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Food Science and Human Nutrition, Washington State University, Spokane, WA 99201-3899
 |
ABSTRACT |
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KEY WORDS: • dairy products • blood pressure • stroke • cardiovascular disease • calcium • potassium • magnesium
|
INTRODUCTION |
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. Strokes account for 17% of cardiovascular disease
(CVD),3
and rates of death are 35% higher in blacks than whites
(2)
. The majority of strokes can be classified as
ischemic, in which tissue damage or death is caused by blockage of the
blood supply to the brain by emboli. The clots may break off from
atherosclerotic plaques and often block arteries occluded by plaques. A
much smaller proportion of strokes are hemorrhagic in origin; here,
blood vessels leak blood into either the subdural space or into
tissues, putting pressure on cells and eventually causing them to
malfunction or die.
The National Stroke Association (3)
and American Heart
Association guidelines (4)
for the prevention of a first
stroke identify 10 important stroke risk factors, six medical
(hypertension, myocardial infarction, atrial fibrillation, diabetes,
blood lipids and asymptomatic carotid artery disease) and four
lifestyle (smoking, excessive alcohol use, physical inactivity and poor
diet). Although the risk factors vary in strength for the two types of
strokes, they all contribute to risk for any type of stroke.
Consumption of milk, or of calcium (Ca), potassium (K) and magnesium
(Mg), the three minerals found in large quantities in milk, affects at
least four of these 10 factors in beneficial directions, i.e., blood
pressure (BP), insulin resistance, platelet aggregation and
atherosclerotic processes.
|
Dairy Foods and Stroke. |
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in the Honolulu Heart Program reported that men of Japanese ancestry
aged 55–68 y at baseline who were nondrinkers of milk experienced
thromboembolic stroke at twice the rate of men who consumed two or more
240-mL glasses of milk per day (7.9 vs. 3.7 cases per 100,
respectively) in 22 y of follow-up. Although intake of total
dietary Ca was associated with a reduced risk of stroke, Ca intake from
nondairy sources was not related to stroke. These findings suggest that
other constituents of milk, possibly K, may be important in addition to
Ca. Men in the highest Ca quartile had a 783 mg greater intake of
dietary K than men in the lowest quintile. The 480 mL of milk that was
reported to be protective contains 740 mg K. Mg intake was not
assessed.
The second study, by Iso et al. (6)
found in the Nurses’
Health Study that intakes of three minerals abundant in milk, Ca, K and
Mg, were each associated with reduced relative risk (RR) of ischemic
stroke, but not with other types of stroke. Age- and
smoking-adjusted RR and 95% confidence interval for the highest
quintile were Ca [0.72 (0.53–0.98), P < 0.04],
K [0.71 (0.52–0.96), P < 0.07] and Mg [0.73
(0.52–0.01), P < 0.06]. The increase in risk was
limited to the lowest quintile of Ca intake, <600 mg/d; similar
patterns were seen with K and Mg intakes, with cut-off values of
2220 mg K/d and 230 mg Mg/d defining the lowest quintile. When RR
associated with Ca was adjusted for K intake, the relationship
weakened, but not when adjusted for Mg intake. Similarly, the
association of K intake was weakened when adjusted for Ca intake. The
inverse association was stronger for dairy Ca intake than for nondairy
Ca intake; RR ratios for dairy calcium were 0.56, 0.83, 0.59 and 0.70
for quintiles 2–5 compared with the lowest quintile (P
< 0.08), and for nondairy calcium 1.31, 0.95, 1.03 and 0.91,
respectively (P < 0.25). Together, the data
suggest that both the Ca and K obtained from dairy foods contribute to
reducing ischemic stroke risk, with a possible benefit from Mg.
|
Dairy Food Nutrients and Stroke. |
|---|
reported that no
stroke-related mortality was associated with a 24-h recall of
dietary K intakes in the top tertile, >76 mmol/d for men, 67 mmol/d
for women. Overall, after adjustment for energy, age and sex, each 10
mmol increase in K was associated with a 40% reduction in risk of
stroke, which was independent of BP; 240 mL of milk contains 9.5 mmol K
(381 mg). Ca and Mg intakes were not associated with stroke risk when
considered individually.
In an 8-y prospective study of male health professionals, Ascherio et
al. (8)
found that dietary K, Mg and cereal fiber were
each inversely associated with risk of stroke. Although significant
when the entire group was considered, these associations disappeared
for normotensive men, but strengthened for hypertensive men when the
two subgroups were analyzed separately. The RR were 0.53 and 0.64, and
0.53 and 0.58 for the two highest quintiles of K and Mg intake,
respectively. Intakes of K and Mg were highly correlated. Neither total
Ca intake nor dairy Ca intake was associated with stroke risk in this
study.
