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Division of Human Nutrition and Epidemiology, Wageningen Agricultural University, Dreÿenlaan 6703 HA Wageningen, The Netherlands
2To whom correspondence should be addressed.
| ABSTRACT |
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to 39% for 25-hydroxy vitamin D and 42% for vitamin B-12. These were corrected after 17 wk
in the two groups receiving the nutrient-dense foods, whereas no significant changes were observed in the control or exercise group.
Biochemical and hematologic indicators at baseline were within the reference ranges (mean albumin, 46 g/L; prealbumin, 0.25 g/L;
hemoglobin, 8.6 mmol/L) and were not affected by any of the interventions. The long-term protective effects of nutrient
supplementation and exercise, by maintaining optimal nutrient levels and thereby reducing the initial chance of developing critical
biochemical values, require further investigation. Other indicative functional variables for suboptimal nutritional status, in addition to
those currently selected, should also be explored.
KEY WORDS: biochemical indicators elderly humans nutrient-dense foods physical exercise dietary intake
| INTRODUCTION |
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Blood concentrations of water-soluble vitamins often show the fastest decline in elderly people with inadequate dietary intake
because body reserves are limited (Machlin 1984
), but
marginal deficiencies of vitamin D and minerals such as iron, magnesium
and zinc are reported as well (Commissie Voeding van de Oudere Mens Voedingsraad 1995
, Payette and Gray-Donald 1991
, Schrijver et al. 1985
, Tucker 1995
, van-der Wielen et al. 1995
).
To date, only a few studies have investigated the influence of nutrient supplementation and/or exercise on multiple indicators of nutritional
status in elderly people classified as frail or "at risk"
(Fiatarone et al. 1994
, Gray-Donald et al. 1995
, Lipschitz et al. 1985
, Meredith et al. 1992
). Physical exercise is reported to increase energy
expenditure (Poehlman 1992
, Titchenal 1988
), resulting in a possible increment in total dietary
intake (Mensink and Arab 1989
). Additionally, a slowing
down or reversal of the overall age-related decline in physiologic
functioning may occur (Fielding 1995
). This may be reflected in the enhancement of a multitude of bodily processes,
including nutrient metabolism (Morris and Hardman 1997
),
organ system functioning (Young 1997
), hormone secretion
(Lee et al. 1998
, Martin et al. 1997
) and
perhaps gastrointestinal nutrient absorption (Lovat 1996
). Mann et al. (1987)
showed that
multivitamin supplementation increased blood levels of the water-soluble vitamins. This was not observed for fat-soluble
vitamins, thereby confirming the theory that greater storage pools of the fat-soluble vitamins exist in the liver and fat tissue.
To date, well-controlled trials investigating possible benefits of all-round physical exercise and/or physiologically dosed micronutrient-dense foods on functional biochemical indicators of nutritional status in frail elderly people have not been published. Previous studies investigated the effects of nutritional supplements only, had small sample size or focused on other outcomes.
For this trial, we hypothesized that either supplementation with a
physiologic dose of micronutrients (resulting in a beneficial increase
in nutrient status) or a progressive all-round exercise program
(which would increase daily energy expenditure and dietary intake)
would affect selected biochemical and hematologic indicators of
nutritional and health status in a group of community-dwelling
frail elderly people. Because exercise might also lead to more
efficient nutrient absorption and overall metabolism, a combination of
both interventions may be even more beneficial. Nutrient intake, blood
nutrient levels as indicators of available body pools (Garry and Koehler 1989
) and functional biochemical indicators of overall
nutritional and health status were addressed.
| MATERIALS AND METHODS |
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The study population consisted of 217 free-living frail elderly
Dutch people. The following criteria were used: requirement of health
care, such as home care or meals-on-wheels service; age (
70 y);
no regular exercise; body mass index
(BMI)3
below average (
25 kg/m2 on the basis of self-reported
weight and height) or recent weight loss; no use of multivitamin
supplements; and ability to understand the study procedures.
