Lactose Malabsorption and Intolerance in the Elderly
Background: Lactase activity declines with age in rats, but it is not
clear whether this model is also shared by humans. Few studies have
evaluated lactose intolerance and malabsorption in the elderly and no
definite conclusions can be drawn. The aim of our study was therefore
to verify the impact of age on lactose intolerance and malabsorption.
Methods: Eighty-four healthy subjects took part in the study.
Thirty-three were <65 years, 17 were between 65 and 74 years and 34
were >74 years. All the subjects underwent a preliminary evaluation of
intestinal gas production capacity and oro-cecal transit time by H2/
CH4 breath test after lactulose. After a 3-day period, an H2/CH4
breath test after lactose was performed . The occurrence of
intolerance symptoms during the test and in the 24 h after the test
was recorded.
Results: Breath H2 and CH4 excretion parameters at fasting and after lactulose did not differ between the three groups. Cumulative breath
H2 excretion after lactose was higher in subjects >74 years than in
subjects <65 years and in subjects aged 65–74 years, while no
difference was found between the latter two groups. In subjects >74
years, the prevalence of lactose malabsorption was higher than in the
other two groups, while no significant difference was observed between
subjects <65 years and subjects aged 65–74 years. Within the
malabsorber subjects, the prevalence of lactose intolerance was higher
in subjects <65 years than in those aged 65–74 years and in those aged
>74 years. No significant difference was found between the latter two
groups. No difference was found between the three groups in terms of
daily calcium intake and a significant negative correlation between
symptom score and daily calcium intake was only found in the group of
subjects aged <65 years.
Conclusions: As age increases, the prevalence of lactose malabsorption
shows an increase while the prevalence of intolerance symptoms among malabsorbers shows a decrease . Accordingly, daily calcium intake was
similar among the adults and elderly studied.
Key words: Elderly; H2-breath test; intestinal gas production; lactose intolerance; lactose malabsorption; methane production
Human adult-type hypolactasia is widespread throughout the world due
to a genetically determined decline of lactase activity inherited
through an autosomal recessive gene (1). Its prevalence is highly
variable, ranging from 5% in north-west Europe to almost 100% in some
Asian populations (2). On clinical grounds, hypolactasia is
responsible for lactose malabsorption, which may cause symptoms such
as abdominal pain, bloating, flatulence and diarrhea, evoked by milk
consumption (3).
In human beings, the lactase decline pattern is similar to that
observed in mammals such as rats (4). However, although in rats
lactase activity declines further in old age (5–7), it is not very
clear whether this model is also shared by humans. The measurement of
lactase activity, in fact, gave conflicting results (8, 9) probably
because of the marked effect of small differences in the biopsy site
(10). Only a few studies have evaluated lactose intolerance and
malabsorption in the elderly by means of the hydrogen (H2) breath test
(11–14), but, again, no definite conclusions could be drawn owing to
differences in the methods used and in the ethnic background of the
subjects.
Accordingly, the aim of this study was to verify the impact of age on
lactose intolerance and malabsorption assessed by the H2 breath test.
Unlike previous studies, breath H2 and methane (CH4) excretion after
lactulose administration were first evaluated in all subjects to
exclude the possible interference of unrelated factors such as
differences in (a) H2 production capacity (15), (b) small intestine
transit time (16), (c) occurrence of bacterial overgrowth (17) and (d)
colonic H2 consumption (18).
Subjects and Methods
Patients
 Eighty-four healthy subjects (60 women, 24 men; age range 23–94 years)
took part in the study. Thirty-three subjects were <65 years (23
women, 10 men; mean age 45 +/- 15 years). Seventeen subjects were
between 65 and 74 years (12 women, 5 men; mean age 69 +/- 3 years) and
34 subjects were >74 years (25 women, 9 men; mean age 81 +/- 4 years).
