and regular-fat cheese enriched in γ-aminobutyric acid (GABA) influences daytime ambulatory blood pressure (BP) and other cardiometabolic risk factors. Methods: In this crossover controlled feeding study, 55 healthy men and women with high-normal daytime BP were randomly assigned to sequences of three 6-wk isoenergetic diets, each comprising 1) no dairy (control diet), 2) 3 daily servings of 1% fat milk, and 3) 1 daily serving of 31% fat cheddar cheese naturally enriched in GABA. Total proteins, carbohydrates, and fats were matched across all 3 diets. The additional 2% of energy from SFAs in the cheese diet was replaced by n-6 PUFAs in the other diets. Results: Comparison of postdiet ambulatory systolic BP revealed no difference (P = 0.34), which was also the case for ambulatory diastolic BP (P = 0.45). The cheese diet increased serum LDL-cholesterol concentrations compared with the control and milk diets (+5.8%, P = 0.006 and +7.0%, P = 0.0008, respectively) and increased LDL particle size compared with the milk diet (P = 0.02). HDL-cholesterol concentrations after the milk diet were lower than after the control diet (-4.1%; P = 0.009). The milk and cheese diets increased triglycerides compared with the control diet (+9.9%, P = 0.01 and +10.5%, P = 0.007, respectively). There was no significant difference between all diets for C-reactive protein concentrations and markers of glucose/insulin homeostasis. Conclusions: These results suggest that short-term consumption of dairy products, whether low or regular in fat, has no overall effect on daytime ambulatory BP compared with a dairy-free diet. Other cardiometabolic risk factors may be differently modified according to the fat content of the dairy product. This trial was registered at clinicaltrials.gov as NCT02763930.
... As mentioned above, some clinical trial evidence has also been published since the NEL review. Hilpert et al. 32 conducted a randomized crossover study in 23 adults with stage 1 hypertension to determine the effects of dairy food consumption on blood pressure. Three experimental diets were used in the study: a dairy-rich diet (>3 servings per day) high in fruits and vegetables, a diet high in fruits and vegetables, and an average Western diet. ...
... A 6-month clinical trial was conducted by Wennersberg et al. 36 to evaluate the effects of increased dairy intake on body composition and markers of metabolic health in overweight subjects with Ն2 criteria for metabolic syndrome. Subjects in both the higher-dairy and control groups were instructed to maintain their body 30 Observational Intake of dairy products other than cheese, cheese alone, and calcium ↓ DBP; ↔ SBP Ivey et al. (2011) 31 Observational Dairy intake ↔ SBP or DBP Hilpert et al. (2009) 32 Clinical trial Addition of dairy to a diet rich in fruits and vegetables ↔ SBP or DBP Dairy intake ↓ DBP in subgroup with decreases in intracellular calcium Zemel et al. (2009) 33 Clinical trial Weight loss ↓ SBP and DBP Dairy intake ↔ SBP or DBP Alonso et al. (2009) 34 Clinical trial Low-fat dairy intake ↔ SBP or DBP Full-fat dairy intake ↑ SBP; ↔ DBP Van Meijl & Mensink (2011) 35 Clinical trial Low-fat dairy intake ↓ SBP but ↔ DBP Wennersberg et al. (2009) 36 Clinical trial Dairy consumption ↔ SBP or DBP Zemel et al. (2010) 37 Clinical trial Intake of dairy-based smoothies ↔ SBP or DBP Stancliffe et al. (2011) 38 Clinical trial Dairy intake ↓ SBP, with progressive reductions from days 7-84 Dairy intake ↓ DBP in obese subjects at day 84 Ralston et al. (2012) 5 Systematic review and meta-analysis Total dairy intake ↓ risk of elevated blood pressure Low-fat dairy intake ↓ risk of elevated blood pressure Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure; ↔, no association/effect,;↓, inverse association/effect,; ↑, positive association/effect. ...
... A 6-month clinical trial was conducted by Wennersberg et al. 36 to evaluate the effects of increased dairy intake on body composition and markers of metabolic health in overweight subjects with Ն2 criteria for metabolic syndrome. Subjects in both the higher-dairy and control groups were instructed to maintain their body 30 Observational Intake of dairy products other than cheese, cheese alone, and calcium ↓ DBP; ↔ SBP Ivey et al. (2011) 31 Observational Dairy intake ↔ SBP or DBP Hilpert et al. (2009) 32 Clinical trial Addition of dairy to a diet rich in fruits and vegetables ↔ SBP or DBP Dairy intake ↓ DBP in subgroup with decreases in intracellular calcium Zemel et al. (2009) 33 Clinical trial Weight loss ↓ SBP and DBP Dairy intake ↔ SBP or DBP Alonso et al. (2009) 34 Clinical trial Low-fat dairy intake ↔ SBP or DBP Full-fat dairy intake ↑ SBP; ↔ DBP Van Meijl & Mensink (2011) 35 Clinical trial Low-fat dairy intake ↓ SBP but ↔ DBP Wennersberg et al. (2009) 36 Clinical trial Dairy consumption ↔ SBP or DBP Zemel et al. (2010) 37 Clinical trial Intake of dairy-based smoothies ↔ SBP or DBP Stancliffe et al. (2011) 38 Clinical trial Dairy intake ↓ SBP, with progressive reductions from days 7-84 Dairy intake ↓ DBP in obese subjects at day 84 Ralston et al. (2012) 5 Systematic review and meta-analysis Total dairy intake ↓ risk of elevated blood pressure Low-fat dairy intake ↓ risk of elevated blood pressure Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure; ↔, no association/effect,;↓, inverse association/effect,; ↑, positive association/effect. ...
Article
The Dietary Guidelines for Americans, 2010 indicated there is moderate evidence for an association between the consumption of dairy foods and lower blood pressure in adults; however, it also stated that more evidence was needed, especially in clinical trials, to fully delineate a causal relationship. The purpose of this review is to provide background by examining the historical literature and the evidence reviewed by the 2010 Dietary Guidelines Advisory Committee, to examine the gaps in knowledge indicated by that committee, and to determine if recently published evidence is sufficient to elucidate or dismiss an association between dairy foods and blood pressure maintenance. Examination of the newly published literature, together with evaluation of the evidence as a whole, shows that the preponderance of evidence indicates dairy foods are beneficially associated with blood pressure; however, additional research is necessary to identify the mechanism of action of dairy foods. New evidence should come from carefully designed clinical trials that examine not only blood pressure outcomes but also the ability of dairy foods to affect the vasculature.
... In recent years several published reports have suggested a new role for Ca, which seems not only to be a component of bone structure, a trigger for neurotransmitter release and a factor necessary for muscle contraction and blood coagulation, but also a regulator of energy and metabolism (1) . According to this concept, low dietary Ca intake may be involved in the pathogenesis of obesity (2) , hypertension (3)(4)(5) , insulin resistance and type 2 diabetes (6) . There are several data on the beneficial effects of Ca intake on the reduction of blood pressure (BP) in patients with hypertension (3)(4)(5) , on improving body composition (7) and on lowering body weight (1) . ...
... According to this concept, low dietary Ca intake may be involved in the pathogenesis of obesity (2) , hypertension (3)(4)(5) , insulin resistance and type 2 diabetes (6) . There are several data on the beneficial effects of Ca intake on the reduction of blood pressure (BP) in patients with hypertension (3)(4)(5) , on improving body composition (7) and on lowering body weight (1) . It should be mentioned that data on the influence of dairy products on body mass loss are inconclusive and difficult to compare owing to different time intervals and sources of Ca (supplements v. diet). ...
... There are some controversies regarding the influence of Ca intake on cardiovascular risk. On one hand, a reduction of BP in patients with hypertension consuming a Ca-rich diet was shown (3)(4)(5) ; on the other, administration of Ca supplements was related to an increased risk of myocardial infarction when taken alone without vitamin D (11) . Low Ca supply induces compensatory elevation of parathyroid hormone and 1,25-dihydroxyvitamin D, contributing to BP increase. ...
Article
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Objective: Dietary Ca is now being recognized to play an important role not only in skeletal integrity, but also in the regulation of energy and metabolism. The aim of the present study was to estimate the relationship of dairy Ca intake with BMI and blood pressure (BP) in a sample derived from the Polish population. Design: Ca intake was calculated from an interviewer-administered semi-quantitative FFQ. BMI was calculated from measured weight and height, and BP was measured by a physician. Setting: Cross-sectional epidemiological study on osteoporosis risk factors in Poland. Subjects: Randomly selected healthy adult persons (n 1259; 750 women and 509 men). Results: Dairy Ca intake was significantly lower in individuals with overweight/obesity (BMI≥25·00 kg/m2) and/or with elevated BP (systolic/diastolic ≥140/≥90 mmHg) than in those with normal body mass and BP, respectively. Ca intake was negatively correlated with BMI (r=-0·12, P<0·001), systolic BP (r=-0·11, P<0·001) and diastolic BP (r=-0·08, P<0·01). Daily dairy Ca intake below 1000 mg was a predictor for BMI≥25·0 kg/m2 (OR=1·44, P<0·005). This relationship was stronger in women, particularly premenopausal women. Conclusions: The obtained results indicate the role of low dairy Ca intake in the development of obesity and hypertension, notably in premenopausal women.
... With the identification of an inverse relationship of CVD and blood pressure to consumption of dairy products (McCarron et al., 1984), one such dietary modifications that has been widely recommended is the Dietary Approaches to Stop Hypertension (DASH) eating plan. The DASH eating plan is high in fruits, vegetables, and low-and nonfat dairy products, but low in total fat and sodium, and has been shown to reduce blood pressure in individuals with elevated blood pressure (Blumenthal et al., 2010;Buonopane et al., 1992;Hilpert et al., 2009;Svetkey et al., 1999Svetkey et al., , 2004Van Beresteijn et al., 1990). In one of the first DASH interventional studies (Appel et al., 1997), subjects completed one of three dietary interventions: (1) Typical Western diet, (2) diet high in fruits and vegetables, and (3) DASH diet. ...
... It should be noted, however, that the hypotensive effects of the DASH diet could not be ascribed to dairy products alone because other dietary changes (e.g., a reduction in total fat and saturated fat) were also incorporated. These findings demonstrate the ability of low-and nonfat dairy products to reduce blood pressure and have been supported by other interventional studies incorporating a similar DASH eating plan (Blumenthal et al., 2010;Buonopane et al., 1992;Hilpert et al., 2009;Svetkey et al., 1999Svetkey et al., , 2004Van Beresteijn et al., 1990). Although most of these studies have demonstrated hypotensive effects with increased daily amounts of low-and nonfat dairy products in the diet, these studies also included other dietary or lifestyle changes (e.g., weight loss, increased physical activity). ...
Chapter
In the present review, we describe the dysfunction in arteries that occurs with advanced aging and review how increased dairy product consumption ameliorates age-related arterial dysfunction and lowers the risk of cardiovascular disease (CVD) as well as type 2 diabetes. High consumption of low- and nonfat dairy products is inversely related to key markers of arterial dysfunction, including elevated blood pressure, arterial stiffening, and endothelial dysfunction. Importantly, adoption of a diet that is high in low- and nonfat dairy products is able to lower blood pressure and reduce arterial stiffness and ameliorate endothelial dysfunction in humans. More importantly, simply adding nonfat dairy products to the normal routine diet results in the amelioration of age-related arterial dysfunction. Consumption of a diet that is high in dairy products is also inversely related to risk of type 2 diabetes, which itself is a major risk factor for the development of CVD. Indeed, there is a substantial overlap of risk factors between type 2 diabetes and CVD, most of which are affected by age-related arterial dysfunction. These risk factors also appear to be ameliorated by high consumption of low- and nonfat dairy products. Nevertheless, the information pertaining to the relation between dairy intake and arterial dysfunction is currently limited, and it is clear that more research is warranted.
... (3) other studies have already investigated the relationship of erythrocyte [Ca 2þ ] i and dietary Ca or hypertension (55,56) . A high intake of dairy products was able to reduce [Ca 2þ ] i in erythrocytes and BP in hypertensive subjects when compared with a diet rich in fruits and vegetables and with a classical occidental diet (55) . ...
... (3) other studies have already investigated the relationship of erythrocyte [Ca 2þ ] i and dietary Ca or hypertension (55,56) . A high intake of dairy products was able to reduce [Ca 2þ ] i in erythrocytes and BP in hypertensive subjects when compared with a diet rich in fruits and vegetables and with a classical occidental diet (55) . Alterations in [Ca 2þ ] i and changes in the kinetics of Ca transport were also identified in platelets, adipocytes and lymphocytes (57,58) . ...
Article
Full-text available
Recent studies have suggested that dietary Ca may have beneficial effects on adiposity, insulin resistance, dyslipidaemia and blood pressure (BP). One potential mechanism underlying these benefits involves modifications in intracellular Ca concentration ([Ca2+]i). The present study aimed to evaluate the associations of dietary Ca with adiposity, erythrocyte [Ca2+]i, metabolic profile, BP, inflammatory state and endothelial function in healthy pre-menopausal women. In the present cross-sectional study, seventy-six women aged 18-50 years were submitted to the evaluation of dietary intake, anthropometric parameters, body composition, erythrocyte [Ca2+]i, biochemical variables, endothelial function and BP. A FFQ was used to assess usual dietary intake. Endothelial function was evaluated by serum concentrations of adhesion molecules and by the peripheral arterial tonometry (PAT) method, using Endo-PAT 2000®. Participants were allocated into two groups according to Ca intake: low-Ca group (LCG; n 32; < 600 mg/d) and high-Ca group (HCG; n 44; ≥ 600 mg/d). Women in the LCG compared with those in the HCG exhibited, after adjustments for potential confounders, higher values of BMI, waist circumference, waist:height ratio, percentage of body fat, insulin, homeostasis model assessment of insulin resistance, leptin, diastolic and mean BP; and lower levels of HDL-cholesterol, adiponectin and vascular cell adhesion molecule 1. Endothelial function assessed by PAT and [Ca2+]i was similar in both groups. Subjects in the HCG had lower OR for prevalent overweight, obesity, abdominal obesity, insulin resistance, HDL-cholesterol < 600 mg/l and systolic BP >120 mmHg. The findings of the present study suggest that high Ca intake is inversely associated with some cardiovascular risk factors.
