| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Technical Briefs |
1
Department of Clinical Nutrition and
2
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, A-6020 Innsbruck, Austria
a address
correspondence to this author at: Universitätsklinik Innsbruck, Abteilung für Ernährungsmedizin, Anichstrasse 35, A-6020 Innsbruck, Austria; fax 43-512-504-2017, e-mail
maximilian.ledochowski{at}uibk.ac.at
Fructose malabsorption syndrome is a disease that was first
described less than 15 years ago (1)(2).
In some patients, fructose malabsorption probably reflects a defect in
the duodenal fructose transporter GLUT-5, a facilitative hexose
transporter with limited capacity (3). In patients
with fructose malabsorption, large quantities of fructose reach the
colon where they are broken down by bacteria into short fatty acids,
CO2, and H2 (4).
Bloating, abdominal discomfort, and sometimes osmotic diarrhea are
induced by the degradation products produced by the colonic bacteria.
It is believed that 
36% of the European population has fructose
malabsorption in a more or less severe form, and approximately one-half
of those affected are symptomatic (5).
We recently found that fructose malabsorption is associated with early signs of mental depression (6), folic acid deficiency (7), and lower plasma tryptophan concentrations (8). We have examined whether serum zinc and iron are changed in fructose malabsorbers compared with lactose maldigestors.
One hundred forty-seven otherwise healthy adult outpatients (104 women and 43 men), ages 16–76 years (mean ± SD, 44.7 ± 13.2 years), who visited a physician’s office for a medical health check-up and reported gastrointestinal complaints in a health questionnaire were studied. None of the patients showed signs of inflammatory bowel disease or any other chronic or infectious diseases, and none was taking medication except for contraceptives in some women. All 147 patients underwent H2 breath testing after an oral load of fructose, and 128 patients underwent oral load with lactose 1 week apart. Blood samples were taken after an overnight fast for determination of zinc, iron, transferrin, and ferritin. To rule out non-H2-producers, a single H2 breath test or a lactulose H2 breath test was performed in nonfasting individuals some days before fructose H2 breath testing. Non-H2-producers were excluded from the study.
Breath hydrogen (H2) was measured with an
analyzer (9)(10) from Bedfont Ltd. (Lahner,
Salzburg). All tests were performed between 0800 and 0830, and body
weight and height were measured. After a 12-h overnight fast, a
baseline H2-breath test was performed. An oral
dose of 50 g of fructose or 50 g of lactose was given in 250
mL of tap water, and H2 exhalation was monitored
in 30-min intervals for at least 2 h. Maximum
H2 exhalation after the sugar load was monitored,
and the differences from baseline concentrations
(
H2) were calculated.
Blood samples were drawn with a 7.5-mL trace-element-free syringe with a zinc-free needle from fasting subjects for serum zinc, iron, transferrin, and ferritin measurements. Zinc was measured colorimetrically (Wako Chemicals) according to the manufacturer’s instructions (11). Iron and albumin were measured by a BM/Hitachi 917 system (Boehringer Mannheim), and transferrin and ferritin were measured by immunoturbidimetric assays (Boehringer Mannheim). Iron-binding capacity was calculated using the formula: Fe (µg/dL)/transferrin (mg/dL) x 100. Cutoff values were 10.7 µmol/L for zinc deficiency, 600 µg/L for iron deficiency, and 15 µg/L for ferritin deficiency. The reference interval for calculated iron-binding capacity was 20–50%.
The cutoff point for the diagnosis of fructose malabsorption or lactose
maldigestion was an increase of breath H2
concentrations 
20 ppm over baseline (1). The serum
concentrations of zinc, iron, and ferritin in the two corresponding
groups were compared by the Student t-test, and the
correlation of zinc deficiency with fructose malabsorption was
calculated by the Fisher exact test, using a standard PC statistical
program (STATISTICA for Windows, Ver. 6.0) (12).
After oral fructose administration, 102 of 147 (69%) patients
(33 men and 69 women; 45.0 ± 13.1 years) presented with a
H2 20 ppm. Breath tests after lactose
loading were positive (H2 20 ppm) in 25 of
128 (20%) subjects (6 men and 19 women; 44.6 ± 13.0 years).
