LE Magazine November 2002
Page 2 of 4
Maintenance of trabecular structure
and bone volume by vitamin K(2) in mature rats with long-term
tail suspension.
Bone volume loss is one of the major health problems during
long-term spaceflight. We examined the effects of vitamin K(2)
on bone abnormalities in tail-suspended mature male
Sprague-Dawley rats (13 weeks old). In this model, increased
bone resorption and sustained suppression of bone formation
resulted in progressive bone loss in four weeks, which
simulates bone changes in humans during spaceflight. A
significant decrease in bone mineral density (BMD), as well as
a decreased mineral apposition rate (MAR), increased the
number of osteoclasts per bone perimeter (N.Oc/B.Pm), and
increased osteoclast surface per bone surface (Oc.S/BS) in the
suspended group was effectively prevented by vitamin K(2),
given orally (menatetrenone, 22 mg/kg body weight). Microfocus
computed tomography (CT) and node-strut analyses revealed that
the volume and structure of trabecular bone were maintained
near normal by the vitamin K(2) treatment. A recent report has
suggested the abnormal metabolism or action of vitamin K in a
microgravity environment, and our data therefore suggest that
vitamin K(2) may be useful for the prevention of bone loss and
for the maintenance of normal trabecular structure during
spaceflight.
J Bone Miner Metab
2002;20(4):216-22
Vitamin K intake and hip fractures in
women: a prospective study.
BACKGROUND: Vitamin K mediates the gamma-carboxylation of
glutamyl residues on several bone proteins, notably
osteocalcin. High serum concentrations of undercarboxylated
osteocalcin and low serum concentrations of vitamin K are
associated with lower bone mineral density and increased risk
of hip fracture. However, data are limited on the effects of
dietary vitamin K. OBJECTIVE: We investigated the hypothesis
that high intakes of vitamin K are associated with a lower
risk of hip fracture in women. DESIGN: We conducted a
prospective analysis within the Nurses’ Health Study
cohort. Diet was assessed in 72,327 women aged 38 to 63 y with
a food-frequency questionnaire in 1984 (baseline). During the
subsequent 10 y of follow-up, 270 hip fractures resulting from
low or moderate trauma were reported. RESULTS: Women in
quintiles 2 to 5 of vitamin K intake had a significantly lower
age-adjusted relative risk (RR: 0.70; 95% CI: 0.53, 0.93) of
hip fracture than women in the lowest quintile (< 109
microg/d). Risk did not decrease between quintiles two and
five and risk estimates were not altered when other risk
factors for osteoporosis, including calcium and vitamin D
intakes, were added to the models. Risk of hip fracture was
also inversely associated with lettuce consumption (RR: 0.55;
95% CI: 0.40, 0.78) for one or more servings per day compared
with one or fewer servings per week), the food that
contributed the most to dietary vitamin K intakes.
CONCLUSIONS: Low intakes of vitamin K may increase the risk of
hip fracture in women. The data support the suggestion for a
reassessment of the vitamin K requirements that are based on
bone health and blood coagulation.
Am J Clin Nutr 1999
Jan;69(1):74-9
Warfarin exposure and calcification of
the arterial system in the rat.
There is evidence from knock-out mice that the extrahepatic
vitamin K-dependent protein, matrix gla protein, is necessary
to prevent arterial calcification. The aim of this study was
to determine if a warfarin treatment regimen in rats, designed
to cause extra-hepatic vitamin K deficiency, would also cause
arterial calcification. Sprague-Dawley rats were treated from
birth for five to 12 weeks with daily doses of warfarin and
concurrent vitamin K1. This treatment causes an extrahepatic
vitamin K deficiency without affecting the vitamin K-dependent
blood clotting factors. At the end of treatment the rats were
killed and the vascular system was examined for evidence of
calcification. All treated animals showed extensive arterial
calcification. The cerebral arteries and the veins and
capillaries did not appear to be affected. It is likely that
humans on long-term warfarin treatment have extrahepatic
vitamin K deficiency and hence they are potentially at
increased risk of developing arterial calcification.
Int J Exp Pathol 2000
Feb;81(1):51-6
High blood pressure and bone-mineral
loss in elderly white women: a prospective study. Study of
Osteoporotic Fractures Research Group.