... In their metaanalysis, Benatar et al. (14) reported no significant effect of total dairy intake on systolic and diastolic BP. Additional RCTs in hypertensive subjects provided mixed results regarding the impact of high dairy intake compared with low or no dairy over periods of 4-5 wk on BP outcomes (57)(58)(59). Two studies saw no effect of dairy intake on systolic and diastolic BP (57,58), whereas we reported that consumption of 3 daily servings of regular-fat dairy (30 g regular-fat cheddar cheese/d, 175 g 1.5%-fat yogurt/d, and 375 mL 1% fat milk/d) significantly reduced mean daytime systolic BP compared with a dairy-free control diet in men (mean 6 SD: 142 6 10 compared with 144 6 10 mm Hg, P = 0.05) (59). ...
... Additional RCTs in hypertensive subjects provided mixed results regarding the impact of high dairy intake compared with low or no dairy over periods of 4-5 wk on BP outcomes (57)(58)(59). Two studies saw no effect of dairy intake on systolic and diastolic BP (57,58), whereas we reported that consumption of 3 daily servings of regular-fat dairy (30 g regular-fat cheddar cheese/d, 175 g 1.5%-fat yogurt/d, and 375 mL 1% fat milk/d) significantly reduced mean daytime systolic BP compared with a dairy-free control diet in men (mean 6 SD: 142 6 10 compared with 144 6 10 mm Hg, P = 0.05) (59). Unexpectedly, mean daytime diastolic BP was higher after the dairy diet than after the control phase in women (mean 6 SD: 85 6 9 compared with 84 6 8 mm Hg, P = 0.05), but not in men (59). ...
Article
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Because regular-fat dairy products are a major source of cholesterol-raising saturated fatty acids (SFAs), current US and Canadian dietary guidelines for cardiovascular health recommend the consumption of low-fat dairy products. Yet, numerous randomized controlled trials (RCTs) have reported rather mixed effects of reduced- and regular-fat dairy consumption on blood lipid concentrations and on many other cardiometabolic disease risk factors, such as blood pressure and inflammation markers. Thus, the focus on low-fat dairy in current dietary guidelines is being challenged, creating confusion within health professional circles and the public. This narrative review provides perspective on the research pertaining to the impact of dairy consumption and dairy fat on traditional and emerging cardiometabolic disease risk factors. This comprehensive assessment of evidence from RCTs suggests that there is no apparent risk of potential harmful effects of dairy consumption, irrespective of the content of dairy fat, on a large array of cardiometabolic variables, including lipid-related risk factors, blood pressure, inflammation, insulin resistance, and vascular function. This suggests that the purported detrimental effects of SFAs on cardiometabolic health may in fact be nullified when they are consumed as part of complex food matrices such as those in cheese and other dairy foods. Thus, the focus on low-fat dairy products in current guidelines apparently is not entirely supported by the existing literature and may need to be revisited on the basis of this evidence. Future studies addressing key research gaps in this area will be extremely informative to better appreciate the impact of dairy food matrices, as well as dairy fat specifically, on cardiometabolic health.
... In addition, the present study showed no significant impact of additional elemental calcium+D on blood pressures. It seems that the antihypertensive effect of calcium may be more pronounced with dairy-derived calcium [36,37] than elemental calcium [32,34]. The former was examined in studies that carried out over short terms (5 weeks to 16 weeks), while the latter was used in moderate or long-term studies (6 months and 2 years). ...
... In addition, the present study showed no significant impact of additional elemental calcium+D on blood pressures. It seems that the antihypertensive effect of calcium may be more pronounced with dairy-derived calcium [36,37] than elemental calcium [32,34]. The former was examined in studies that carried out over short terms (5 weeks to 16 weeks), while the latter was used in moderate or long-term studies (6 months and 2 years). ...
Article
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Background Recent evidence suggests that higher calcium and/or vitamin D intake may be associated with lower body weight and better metabolic health. Due to contradictory findings from intervention trials, we investigated the effect of calcium plus vitamin D3 (calcium+D) supplementation on anthropometric and metabolic profiles during energy restriction in healthy, overweight and obese adults with very-low calcium consumption. Methods Fifty-three subjects were randomly assigned in an open-label, randomized controlled trial to receive either an energy-restricted diet (−500 kcal/d) supplemented with 600 mg elemental calcium and 125 IU vitamin D3 or energy restriction alone for 12 weeks. Repeated measurements of variance were performed to evaluate the differences between groups for changes in body weight, BMI, body composition, waist circumference, and blood pressures, as well as in plasma TG, TC, HDL, LDL, glucose and insulin concentrations. Results Eighty-one percent of participants completed the trial (85% from the calcium + D group; 78% from the control group). A significantly greater decrease in fat mass loss was observed in the calcium + D group (−2.8±1.3 vs.-1.8±1.3 kg; P=0.02) than in the control group, although there was no significant difference in body weight change (P>0.05) between groups. The calcium + D group also exhibited greater decrease in visceral fat mass and visceral fat area (P<0.05 for both). No significant difference was detected for changes in metabolic variables (P>0.05). Conclusion Calcium plus vitamin D3 supplementation for 12 weeks augmented body fat and visceral fat loss in very-low calcium consumers during energy restriction. Trial registration ClinicalTrials.gov (NCT01447433, http://clinicaltrials.gov/).
... A recent randomized, cross-over, clinical trial in 23 stage 1 hypertensive Caucasian adults evaluated the hypotensive effects of a dairy-rich diet and whether the effects differed according to changes in intracellular Ca 2ϩ [99]. The experimental diets lasted 5 wks and included a high dairy, high fruits and vegetables diet (D-F&V; 30% fat, 7% saturated fat (SFA), 3.4 servings/d dairy), a low dairy, high fruits and vegetables diet (F&V; 30% fat, 7% SFA, 0.4 servings/d dairy), and an average Western diet as a control (AWD; 36% fat, 15% SFA, 0.4 servings/d dairy). ...
Article
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High blood pressure (BP) is a major risk factor for heart disease, stroke, congestive heart failure, and kidney disease. Inverse associations between dairy product consumption and systolic blood pressure (SBP) and diastolic blood pressure (DBP) have been observed in cross-sectional studies; some studies, however, have reported an inverse association with only one BP parameter, predominantly SBP. Randomized clinical trials examining the effect of calcium and the combination of calcium, potassium and magnesium provide evidence for causality. In these studies, reductions in BP were generally modest (-1.27 to -4.6 mmHg for SBP, and -0.24 to -3.8 mmHg for DBP). Dairy nutrients, most notably calcium, potassium and magnesium, have been shown to have a blood pressure lowering effect. A low calcium intake increases intracellular calcium concentrations which increases 1,25-dihydroxyvitamin D(3) and parathyroid hormone (PTH), causing calcium influx into vascular smooth muscle cells, resulting in greater vascular resistance. New research indicates that dairy peptides may act as angiotensin converting enzyme (ACE) inhibitors, thereby inhibiting the renin angiotensin system with consequent vasodilation. A growing evidence base shows that dairy product consumption is involved in the regulation of BP. Consequently, inclusion of dairy products in a heart healthy diet is an important focal point to attain BP benefits.
... Because these aforementioned studies evaluated the association between dairy products and the risk of hypertension, the causal link between dairy consumption and BP reduction remains unclear. In fact, randomized clinical trials that have attempted to assess this relationship either were not designed to identify nutrients that lower BP or used small sample sizes [8,[17][18][19]. For example, in the original DASH study, the diet rich in fruits, vegetables and low-fat dairy products led to a greater reduction in BP than the control diet without dairy products [8]. ...
Article
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Several studies have presented evidence suggesting that dairy consumption has beneficial effects on blood pressure (BP) in healthy subjects; however, only a few studies have examined this possibility in patients with established essential hypertension using ambulatory blood pressure monitoring. The objective of this study was to investigate how consuming dairy products impacts mean daytime systolic and diastolic BP in men and women with mild to moderate essential hypertension. Eighty-nine men and women with systolic BP ≥ 135 mm Hg and ≤ 160 mm Hg and diastolic BP ≤ 110 mm Hg were enrolled in this single-blind, randomized, cross-over, controlled study. Participants had to incorporate three daily servings of dairy products or control products equivalent in macronutrients and sodium during four-week treatment phases. Twenty-four hour ambulatory BP and endothelial function were assessed at screening and at the end of each dietary phase. The consumption of three daily servings of dairy products led to a significant reduction in mean daytime ambulatory systolic BP (-2 mm Hg; P = 0.05) in men compared with readings after the control phase. In women, dairy consumption had no effect on ambulatory systolic BP. Moreover, endothelial function was significantly improved by dairy consumption in the whole cohort. These data indicate that the consumption of three daily servings of dairy products have beneficial effects on daytime systolic ambulatory BP compared to a heart-healthy, dairy-free, diet in men with mild to moderate essential hypertension. Trial registration This trial is registered at clinicaltrials.gov as NCT01776216.
... Although few randomized clinical trials have been conducted to evaluate the effects of dairy food consumption on components of CMS, results from published trials to date indicate neutral or beneficial effects on TG, HDL-C levels, blood pressure, fasting glucose, and/or waist circumference (13)(14)(15). One 8-wk clinical trial demonstrated a beneficial effect of low-fat dairy intake on systolic blood pressure and neutral effects on plasma TG and fasting glucose (14). ...
Article
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Cardiometabolic syndrome (CMS), a cluster of metabolic abnormalities that increases the risk of cardiovascular disease (CVD) and type 2 diabetes, affects over one-third of American adults and accounts for billions of dollars in health care costs annually. Current evidence indicates an inverse association between consumption of dairy foods and risk of CMS and its related disease outcomes. Although the specific mechanism(s) underlying the beneficial effects of dairy consumption on the development of CMS, CVD, and type 2 diabetes have not been fully elucidated, there is evidence that specific components within dairy such as milkfat, vitamin D, calcium, magnesium, potassium, and whey proteins may be individually or collectively involved. Specifically, each of these dairy components has been implicated as having a neutral or beneficial effect on one or more elements of CMS, including the serum lipid profile, blood pressure, fasting glucose, and body composition. Although several mechanisms have been identified by which components in dairy may beneficially affect symptoms associated with CMS, further research is required to better understand how dairy and its components may contribute to metabolic health. The purpose of this review is to present the mechanisms by which specific dairy components modulate risk factors for CMS and identify opportunities for future research.
... The increased consumption of dairy foods did not affect other cardiometabolic parameters including blood pressure, which is postulated to benefit from dairy consumption [24,[56][57][58]. However, blood pressure reductions are usually demonstrable only in hypertensives and our population was clearly normotensive. ...
Article
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A growing body of research suggests that regular consumption of dairy foods may counteract obesity and other components of the metabolic syndrome. However, human intervention trials are lacking. We aimed to determine the cardiometabolic health effects of increasing the consumption of reduced fat dairy foods in adults with habitually low dairy intakes in the absence of energy restriction. An intervention trial was undertaken in 61 overweight or obese adults who were randomly assigned to a high dairy diet (HD, 4 serves of reduced fat dairy/day) or a low dairy control diet (LD, ≤1 serve/day) for 6 months then crossed over to the alternate diet for a further 6 months. A range of anthropometric and cardiometabolic parameters including body composition, metabolic rate, blood lipids, blood pressure and arterial compliance were assessed at the end of each diet phase. Total energy intake was 1120 kJ/day higher during the HD phase, resulting in slight weight gain during this period. However, there were no significant differences between HD and LD in absolute measures of waist circumference, body weight, fat mass or any other cardiometabolic parameter. Recommended intakes of reduced fat dairy products may be incorporated into the diet of overweight adults without adversely affecting markers of cardiometabolic health. The trial was registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12608000538347) on 24th October, 2008.
... Although few randomized clinical trials have been conducted to evaluate the effects of dairy food consumption on components of CMS, results from published trials to date indicate neutral or beneficial effects on TG, HDL-C levels, blood pressure, fasting glucose, and/or waist circumference (13)(14)(15). beneficial effect of low-fat dairy intake on systolic blood pressure and neutral effects on plasma TG and fasting glucose (14). The authors also reported decreased plasma HDL-C levels, although the decrease may have been attributable to the exchange of carbohydrate for protein intake when participants switched from the control diet to the low-fat dairy diet (14). ...
... 7 Results from other cross-sectional and prospective observational studies and randomized clinical trials have also suggested an inverse association between consumption of dairy products, particularly low-fat products, and the risk of developing hypertension. [8][9][10][11][12][13][14][15][16][17][18][19][20] A recent metaanalysis reported a relative risk of 0.87 (95% confidence interval, 0.81-0.94) for the development of elevated blood pressure in adults consuming higher versus lower quantities of dairy. ...