All subjects gave their written informed consent. The study protocol was approved by the Medical Ethical Committee of the Division of Human Nutrition and Epidemiology of the Wageningen Agricultural University. Pre- and postintervention measurement(s) were available for 165 subjects. Reasons for drop out (n = 52, 24%) were mainly health problems, including (terminal) disease, hospital admittance, a recent fall and/or fracture. Valid (pre- and postintervention) biochemical variables were available for 145 subjects. Four subjects were excluded because the time between pre- and postintevention measurement was <13 wk as a result of hospitalization; three subjects were not able to visit our research center after intervention because of illness and therefore ended the trial with incomplete blood samples. Venipuncture did not succeed in one subject and 12 subjects were excluded from analyses because of multivitamin use.
Design.
Enrollment took place between January and June 1997. Subjects were randomly assigned to one of four intervention groups. The first group (nutrition) received nutrient-dense products and a social program; the second group (exercise) received regular products and an exercise program; the third group (combination) received nutrient-dense products with an exercise program; and the fourth group (control) received regular products and a social program. The intervention period was 17 wk, and data were collected at baseline (wk 0) and after 17 wk (in wk 18). Dietary intake data were collected at baseline and during the last week of intervention (wk 17).
Nutrient-dense products.
Subjects were asked to consume two products a day, one from a series of
fruit products and one from a series of dairy products. Availability of
a variety of products was intended to prevent monotony and to increase
acceptability of the products. Fresh 100-g servings of fruit-based
products (two types each of both fruit juice and compote) and 100-g
servings of dairy products (vanilla custard, two types of fruit yogurt
and 75 g of cheese curd with fruits) were provided weekly. Daily
consumption of two enriched products delivered ~100% of the Dutch
recommended daily allowance (RDA) (Commissie Voeding van de Oudere Mens Voedingsraad 1995
, Commissie Voedingsnormen Voedingsraad 1989
) of the
following vitamins: D, E, thiamin, riboflavin, B-6, folic acid, B-12
and C and ~25100% of the Dutch RDA of the following minerals:
calcium (25%), magnesium (25%), zinc (50%), iron (50%) and iodine
(100%). Subjects in the control and exercise group received the
natural amount of the regular products (amount of vitamins and minerals
in regular products at the highest 15% of the concentration in
enriched products). Both the enriched and regular products had an
energy content of ~0.48 MJ/product.
Exercise program.
The main objective of the exercise program was to maintain and/or
improve mobility and performance of daily activities essential for
independent functioning by maintaining versatility in movement. Perhaps
nutritional status could also be improved via more efficient nutrient
absorption and metabolism (Lovat 1996
, Martin et al. 1997
, Morris and Hardman 1997
, Young 1997
). Emphasis was placed on skill training; muscle strength,
coordination, flexibility, speed and endurance were improved by
exercises such as walking, stooping and chair stands. Materials
included balls, ropes, weights and elastic bands. The second objective
was to improve nutritional status through increasing daily activity
level, overall energy expenditure and, consequently, dietary intake.
Group sessions were organized twice a week for 45 min and were of
moderate, gradually increasing intensity. Because participants were
assumed to be fairly inactive at baseline, two sessions per week was
considered the maximum number that would achieve adequate compliance.
From earlier studies, we knew that with such a program, beneficial
effects in functional capacity and muscle strength could be detected
(Lord et al. 1996
, McMurdo and Rennie 1993
). Sessions were supervised by skilled teachers to improve
safety and prevent incorrect or harmful movements. To guarantee
uniformity, sessions were extensively rehearsed with all teachers
together, and an instruction video and manual were prepared in advance.
A social program served as a control (for attention) program for the
exercise program. Sessions of 90 min were organized once every 2 wk by
a skilled creative therapist. This program focused on creative
activities, social activities and lectures on topics of interest to
elderly people. Transport to and from all sessions was arranged.
Questionnaires.