Thirty-three subjects (all <65 years) were members of medical or
paramedical staff of our hospital, while 51 were members of the ‘Third
Age University’, an association organizing cultural and recreational
events for elderly people. All were compliant and gave their informed
consent to the study. Subjects with intestinal, liver, renal, chest,
cardiac, metabolic or neurologic disease or who were taking
antibiotics, prokinetics, laxatives or any other drug known to
influence colonic flora in the month preceding the study were
excluded.
In all subjects nutritional status was assessed by anthropometric
criteria. As given in Table I,
there was no significant difference between the three groups of
subjects in terms of body mass index, thickness of tricipital skin
fold and middle arm circumference.
Daily calcium intake was assessed in each subject by completing a
dietary diary for three non-consecutive days (two non-consecutive
weekdays and one weekend day) listing all the food eaten and the
respective quantities, evaluated on the basis of usual portion sizes
(19). The diaries were then checked by one of the authors, who was
unaware of the clinical details of the subjects and analyzed on the
basis of food-composition tables provided by the Italian National
Institute of Nutrition (20). Moreover, each subject was asked whether
milk and dairy product consumption led to appreciable abdominal
symptoms.
Breath testing
In order to avoid prolonged intestinal gas production, because of the
presence of non-absorbable or slowly fermentable material in the
colonic lumen, the breath test was preceded by a preparation procedure
based on the consumption, the evening before the test day, of a meal
consisting of only rice, meat and olive oil (21). This meal was then
followed by a 12-h fasting period. Breath testing started between 0830
h and 0930 h, after thorough mouth washing with 40 mL of 1%
chlorhexidine solution. Smoking and physical exercise were not allowed
for 1 h prior to and throughout the test.
Sampling of alveolar air was performed by means of a commercial device
(Gasampler Quintron, Milwaukee, Wis., USA), which allows the first 500
mL of dead space air to be separated and discarded while the remaining
700 mL of end-alveolar air are collected in a gas-tight bag. Subjects
were instructed to avoid deep inspiration and not to hyperventilate
before exhalation. A gas chromatograph dedicated to the detection of
H2 and CH4 in air samples was used for breath samples analysis (Model
DP12, Quintron Instrument, Milwaukee, Wis., USA). The accuracy of the
detector was +/- 2 ppm with a linear response range between 2 and 150
ppm of H2 and between 2 and 50 ppm of CH4.
All the subjects underwent a preliminary evaluation of intestinal gas
production capacity and oro-cecal transit time by H2 breath test after
the ingestion of 400 mL of an iso-osmotic solution containing 20 g of
lactulose, a nonabsorbable disaccharide, which is fermented by colonic
flora. Breath samples were taken at fasting and every 10 min for a 4-
h period. Subjects were considered low H2 excretors if no breath
sample contained an H2 concentration exceeding 20 ppm (15) and the
test was considered a false-negative if an increase of breath H2
excretion greater than 20 ppm over the baseline was not evident (22).
A 67-old-woman and a 75-oldwoman fulfilled these criteria and were
excluded from the subsequent stages of the study. For each subject
fasting, peak – that is the maximum increase over the baseline – and
total excretion – evaluated by means of area under the time
concentration curve calculation (23) – of H2 were recorded. Oro-cecal
transit time was indicated by the presence of three sustained
increments of H2 breath excretion of at least 10 ppm over the baseline
(24).
Breath methane (CH4) excretion, the most important metabolic pathway
of H2 consumption (25), was also measured and the prevalence of CH4
producers, i.e. subjects with mean breath CH4 excretion higher than 5
ppm, and the maximum peak, the time of appearance of the maximum peak
and total breath CH4 excretion, were calculated.
After at least a 3-day period, the H2/CH4 breath test after lactose
ingestion was performed. The test solution consisted of 400 mL of
semi-skimmed milk, containing 20 g of lactose. Breath samples were
taken at fasting and every 30 min for a 4-h period. The test was
considered as indicative of the presence of lactose malabsorption when
the peak of H2 breath excretion over the baseline was > 20 ppm (26,
27).