Article
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This randomized crossover trial assessed the effects of 5 weeks of consuming low-fat dairy (one serving/day each of 1% fluid milk, low-fat cheese, and low-fat yogurt) versus nondairy products (one serving/day each of apple juice, pretzels, and cereal bar) on systolic and diastolic blood pressures (SBP and DBP), vascular function (reactive hyperemia index [RHI] and augmentation index), and plasma lipids. Patients were 62 men and women (mean age 54.5 years, body mass index 29.2 kg/m(2)) with prehypertension or stage 1 hypertension (mean resting SBP/DBP 129.8 mmHg/80.8 mmHg) while not receiving antihypertensive medications. A standard breakfast meal challenge including two servings of study products was administered at the end of each treatment period. Dairy and nondairy treatments did not produce significantly different mean SBP or DBP in the resting postprandial state or from premeal to 3.5 hours postmeal (SBP, 126.3 mmHg versus 124.9 mmHg; DBP, 76.5 mmHg versus 75.7 mmHg), premeal (2.35 versus 2.20) or 2 hours postmeal (2.33 versus 2.30) RHI, and premeal (22.5 versus 23.8) or 2 hours postmeal (12.4 versus 13.2) augmentation index. Among subjects with endothelial dysfunction (RHI ≤ 1.67; n = 14) during the control treatment, premeal RHI was significantly higher in the dairy versus nondairy condition (2.32 versus 1.50, P = 0.002). Fasting lipoprotein lipid values were not significantly different between treatments overall, or in subgroup analyses. No significant effects of consuming low-fat dairy products, compared with low-fat nondairy products, were observed for blood pressures, measures of vascular function, or lipid variables in the overall sample, but results from subgroup analyses were consistent with the hypothesis that dairy foods might improve RHI in those with endothelial dysfunction.
... Although sunlight exposition might be the more physiological way, the ultraviolet (UV)-B rays-induced skin synthesis of vitamin D is hard to quantify and thus poorly investigated [140,151] . Oral supplementation has been preferred because easier to manage (despite some variability in intestinal absorption may exist) if provided through diet regimen [147] , nutritional supplements [146] or direct vitamin D administration (daily intake [137][138][139]141,143,144,[152][153][154][155][156][157] or loading dose [142,[148][149][150]158] ...
Article
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Vitamin D deficiency has been indicated as a pandemic emerging public health problem. In addition to the well-known role on calcium-phosphorus homeostasis in the bone, vitamin D-mediated processes have been recently investigated on other diseases, such as infections, cancer and cardiovascular diseases. Recently, both the discovery of paracrine actions of vitamin D (recognized as "local vitamin D system") and the link of vitamin D with renin-angiotensin-aldosterone system and the fibroblast growth factor 23/klotho pathways highlighted its active cardiovascular activity. Focusing on hypertension, this review summarizes the more recent experimental evidence involving the vitamin D system and deficiency in the cardiovascular pathophysiology. In particular, we updated the vascular synthesis/catabolism of vitamin D and its complex interactions between the various endocrine networks involved in the regulation of blood pressure in humans. On the other hand, the conflicting results emerged from the comparison between observational and interventional studies emphasize the fragmentary nature of our knowledge in the field of vitamin D and hypertension, strongly suggesting the need of further researches in this field.
... (P<0.05) (Hilpert, et al. 2009). Potential benefits of dairy products on lowering blood pressure have also been reported by the DASH trial. ...
... 18 Males aged 18-55 years consume about 700-900 mg/d dietary calcium without supplementation and females in the same age category consume < 700 mg/d 19 ; both genders do not reach the recommended intake of 1,000-1,200 mg/d. 20 Low calcium intake can increase the risk for osteoporosis, 21-23 hypertension, [24][25][26][27][28] and some cancers. 29,30 The primary published approach to reversing or lessening food aversions in humans is repeat exposure to the adverse agent. ...
Article
To determine whether a 21-day milk-drinking intervention could reverse milk aversion. Participants consumed increasing amounts of cow's milk for 21 days. Milk and dairy consumption, aversion, and likeness were assessed pre- and post-intervention and at 3 and 6 months post-intervention. A large Midwestern university. Twenty-seven milk-averse individuals completed the intervention, 26 completed the 3-month follow-up, and 24 completed the 6-month follow-up. Participants self-reported milk and dairy consumption, aversion, and degree to which they liked milk. Analysis of variance determined between-subject effects. Independent samples t test determined the effect of time. Fisher exact test determined factors affecting milk consumption. Lactose digesters and maldigesters showed a significant decrease in overall symptom scores after the milk intervention, with no significant difference between groups. Independent of digestive status, subjects demonstrated a significant decrease in aversion, an increase in the amount to which they liked milk, and an increase in milk and overall calcium consumption at 3 and 6 months post-intervention. The results suggest a reversal of milk avoidance and the possibility that milk avoiders can increase likeness and incorporate milk into their diet after exposure. Copyright © 2015 Society for Nutrition Education and Behavior. Published by Elsevier, Inc. All rights reserved. Published by Elsevier Inc. All rights reserved.
... Dairy intake has been related to changes in intracellular calcium in responsive individuals, resulting in improved blood pressure (62); and it has been shown, for example, that intracellular calcium favors insulin secretion and glucose uptake. In addition, individuals with calcium deficiency may have a high risk of diabetes (59). ...
Article
The effects of dairy consumption on the prevention of type 2 diabetes remain controversial and depend on the dairy subtype. Yogurt intake has received special attention because its association with health benefits is more consistent than that of other types of dairy products. In the present article, we review those observational studies that evaluated the association between yogurt consumption and type 2 diabetes. We also discuss the possible mechanisms involved in these associations. We found that 13 prospective studies evaluated the association between yogurt intake and type 2 diabetes, most of which showed an inverse association between the frequency of yogurt consumption and the risk of diabetes. In addition to the scientific evidence accumulated from individual prospective studies, several meta-analyses have shown that yogurt consumption has a potential role in diabetes prevention. The most recent analysis shows a 14% lower risk of type 2 diabetes when yogurt consumption was 80-125 g/d compared with no yogurt consumption. The intake of fermented dairy products, especially yogurt, has been inversely associated with variables of glucose metabolism. Yogurt may have probiotic effects that could modulate glucose metabolism. We conclude that yogurt consumption, in the context of a healthy dietary pattern, may reduce the risk of type 2 diabetes in healthy and older adults at high cardiovascular risk. Large-scale intervention studies and randomized clinical trials are warranted to determine if yogurt consumption has beneficial effects on insulin sensitivity and reduces the risk of type 2 diabetes.
... In animal studies, a high calcium diet reduces hypertension associated with oral contraceptive treatment, by improving diuresis and vasorelaxant responses [9]. A high dairy diet has been found to reduce systolic and diastolic blood pressure by about 2 mmHg, an effect correlated with reduction in intracellular calcium [10]. An alternative mechanism whereby calcium supplementation might lower blood pressure is by mitigating the hypertensive effect of sodium chloride (common salt) [11]. ...
Article
Background: Epidemiological findings suggest that the link between poverty and pre-eclampsia might be dietary calcium deficiency. Calcium supplementation has been associated with a modest reduction in pre-eclampsia, and also in blood pressure (BP). Methods: This exploratory sub-study of the WHO Calcium and Pre-eclampsia (CAP) trial aims to determine the effect of 500mg/day elemental calcium on the blood pressure of non-pregnant women with previous pre-eclampsia. Non-pregnant women with at least one subsequent follow-up trial visit at approximately 12 or 24weeks after randomization were included. Results: Of 836 women randomized by 9 September 2014, 1st visit data were available in 367 women of whom 217 had previously had severe pre-eclampsia, 2nd visit data were available in 201 women. There was an overall trend to reduced BP in the calcium supplementation group (1-2.5mmHg) although differences were small and not statistically significant. In the subgroup with previous severe pre-eclampsia, the mean diastolic BP change in the calcium group (-2.6mmHg) was statistically larger than in the placebo group (+0.8mmHg), (mean difference -3.4, 95% CI -0.4 to -6.4; p=0.025). The effect of calcium on diastolic BP at 12weeks was greater than in those with non-severe pre-eclampsia (p=0.020, ANOVA analysis). Conclusions: There is an overall trend to reduced BP but only statistically significant in the diastolic BP of women with previous severe pre-eclampsia. This is consistent with our hypothesis that this group is more sensitive to calcium supplementation, however results need to be interpreted with caution.
... Calcium channel blockers, such as nifedipine and verapamil, are valuable antihypertensive drugs as they inhibit Ca 2+ entry to the cell and reduce [Ca 2+ ] i . In the same way, calcium supplementation in subjects with low calcium intake has been described to decrease [Ca 2+ ] i [43,44], hence diminishing blood pressure. It has been shown that PTH increases calcium entry into a variety of mammalian tissues and cell lines, such as cardiomyocytes [45], enterocytes [46], kidney [47], liver [48], peripheral nerves [49], osteosarcoma cells [50], and osteoblastlike cells [51]. ...
Article
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There is increasing epidemiologic and animal evidence that a low calcium diet increases blood pressure. The aim of this review is to compile the information on the link between low calcium intake and blood pressure. Calcium intake may regulate blood pressure by modifying intracellular calcium in vascular smooth muscle cells and by varying vascular volume through the renin–angiotensin–aldosterone system. Low calcium intake produces a rise of parathyroid gland activity. The parathyroid hormone increases intracellular calcium in vascular smooth muscles resulting in vasoconstriction. Parathyroidectomized animals did not show an increase in blood pressure when fed a low calcium diet as did sham-operated animals. Low calcium intake also increases the synthesis of calcitriol in a direct manner or mediated by parathyroid hormone (PTH). Calcitriol increases intracellular calcium in vascular smooth muscle cells. Both low calcium intake and PTH may stimulate renin release and consequently angiotensin II and aldosterone synthesis. We are willing with this review to promote discussions and contributions to achieve a better understanding of these mechanisms, and if required, the design of future studies.
... This suggests that serum total calcium might be a risk factor for hypertension. In contrast to serum total calcium, serum ionized calcium has been shown to be inversely associated with blood pressure or hypertension in several studies (28)(29)(30)(31)(32) ; however, ionized calcium was not measured in the present study. Calcium's effect on blood pressure is most prominent in its influence on muscle contraction and vascular resistance (33,34) . ...
Article
Objective The present epidemiological study aimed to evaluate the association of serum electrolyte levels with hypertension in a population with a high-salt diet. Design Secondary analysis of epidemiology data from the Northeast China Rural Cardiovascular Health Study conducted in 2012–2013. Blood pressure and hypertension status were analysed for association with serum sodium, potassium, chloride, total calcium, phosphate and magnesium levels using regression models. Setting High-salt diet, rural China. Participants Adult residents in Liaoning, China. Results In total 10 555 participants were included, of whom 3287 had incident hypertension (IH) and 1655 had previously diagnosed hypertension (PDH). Fifty-six per cent of participants had electrolyte disturbance. Sixty-two per cent of hypercalcaemic participants had hypertension, followed by hypokalaemia (56 %) and hypernatraemia (54 %). Only hypercalcaemia showed significant associations with both IH (OR=1·70) and PDH (OR=2·25). Highest serum calcium quartile had higher odds of IH (OR=1·58) and PDH (OR=1·64) than the lowest quartile. Serum sodium had no significant correlation with hypertension. Serum potassium had a U-shaped trend with PDH. Highest chloride quartile had lower odds of PDH than the lowest chloride quartile (OR=0·65). Highest phosphate quartile was only associated with lower odds of IH (OR=0·75), and the higher magnesium group had significantly lower odds of IH (OR=0·86) and PDH (OR=0·77). Conclusions We have shown the association of serum calcium, magnesium and chloride levels with IH and/or PDH. In the clinical setting, patients with IH may have concurrent electrolyte disturbances, such as hypercalcaemia, that may indicate other underlying aetiologies.
... Hilpert et al. [12] fed adults with stage 1 hypertension a dairy-rich, high fruits and vegetables diet (DFV), a high fruits and vegetables (FV) diet and an average Western diet (control) for 5 weeks each. They concluded that consumption of dairy products beneficially affect the erythrocyte (Ca) (i) resulting in improved BP which they defined as (Ca) (i) response. ...
Article
To assess the contribution of dairy products to the intake of various vitamins and minerals in several life stages in the Dutch population. Data from 3 Dutch Food Consumption Surveys and the Leiden Longevity Study were used to estimate the contribution of dairy products--as percentage of total intake--to the intake of iron, copper, selenium, zinc, calcium, folic acid, vitamin D, vitamin C, and vitamin B(12). In young children, dairy products contributed substantially to the intake of calcium (73%), selenium (21%), iron (8%), zinc (39%), copper (12%), folic acid (24%), vitamin C (18%), vitamin D (16%), and vitamin B(12) (58%). Of all dairy products, milk contributed the most to the intake of these nutrients. In adults and elderly subjects, the contribution of dairy products to total micronutrient intake was 65%-68% for calcium, 18%-19% for selenium, 3%-4% for iron, 28%-31% for zinc, 6%-7% for copper, 17%-19% for folic acid, 10%-14% for vitamin C, 11%-16% for vitamin D, and 44%-46% for vitamin B(12). Milk as well as cheese contributed the most to the intake of these nutrients. Dairy products are an important source of vitamins and minerals in the Dutch population. Dairy products, especially milk and cheese, contribute substantially to the intake of calcium, selenium, zinc, and vitamin B(12).
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Hypertension is a major risk factor for development of stroke, coronary heart disease, heart failure, and end-stage renal disease. In a systematic review of the evidence published from 2004 to 2009, the 2010 Dietary Guidelines Advisory Committee (DGAC) concluded there was moderate evidence of an inverse relationship between the intake of milk and milk products (dairy) and blood pressure. This review synthesizes results from studies published over the past year on the relationship between dairy intake, blood pressure, and hypertension risk. The influence of dairy micronutrients including calcium, vitamin D, potassium, and phosphorous on blood pressure and incident hypertension is examined. Emerging research on bioactive dairy peptides is also reviewed. Lastly, recent evidence on effects of dairy fat content on blood pressure and hypertension risk, and the impact of inclusion of low-fat dairy in dietary patterns is also investigated.