A general questionnaire asked for information on age, sex, marital
status, education, living conditions, illness, medicine and supplement
use, and smoking habits. Physical activity was assessed using the
validated Physical Activity Scale for Elderly (PASE) (Schuit et al. 1997
, Washburn et al. 1993
).
Anthropometry.
All anthropometric measurements were performed with subjects wearing
underclothes. Body weight was measured to the nearest 0.01 kg using a
digital scale (ED-6-T; Berkel, Rotterdam, The Netherlands) and height
was measured to the nearest 0.001 m using a wall-mounted
stadiometer. BMI was calculated as weight in kilograms divided by
height in meters squared (Fidanza 1991
).
Dietary intake.
A 3-d (two weekdays and one weekend day; nonconsecutive) estimated
dietary record was obtained by three trained dietitians at baseline (wk
0) and in the last week of intervention (wk 17). During a home visit
before the intervention period, dietitians provided subjects with a
clear explanation of the way to record and estimate portion sizes in
household measures. During a second visit, they checked the diary and
weighed the portion sizes of the most frequently consumed foods in
household measures. Subjects who had problems with writing could use a
voice tape recorder. In case of problems occurring during the 3 d
of recording, subjects could telephone the dietitians during the
daytime or evening. Food consumption data were coded (with frequent
cross-checking by all three dietitians), and energy and nutrients
were calculated with the computerized Dutch Food Composition Table
of
1997 and a supplement (1995) for folate and vitamin B-12 (Stichting Nederlands Voedingsstoffenbestand 1995
and 1997
).
|
Pre- and postintervention blood samples were collected from fasting
subjects between 0700 and 0900 h for all indicators, except
samples for complete blood count and vitamin C; for practical reasons,
these samples were collected in our research center at 1200 h and
immediately put on ice before further processing. Within 1 h of
collecting samples for vitamin C analysis, 0.5 mL EDTA plasma was mixed
with 2.0 mL metaphosphoric acid (50 g/L, J. T. Baker Bakergrade,
Deventer, The Netherlands) to deproteinize the vitamin C sample
(analyzed with HPLC-fluorimetry, the CV between runs was 510%)
(Fidanza 1991
, van den Berg et al. 1993
).
A fresh 3-mL EDTA sample was used for a complete blood count (Coulter
Counter type T-860, Coulter, Miami, FL).
For fasting blood samples, 3 mL serum was used for analyses of the
serum proteins, including albumin (bromocresol-green), prealbumin,
C-reactive protein (CRP), transferrin, ferritin and thyroxine (T4)
(immunoturbidimetric principle). A Hitachi-911 automatic analyzer
(Hitachi Instrument Division, Japan) and a AIA-600 Enzyme Immunoassay
Analyzer (Tosoh, Toyama, Japan) were used with a CV between
runs of 18%. For thiamin and riboflavin, erythrocyte transketolase
(ETK) activity and erythrocyte glutathione reductase (EGR) activity
were determined, respectively (kinetic spectrophotometric enzyme
determination), with between-run CV of 79% (Fidanza 1991
, van den Berg et al. 1993
). Samples (3 mL)
were hemolyzed after slow centrifugation (2000 g,
twice for 5 min and once for 10 min) and washed with an equal amount of
9 g/L NaCl. After three washing procedures, the erythrocytes were
diluted with an equal volume of Nonidet P40 (Boom, Meppel, The
Netherlands). For vitamin B-6, serum pyridoxal-5'-phosphate (1 mL) was
measured by HPLC-fluorometry with a between-run CV of 510%
(Fidanza 1991
, van den Berg et al. 1993
);
for vitamin B-12, a 0.5-mL plasma sample was analyzed with the IMx
automated immunoassay system (Kuemmerle et al. 1992
),
and 25-hydroxy vitamin D concentrations were analyzed in a 0.5-mL serum
sample for vitamin D with a between-run CV of 510% (van den Berg et al. 1991
).