BACKGROUND: High blood pressure is associated with
abnormalities in calcium metabolism. Sustained calcium loss
may lead to increased bone-mineral loss in people with high
blood pressure. We investigated the prospective association
between blood pressure and bone-mineral loss over time in
elderly white women. METHODS: We studied 3,676 women who were
initially assessed in 1988 to 90 (mean age 73 years [SD 4,
range 66-91 years]; mean bodyweight 65.3 kg [11.5]; blood
pressure 137/75 mm Hg [17/9]) who were not on thiazide
diuretics. Mean follow-up was 3.5 years. Anthropometry, blood
pressure and bone-mineral density at the femoral neck were
measured at baseline and bone densitometry was repeated after
3.5 years by dual-energy X-ray absorptiometry. FINDINGS: After
adjustment for age, initial bone-mineral density, weight and
weight change, smoking and regular use of hormone-replacement
therapy, the rate of bone loss at the femoral neck increased
with blood pressure at baseline. In the quartiles of systolic
blood pressure, yearly bone losses increased from 2.26 mg/cm2
(95% CI 1.48-3.04) in the first quartile to 3.79 mg/cm2 in the
fourth quartile (3.13-4.45; test for heterogeneity, p=0.03;
test for linear trend, p=0.01), equivalent to yearly changes
of 0.34% (0.20-0.46) and 0.59% (0.49-0.69; test for
heterogeneity, p=0.02; test for linear trend, p=0.005). There
was no significant interaction with age. The exclusion of
women on antihypertensive drugs did not alter the results. For
diastolic blood pressure, there was an association with bone
loss in women younger than 75 years. INTERPRETATION: Higher
blood pressure in elderly white women is associated with
increased bone loss at the femoral neck. This association may
reflect greater calcium losses associated with high blood
pressure, which may contribute to the risk of hip
fractures.
Lancet 1999 Sep
18;354(9183):971-5
Vertebral fractures and mortality in
older women: a prospective study. Study of Osteoporotic
Fractures Research Group.
BACKGROUND: Osteoporotic fractures, including clinically
detected vertebral fractures, are associated with increased
mortality. However, only one-third of vertebral fractures are
diagnosed. It is unknown whether vertebral fractures, whether
clinically apparent or not, are associated with greater
mortality. OBJECTIVES: To test the hypothesis that women with
prevalent vertebral fractures have greater mortality than
those without fractures and to describe causes of death
associated with vertebral fractures. DESIGN: Prospective
cohort study with mean follow-up of 8.3 years. SETTING: Four
clinical centers in the United States. PARTICIPANTS: A total
of 9,575 women aged 65 years or older and enrolled in the
Study of Osteoporotic Fractures. MEASUREMENTS: Vertebral
fractures by radiographic morphometry; calcaneal bone mineral
density; demographic, medical history and lifestyle variables;
blood pressure; and anthropometric measures. In a subset of
606 participants, thoracic curvature was measured during a
second clinic visit. MAIN OUTCOME MEASURES: Hazard ratios for
mortality and cause-specific mortality. RESULTS: At baseline,
1,915 women (20.0%) were diagnosed as having vertebral
fractures. Compared with women who did not have a vertebral
fracture, women with one or more fractures had a 1.23-fold
greater age-adjusted mortality rate (95% confidence interval,
1.10-1.37). Mortality rose with greater numbers of vertebral
fractures, from 19 per 1000 woman-years in women with no
fractures to 44 per 1000 woman-years in those with five or
more fractures (P for trend, <.001). In particular,
vertebral fractures were related to the risk of subsequent
cancer (hazard ratio, 1.4 95% confidence interval, 1.1-1.7)
and pulmonary death (hazard ratio, 2.1 95% confidence
interval, 1.4-3.0). In the subset of women who underwent
thoracic curvature measurements, severe kyphosis was also
related to pulmonary deaths (hazard ratio, 2.6;95% confidence
interval, 1.3-5.1). CONCLUSION: Women with radiographic
evidence of vertebral fractures have an increased mortality
rate, particularly from pulmonary disease and cancer.
Arch Intern Med 1999 Jun
14;159(11):1215-20
Whey protein
The bovine protein alpha-lactalbumin
increases the plasma ratio of tryptophan to the other large
neutral amino acids, and in vulnerable subjects raises brain
serotonin activity, reduces cortisol concentration, and
improves mood under stress.
BACKGROUND: Increased brain serotonin may improve the
ability to cope with stress, whereas a decline in serotonin
activity is involved in depressive mood. The uptake of the
serotonin precursor, tryptophan, into the brain is dependent
on nutrients that influence the cerebral availability of
tryptophan via a change in the ratio of plasma tryptophan to
the sum of the other large neutral amino acids (Trp-LNAA
ratio). Therefore, a diet-induced increase in tryptophan
availability may increase brain serotonin synthesis and
improve coping and mood, particularly in stress-vulnerable
subjects. OBJECTIVE: We tested whether alpha-lactalbumin, a
whey protein with a high tryptophan content, may increase the
plasma Trp-LNAA ratio and reduce depressive mood and cortisol
concentrations in stress-vulnerable subjects under acute
stress. DESIGN: Twenty-nine highly stress-vulnerable subjects
and 29 relatively stress-invulnerable subjects participated in
a double-blind, placebo-controlled study. Subjects were
exposed to experimental stress after the intake of a diet
enriched with either alpha-lactalbumin or sodium-caseinate.