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Although evidence has linked the consumption of saturated fat (SF) to increased LDL levels and an increased risk of the development of cardiovascular disease (CVD), recent findings have indicated that the link between CVD and SF may be less straightforward than originally thought. This may be due to the fact that some food sources high in SF contain an array of saturated and unsaturated fatty acids, each of which may differentially affect lipoprotein metabolism, as well as contribute significant amounts of other nutrients, which may alter CVD risk. The purpose of this review is to examine the published research on the relationship between milk fat containing dairy foods and cardiovascular health. The findings indicate that the majority of observational studies have failed to find an association between the intake of dairy products and increased risk of CVD, coronary heart disease, and stroke, regardless of milk fat levels. Results from short-term intervention studies on CVD biomarkers have indicated that a diet higher in SF from whole milk and butter increases LDL cholesterol when substituted for carbohydrates or unsaturated fatty acids; however, they may also increase HDL and therefore might not affect or even lower the total cholesterol:HDL cholesterol ratio. The results from the review also indicate that cheese intake lowers LDL cholesterol compared with butter of equal milk fat content. In addition, the review highlights some significant gaps in the research surrounding the effects of full-fat dairy on CVD outcomes, pointing to the need for long-term intervention studies.
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Background: Recent evidence suggests that higher calcium and/or vitamin D intake may be associated with lower body weight and better metabolic health. Due to contradictory findings from intervention trials, we investigated the effect of calcium plus vitamin D3 (calcium+D) supplementation on anthropometric and metabolic profiles during energy restriction in healthy, overweight and obese adults with very-low calcium consumption. Methods: Fifty-three subjects were randomly assigned in an open-label, randomized controlled trial to receive either an energy-restricted diet (−500 kcal/d) supplemented with 600 mg elemental calcium and 125 IU vitamin D3 or energy restriction alone for 12 weeks. Repeated measurements of variance were performed to evaluate the differences between groups for changes in body weight, BMI, body composition, waist circumference, and blood pressures, as well as in plasma TG, TC, HDL, LDL, glucose and insulin concentrations. Results: Eighty-one percent of participants completed the trial (85% from the calcium + D group; 78% from the control group). A significantly greater decrease in fat mass loss was observed in the calcium + D group (−2.8±1.3 vs.-1.8±1.3 kg; P=0.02) than in the control group, although there was no significant difference in body weight change (P>0.05) between groups. The calcium + D group also exhibited greater decrease in visceral fat mass and visceral fat area (P<0.05 for both). No significant difference was detected for changes in metabolic variables (P>0.05). Conclusion: Calcium plus vitamin D3 supplementation for 12 weeks augmented body fat and visceral fat loss in very-low calcium consumers during energy restriction. Trial registration: ClinicalTrials.gov (NCT01447433, http://clinicaltrials.gov/ ).
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Hypertension (HTN) or high blood pressure (BP) is among the most prevalent forms of cardiovascular disease and occurs in approximately one of every three adults in the United States. The purpose of this Evidence Analysis Library (EAL) guideline is to provide an evidence-based summary of nutrition therapy for the management of HTN in adults aged 18 years or older. Implementation of this guideline aims to promote evidence-based practice decisions by registered dietitian nutritionists (RDNs), and other collaborating health professionals to decrease or manage HTN in adults while enhancing patient quality of life and taking into account individual preferences. The systematic review and guideline development methodology of the Academy of Nutrition and Dietetics were applied. A total of 70 research studies were included, analyzed, and rated for quality by trained evidence analysts (literature review dates ranged between 2004 and 2015). Evaluation and synthesis of related evidence resulted in the development of nine recommendations. To reduce BP in adults with HTN, there is strong evidence to recommend provision of medical nutrition therapy by an RDN, adoption of the Dietary Approaches to Stop Hypertension dietary pattern, calcium supplementation, physical activity as a component of a healthy lifestyle, reduction in dietary sodium intake, and reduction of alcohol consumption in heavy drinkers. Increased intake of dietary potassium and calcium as well as supplementation with potassium and magnesium for lowering BP are also recommended (fair evidence). Finally, recommendations related to lowering BP were formulated on vitamin D, magnesium, and the putative role of alcohol consumption in moderate drinkers (weak evidence). In conclusion, the present evidence-based nutrition practice guideline describes the most current recommendations on the dietary management of HTN in adults intended to support the practice of RDNs and other health professionals.
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We determined the effect of consuming low glycemic index (LGI) skim milk compared to a high glycemic index (HGI) sports drink, following evening exercise on fat oxidation and blood lipids after a subsequent high-energy breakfast. We hypothesized that post-exercise skim milk consumption, compared to sports drink, would increase fat oxidation, and lower harmful blood lipid and glucose concentrations after a next day high-energy breakfast. In this randomized counterbalanced crossover trial, 20 overweight-obese participants (BMI ≥ 25 kg/m²) underwent 4 conditions: 90-min exercise (50% VO2peak) followed by sports drink (EX-HGI); exercise followed by isocaloric skim milk (EX-LGI); exercise followed by water (Exercise); a control condition. The amount of the sports drink or milk consumed post-exercise was based on the calories used during exercise plus 10%. Blood lipids, glucose and fat oxidation were assessed before and for 6 h after a high-energy breakfast the next morning. Fat oxidation was highest for EX-LGI (6.7 ± 2.7 g/h) and lowest for EX-HGI (6.0 ± 1.8 g/h) (condition main effect; P = .042). Triglyceride concentration and total area under the curve with EX-HGI was higher than Exercise (1.7 ± 1.6 vs. 1.3 ± 1.0 mmol/l, P = .037, and 11.7 ± 9.4 vs. 8.6 ± 6.0 mmol l⁻¹ h, P = .005, respectively). Glucose concentration with EX-LGI was lower than EX-HGI (4.1 ± 1.1 vs. 4.4 ± 1.1 mmol/l, P = .027). Homeostatic Model Assessment of Insulin Resistance was higher with EX-HGI than Control (2.32 ± 1.15 vs. 1.86 ± 0.97, P = .005). In conclusion, evening post-exercise skim milk consumption, compared with a high-GI sports drink, significantly reduced blood glucose and possibly increased fat oxidation after a high-energy breakfast the next morning.
Chapter
Lipids and lipoproteins play an important role in modulating risk of coronary heart disease (CHD). It is well established that elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) increase CHD risk. In contrast, elevated high-density lipoprotein cholesterol (HDL-C) exerts a cardioprotective effect. Thus, a greater ratio of TC to HDL-C (TC/HDL-C) indicates an increased CHD risk. Many epidemiologic and controlled clinical studies have demonstrated effects of single nutrients, specific foods, and dietary patterns, on lipids and lipoproteins. Diet can increase or decrease CHD risk via changes in the blood lipid profile as well as other risk factors (e.g., elevated blood pressure, inflammation, oxidative stress). This research has led to dietary recommendations that can markedly lower the risk of CHD. Consequently, a healthy diet is important in the prevention of CHD.
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American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice are systematically developed statements to assist health care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.
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We summarized existing evidence stemming from laboratory, clinical, and epidemiological studies regarding the differential association between low-fat or whole-fat dairy products and blood pressure control. We identified seven, large, prospective cohorts and one randomized trial that addressed the differential effect of low-fat versus whole-fat dairy products on blood pressure control or on the incidence of hypertension. An inverse association between low-fat dairy consumption and the risk of hypertension was found in most studies, whereas no risk reduction was observed for whole-fat dairy products. Several mechanisms might account for the blood-pressure-lowering effect of dairy products. The observed differential association may be attributable to the detrimental effect of saturated fat. In conclusion, low-fat dairy products but not whole-fat dairy products may contribute to improve blood pressure control and to reduce the incidence of hypertension.
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The occurrence and differences of resistant regions containing IgE-binding epitopes of αS1-casein (αS1-CN) variants B and C, as well as αS2-CN A and B, after in vitro gastrointestinal digestion was investigated using mass spectrometry. The amino acid substitutions characterising the genetic variants affected the peptide pattern arising from the caseins and thus modifications in their allergenic epitopes occurred. Peptides f174–193 in αS1-CN B and f179–198 in αS1-CN C correspond to the IgE-binding epitope f173–194, which has been reported as one of the major epitopes in αS1-CN B. Within αS2-CN, the two variant-specific peptides, f7–29 from variant A and f1–22 from variant B, contain the previously identified IgE-binding epitope f1–20. These peptides, and in consequence the protein variants, may exhibit different immunoreactions, which could be significant in the production of milk with improved nutritional properties, such as hypoallergenic quality, by selection and breeding of cows with particular milk protein genotypes.
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Dairy products are considered as nutrient-dense foods and consumed by many people in western countries, as well as an increasing number of Asian people. Excessive and frequent application of pesticides on vegetables and fruits leads to a potential health hazard to consumers. The organophosphate insecticide chlorpyrifos has been reported to bind with human and bovine serum albumin. Thus, it is necessary to explore the interaction between food protein and chlorpyrifos. In this study, equilibrium dialysis and fluorescence spectra were used to demonstrate binding of milk proteins to chlorpyrifos. The amount of milk protein bound was 0.03 ± 0.01 mg/g. Moreover, the milk protein-chlorpyrifos complexes were stable at pH 3.5 to 9.5 and ion concentrations from 0.1 to 1.0 M. The amount of chlorpyrifos bound to milk proteins decreased to 50% after being in vitro digested by pepsin and trypsin. The results showed that the interaction between food proteins and the pesticide might partially remove the insecticide and reduce the concentration of pesticide absorbed into the blood and, thus, alleviate the corresponding toxicity.
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The increase of obesity, which is confirmed by the latest studies, appears progressive and unrestrainable, reaching in the US a prevalence of 30% and more. In order to tackle this epidemy numerous measures - with either an educational or a punitive aim - often contradictory and largely ineffective yet, have been proposed and implemented. The reason of these failures is probably the complexity of hunger and satiety mechanisms of regulation, which are based on a complex gastrointestinal-brain-adipocytes axis, which involves many factors, including hormones such as ghrelin, leptin and insulin. An important preventive role is played by breakfast, often erroneously considered irrelevant if not entirely eliminated. Many studies have shown that the habit of skipping or reducing breakfast is associated with an increased risk of overweight. Right within Italian breakfast, milk and its derivatives (yogurt) play a particularly important role in preventing obesity, also possibly because of protein and amino acid consumption of milk. In this review the authors analyze the role of breakfast, as well as, the consumption of milk and dairy products on the prevention of overweight and obesity.
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To examine associations between milk consumption and incident heart disease and stroke. A representative population sample of men was asked to weigh and record their food intake for seven days. The total consumption of milk was obtained from these records. Details of all deaths and vascular events were collected during the following 20 years. Incident ischaemic strokes and heart disease events were diagnosed by standard criteria. The Caerphilly cohort, a representative population sample of men in South Wales, aged 45-59 when first seen in 1979-83. A representative 3:10 subsample of the men in the cohort. 665 men (87% of those approached) returned satisfactory seven day diet diaries. After adjustment, the relative odds of an event in the men whose milk consumption was the median or higher, relative to those with lower intakes of milk, were 0.52 (0.27 to 0.99) for an ischaemic stroke and 0.88 (0.56 to 1.40) for an ischaemic heart disease event. Deaths from all causes were similar in the two milk consumption groups (relative odds 1.08; 0.74 to 1.58). These results give no convincing evidence of an increased risk of vascular disease from milk drinking. Rather, the subjects who drank more than the median amount of milk had a reduced risk of an ischaemic stroke, and possibly a reduced risk of an ischaemic heart disease event. These conclusions are in agreement with the results of a previously reported overview of 10 large, long term cohort studies based on food frequency intake records.
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Although previous studies showed some benefits from dairy consumption with respect to obesity and insulin resistance syndrome, epidemiologic data on the association between dairy intakes and metabolic syndrome are sparse. The objective was to evaluate the relation between dairy consumption and metabolic syndrome in Tehranian adults. Dairy consumption and features of metabolic syndrome were assessed in a population-based cross-sectional study of 827 subjects (357 men and 470 women) aged 18-74 y. Metabolic syndrome was defined according to guidelines of the Adult Treatment Panel III. Multivariate logistic regression adjusted for lifestyle and nutritional confounders was used in 4 models. Mean (+/-SD) consumption of milk, yogurt, and cheese was 0.7 +/- 0.2, 1.06 +/- 0.6, and 0.9 +/- 0.3 servings/d, respectively. Subjects in the highest quartile of dairy consumption had lower odds of having enlarged waist circumference [odds ratio (OR) by quartile: 1, 0.89, 0.74, 0.63; P for trend < 0.001], hypertension (OR by quartile: 1, 0.88, 0.79, 0.71; P for trend < 0.02), and metabolic syndrome (OR by quartile: 1, 0.83, 0.74, 0.69; P for trend < 0.02). The values of ORs became weaker after further adjustment for calcium intake. Dairy consumption is inversely associated with the risk of having metabolic syndrome. It seems that this relation is somewhat attributed to calcium.