All samples were stored at -80°C until analysis. Pre- and postintervention samples were analyzed in the same batch. Analyses were performed by the TNO Nutrition and Food Research Institute, Zeist, The Netherlands, the Department of Clinical Chemistry, University Hospital Nijmegen, The Netherlands (B-12), and the Division of Human Nutrition and Epidemiology, Wageningen Agricultural University, The Netherlands (Coulter counter).
Statistical analysis.
Data were analyzed using SAS (version 6, SAS Institute, Cary, NC).
Means ± SD, medians (10th90th percentiles) or
percentages of (baseline) values were calculated for all intervention
groups. The prevalence of subjects deviating from the reference was
calculated as a frequency. Absolute changes ± SD per
intervention group were calculated and compared with changes in the
control group using an unpaired t test. Because many
subjects had a lower CRP level than the detection limit of 0.30 mg/L,
we set those values at 0.15 mg/L in order to calculate changes on a
continuous scale for the whole population. Multiple regression was used
to determine the effect of both interventions and a possible
interaction on the change in biochemical variables. Because no evidence
of an interaction was observed between interventions, comparisons were
made between the supplemented group and the nonsupplemented group, and
the exercising group and the nonexercising group. For all changes in
the variables studied, confounding by baseline age, supplement use and
corresponding baseline biochemical value was checked (e.g., for change
in albumin, the model was adjusted for baseline albumin and so forth).
In the adjusted regression model, only the corresponding baseline
biochemical value was added as a confounder because age and supplement
use did not contribute significantly to the model. A
P-value
0.05 was considered significant.
| RESULTS |
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The baseline values of dietary intake for men and women and percentage
of subjects below two thirds of the Dutch RDA (Commissie Voeding van de Oudere Mens Voedingsraad 1995
, Commissie Voedingsnormen Voedingsraad 1989
) are presented in Table 2
. Comparing the mean intake data of our population with that of healthy
Dutch elderly people (Amorim Cruz et al. 1996
,
Bergstein and Van Die 1988
, Commissie Voeding van de
Oudere Mens Voedingsraad 1995
, van-der Wielen et al. 1996
, van Asselt et al. 1998
), energy intake
in our population was lower, as were protein and fat intakes. Vitamins
intakes of riboflavin, B-12, C, D and E were especially below the
intake of healthy Dutch elderly people. When two thirds of the Dutch
RDA is taken as a cut-off value, macronutrient intake was adequate
in our population, whereas vitamin D, E and A in particular were below
this cut-off value. Fourteen percent of the men and 34% of the
women had energy intakes below 6.3 MJ, the level at which several
micronutrient deficiencies can be expected. Mean intake data of each of
the three intervention groups (i.e., nutrition, exercise and
combination group) were compared with the control group (Table 3
). Both the exercise and the combination group had a slightly lower
energy (P = 0.051) and carbohydrate intake
(P < 0.05) than the control group at baseline. At the
end of the intervention, the combination and nutrition group had
significantly increased their intakes of those micronutrients, which
had been added to the nutrient-dense foods. No significant
increases were found in the exercise group compared with the control
group.
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(as a measure for thiamin) and EGR-
(as a measure for
riboflavin) both decreased. The change in ETK-
tended to be
significant in the nutrition group (P = 0.07) and the
change in EGR-
was significant (P < 0.05) in the
combination group. Because values >1.25 are unfavorable
(Schrijver et al. 1985
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0.05) noted in the nutrition group compared with the control
group. Hemoglobin, hematocrit and number of red blood cells tended
(P < 0.05) to decline in all groups, whereas the
mean number of white blood cells and lymphocytes increased slightly but
not significantly (0.14 < P < 0.97) compared to
baseline.