During the test, all the subjects were asked to record the occurrence
of intolerance symptoms experienced during the 24-h period after the
test. Bloating, abdominal pain or cramps, diarrhea and flatulence were
ranked as follows: 0 = absence of the symptoms, 1 = trivial symptoms,
2 = mild symptoms, 3 = moderate symptoms, 4 = strong symptoms, 5 =
severe symptoms (28). The individual scores were then added together
and a mean of the individual values was given. The individual maximum
score was 5.
Data analysis
All variables were expressed as mean +/- standard deviation (s). All
continuous variables showed a normal distribution with the Kolmogorov-Smirnov
normality test. The unpaired t test was computed for the comparison
between two groups and parametric one-way analysis of variance and
Duncan’s test were used for the comparison of the means of more than
Table I. Mean body mass index (BMI), triceps skin fold (TSF) and
middle arm circumference (MAC) in 84 healthy subjects according to age two groups and for the multiple comparisons of the means between the
pairs of groups, respectively. Differences between proportions were
assessed by the chi-squared test. Pearson’s correlation coefficient
was computed for the parametric estimates of the level of association
between two variables. A P value <0.05 was considered significant.
Results
Table II indicates that subjects <65 years, between 65 and 74 years
and >74 years did not significantly differ as regards a series of
breath H2 and CH4 excretion parameters at fasting and after 20 g of
lactulose.
Fasting breath H2 concentrations (21) and the analysis of the breath
H2 excretion after lactulose administration (29) did not suggest the
presence of small intestine bacterial overgrowth in any subject.
Mean cumulative breath H2 excretion after lactose administration was
significantly higher in subjects >74 years (236 +/- 35 ppm * min) than
in subjects <65 years (123 +/- 17 ppm * min; P < 0.005) and in
subjects aged 65–74 years (159 +/- 36 ppm * min; P < 0.01), while no
significant difference was found between the latter two groups (Fig.
1). The prevalence of lactose malabsorption is shown in Fig. 2. In
subjects >74 years, this prevalence (83%) was significantly higher
than in the other two groups.
 Again, no significant difference was
observed between subjects <65 years (58%) and subjects aged 65–74
years (65%).
As regards lactose intolerance, all subjects but two (aged 36 and 44
years) who complained of appreciable abdominal symptoms after milk and
dairy product consumption turned out to be malabsorbers at the H2
breath test. Fig. 2 also shows that within the subjects with
documented lactose malabsorption the prevalence of lactose intolerance
was significantly higher in subjects <65 years (80%) than in those
aged 65–74 years (50%) and in those aged >74 years (48%). No
significant difference was found between the latter two groups.
As regards severity of intolerance, mean symptom scores showed no
significant differences between the three groups of subjects studied
(2.7 +/- 2.5 for subjects <65 years, 2.4 +/- 2.2 for subjects aged
65–74 years and 2.5 +/- 2.2 for subjects >74 years). No difference was
found between the three groups in terms of daily calcium intake (695
+/- 85 mg/day for subjects <65 years, 785 +/- 92 mg/day for subjects
aged 65–74 years and 810 +/- 110 for subjects >74 years). A
significant correlation (r = ¡0.73, P < 0.001) between symptom score
and daily calcium intake was only found in the group of subjects aged
<65 years (r = ¡0.08, for the group of subjects aged 65–74 years, and
r = ¡0.22, for the group of subjects aged >74 years).