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To examine whether and to what extent intakes of calcium and vitamin D are related to the metabolic syndrome in middle-aged or older women. We analyzed data from 10,066 women aged > or =45 years participating in the Women's Health Study who were free of cardiovascular disease, cancer, or diabetes and who never used postmenopausal hormones. We used multiple logistic regression models to estimate multivariable odds ratios (ORs) and 95% CIs comparing different dietary intake levels of calcium and vitamin D. In age- and calorie-adjusted analyses, higher intakes of total, dietary, and supplemental calcium were significantly and inversely associated with the prevalence of metabolic syndrome. After further adjusting for smoking status, exercise, alcohol intake, multivitamin use, and parental history of myocardial infarction before age 60 years, the ORs of having the metabolic syndrome for increasing quintiles of total calcium intake were 1.00 (reference), 0.82 (95% CI 0.70-0.97), 0.84 (0.71-0.99), 0.70 (0.59-0.83), and 0.64 (0.54-0.77) (P for trend <0.0001). This association was not appreciably altered by additional adjustment for other dietary factors or total vitamin D intake. In contrast, neither total (P for trend = 0.13) nor supplemental (P for trend = 0.45) vitamin D was significantly associated with metabolic syndrome. Dietary vitamin D was inversely associated with prevalence of metabolic syndrome but was not independent of total calcium intake. Similar strong relations between intakes of dairy products and metabolic syndrome were also observed. After adjustment for lifestyle and dietary factors, the multivariable ORs comparing highest with lowest intake categories were 0.66 (0.55-0.80) (P for trend <0.0001) for total dairy products and 0.85 (0.71-1.02) (P for trend = 0.05) for total milk intake. Our results indicate that intakes of calcium and dairy products may be associated with lower prevalence of the metabolic syndrome in middle-aged and older women.
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The purpose of this study was to prospectively examine the association between vitamin D and calcium intake and risk of type 2 diabetes. In the Nurses' Health Study, we followed 83,779 women who had no history of diabetes, cardiovascular disease, or cancer at baseline for the development of type 2 diabetes. Vitamin D and calcium intake from diet and supplements was assessed every 2-4 years. During 20 years of follow-up, we documented 4,843 incident cases of type 2 diabetes. After adjusting for multiple potential confounders, there was no association between total vitamin D intake and type 2 diabetes. However, the relative risk (RR) of type 2 diabetes was 0.87 (95% CI 0.75-1.00; P for trend = 0.04) comparing the highest with the lowest category of vitamin D intake from supplements. The multivariate RRs of type 2 diabetes were 0.79 (0.70-0.90; P for trend <0.001) comparing the highest with the lowest category of calcium intake from all sources and 0.82 (0.72-0.92; P for trend <0.001) comparing the highest with the lowest category of calcium intake from supplements. A combined daily intake of >1,200 mg calcium and >800 IU vitamin D was associated with a 33% lower risk of type 2 diabetes with RR of 0.67 (0.49-0.90) compared with an intake of <600 mg and 400 IU calcium and vitamin D, respectively. The results of this large prospective study suggest a potential beneficial role for both vitamin D and calcium intake in reducing the risk of type 2 diabetes.
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Although studies have indicated that increased dairy intake may reduce risk of overweight and insulin resistance syndrome, data directly relating dairy intake to type 2 diabetes remain sparse. We prospectively examined the associations between intake of dairy foods and calcium and incident type 2 diabetes in 37,183 women without a history of diabetes, cardiovascular disease, and/or cancer at baseline. During an average of 10 years of follow-up, we documented 1,603 incident cases. After adjusting for potential confounders including BMI, smoking status, physical activity, family history of diabetes, alcohol consumption, history of hypertension, use of hormones, and high cholesterol, the relative risk for type 2 diabetes among women in the highest quintile of dairy intake was 0.79 (95% CI 0.67-0.94; P for trend = 0.007) compared with those in the lowest quintile. Each serving-per-day increase in dairy intake was associated with a 4% lower risk (0.96 [0.93-1.01]). The inverse association with type 2 diabetes appeared to be mainly attributed to low-fat dairy intake; the multivariate relative risks comparing the highest to the lowest quintiles was 0.79 (0.67-0.93; P for trend = 0.002) for low-fat dairy. The inverse relation between dairy intake and incident type 2 diabetes remained unchanged after further adjustment for dietary calcium, vitamin D, glycemic load, fat, fiber, and magnesium intake. These associations also did not vary significantly according to BMI. A dietary pattern that incorporates higher low-fat dairy products may lower the risk of type 2 diabetes in middle-aged or older women.
Article
Background: Although previous studies showed some benefits from dairy consumption with respect to obesity and insulin resistance syndrome, epidemiologic data on the association between dairy intakes and metabolic syndrome are sparse. Objective: The objective was to evaluate the relation between dairy consumption and metabolic syndrome in Tehranian adults. Design: Dairy consumption and features of metabolic syndrome were assessed in a population-based cross-sectional study of 827 subjects (357 men and 470 women) aged 18–74 y. Metabolic syndrome was defined according to guidelines of the Adult Treatment Panel III. Multivariate logistic regression adjusted for lifestyle and nutritional confounders was used in 4 models. Results: Mean (±SD) consumption of milk, yogurt, and cheese was 0.7 ± 0.2, 1.06 ± 0.6, and 0.9 ± 0.3 servings/d, respectively. Subjects in the highest quartile of dairy consumption had lower odds of having enlarged waist circumference [odds ratio (OR) by quartile: 1, 0.89, 0.74, 0.63; P for trend < 0.001], hypertension (OR by quartile: 1, 0.88, 0.79, 0.71; P for trend < 0.02), and metabolic syndrome (OR by quartile: 1, 0.83, 0.74, 0.69; P for trend < 0.02). The values of ORs became weaker after further adjustment for calcium intake. Conclusion: Dairy consumption is inversely associated with the risk of having metabolic syndrome. It seems that this relation is somewhat attributed to calcium.
Article
Objectives: To estimate the impact of small reductions in the population distribution of diastolic blood pressure (DBP), such as those potentially achievable by population-wide lifestyle modification, on incidence of coronary heart disease (CHD) and stroke. Design: Published data from the Framingham Heart Study, a longitudinal cohort study, and from the National Health and Nutrition Examination Survey II, a national population survey, were used to examine the impact of a population-wide strategy aimed at reducing DBP by an average of 2 mm Hg in a population including normotensive subjects. Setting/Participants: White men and women aged 35 to 64 years in the United States. Main Outcome Measures: Incidence of CHD and stroke, including transient ischemic attacks (TIAs). Results: Data from overviews of observational studies and randomized trials suggest that a 2—mm Hg reduction in DBP would result in a 17% decrease in the prevalence of hypertension as well as a 6% reduction in the risk of CHD and a 15% reduction in risk of stroke and TIAs. From an application of these results to US white men and women aged 35 to 64 years, it is estimated that a successful population intervention alone could reduce CHD incidence more than could medical treatment for all those with a DBP of 95 mm Hg or higher. It could prevent 84% of the number prevented by medical treatment for all those with a DBP of 90 mm Hg or higher. For stroke (including TIAs), a population-wide 2—mm Hg reduction could prevent 93% of events prevented by medical treatment for those with a DBP of 95 mm Hg or higher and 69% of events for treatment for those with a DBP of 90 mm Hg or higher. A combination strategy of both a population reduction in DBP and targeted medical intervention is most effective and could double or triple the impact of medical treatment alone. Adding a population-based intervention to existing levels of hypertension treatment could prevent an estimated additional 67 000 CHD events (6%) and 34 000 stroke and TIA events (13%) annually among all those aged 35 to 64 years in the United States. Conclusions: A small reduction of 2 mm Hg in DBP in the mean of the population distribution, in addition to medical treatment, could have a great public health impact on the number of CHD and stroke events prevented. Whether such DBP reductions can be achieved in the population through lifestyle interventions, in particular through sodium reduction, depends on the results of ongoing primary prevention trials as well as the cooperation of the food industry, government agencies, and health education professionals.(Arch Intern Med. 1995;155:701-709)
Article
Objective To determine the effects of dietary patterns on blood pressure in subgroups. Methods Dietary Approaches to Stop Hypertension (DASH) was a randomized controlled feeding study conducted at 4 academic medical centers. Participants were 459 adults with untreated systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. For 3 weeks, participants were fed a "control" diet. They were then randomized to 8 weeks of (1) control diet; (2) a diet rich in fruits and vegetables; or (3) a combination diet rich in fruits, vegetables, and low-fat dairy foods, and reduced in saturated fat, total fat, and cholesterol (the DASH combination diet). Weight and salt intake were held constant. Change in diastolic blood pressure was the primary outcome variable, and systolic blood pressure a secondary outcome. Subgroups analyzed included race, sex, age, body mass index, years of education, income, physical activity, alcohol intake, and hypertension status. Results The combination diet significantly lowered systolic blood pressure in all subgroups (P<.008), and significantly lowered diastolic blood pressure (P<.01) in all but 2 subgroups. The fruits-and-vegetables diet also reduced blood pressure in the same subgroups, but to a lesser extent. The combination diet lowered systolic blood pressure significantly more in African Americans (6.8 mm Hg) than in whites (3.0 mm Hg), and in hypertensive subjects (11.4 mm Hg) than in nonhypertensive subjects (3.4 mm Hg) (P<.05 for both interactions). Conclusions The DASH combination diet, without sodium reduction or weight loss, significantly lowered blood pressure in virtually all subgroups examined, and was particularly effective in African Americans and those with hypertension. The DASH combination diet may be an effective strategy for preventing and treating hypertension in a broad cross section of the population, including segments of the population at highest risk for blood pressure–related cardiovascular disease.
Article
Alterations in intracellular cation metabolism have been implicated in the pathophysiology of essential hypertension. Total magnesium, calcium, sodium and potassium levels were studied in serum erythrocytes and platelets, from 154 subjects (76 hypertensive and 78 normotensives; 104 blacks and 50 whites). In the combined black and white hypertensive group, platelet sodium and calcium and erythrocyte calcium were elevated and serum potassium, serum magnesium and platelet magnesium decreased. In the black hypertensive patients, platelet sodium and calcium and erythrocyte calcium were increased, whereas serum magnesium, serum potassium, platelet magnesium and erythrocyte magnesium were decreased. In the white hypertensive group, platelet sodium and erythrocyte calcium were raised and platelet magnesium was decreased. In the black hypertensive patients, serum and platelet magnesium and serum calcium were negatively and erythrocyte and platelet calcium positively correlated with mean arterial pressure. In the w...
Article
To assess the relationship between intracellular Mg2+, Ca2+, Na+ and K+ and cell membrane adenosine triphosphatase (ATPase) activity in normotensive and hypertensive blacks. Intracellular cations and cell membrane ATPase activity were studied in black patients with untreated essential hypertension and age-, weight- and height-matched normotensive controls. Platelet, erythrocyte and serum Mg2+, Ca2+, Na+ and K+ levels as well as platelet and erythrocyte membrane Na+,K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase activities were measured in all subjects. Intracellular Na+ and K+ were measured by flame photometry and Mg+ and Ca+ by atomic absorption spectrophotometry. Cell membrane ATPase activity was determined by a colorimetric method. The hypertensive group consistently demonstrated depressed activity of each ATPase studied, with significantly lower serum Mg2+, serum K+, erythrocyte Mg2+ and platelet Mg2+ levels compared with the normotensive group. Platelet Na+ and Ca2+ and erythrocyte Ca2+ were significantly elevated in the hypertensive group. In the hypertensive group, mean arterial pressure (MAP) was inversely correlated with platelet and erythrocyte membrane Na+,K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase. Serum Mg2+, serum Ca2+ and platelet Mg2+ were negatively correlated with MAP in the hypertensive group whilst erythrocyte and platelet Ca2+ were positively correlated. In the normotensive group, platelet Mg2+ and MAP were negatively, and erythrocyte Ca2+ and MAP, positively correlated. Black patients with essential hypertension have widespread depression of cell membrane Na+,K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase activities with serum and intracellular Mg2+ depletion and cytosolic Na+ and Ca2+ overload, which may reflect an underlying membrane abnormality in essential hypertension. These cellular abnormalities may be related to the defective transport mechanisms that in turn may be aggravated by Mg2+ depletion.
Alterations in intracellular cation metabolism have been implicated in the pathophysiology of essential hypertension. Total magnesium, calcium, sodium and potassium levels were studied in serum erythrocytes and platelets, from 154 subjects (76 hypertensive and 78 normotensives; 104 blacks and 50 whites). In the combined black and white hypertensive group, platelet sodium and calcium and erythrocyte calcium were elevated and serum potassium, serum magnesium and platelet magnesium decreased. In the black hypertensive patients, platelet sodium and calcium and erythrocyte calcium were increased, whereas serum magnesium, serum potassium, platelet magnesium and erythrocyte magnesium were decreased. In the white hypertensive group, platelet sodium and erythrocyte calcium were raised and platelet magnesium was decreased. In the black hypertensive patients, serum and platelet magnesium and serum calcium were negatively and erythrocyte and platelet calcium positively correlated with mean arterial pressure. In the white hypertensive patients platelet sodium was directly related to mean arterial pressure. These results suggest that intracellular sodium and calcium overload and magnesium depletion may be important in the pathophysiology of hypertension. Magnesium disturbances are more consistent and widespread in black hypertensive patients than in white hypertensive patients.
Article
The effect of consumption of 400 mg vs 1,500 mg of dietary calcium per day was examined in 13 male volunteers who had been diagnosed as hypertensive. Dietary calcium consumption was varied by manipulation of the intake of dairy products over 4-week periods. Caffeine intake (mean = 500 mg/day) was monitored. Neither laboratory blood pressure measured by standard sphygmomanometry nor ambulatory blood pressure monitored by automated sphygmomanometry varied significantly among men consuming baseline, low-calcium, or high-calcium diets (laboratory blood pressure = 136/83, 133/83, and 137/84 mm Hg, respectively; ambulatory blood pressure = 136/86, 138/87, and 138/87 mm Hg, respectively). Serum ionized calcium values did not vary with the three diets (1.25, 1.26, and 1.25 mmol/L, respectively). The parathyroid hormone level decreased (39 mmol/L vs 37 mmol/L) and the urinary calcium:creatinine ratio was elevated (0.41 vs 0.50) in the high-calcium diet. Consumption of a diet containing 1,500 mg calcium per day over 4 weeks did not produce a significant decrease in blood pressure or alterations in calcium metabolic indexes.