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In Table 6
,adjusted (for baseline values) differences in change in selected
biochemical and hematologic variables between the nutrient-dense
and regular food groups and the exercise vs. nonexercise groups are
shown. Only the levels of albumin and prealbumin were significantly
improved after 17 wk of consuming nutrient-dense foods. No
meaningful differences were found in the other variables between either
consumers of nutrient-dense foods and regular foods, or between
exercisers and nonexercisers.
|
| DISCUSSION |
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In affluent societies, nutritional deficiencies are not common in
healthy elderly people (Lowik et al. 1990
), but low
dietary intakes and clinically relevant deficiencies are evident in
institutionalized elderly people. This latter group is physically
inactive, may have reduced energy needs and is deteriorating in health
(Rosenberg 1994
). Our population of
community-dwelling frail elderly people can be (to a lesser extent)
regarded as such a group. From several selected indicators, it appeared
that we studied an elderly group whose health profile was indeed worse
than that of apparently healthy Dutch elderly people. Their mean BMI
was lower than that of the Dutch elderly in the European Seneca study
(24 kg/m2 vs. 26 kg/m2 in
men and 28 kg/m2 in women) (de Groot et al. 1996
); self-rated health was lower (7.0 vs. 7.7) as was
their activity level (PASE score 64 vs. 85) (Schuit 1997
, Schuit et al. 1997
). Mean scores on physical fitness tests were below
average as well (Chin A Paw et al., unpublished data). In addition,
34% of our female subjects had a low energy intake (<6.3 MJ) and
relatively low intakes of several vitamins. Blood vitamin deficiency
rates of the total group varied from 42% for vitamin B-12 and 39% for
serum 25-hydroxy vitamin D to 3% for EGR-
(a functional measure of
riboflavin). For most vitamins, blood concentrations in our study
population were lower than values in healthy Dutch elderly people
(Haller et al. 1996
, Lowik et al. 1990
, 1992
and 1993
, Ooms 1994
, Schrijver et al. 1985
, van-der Wielen et al. 1995
, van Asselt et al. 1998
).
On the group level, however, no clinically relevant deficiencies of functional variables were noted. Indicators of poor protein status or of chronic or acute illness such as low albumin, prealbumin and transferrin levels, low lymphocyte count or high CRP levels were not notably prevalent in our frail population. This may provide an explanation for the fact that despite the observed significant improvement in blood vitamin levels in the supplemented groups (confirming that our nutrient-dense foods had indeed been consumed and that the vitamins provided were indeed circulating in blood), we did not detect many clinically relevant beneficial changes in the selected indicators. Only albumin and prealbumin improved significantly after the 17-wk nutritional intervention, although levels were regarded as adequate at baseline. However, the relevance of these increases is equivocal, i.e., the change in (pre)albumin may be attributed only to chance. In a subgroup with measurable values of CRP, supplementation and exercise seemed to be beneficial, but due to a small sample size, this finding should also be interpreted with caution.
Mann et al. (1987)
observed that 4 mo of daily
multivitamin supplementation with tablets improved blood levels of the
water-soluble vitamins in elderly people. For the fat-soluble
vitamins, this was not shown. In our supplemented groups, the
water-soluble vitamins increased significantly. Because we measured
only vitamin D, a fat-soluble vitamin that frequently is low in
elderly people, we cannot comment on improvement of fat-soluble
vitamins in general.
Until now, the clinical importance of improved vitamin levels as such
has not been evaluated in well-controlled intervention trials. Very
few studies have focused on the effects of both exercise and nutrition
on several nutritional and health indicators in frail elderly people
(Fiatarone et al. 1994
), and only very limited
information is available about improvements in functional (biochemical
and hematologic) indicators by either type of intervention
(Lipschitz et al. 1985
, Meredith et al. 1992
). Also, as far as we know, studies with an all-round
progressive exercise program combined with provision of a physiologic
dose of micronutrients have not been performed in
community-dwelling frail elderly people. It was hypothesized that
the physical exercise program would improve activity level, energy
expenditure and hence dietary intake. In addition, other beneficial
effects on a multitude of bodily processes may be attributed to
exercise as well. Gastrointestinal dysmotility, for example, may be
caused by hypothyroidism and may be enhanced by physical exercise
(Lovat 1996
). Others have postulated that not only
thyroid hormone levels (Lee et al. 1998
, Zerath et al. 1997
) but also growth hormone (Martin et al. 1997
), insulin and glucose dynamics and lipoprotein metabolism
(Morris and Hardman 1997
) can be affected by certain
types of programmed exercise. Serum albumin has been positively
associated with skeletal muscle mass (Baumgartner et al. 1996
) and may therefore be influenced by physical activity.