Fang et al. (9)
reported similar findings in the National
Health and Nutrition Examination Survey I Epidemiological Follow-Up
Study; each tertile increase in dietary K was inversely associated with
stroke mortality, but only in hypertensive men (RR = 2.13) and
black men (RR = 4.27). The higher risk ratio in black men may be
related to their lower dietary K intake (<1260 and >2206 mg/d,
tertile I and III, respectively) compared with white men (<2003 and
>2879 mg/d). There were no significant associations in hypertensive
women or normotensive individuals.
|
Dairy Foods and Blood Pressure. |
|---|
,4)
.
Although the presence of hypertension is the greatest risk, 50% of
strokes occur in individuals with normal or high normal BP
(3)
; thus, reductions in BP even within the normal range
are likely to be beneficial.
Results of the Dietary Approaches to Stop Hypertension (DASH)
intervention study (10)
were similar to those of Fang et
al. (9)
, i.e., hypertensive and minority individuals had
greater reductions in BP with added milk. The dietary intakes of Ca, K
and Mg in the DASH combination diet, which included 360 mL low fat or
fat-free milk, 86 g yogurt and 39 g cheese, were 731, 314
and 57 mg greater, respectively, than in the fruit and vegetable low
dairy diet. Substituting the dairy foods for 33 g of meat and
poultry and 17 g of fat and oil in a high fruit and vegetable diet
for 8 wk resulted in a greater decrease in BP of 2.7/1.9 mm Hg in the
total group of 459 participants; however, the reduction was greater in
minority (3.2/3.6) and stage 1 hypertensive (4.1/7.2) participants.
Similar results were seen with ambulatory BP as random-zero BP
(11)
. The DASH combination diet, which contains
three servings of dairy products daily, was twice as effective in
African Americans and those with hypertension (12)
.
The first DASH diets contained a moderate, fairly typical sodium (Na)
level of 3000 mg/d (130 mmol). Lower Na intakes are recommended for
hypertensive individuals (13)
. Supplementation with K and
Ca has been reported to be less effective when lower Na diets were
consumed (14)
; thus the interaction of the combination
diet with three levels of Na was studied in DASH II. DASH II was an
intervention trial comparing the typical American diet (control) and
the combination diet with milk fed at the following three Na levels:
143 mmol, a typical American intake; 106 mmol, slightly above the upper
limit of current dietary guidelines; and 65 mmol, a possibly optimal
level. The greatest reduction in BP was found in the group consuming
the combination diet with lowest Na, with a 8.9 and 4.5 mm Hg decrease
in systolic blood pressure (SBP) and diastolic blood pressure (DBP),
respectively (15)
. Miller et al. (16)
and
McCarron and Reusser (17)
recently published extensive
reviews of both observational and clinical studies on the dietary
Ca–BP relationship with an analysis of the mineral metabolism and the
DASH diet results.
There have been five reports of trials of high and low dairy food
intake and BP. In 1987, Bierenbaum et al. (18)
reported
that substitution of one quart (1.14 L) of fortified skim milk
containing 1300 mg/d Ca for other beverages reduced BP 4/3 mm Hg for
the total cohort. A subgroup of 27 hypertensive individuals had a
reduction in BP of 9/3 mm Hg. Van Beresteijn et al. (19)
found that supplementing young normotensive females with 1 L milk daily
for 6 wk resulted in a 3 mm Hg reduction in SBP, with no effect on DBP.
Zemel et al. (20)
reported that 600 mg/d Ca as yogurt was
more effective than Ca carbonate supplements in reducing SBP and
intracellular Ca in black noninsulin-dependent diabetic
hypertensives. In contrast, Kynast-Gales and Massey
(21)
found no difference in ambulatory or clinic BP in a
4-wk crossover study of six high normal and seven mildly hypertensive
males consuming low Ca (400 mg) and high Ca (1500 mg from dairy
products) diets. However, Buchner et al. (22)
reanalyzed
their data and found the mean difference for SBP was -9 mm Hg in the
seven hypertensive subjects, with no difference in diastolic BP (DBP).