Article
To investigate the association of hypertension and insulin resistance, we utilized 31P-NMR spectroscopy to noninvasively assess intracellular free magnesium levels (Mgif) in erythrocytes of normotensive (n = 20) and essential hypertensive (n = 20) subjects given an oral 100 g glucose load. In hypertensive compared with normotensive subjects, fasting glucose and insulin levels were similar, but the integrated insulinemic responses to glucose were 45% greater (312 +/- 13.4 v 215 +/- 7.5 microU/mL, P less than .001). In hypertension, Mgif levels were significantly reduced (183 +/- 9 v 251 +/- 9 mumol/L, P less than .001), and for all subjects were closely and inversely related to systolic (r = -0.77, P less than .001) and diastolic (r = -0.81, P less than .001) blood pressures, and to the integrated insulin response (r = -0.72, P less than .001). Furthermore, while insulin responses were also related to the underlying systolic (r = 0.69, P less than .001) and diastolic (r = .73, P less than .001) pressures, these relations were no longer significant when adjusted for Mgif levels. We hypothesize that hypertension and peripheral insulin resistance may be different clinical expressions of a common abnormal intracellular ionic environment, characterized at least in part by suppressed levels of intracellular free magnesium.
Article
Plasma ionized calcium, platelet cytosolic calcium (using the fura-2 method in gel-filtered platelets), parathyroid hormone (both the intact hormone and a midmolecule portion), calcitriol, and calcidiol were measured in 19 untreated male patients with essential hypertension and 19 age-matched normotensive male research subjects. Mean levels of platelet cytosolic calcium, parathyroid hormone, calcitriol, and calcidiol were all significantly higher, whereas plasma ionized calcium was significantly lower, in the hypertensive group compared with the normotensive group. Both platelet cytosolic calcium and intact parathyroid hormone were positively correlated with mean arterial pressure (r = 0.58, p less than 0.001; r = 0.54, p less than 0.001, respectively), whereas plasma ionized calcium was inversely correlated with mean arterial pressure (r = -0.60, p less than 0.001) in the combined group of all study subjects. All three of these correlations were significant in the hypertensive group alone but not in the normotensive group alone. When analyzed with plasma ionized calcium, body mass index, serum calcitriol, and calcidiol in a multivariable regression model, the significance of the partial regressions of platelet cytosolic calcium and parathyroid hormone with mean arterial pressure persisted. Intact parathyroid hormone was positively correlated to platelet cytosolic calcium (r = 0.43, p less than 0.01) and plasma ionized calcium was inversely correlated to platelet cytosolic calcium (r = -0.44, p less than 0.01). These results confirm previous reports of disturbances of calcium metabolism in essential hypertension and suggest that the elevated platelet cytosolic calcium observed in essential hypertension may be linked to one or more of these alterations of calcium metabolism.
Article
In GH4C1 rat pituitary cells, 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] amplifies the TRH-induced spike phase of increase in cytosolic free calcium ([Ca2+]i). In the present report we describe the results of investigations on the mechanisms of action of 1,25-(OH)2D3 on Ca2+ homeostasis in these cells. Pretreatment with 1 nM 1,25-(OH)2D3 for at least 24 h caused no change in basal uptake of 45Ca2+ compared with that in control cells or in 45Ca2+ uptake induced by the calcium channel agonist Bay K 8644. However, when the cells were depolarized with 50 mM K+, 1,25-(OH)2D3-treated cells showed an up to 90% enhancement of uptake (3-120 min) of 45Ca2+. An enhanced increase in [Ca2+]i was also observed in fura-2-loaded cells. The effect was specific and dose dependent for 1,25-(OH)2D3. The calcium channel antagonists nimodipine and verapamil inhibited completely the enhancing action of 1,25-(OH)2D3 as did the protein synthesis inhibitor cycloheximide. No enhanced uptake of 45Ca2+ into intracellular stores was detected when cells were incubated with 1,25-(OH)2D3. Na+/Ca2+ exchange was determined by measuring exchange of extracellular 45Ca2+ for intracellular Na+. Na+/Ca2+ exchange was dependent on intracellular Na+, was inactive when Li+ replaced Na+, was insensitive to calcium channel antagonists, and showed electrogenic properties. In cells incubated with 1,25-(OH)2D3 for at least 24 h, Na+/Ca2+ exchange was enhanced up to 54% compared with that in control cells. Enhanced exchange was dose dependent and specific for 1,25-(OH)2D3. Ca2+ channel antagonists were without effect while dichlorobenzamil inhibited partially the 1,25-(OH)2D3 enhancement of Na+/Ca2+ exchange. Cycloheximide abolished completely the action of 1,25-(OH)2D3 on Na+/Ca2+ exchange. We conclude that in GH4C1 cells, 1,25-(OH)2D3 enhances membrane calcium transport by modulating voltage-operated Ca2+ channels and activating Na+/Ca2+ exchange by mechanisms requiring new protein synthesis.
Article
1. Fifty-two normotensive and essential hypertensive subjects were studied. Intracellular free calcium concentration ([Ca2+]i) was measured in lymphocytes (37 subjects) and platelets (18 subjects) by means of the fluorescent indicators, quin 2 and fura-2. In 31 subjects, plasma ionized calcium concentration was also measured. 2. There was a positive correlation between platelet [Ca2+]i and systolic blood pressure (r = 0.485, P < 0.05), diastolic blood pressure (r = 0.542, P < 0.02) and mean blood pressure (r = 0.534, P < 0.02). 3. No statistically significant relationship was observed between plasma ionized calcium and blood pressure. 4. No relationship was found between lymphocyte [Ca2+]i and blood pressure, or between lymphocyte [Ca2+]i and plasma ionized calcium. 5. There was no relationship between [Ca2+]i of lymphocytes and platelets measured simultaneously from the same subject. 6. These findings reconcile previous conflicting reports and show a relationship between platelet but not lymphocyte [Ca2+]i and blood pressure in man.
Article
The role of dietary salt and calcium on changes in cellular cation metabolism has been evaluated in 11 salt-sensitive hypertensive black adults maintained on the following four metabolic diets for 56 days, 14 days on each diet in a repeated measures format: 356 mg Ca-1000 mg sodium (NA); 356 mg Ca-4000 mg Na; 934 Ca-1000 mg Na; and 934 mg Ca-4000 mg Na. Increasing dietary Na at the lower Ca intake caused significant (P less than 0.05) increases in parathyroid hormone (PTH) and 24-hour cyclic AMP excretion that were associated with significant (P less than 0.01) increases in erythrocyte intracellular calcium (from 5.4 +/- 0.7 to 11.1 +/- 3.7 microM), Ca-ATPase (from 37.2 +/- 2.4 to 42.2 +/- 2.1 pmol/min/10(6) cells) and intracellular sodium (from 220.5 +/- 7.4 to 262.0 +/- 8.3 micrograms/mL) and decreases (P less than 0.05) in Na/K-ATPase (from 1.90 +/- 0.55 to 1.48 +/- 0.47 pmol/min/10(6) cells) and intracellular magnesium (Mg) (from 52.4 +/- 3.5 to 43.8 +/- 2.4 micrograms/mL). Adding calcium to this high sodium diet reversed these effects, whereas adding calcium to the low sodium diet was without significant effect. These results indicate that dietary salt causes increases in intracellular sodium and calcium and that the antihypertensive effect of dietary calcium in salt-sensitive individuals may be attributable in part to preventing this salt-induced elevation in intracellular calcium. This increase in intracellular calcium could be due to the observed increase in PTH levels or to the salt-induced reduction in intracellular magnesium that appears to suppress Na/K-ATPase and thereby increases intracellular sodium.
Article
Relationships between cytosolic free calcium ([Ca2+]i) in platelets, indices of systemic calcium metabolism and blood pressure were examined in 86 subjects; 29 patients with untreated and 29 patients with treated essential hypertension, six patients with borderline hypertension and 22 healthy reference subjects. In order to analyse interactions between the variables, multivariate statistical analyses were employed. The patients with untreated hypertension had higher [Ca2+]i values in non-activated platelets (P = 0.04) and lower levels of plasma ionized calcium (P = 0.02) than the reference subjects. In multivariate models analysing platelet [Ca2+]i mean blood pressure (MBP), plasma ionized calcium, serum parathyroid hormone (PTH) and body mass index (BMI), the relationship between platelet [Ca2+]i and blood pressure was attenuated (P = 0.13), whereas the inverse relationships between plasma ionized calcium and MBP (P = 0.01) and between platelet [Ca2+]i and serum PTH (P = 0.06) seen in univariate analyses persisted. According to the multivariate models the [Ca2+]i value explained only 5% of the MBP variability. Thus, the data from this investigation do not support a close relationship between basal platelet [Ca2+]i and blood pressure. The inverse relationship between plasma ionized calcium and blood pressure, independent of platelet [Ca2+]i and serum PTH, suggests a direct interaction between plasma ionized calcium and blood pressure regulation.
Article
The present report analyzes the relation between different categories of consumption of varied calcium-rich foods and blood pressure in a population sample of 5,049 Italian men and women aged 20-59, examined between November 1978 and May 1979. The consumption pattern of the various foods was estimated with the use of a food frequency questionnaire. The findings are consistent with an inverse association between whole milk consumption and systolic, but not diastolic, blood pressure. Daily consumption of cheese, on the other hand, is not associated with reduced blood pressure levels. The possibility of an adverse effect of the high saturated fats and sodium content on blood pressure that could counteract the beneficial effect of calcium is discussed. Daily skim milk consumption is surprisingly associated with higher systolic, but not diastolic, pressure, compared with infrequent consumption. The possibility of these findings being the result of pre-existing health problems leading to the selection of skim milk over whole milk is discussed. Daily consumption of legumes is associated with lower systolic pressure than infrequent consumption, but the differences do not reach statistical significance, probably because of limited statistical power. These associations are similar in both males and females.
Article
This review of epidemiological studies has several general implications. First, the most relevant population data for extrapolation in providing public health or medical advice should come from intra-population studies, either observational or interventional. Second, the observational studies require follow-up with long-term intervention trials in representative segments of the population before broad pronouncements are made. Third, not all people respond uniformly to changes in the intake of a single electrolyte, at the levels that can be safely achieved in our society. Finally, there are clear indications of useful directions in which to alter dietary electrolytes, either singly or multiply, but the most effective, safe and achievable combinations of dietary change remain to be defined and tested over prolonged periods in naturalistic settings.
Article
Intracellular free calcium has been implicated in vascular smooth-muscle contraction and in the pathophysiology of essential hypertension. We studied free-calcium levels in blood platelets, which have many features in common with vascular smooth-muscle cells. With use of an intracellularly trapped fluorescent dye, the free-calcium concentration in platelets was found to be elevated in 9 patients with borderline hypertension and 45 patients with established essential hypertension, who were compared with 38 normotensive subjects. There was a close correlation between the free-calcium level and both systolic and diastolic blood pressure (n = 92; r = 0.883 for systolic pressure and 0.931 for diastolic pressure; P less than 0.001 for both). Antihypertensive treatment with calcium-entry blockers (n = 15), beta-adrenoceptor blockers (n = 12), or a diuretic (n = 6) resulted in a reduction in free calcium, and this correlated with the fall in blood pressure (P less than 0.001). The intracellular free-calcium concentration in platelets may be determined by the same humoral or pharmacologic factors that determine the height of blood pressure.
Article
We studied the relation of plasma renin activity to serum levels of ionized calcium and magnesium in 102 normotensive patients and in 98 patients with essential hypertension who were divided into low-renin, normal-renin, and high-renin groups. Serum magnesium levels were higher in patients with low-renin hypertension and lower in patients with high-renin hypertension than in those with normal-renin hypertension (P less than 0.025 for both comparisons) or in normotensive controls (P less than 0.005, P less than 0.05, respectively). In contrast, serum levels of ionized calcium were lower in patients with low-renin hypertension and higher in patients with high-renin hypertension than in those with normal-renin hypertension (P less than 0.001, P less than 0.05, respectively) or in normotensive controls (P less than 0.001, P less than 0.05, respectively). Altogether, the range of plasma renin activity in essential hypertension shows a continuous negative correlation with the serum magnesium level (r = -0.60, P less than 0.001) and a positive correlation with the serum ionized calcium level (r = 0.44, P less than 0.001). Accordingly, plasma renin activity in hypertension may reflect or contribute to changes in calcium and magnesium fluxes across cell membranes.
Article
The baseline observations in the Puerto Rico Heart Health Program during 1965-1968 involved blood pressure determinations, other measurements, and a 24-hour dietary recall in 7932 men aged 45-64 years. This extensive data base provided an opportunity to test the hypothesis that low calcium intake is related to increased blood pressure level. Among men without baseline coronary heart disease and not taking antihypertensive medication, there was an inverse relationship between milk consumption and definite hypertension in urban Puerto Rican men and older rural men. When data from all age and area groups had been averaged, a twofold increase in hypertension was found in subgroups who drank no milk compared to those who consumed over 1 quart of milk a day. Similar trends were found when an estimate of total calcium intake from food, principally from milk, was used. With multivariate analysis while known correlates of blood pressure were simultaneously considered, an independent effect persisted between milk consumption and blood pressure. These results appeared to confirm an inverse association between calcium and hypertension. It was still not possible to ascribe a causal relationship between calcium and blood pressure, however, due to the intricate network of covarying food intakes, the factors related to absorption or lack of absorption of calcium, and the possible role that unmeasured social and cultural factors may play in the observed relations.