Perhaps several other (still unknown) beneficial effects on metabolism
and organ function in aging persons may be induced by regular exercise.
Our program may unintentionally have been of too low an intensity or of
too short duration to induce any change in energy expenditure and
dietary intake, or gastrointestinal absorption and metabolism. Hence,
individual deficient nutrient blood levels were not corrected in the
exercising group during the intervention period. Yet, the expected
beneficial effects of exercise might be expressed in the long term as
maintenance of bodily tissues, organ systems and biochemical variables.
Additionally, it is possible that favorable effects on biochemical
indicators could have been found in a frailer, bedridden, elderly
population.
Our findings are in agreement with observations of Lipschitz et al. (1985)
who studied supplementation in a
"meals-on-wheels elderly population." They observed no change in
serum ferritin levels, hemoglobin levels (not even in persons with
anemia) or lymphocyte count but found a modest rise in serum albumin
and in several selected nutrient concentrations. Additionally,
Meredith et al. (1992)
found normal nutritional
biochemical values at baseline and no change in these variables after a
refeeding program during physical rehabilitation in elderly men.
It has been suggested that the failure of most functional indicators to
improve with nutritional support implies that abnormalities are age or
disease related rather than nutrition related (Lipschitz et al. 1985
). Other explanations also exist. Slight alterations in
(micro)nutrient metabolism due to organ dysfunction may prevent the
corrected blood nutrient levels from being of benefit. Another
possibility is the occurrence of normal blood plasma or red cell
concentrations as a result of resorption from other tissues in
chronically deficient people. For the activity coefficients of ETK and
EGR, long-term deficiency may be masked by decreased synthesis or
kinetic functions of the apoenzyme involved, thereby establishing a new
balance (Buttery et al. 1982
, Cooperman 1984
, Glatzle et al. 1970
, Warnock 1970
). Perhaps the reference values for clinically relevant
deficiencies require some reevaluation against recently postulated
"optimal nutrient levels." The relatively short intervention period
of this study should also be noted. Long-term protective effects of
nutrient supplementation on biochemical and hematologic variables may
occur because of maintenance of the optimal nutrient levels. However,
benefits from this maintenance may be measurable only after many years.
Alternatively, because no multiple clinically relevant deficiencies at
baseline were found, no relevant improvements might be expected after
17 wk of intervention. The fact that our variables did not change after
intervention is consistent with earlier studies (Lipschitz et al. 1985
, Meredith et al. 1992
). It suggests
that improving these currently selected biochemical and hematologic
indicators in these specific community-dwelling frail elderly
populations may not necessarily be the first aim. On the other hand,
the risk of developing a "delayed" suboptimal nutritional state in
the long term as a result of exhausted body reserves may be present in
these frail groups. This may not be detected immediately because a
renewed but unfavorable balance through tissue resorption may be
initiated in the first place. Long-term effects of supplementation
and also exercise should therefore be investigated; the mechanisms at
work within subjects that are deficient must be understood. In
addition, the relationships between and effects on other functional
indicators such as incidence of (infectious) diseases, osteoporosis and
physical fitness and functioning should be the topic of further
research in this frail elderly community-dwelling population.
| ACKNOWLEDGMENTS |
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| FOOTNOTES |
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3 Abbreviations used: BMI, body mass index; CRP, C-reactive protein; EGR, erythrocyte glutathione reductase; ETK,
erythrocyte transketolase; PASE, Physical Activity Scale for Elderly; RDA, recommended daily allowance; T4, thyroxine. ![]()
Manuscript received March 3, 1999. Initial review completed May 8, 1999. Revision accepted July 21, 1999.
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