Recently, Green et al. (23)
reported that free-living
normotensive individuals who consumed 480 mL (2 cups) of skim milk
daily for 8 wk reduced their standing SBP by 3 mm Hg. Standing DBP, and
8-h daytime ambulatory SBP and DBP each decreased 2 mm Hg, but these
decreases were not significantly different. The modest effects of milk
on BP may have been due to the relatively small increase in milk, i.e.,
only 184 mL more than their habitual intake of 296 mL, and the fact
that the subjects were normotensive. Barr et al. (24)
had
204 healthy elderly increase their milk consumption from <1.5 to 2.9
servings/d. Although blood pressure decreased slightly in both the milk
and control group when considered as a whole, in the 32 subjects with
elevated blood pressure in the milk group, DBP decreased by 3.8 mm Hg
compared with 0.8 mm Hg in the controls. Overall, the data show that
hypertensive individuals are most likely to benefit from increased milk
consumption.
Meta-analyses of the pressor effects of Ca, K and Mg supplementation
have been published. For Ca, Griffith et al. (25)
estimated BP reduction was 2.1 mm Hg for SBP and 1.1 mm Hg for DBP for
nine dietary Ca trials of various design; comparable values for
nondietary Ca supplementation were reductions of 1.1 and 0.9 mm Hg,
respectively, which although less, were not significantly different.
Griffith et al. (25)
reported that there was greater
consistency in the results for dietary calcium compared with the
nondietary calcium trials. For K, Whelton (14)
concluded
that K supplements reduced mean BP by 1.8/1.0 in normotensive subjects
and 4.4/2.5 mm Hg in hypertensive subjects. Mizushima et al.
(26)
reviewed 29 studies of Mg supplements and BP and
concluded that there was a negative association between Mg intake and
BP. However, they were unable to quantify the magnitude of the
association because of methodological problems. Like individual
minerals, combinations of minerals as supplements have been
inconsistent in their effects on BP. Patki et al. (27)
supplemented hypertensive patients with 60 mmol/d K, then 60 mmol/d K
plus 20 mmol/d Mg for 8 wk each in a crossover design. K
supplementation reduced BP 12.1/13.1 mm Hg; adding Mg had no additional
effect. Geleijnse et al. (28)
had 97 hypertensive elders
replace table salt and some foods prepared with common salt (sodium
chloride) with similar foods and table salt prepared from a high
mineral salt rich in K and Mg. BP decreased by 9.7 and 4.2 mm Hg for
SBP and DBP, respectively, by 8 wk and stayed at that level for the
remaining 16 wk of the study. Sacks et al. (29)
in 1995
randomly allocated hypertensive patients to 60 mmol/d K plus 25 mmol/d
Ca, 60 mmol K plus 15 mmol Mg, all three minerals or placebo. After 6
mo, the BP differences were small and not significant. Hypothesizing
that only individuals who had low habitual intakes of K, Mg and Ca
would be responsive, Sacks et al. (30)
then supplemented
normotensive women with mineral intakes between the 10th and 15th
percentiles and measured ambulatory BP for 16 wk. Only K, either alone
or in combination with Ca or Mg, reduced BP, and then only modestly,
2.0/1.7 mm Hg. Overall, the data indicate that the K concentration of
milk is a major effector of reduced BP, with lesser BP reductions due
to its high Ca and Mg concentration.
Recently, the FDA approved a health claim that "diets containing
foods that are good sources of K and low in Na may reduce the risk of
high blood pressure and stroke" (31)
. Qualifying foods
must contain at least 350 mg K, <140 mg Na, <3 g total fat, 
1
g saturated fat and not >15% of energy from saturated fatty
acids. Several low fat dairy products meet these guidelines,
including low fat and nonfat milk, and low fat yogurt.
|
Other Cardiovascular Effects of Dairy Foods and Their Nutrients. |
|---|
and Ascherio et al. (9)
; thus, it is not
surprising that other protective mechanisms have been demonstrated for
dairy foods and their nutrients. Resnick (32)
hypothesized
from his analysis and synthesis of data that hypertension and its
associated disorders in metabolic syndrome, obesity, hyperlipidemia and
insulin resistance are all related to elevated intracellular Ca and
depressed intracellular Mg. These cellular ionic disturbances have been
clearly related to vasoconstriction, increased platelet aggregation and
thrombosis, insulin resistance and salt sensitivity. The altered
divalent cation metabolism can be affected by dietary manipulations of
Ca, Mg, K and Na in directions parallel to those seen in the
epidemiologic and clinical studies described above. Similarly for K,
Young et al. (33)
reviewed evidence that provides the
basis for four other possible mechanisms. An elevation of plasma K has
the following effects: 1) it inhibits free radical
formation from vascular endothelial cells and macrophages;
2) it inhibits proliferation of vascular smooth muscle
cells; 3) it inhibits platelet aggregation and arterial
thrombosis; and 4) it reduces renal vascular resistance
and increases glomerular filtration rate. Although not studied as
extensively as Ca or K because of technical difficulties in its
measurement, Mg appears to regulate vascular tone and reactivity in a
similar manner by modulating intracellular Ca, Na, K and pH
(34)
. Manifestations include arrhythmias, hypertension,
increased platelet aggregation and atherosclerosis. Several possible
biochemical pathways are reviewed by Laurant and Touyz
(35)
.