Article
A data base of the National Center for Health Statistics, Health and Nutrition Examination Survey I (HANES I), was used to perform a computer-assisted, comprehensive analysis of the relation of 17 nutrients to the blood pressure profile of adult Americans. Subjects were 10,372 individuals, 18 to 74 years of age, who denied a history of hypertension and intentional modification of their diet. Significant decreases in the consumption of calcium, potassium, vitamin A, and vitamin C were identified as the nutritional factors that distinguished hypertensive from normotensive subjects. Lower calcium intake was the most consistent factor in hypertensive individuals. Across the population, higher intakes of calcium, potassium, and sodium were associated with lower mean systolic blood pressure and lower absolute risk of hypertension. Increments of dietary calcium were also negatively correlated with body mass. Even though these correlations cannot be accepted as proof of causation, they have implications for future studies of the association of nutritional factors and dietary patterns with hypertension in America.
Article
To compare the blood pressure responses of men with hypertension consuming low-sodium (Na) metabolic diets differing in dietary calcium (Ca) for two 6-week periods. White men who had hypertension, were nonsmokers, and were sedentary. This study consisted of two separate 6-week metabolic feeding periods. In the first period, a high-Ca group (n = 6) was fed 1,400 mg Ca per day. In the second period, a low-Ca group (n = 5) was fed 400 mg Ca per day. Both groups were fed 1,500 mg Na per day. Blood pressure; urine and blood measured for electrolyte, calcitriol, renin, and parathyroid hormone (PTH) levels. To measure typical nutrient intakes, 3-day dietary records were collected before the beginning of each treatment period. Repeated-measures analysis of variance and split-plot analysis of variance were used to analyze, respectively, blood pressure responses and response variables over time. In both groups, serum Na level decreased (P < .05) over the 6-week period; urine Na decreased (P < .05) only in the low-Ca group. Serum PTH level decreased (P < .05) in the high-Ca group and increased (P < .05) in the low-Ca group; no change occurred in serum calcitriol level. Diastolic blood pressure decreased (8 mm Hg) in the low-Ca group (P < .05). The low-Ca group showed an 8% to 9% decrease in both systolic and diastolic blood pressure vs a 2% to 3% decrease in the high-Ca group. We also examined how the metabolic diet differed from subjects' typical diet. Results showed a positive correlation between the change in Na intake (usual to metabolic diet) and the change in systolic and diastolic blood pressure in both groups (P < .04). Results also showed a negative correlation between the change in the ratio of Na to Ca (usual to metabolic diet) and the change in diastolic blood pressure in the low-Ca group (P < .03). Directional change in blood pressure (either increase or decrease) could be predicted on the basis of how much the Na and Ca in the metabolic diet differed from subject's typical diet. Results of this study suggest that in the dietary management of hypertension it may be more important to focus on specific changes in a person's diet (eg, decreasing Na intake by 1,000 mg/day and increasing Ca intake by 400 mg/day) rather than setting specific levels of Na and Ca to be consumed.
Article
To estimate the impact of small reductions in the population distribution of diastolic blood pressure (DBP), such as those potentially achievable by population-wide lifestyle modification, on incidence of coronary heart disease (CHD) and stroke. Published data from the Framingham Heart Study, a longitudinal cohort study, and from the National Health and Nutrition Examination Survey II, a national population survey, were used to examine the impact of a population-wide strategy aimed at reducing DBP by an average of 2 mm Hg in a population including normotensive subjects. White men and women aged 35 to 64 years in the United States. Incidence of CHD and stroke, including transient ischemic attacks (TIAs). Data from overviews of observational studies and randomized trials suggest that a 2-mm Hg reduction in DBP would result in a 17% decrease in the prevalence of hypertension as well as a 6% reduction in the risk of CHD and a 15% reduction in risk of stroke and TIAs. From an application of these results to US white men and women aged 35 to 64 years, it is estimated that a successful population intervention alone could reduce CHD incidence more than could medical treatment for all those with a DBP of 95 mm Hg or higher. It could prevent 84% of the number prevented by medical treatment for all those with a DBP of 90 mm Hg or higher. For stroke (including TIAs), a population-wide 2-mm Hg reduction could prevent 93% of events prevented by medical treatment for those with a DBP of 95 mm Hg or higher and 69% of events for treatment for those with a DBP of 90 mm Hg or higher. A combination strategy of both a population reduction in DBP and targeted medical intervention is most effective and could double or triple the impact of medical treatment alone. Adding a population-based intervention to existing levels of hypertension treatment could prevent an estimated additional 67,000 CHD events (6%) and 34,000 stroke and TIA events (13%) annually among all those aged 35 to 64 years in the United States. A small reduction of 2 mm Hg in DBP in the mean of the population distribution, in addition to medical treatment, could have a great public health impact on the number of CHD and stroke events prevented. Whether such DBP reductions can be achieved in the population through lifestyle interventions, in particular through sodium reduction, depends on the results of ongoing primary prevention trials as well as the cooperation of the food industry, government agencies, and health education professionals.
Article
Vascular smooth muscle tone is regulated primarily by the sarcoplasmic free Ca2+ concentration, which determines the level of myosin phosphorylation. Stimulation of the muscle results in an increase in free [Ca2+], whereupon Ca2+ binds to calmodulin, inducing a conformational change enabling calmodulin to interact with and activate myosin light chain kinase. The active Ca2+.calmodulin.myosin light chain kinase complex catalyses the phosphorylation of serine-19 of the two 20-kDa light chains of myosin; this triggers cross-bridge cycling and the development of force. Relaxation follows restoration of free [Ca2+] to the resting level, whereupon calmodulin dissociates from myosin light chain kinase, which is thereby inactivated, and myosin is dephosphorylated by myosin light chain phosphatase and remains detached from actin. Overwhelming evidence now exists in favour of the central role of myosin phosphorylation-dephosphorylation in smooth muscle contraction-relaxation. However, considerable evidence supports the existence of additional, secondary mechanisms that can modulate the contractile state of smooth muscle either by altering the Ca2+ sensitivity of the contractile response or otherwise modulating one of the molecular events occurring downstream of the Ca2+ signal, e.g., the interaction of phosphorylated myosin heads with actin. The interplay of several regulatory elements confers on the contractile response of vascular smooth muscle the high degree of flexibility and adaptability required for the effective regulation of blood pressure.
Article
Clinical and in vitro evidence suggests a role for the calcium regulating hormone, 1,25-dihydroxyvitamin D (1,25D) in human and experimental hypertension. To establish the cellular basis for this association, we utilized the whole-cell version of the patch clamp method and fluorescence spectroscopic techniques to measure voltage-dependent calcium channel activity and cytosolic free calcium concentrations ([Ca2+]i) in rat tail artery-derived smooth muscle cells, before and after the addition of 1,25D. 1,25D significantly increased the calcium channel current over the range of test pulses, from -40 to +60 mV, in a dose- and time-dependent manner, appearing by 5 to 10 min of exposure, with maximum effects by 15 min. At 10 and 30 nmol/L, the current increased to 149 +/- 10% and 221 +/- 13% of basal activity of 37.75 +/- 7.7 pA and 37.7 +/- 4.5 pA, respectively. Similarly, at 10 and 100 nmol/L, 1,25D increased cytosolic free calcium levels 115 +/- 2% and 171 +/- 11%, from basal values of 99 +/- 32 nmol/L and 116 +/- 10 nmol/L, respectively. These effects of [Ca2+]i developed slowly over 3 to 4 min. Peak values were achieved by 30 min of incubation and were reversible with removal of 1,25D from the medium. Altogether, these direct effects of 1,25D on calcium current and [Ca2+]i in vascular smooth muscle cells support a role for 1,25D in vascular physiology, and provide a cellular basis for better understanding the involvement of 1,25D in hypertensive vascular disease.
Article
A double-blind, placebo-controlled parallel-group study was conducted on the effect of a high level of daily oral calcium supplementation (1 g elemental calcium given twice a day for 16 weeks) in normal male subjects on blood pressure, intracellular cationic concentrations and transmembrane cation transport systems, plasma total and ionized calcium, and calciotropic hormones. After a 1-month run-in period with a limited intake of dairy products, the 32 subjects were allocated to a placebo or a calcium group. Placebo or 1 g elemental calcium was administered twice a day, in the morning and evening, for 16 weeks. All subjects were investigated at baseline and after 1, 2, 4, 8 and 16 weeks of placebo or calcium administration. Compared with the placebo group, standing systolic blood pressure was decreased in the calcium group, whereas the standing diastolic blood pressure tended to decrease. The changes in supine systolic and diastolic blood pressure did not differ between the placebo and calcium groups. Decreased intra-erythrocyte and intraplatelet sodium and calcium concentrations, an increased activity of platelet and erythrocyte sodium-pump activity and a reduced membrane cholesterol content were observed in the calcium-treated subjects. Erythrocyte membrane surface and core microviscosity, however, did not change during calcium supplementation. Oral calcium supplementation in these men was accompanied by a reduction in the plasma concentrations of intact parathormone and 1,25-dihydroxyvitamin D3, and an increase in 24 h urinary calcium excretion, but no change in the plasma total calcium concentration, serum ionized calcium level, or plasma phosphate or 25-hydroxyvitamin D3. The intra-erythrocyte and intraplatelet potassium and magnesium concentrations as well as the activities of the erythrocyte Na,Li-countertransporter and Na,K-cotransporter, and sodium and potassium leakage did not change during calcium administration. The lowering of standing blood pressure seen in men with a high calcium intake is accompanied by a decrease in cytosolic free platelet calcium and total erythrocyte calcium, by a reduction in intraplatelet and intra-erythrocyte sodium concentration and erythrocyte membrane cholesterol and by an increase in the activity of the erythrocyte and platelet sodium-pump.
Article
Evidence suggests that dietary calcium is protective against hypertension. This report examines whether the effect has an influence on thromboembolic stroke. Since 1965, the Honolulu Heart Program has followed a cohort of men in a study of cardiovascular disease. This report examines the effect of baseline dietary calcium and milk intake on stroke risk in 22 years of follow-up in 3150 older middle-aged men (55 to 68 years). Men who were nondrinkers of milk experienced stroke at twice the rate (P < .05) of men who consumed 16 oz/d or more (7.9 versus 3.7 per 100, respectively). While the rate of stroke decreased with increasing milk intake (P < .05), the decline in stroke risk with increased consumption was modest for those who consumed under 16 oz/d. Intake of dietary calcium was also associated with a reduced risk of stroke (P < .01), although its association was confounded with milk consumption. Calcium intake from nondairy sources was not related to stroke, suggesting that other constituents or covariates related to milk consumption may be important. We conclude that an association between milk consumption and a reduced risk of stroke in older middle-aged men cannot be explained by intake of dietary calcium. Since milk is often part of a diverse pattern of dietary intake, it is difficult to determine whether milk consumption has a direct role in reducing the risk of stroke. Data suggest that consumption of milk in older middle age is not harmful, and when combined with a balanced diet, weight control, and physical activity, reductions in the risk of stroke may occur.
Article
We evaluated the effect of oral calcium supplementation on blood pressure, calcium metabolism, and insulin resistance in essential hypertension. After receiving a standard diet with 500 mg of calcium per day during a 4-week period, 20 nondiabetic, essential hypertensive patients were randomized in a double-blind fashion to receive oral calcium supplementation (1500 mg of calcium per day) or placebo for 8 weeks. At the end of the 4-week period of low-calcium diet and after the 8-week period of intervention, we measured blood pressure (by both office and 24-hour ambulatory blood pressure monitoring), calcium-regulating hormones [urinary hydroxyproline and serum osteocalcin, parathormone, and 1,25(OH)2-vitamin D3], intraplatelet free calcium concentration, fasting plasma glucose and insulin levels, and the insulin-sensitivity index (euglycemic-hyperinsulinemic clamp). Compared with patients maintained at low calcium intake, essential hypertensive patients under oral calcium supplementation significantly reduced serum osteocalcin (from 22.2 +/- 1.9 to 17.9 +/- 2.0 micrograms/L; P = .0015), parathormone (from 4.20 +/- 0.38 to 3.30 +/- 0.36 pmol/L; P = .0003), and 1,25(OH)2-vitamin D3 (from 98.0 +/- 11.0 to 61.6 +/- 5.7 pmol/L; P = .0062). Likewise, we found a significant reduction in intraplatelet free calcium concentration (from 35.9 +/- 1.2 to 26.5 +/- 0.8 nmol/L; P = .0005) and fasting plasma insulin levels (from 71.8 +/- 5.9 to 64.6 +/- 6.2 pmol/L; P = .05) and a significant increase in the insulin-sensitivity index (from 2.89 +/- 0.77 to 4.00 +/- 0.95 mg.kg-1.min-1; P = .0007). None of these parameters were significantly modified in patients maintained at low calcium intake. Office and 24-hour mean values of systolic and diastolic blood pressure did not change after 8 weeks of oral calcium supplementation or placebo.
Article
It is known that obesity, sodium intake, and alcohol consumption factors influence blood pressure. In this clinical trial, Dietary Approaches to Stop Hypertension, we assessed the effects of dietary patterns on blood pressure. We enrolled 459 adults with systolic blood pressures of less than 160 mm Hg and diastolic blood pressures of 80 to 95 mm Hg. For three weeks, the subjects were fed a control diet that was low in fruits, vegetables, and dairy products, with a fat content typical of the average diet in the United States. They were then randomly assigned to receive for eight weeks the control diet, a diet rich in fruits and vegetables, or a "combination" diet rich in fruits, vegetables, and low-fat dairy products and with reduced saturated and total fat. Sodium intake and body weight were maintained at constant levels. At base line, the mean (+/-SD) systolic and diastolic blood pressures were 131.3+/-10.8 mm Hg and 84.7+/-4.7 mm Hg, respectively. The combination diet reduced systolic and diastolic blood pressure by 5.5 and 3.0 mm Hg more, respectively, than the control diet (P<0.001 for each); the fruits-and-vegetables diet reduced systolic blood pressure by 2.8 mm Hg more (P<0.001) and diastolic blood pressure by 1.1 mm Hg more than the control diet (P=0.07). Among the 133 subjects with hypertension (systolic pressure, > or =140 mm Hg; diastolic pressure, > or =90 mm Hg; or both), the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mm Hg more, respectively, than the control diet (P<0.001 for each); among the 326 subjects without hypertension, the corresponding reductions were 3.5 mm Hg (P<0.001) and 2.1 mm Hg (P=0.003). A diet rich in fruits, vegetables, and low-fat dairy foods and with reduced saturated and total fat can substantially lower blood pressure. This diet offers an additional nutritional approach to preventing and treating hypertension.