Serum zinc was significantly lower in fructose malabsorbers (13.1
± 2.2 µmol/L) than in normal fructose absorbers (14.1 ± 2.1
µmol/L; P = 0.007; Fig. 1
). Serum zinc concentrations had a slight tendency to be lower
in lactose maldigestors (13.0 ± 1.9 µmol/L) compared with
normal lactose digesters (13.5 ± 2.2 µmol/L), but this
difference was not significant. There was no influence of sex or age.
|
The mean serum albumin concentration in fructose malabsorbers was 46.8 mg/L (± 3.2 mg/L) compared with 47.1 mg/L (± 3.1 mg/L; P, not significant) in normal absorbers.
In fructose malabsorbers, plasma iron was 787 µg/L (± 307 µg/L), transferrin was 3260 mg/L (± 524 mg/L), and ferritin was 65.7 µg/L (± 71.8 µg/L), which did not differ from normal fructose absorbers [plasma iron, 800 µg/L (± 300 µg/L; P, not significant); transferrin, 3438 mg/L (± 643 mg/L; P, not significant); ferritin, 82.3 µg/L (± 78.9 µg/L; P, not significant)]. Iron-binding capacity was 24.5% (± 9.9%) in fructose malabsorbers and 24.8% (± 10.1%; P, not significant) in normal fructose absorbers.
Ten of 102 subjects (9.8%) with fructose malabsorption had zinc
deficiency (serum zinc concentration 
10.7 µmol/L), whereas in the
group with normal fructose absorption, 45 of 45 subjects had normal
serum zinc concentrations (Fisher exact test, P =
0.02).
Patients with chronic diarrhea are known to exhibit signs of zinc deficiency (13). Fructose malabsorption is one of the most common causes for chronic diarrhea (4). The decreased zinc that we found in subjects with fructose malabsorption was not an effect of differences in sex or age. Ten subjects presented with zinc deficiency, and all suffered from fructose malabsorption. None of these 10 subjects took oral contraceptives or hormones.
Zinc deficiency seems to play a role in cellular turnover of the gastrointestinal mucosa (14) and also has been linked to poor appetite and mental disturbances (15); the latter is interesting because earlier we found signs of depression in subjects with fructose malabsorption (6).
Plasma iron and ferritin showed a tendency toward lower concentrations in fructose malabsorbers, but the differences were not significant. Zinc and iron are likely to be absorbed by the same duodenal metal transporter, DMT-1 (NRAMP-2), which is also responsible for the absorption of other divalent cations, including Cu2+, Mn2+, Co2+, Cd2+, and Pb2+. Because iron is also absorbed via a ß(3) integrin and mobilferrin pathway that is not shared by other nutritional metals (16), a defective DMT-1 transporter system could be masked by compensatory enhancement of the integrin and mobilferrin pathway for iron metabolism, leaving only the absorption of zinc decreased. Thus, our data cannot exclude that zinc deficiency in fructose malabsorbers is attributable to a limited transport capacity of DMT-1.
Because serum zinc is bound to proteins, especially albumin, we determined serum albumin concentrations in a subgroup of 102 individuals. Mean serum albumin concentrations were not decreased in fructose malabsorbers. Because malnutrition is very unlikely in the population studied, the differences in zinc concentrations between fructose malabsorbers and normal absorbers may thus be attributable to the malabsorption of alimentary zinc.
Overproduction of cytokines may be associated with decreased blood zinc concentrations (17) because of increased renal loss of zinc (18). We previously have shown that fructose malabsorption is a promoting factor for small intestinal bacterial overgrowth syndrome and is associated with higher serum neopterin concentrations (19), an indicator of immune activation. The different bacterial composition of the gut could thus be a promoting factor for zinc deficiency in fructose malabsorbers by chronic immune stimulation. It has been shown that dietary carbohydrates, such as sucrose and fructose, reduce the bioavailability of copper by 30% in humans, but not in rats (20). Because zinc is handled very much like copper and high intestinal fructose concentrations are seen in fructose malabsorption, the same phenomenon could play a role in low zinc status in fructose malabsorption.
In summary, fructose malabsorption is associated with lower serum zinc concentrations; in this study, 10 of 147 subjects (6.8%) had zinc deficiency, and all 10 suffered from fructose malabsorption. Although this is probably not attributable to a shortened transit time of a defective DMT-1-transporter, the exact mechanism still remains to be elucidated. Fructose malabsorption may thus reflect only part of a more complex malabsorption syndrome. Because fructose malabsorption can be seen in approximately one-third of the Western European population, fructose malabsorption could be a major etiology of low zinc status.
References
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
indicate means; larger rectangles
indicate ± 1.00 SE; bars indicate ± 1.96
SE.