Consumption of milk and/or cheese, but not meat or fish, was inversely
associated with tissue-type plasminogen activator (t-PA) antigen in
both men and women (36)
. t-PA converts plasminogen
into plasmin, which in turn degrades fibrin and thereby dissolves blood
clots; therefore, a high level of t-PA is beneficial with respect
to CVD. Because the antibody blocks this favorable activity, the
investigators interpreted the lower levels of t-PA antigen
associated with dairy product consumption as reducing the risk of
clotting. There was no association with total dietary Ca; the
investigators did not examine the possible association with dietary K
and Mg.
|
Dairy Foods, Nutrients and Insulin Resistance. |
|---|
. Both dietary and serum Mg levels have been
associated with increased fasting insulin and glucose uptake in
nondiabetic individuals. The Atherosclerosis In Communities Study
investigators reported that in 12,700 participants without disease,
serum Mg levels were inversely associated with fasting serum insulin,
glucose and SBP (38)
. Dietary Mg was inversely associated
with fasting serum insulin, plasma HDL cholesterol, systolic and DBP.
Humphries et al. (39)
found insulin-stimulated glucose
use correlated positively with lean body mass proportional to mg/kg
fat-free body mass in young nondiabetic blacks. There was also
a significant negative correlation of both dietary Mg and K intakes
with the sum of insulin levels measured during an oral glucose
tolerance test. Insulin-resistant individuals had 19% lower
dietary Mg and 25% lower K intakes than insulin-sensitive
subjects; Ca intakes were lower as well but were not significantly
different. More evidence that low dietary Mg is associated with insulin
resistance comes from Rosolova et al. (40)
. They found
that serum Mg within the normal range was significantly associated with
steady-state plasma insulin and glucose concentrations during a 3-h
infusion of insulin and glucose. Although dietary Mg was not measured,
24-h urinary Mg was lower in the lowest tertile; erythrocyte Mg was not
different. The authors calculated that the association between Mg and
insulin sensitivity accounted for 5% of the effect compared with
habitual physical activity and obesity, which each account for
20–25%.
Insulin resistance is only one of the defining characteristics of the
metabolic syndrome, also known as syndrome X. Other major
characteristics are hypertension and hyperlipidemia, also risk factors
for stroke. Mennen et al. (41)
found that men who ate one
or more portions of dairy products per day had a 40% lower prevalence
of metabolic syndrome than those who consumed less. This is similar to
the reduction in risk seen by Abbott et al. (5)
in the
Honolulu Heart Study. DBP, fasting glucose, triglycerides and HDL were
all lower in men with higher dairy consumption, whereas only DBP was
lower in women consuming more dairy products.
|
Dairy Products, Homocysteine and Lipid Peroxidation. |
|---|
and lipid peroxidation (43)
. Elevated
homocysteine has been weakly associated with increased risk of
atherosclerosis and stroke in prospective studies (44)
,
but it is uncertain whether it is a direct endothelial toxin or a
marker of incipient disease and/or poor lifestyle. If homocysteine
proves to be an independent cardiovascular risk factor, then the
observed 0.8 µmol/L difference between the control and
combination diets should lower CVD by 7–9% among persons consuming a
typical American diet who subsequently adopt the DASH combination diet. |
Summary and Conclusions. |
|---|
. Milk and food products made from it, which retain
substantial amounts of K, Ca and Mg, are important dietary sources of
all three of these minerals. In addition, milk is a low Na food, which
as seen in DASH II, provides further benefit in BP reduction. Additional studies are required to evaluate the effects of chronic milk and/or dairy food consumption in controlled diets, not only on BP, but also on insulin sensitivity, lipid oxidation and platelet aggregation to investigate a wider range of possible protective mechanisms. To make appropriate recommendations for prevention of stroke, prospective studies should examine the consumption of foods, not nutrients.
|
FOOTNOTES |
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2 Manuscript received 12 March 2001.
3 Abbreviations used: BP, blood pressure; CVD, cardiovascular disease; DASH, Dietary Approaches to Stop Hypertension; DSP, diastolic blood pressure; RR, relative risk; SDP, systolic blood pressure; t-PA, tissue-type plasminogen activator.
|
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