Article
Ageing in industrialised societies is associated with an increasing prevalence of hypertension, atherosclerotic vascular diseases, reduced insulin sensitivity and non-insulin-dependent diabetes mellitus (NIDDM). It has been suggested that hyperinsulinaemia/insulin resistance and/or hyperglycaemia could play a role in determining and/or exacerbating the hypertension and vascular disease associated with diabetes mellitus and ageing. Insulin-resistant states, such as essential hypertension and NIDDM, as well as "normal" ageing, are characterised by similar intracellular ionic defects, i.e. accumulation of cytosolic free calcium and depletion of free magnesium. The importance of calcium and magnesium ions in regulating cell functions is well-known. A rise in cellular free calcium and a depletion in cellular magnesium may induce cellular insulin resistance and vasoconstriction. Ionic levels quantitatively predict the extent of elevated blood pressure, fasting blood glucose, HBA1c and hyperinsulinaemic response to oral glucose challenge. We suggest that ionic disturbance might be the missing link responsible for the frequent clinical coexistence of hypertension, atherosclerosis and metabolic disorders. Ageing cells may become more vulnerable to ion disturbances, leading to possible elevation of intracellular free calcium and concurrent magnesium depletion. The "ionic hypothesis" of ageing supposes that an alteration in the cellular mechanisms which maintain the homeostasis of cytosolic calcium concentrations may play a key role in the ageing process, and that a sustained accumulation of cellular calcium and/or the depletion of cellular magnesium may also provide the final common pathway for many ageing-associated diseases, including hypertension and NIDDM.
Article
To test the hypothesis that abnormal platelet Ca2+ handling in essential hypertension results from cellular Mg2+ deficiency, cytosolic free Mg2+ concentration ([Mg2+]i) and Ca2+ metabolism were studied in mag-fura 2 and fura 2-loaded platelets from 30 essential hypertensive patients and 30 sex- and age-matched normotensive controls. Basal cytosolic free Ca2+ concentration ([Ca2+]i) and intracellular Ca2+ discharge capacity were higher in hypertensives than in normotensives (22 +/- 5 vs. 18 +/- 5 nM, P < 0.05; 743 +/- 250 vs. 624 +/- 144 nM, P < 0.05, respectively). The thrombin (0. 03-1.0 U/ml)-evoked [Ca2+]i response was also enhanced in platelets from hypertensives in both the absence and presence of extracellular Ca2+. However, basal [Mg2+]i was higher in hypertensives than in normotensives (437 +/- 110 vs. 353 +/- 85 microM, P < 0.05), whereas serum Mg2+ was similar in the two groups. These results oppose the Mg2+ deficiency hypothesis in platelets in essential hypertension.
Article
To determine the effects of dietary patterns on blood pressure in subgroups. Dietary Approaches to Stop Hypertension (DASH) was a randomized controlled feeding study conducted at 4 academic medical centers. Participants were 459 adults with untreated systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. For 3 weeks, participants were fed a "control" diet. They were then randomized to 8 weeks of (1) control diet; (2) a diet rich in fruits and vegetables; or (3) a combination diet rich in fruits, vegetables, and low-fat dairy foods, and reduced in saturated fat, total fat, and cholesterol (the DASH combination diet). Weight and salt intake were held constant. Change in diastolic blood pressure was the primary outcome variable, and systolic blood pressure a secondary outcome. Subgroups analyzed included race, sex, age, body mass index, years of education, income, physical activity, alcohol intake, and hypertension status. The combination diet significantly lowered systolic blood pressure in all subgroups (P<.008), and significantly lowered diastolic blood pressure (P<.01) in all but 2 subgroups. The fruits-and-vegetables diet also reduced blood pressure in the same subgroups, but to a lesser extent. The combination diet lowered systolic blood pressure significantly more in African Americans (6.8 mm Hg) than in whites (3.0 mm Hg), and in hypertensive subjects (11.4 mm Hg) than in nonhypertensive subjects (3.4 mm Hg) (P<.05 for both interactions). The DASH combination diet, without sodium reduction or weight loss, significantly lowered blood pressure in virtually all subgroups examined, and was particularly effective in African Americans and those with hypertension. The DASH combination diet may be an effective strategy for preventing and treating hypertension in a broad cross section of the population, including segments of the population at highest risk for blood pressure-related cardiovascular disease.
Article
Calcitriol, the active metabolite of vitamin D, is a steroid hormone that regulates calcium metabolism and cell differentiation by interacting with its nuclear receptor--the vitamin D receptor (VDR)--and by stimulating gene transcription. During the last decade, calcitriol also has been shown to stimulate rapid signal transduction pathways. This observation supports the hypothesis that a membrane-bound receptor similar to those that mediate peptide hormone biology exists. Recent research provides evidence for such a unique membrane VDR. Future research challenges are to integrate the membrane VDR into existing knowledge of vitamin D biology.
Article
The typical American diet includes high salt and low potassium, a pattern linked to elevated blood pressure (BP) in cross-cultural studies. This study compared resting and stress cardiovascular responses on a high salt, low potassium diet to those observed during 2 interventions: salt restriction and potassium supplementation. Forty-seven percent of the primarily normotensive sample (n = 67 adults) were salt sensitive, showing a decrease in mean arterial pressure > or = 5 mmHg during low salt and equivalent reductions during high potassium. The equivalent benefits of the interventions were maintained, but not enhanced, during exposure to behavioral stress (i.e., no effect on reactivity). Salt resistants (SRs) exhibited no change in resting or stress BP across the diets. High salt increased cardiac index in both groups, whereas vascular tone was decreased only in the SR group. High potassium produced hemodynamic benefits similar to low salt, even with continued high salt intake.
Article
Two central concepts of human hypertensive disease remain poorly understood: (1) elevated blood pressure as merely one component of an underlying systemic condition, characterized by multiple defects in diverse tissues (eg, "Syndrome X"), and (2) the heterogeneity of hypertension, in which different and even opposite clinical responses to different dietary and drug therapies are routinely observed among equally hypertensive subjects. To help explain these clinical phenomena, a unifying "ionic hypothesis" is proposed, in which steady-state elevations of cytosolic free calcium and suppressed intracellular free magnesium levels, characteristic features of all hypertension, concomitantly alter the function of many tissues. In blood vessels this causes vasoconstriction, arterial stiffness, and/or hypertension; in the heart, cardiac hypertrophy; in platelets, increased aggregation and thrombosis; in fat and skeletal muscle, insulin resistance; in pancreatic beta cells, other endocrine tissues, and sympathetic neurons, potentiated stimulus-secretion coupling resulting in hyperinsulinemia, increased sympathetic nerve activity, and so on. Furthermore, an analysis of cellular biochemical, dietary-nutrient, and hormonal factors that normally regulate steady-state levels of these intracellular ions suggests an ionic equivalent to Laragh's volume-vasoconstriction analysis of hypertension. This provides a cellular-based explanation for the heterogeneity of hypertension and a rational basis for individualizing dietary and drug recommendations among different hypertensive subjects.
Article
A double blind, placebo-controlled, parallel study was conducted on the effect of a high daily oral calcium supplementation of 1 g elemental calcium, given twice daily for 16 weeks in normal male subjects, on plasma renin, aldosterone, kallikrein, cGMP, cAMP, and calciotropic hormones, intracellular calcium concentrations, and plasma total and ionized calcium. After a 1-month run-in period on a limited use of dairy products, the subjects (n = 32) were allocated to a placebo or a calcium group. Placebo or 1 g elemental calcium was administered twice daily in the morning and evening for 16 weeks. All subjects were investigated at baseline and after 1, 2, 4, 8, and 16 weeks of placebo or calcium administration. A decreased intraerythrocyte and intraplatelet Ca²⁺ concentration was observed in the calcium-treated subjects. Compared with the placebo group, an increase in the plasma renin activity (PRA) in the calcium group was observed after 4, 8, and 16 weeks of oral calcium administration. However, plasma aldosterone and urinary excretion of aldosterone, kallikrein, cGMP, and cAMP were not changed during calcium administration. Oral calcium supplementation in these men was also accompanied by a reduction in the plasma concentration of intact parathyroid hormone and 1,25-dihydroxyvitamin D3, and an increase in 24-h urinary calcium excretion, but no change in the plasma total Ca²⁺ concentration, serum ionized Ca²⁺ level, and plasma phosphate or 25-hydroxyvitamin D3.Our data show that the increase in PRA observed in men during oral calcium supplementation is accompanied by a reduction in the intracellular free and total Ca²⁺ concentration in platelets and erythrocytes and by a decrease in the plasma concentration of intact parathormone and 1,25-dihydroxyvitamin D3. Am J Hypertens 1999;12:1217–1224 © 1999 American Journal of Hypertension, Ltd.
Article
To determine the impact of dietary patterns on the control of hypertension we studied the subgroup of 133 participants with systolic blood pressure (BP) of 140 to 159 mm Hg and/or diastolic BP of 90 to 95 mm Hg enrolled in the Dietary Approaches to Stop Hypertension (DASH) study. Participants were fed a control diet for a 3-week period and were then randomized to receive for 8 weeks either the control diet; a diet rich in fruits and vegetables, but otherwise similar to control; or a combination diet rich in fruits, vegetables, and low-fat dairy products, including whole grains, fish, poultry, and nuts, and reduced in fats, red meats, sweets, and sugar-containing beverages. Sodium intake and body weight were held constant throughout the study. The combination diet significantly reduced systolic BP (11.4 mm Hg, P < .001) and diastolic BP (−5.5 mm Hg, P < .001). The fruits-and-vegetables diet also significantly reduced systolic BP (−7.2 mm Hg, P < .001) and diastolic BP (−2.8 mm Hg, P = .013). The combination diet produced significantly greater BP effects (P < .05) than the fruits-and-vegetables diet. Blood pressure changes were evident within 2 weeks of starting the intervention feeding. After the 8-week intervention period, 70% of participants eating the combination diet had a normal BP (systolic BP < 140 and diastolic BP < 90 mm Hg) compared with 45% on the fruits-and-vegetables diet and 23% on the control diet. In patients with hypertension, the DASH combination diet effectively lowers BP and may be useful in achieving control of Stage 1 hypertension.
Article
Diet and lifestyle modifications can substantially reduce the risk of type 2 diabetes. While a strong inverse association has been reported between dairy consumption and the insulin resistance syndrome among young obese adults, the relation between dairy intake and type 2 diabetes is unknown. We prospectively examined the relation between dairy intake and incident cases of type 2 diabetes in 41,254 male participants with no history of diabetes, cardiovascular disease, and cancer at baseline in the Health Professionals Follow-up Study. During 12 years of follow-up, we documented 1243 incident cases of type 2 diabetes. Dairy intake was associated with a modestly lower risk of type 2 diabetes. After adjusting for potential confounders, including body mass index, physical activity, and dietary factors, the relative risk for type 2 diabetes in men in the top quintile of dairy intake was 0.77 (95% confidence interval [CI], 0.62-0.95; P for trend, .003) compared with those in the lowest quintile. Each serving-per-day increase in total dairy intake was associated with a 9% lower risk for type 2 diabetes (multivariate relative risk, 0.91; 95% CI, 0.85-0.97). The corresponding relative risk was 0.88 (95% CI, 0.81-0.94) for low-fat dairy intake and 0.99 (95% CI, 0.91-1.07) for high-fat dairy intake. The association did not vary significantly according to body mass index (< 25 vs > or = 25 kg/m(2); P for interaction, .57). Dietary patterns characterized by higher dairy intake, especially low-fat dairy intake, may lower the risk of type 2 diabetes in men.
Article
Previous studies have shown a potential inverse relationship between blood pressure and daily calcium intake. The aim of the study was to assess the independent contribution of dairy product and calcium intake to blood pressure variations at a population level. A sample of 912 men aged 45-64 years was randomly selected from the general population, as part of the French MONICA cross-sectional survey on cardiovascular risk factors (1995-1996). Extensive questionnaires on risk factors were filled out and each participant completed a three-consecutive-day food record. Two blood pressure measurements were performed at rest. In statistical analyses subjects were grouped according to quintiles of dairy product or calcium intakes. Systolic and diastolic blood pressures significantly decreased from the lowest [145.4 (standard error (SE) 1.55) and 89.0 (SE 0.94) mmHg respectively] to the highest quintile [135.6 (SE 1.26) and 85.3 (SE 0.84) mmHg respectively] of dairy product intakes in bivariate analysis. After multivariate linear regression analysis adjusted for confounders [centre, age, daily sodium, magnesium, calcium and alcohol intake, daily energy intake without alcohol, dieting, physical activity, body mass index (BMI), smoking, and use of antihypertensive or lipid-lowering drugs], the difference in systolic blood pressure remained significant. Results were similar when calcium intake was considered. After adjustment for confounders, the association between calcium-dairy product combination and blood pressure was the most significant when intakes of dairy products and calcium were both higher than the median. Dairy products and dietary calcium are both significantly and independently associated with low levels of systolic blood pressure.