Diet-induced changes in the plasma Trp-LNAA ratio and
prolactin were measured. Changes in mood, pulse rate, skin
conductance, and cortisol concentrations were assessed before
and after the stressor. RESULTS: The plasma Trp-LNAA ratio was
48% higher after the alpha-lactalbumin diet than after the
casein diet (P = 0.0001). In stress-vulnerable subjects this
was accompanied by higher prolactin concentrations (P =
0.001), a decrease in cortisol (P = 0.036), and reduced
depressive feelings (P = 0.007) under stress. CONCLUSIONS:
Consumption of a dietary protein enriched in tryptophan
increased the plasma Trp-LNAA ratio and, in stress-vulnerable
subjects, improved coping ability, probably through
alterations in brain serotonin.
Am J Clin Nutr 2000
Jun;71(6):1536-44
Whey protein rich in alpha-lactalbumin
increases the ratio of plasma tryptophan to the sum of the
other large neutral amino acids and improves cognitive
performance in stress-vulnerable subjects.
BACKGROUND: Cognitive performance often declines under
chronic stress exposure. The negative effect of chronic stress
on performance may be mediated by reduced brain serotonin
function. The uptake of the serotonin precursor tryptophan
into the brain depends on nutrients that influence the
availability of tryptophan by changing the ratio of plasma
tryptophan to the sum of the other large neutral amino acids
(Trp-LNAA ratio). In addition, a diet-induced increase in
tryptophan may increase brain serotonergic activity levels and
improve cognitive performance, particularly in high
stress-vulnerable subjects. OBJECTIVE: We tested whether
alpha-lactalbumin, a whey protein with a high tryptophan
content, would increase the plasma Trp-LNAA ratio and improve
cognitive performance in high stress- vulnerable subjects.
DESIGN: Twenty-three high stress-vulnerable subjects and 29
low stress-vulnerable subjects participated in a double-blind,
placebo-controlled, crossover study. All subjects conducted a
memory-scanning task after the intake of a diet enriched with
either alpha-lactalbumin (alpha-lactalbumin diet) or sodium
caseinate (control diet). Blood samples were taken to measure
the effect of dietary manipulation on the plasma Trp-LNAA
ratio. RESULTS: A significantly greater increase in the plasma
Trp-LNAA ratio after consumption of the alpha-lactalbumin diet
than after the control diet (P = 0.0001) was observed; memory
scanning improved significantly only in the high
stress-vulnerable subjects (P = 0.019). CONCLUSION: Because an
increase in the plasma Trp-LNAA ratio is considered to be an
indirect indication of increased brain serotonin function, the
results suggest that dietary protein rich in alpha-lactalbumin
improves cognitive performance in stress-vulnerable subjects
via increased brain tryptophan and serotonin activities.
Am J Clin Nutr 2002
Jun;75(6):1051-6
A pre-exercise
alpha-lactalbumin-enriched whey
protein meal preserves lipid oxidation and decreases
adiposity in rats.
The composition of the pre-exercise food intake is known to
affect substrate utilization during exercise and thus can
affect long-term changes in body weight and composition. These
parameters were measured in male rats exercised two h daily
over five wk, either in the fasting state or 1 h after they
ingested a meal enriched with glucose (Glc), whole milk
protein (WMP), or alpha-lactalbumin-enriched whey protein
(CPalphaL). Compared with fasting, the Glc meal increased
glucose oxidation and decreased lipid oxidation during and
after exercise. In contrast, the WMP and CPalphaL meals
preserved lipid oxidation and increased protein oxidation, the
CPalphaL meal increasing protein oxidation more than the WMP
meal. At the end of the study, body weight was larger in the
WMP-, Glc-, and CPalphaL-fed rats than in the fasted ones.
This resulted from an increased fat mass in the WMP and Glc
rats and to an increased lean body mass, particularly muscles,
in the CPalphaL rats. We conclude that the potential of the
CPalphaL meal to preserve lipid oxidation and to rapidly
deliver amino acids for use during exercise improved the
efficiency of exercise training to decrease adiposity.
Am J Physiol Endocrinol Metab 2002
Sep;283(3):E565-72
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