Discussion
Our study, performed on a cohort of healthy, well-nourished subjects
aged 23–94 years, shows that there is an age-dependent increase of
breath H2 excretion after the ingestion of 400 mL of semi-skimmed
milk. This increase can only be ascribed to lactose malabsorption,
since elderly and younger adult subjects do not differ in terms of H2
production capacity by colonic flora (15), small intestine transit
time (16), occurrence of bacterial overgrowth (17), and colonic H2
consumption via CH4 production (18). The observation that adults and
elderly subjects show the same pattern of intestinal gas production
and consumption permits us to make at least two general observations:
. first, no particular interpretation of the results of H2-breath tests
is necessary for elderly subjects; second, age alone does not
represent a factor predisposing to alterations of intestinal gas
metabolism and should not condition the clinical-diagnostic
classification of elderly patients.
Our study also demonstrates that the prevalence of lactose
malabsorption increases significantly after the age of 74 years. In a
recent study (14) performed in a cohort of 80 healthy Caucasian women
aged 40–79, the prevalence of lactose malabsorption was significantly
higher in subjects aged 60–79 (50%) than in subjects aged 40–59 (15%).
In this study the prevalence of lactose malabsorption in subjects aged
60–79 years was similar to that found in our healthy subjects aged
65–74 years. So, showing a further increase in subjects older than 74
years, our data complete these results, suggesting a more extended
age-related decline of lactase activity during the life span. Lactose
malabsorption is therefore one of the components of the broad spectrum
of the aging gut and its mechanism is not easy to explain. It has been
suggested that the increased enterocyte turnover shown both in aged
animals (30) and humans (31) means that an increased proportion of
relatively undifferentiated epithelial cells line the villi in the
elderly with a consequent functional immaturity and delayed enzyme
expression (5).
As far as the occurrence of symptoms after lactose administration is
concerned, the prevalence of lactose intolerance among malabsorbers
was significantly lower in subjects aged >65 years than in younger
adults and advancing age did not determine a further decline in
lactose intolerance. Our results do not agree with a previous study
(14) showing no difference in prevalence of lactose intolerance
between adults and elderly malabsorbers. However, such a discrepancy
may be explained on the basis of a higher carbohydrate load used by
those authors.
In our elderly subjects, a higher lactose malabsorption and a higher
colonic H2 production after lactose administration were associated
with a lower rate of lactose intolerance. Therefore, it can more
reasonably be suggested that differences of viscerosensitivity between
the age groups studied may be responsible for our results. Recent
papers have shown that intra-esophageal balloon distension may cause a
dramatic decrease in pain perception in elderly volunteers (32) and an
age-related abolishment or reduction of secondary esophageal
peristaltic activity (33) suggesting a possible role of abnormalities
of afferent pathways and/or esophageal mechanoreceptors. It is
therefore possible that similar alterations can involve the
gastrointestinal tract at different levels and further studies are
needed to clarify this issue.
Daily calcium intake did not differ between the three groups and a
significant inverse correlation between severity of symptoms and
calcium intake was evident in adult subjects only. Intolerant patients
avoid milk and other dairy products, drastically reducing their daily
calcium intake and exposing them to the risk of detrimental effects on
bone and mineral metabolism (34). Therefore, in the light of our
results, the lower prevalence of lactose intolerance may exert a
protective effect in the elderly against consequent nutritional
deficits. The symptom score in our malabsorbers was in any case
limited and, considering differences in methods, was substantially
similar to that reported in previous studies (28, 35). It can
therefore be stated that malabsorbers may be allowed to follow a diet
containing dairy products; a very recent paper (36) has even shown
that lactose malabsorption is not an impediment to the ingestion of a
dairy-rich diet supplying around 1500 mg of calcium, the dose
recommended by an NIH Consensus Statement for the prevention of
osteoporosis. Our results do not agree with a recent study (14) which
showed a reduction of calcium intake in malabsorbers aged >70 years
compared to absorbers with similar age. However, this finding was
based on a small number of subjects and, moreover, data on the
prevalence of lactose intolerance are also lacking. In conclusion, on
the basis of our results, the ingestion of dairy products should be
encouraged in the elderly, also because of the known reduced
intestinal capacity to absorb calcium (37) and to adapt to a diet with
low calcium concentration (38).
References
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