Human Nutrition and Metabolism
Long-Term Pharmacologic Doses of Vitamin E Only Moderately Affect
the Erythrocytes of Patients with Type 1 Diabetes Mellitus1
Begon ˜a Manuel y Keenoy,2Honglei Shen, Wendy Engelen, Jan Vertommen,
Guido Van Dessel,* Albert Lagrou* and Ivo De Leeuw
Laboratory of Endocrinology and *Laboratory of Human and Pathological Biochemistry,
University of Antwerp, B-2610 Wilrijk-Antwerp, Belgium
malities in composition and function. To study this relationship, we investigated the effects of a moderate
pharmacologic dose of vitamin E for 1 y on erythrocyte membrane peroxidation in vitro and on its fatty acid
composition, antioxidant capacity and rheological function. In a random and double-blind manner, type 1 diabetic
patients (n ? 44) were assigned to the following two groups: Group S received 250 IU (168 mg) d-? tocopherol 3
times daily for 1 y. Group P received placebo for 6 mo followed by d-?-tocopherol for an additional 6 mo. Variables
were monitored every 3 mo. After 3 mo of supplementation, serum vitamin E doubled (P ? 0.0005), thiobarbituric
acid reactive substances in erythrocyte membranes incubated with tert-butyl hydroperoxide decreased by 25%
(P ? 0.006) and the lagtime of fluorescence increased from 28 ? 16 to 41 ? 28 min (P ? 0.028). Patients who did
not respond to supplementation (13 of 44) had lower serum lipids (P ? 0.017) and body mass index (P ? 0.024).
We did not detect any significant effects of vitamin E supplementation on membrane lipid composition, antioxidant
capacity or blood viscosity. Continuing supplementation for up to 1 y did not further affect serum vitamin E or
membrane peroxidation. Stopping supplementation was followed by a return to inclusion values. These results
show that the decrease in erythrocyte membrane peroxidation after vitamin E supplementation is moderate,
saturable, reversible, restricted to some individuals and has no detectable effect on erythrocyte composition and
function.J. Nutr. 131: 1723–1730, 2001.
In erythrocytes from diabetic patients, increased membrane lipid peroxidation might lead to abnor-
● viscosity ● humans
● vitamin E ● type 1 diabetes mellitus ● erythrocytes ● lipid peroxidation ● membranes
In diabetes mellitus, the high incidence of microvascular
and atherosclerotic disease has been associated with abnormal-
ities of erythrocyte composition and rheological function and
with increased oxidative stress, among many other factors. The
increased blood viscosity seen in diabetes (1) and more so in
patients with established complications (2) has been ascribed
to a decrease in erythrocyte deformability (3) and to changes
in erythrocyte membrane fluidity (4,5). The extent to which
these changes are due solely to alterations in the lipid com-
position of the erythrocyte membrane is still controversial.
Increased cholesterol content and cholesterol/phospholipid ra-
tio, which correlated with the decrease in membrane fluidity
in type 1 diabetes mellitus (T1DM),3were identified as con-
tributing factors (6) in addition to glycation of membrane
proteins (7). In contrast, other authors have found no alter-
ations in erythrocyte membrane lipids of type 2 diabetes mel-
litus (T2DM) patients (8) or even opposite changes such as
decreased cholesterol content (9) or increased phospholipid
content in normolipemic T1DM and T2DM patients (10).
Concerning membrane fatty acid composition, again there is
no consensus on the direction of changes in diabetes. The
relative increase of polyunsaturated acids (PUFA; mainly 20:4
and/or 22:6) found by the three groups mentioned seems in
contradiction to others (11,12).
In T1DM, the unifying mechanism behind all of these
changes has been postulated to be the deficiency in insulin
because it has been observed that insulin treatment, which is
known to improve membrane fluidity (4,5) and blood viscosity
(13), also increases conversion of dietary (n-6) fatty acids
(mainly linoleic acid, 18:2) to PUFA (mainly arachidonic
acid, 20:4) (14).
Another possible mechanism, independent of the effect of
insulin, is suggested by the higher levels of lipid peroxidation
products such as lipofuchsin (15) and malondialdehyde
(MDA) (16,17) found in erythrocytes from diabetic patients.
The increased lipid peroxidation known to exist in diabetes
(18) could target PUFA in membranes in addition to those in
1Data concerning the initial 6 mo of this study were presented in poster form
at the Meeting of the European Society for the Study of Diabetes (EASD),
September 1998, Barcelona, Spain [Manuel y Keenoy, B. Shen, H, L., Engelen,
W., Vertommen, J. & De Leeuw, I.(1998)
on the peroxidability of red blood cell membranes from type 1 diabetic patients.
Diabetologia 41 (suppl. I): A350 (abs.)].
2To whom correspondence should be addressed.
3Abbreviations used: BMI, body mass index; GSH, reduced glutathione;
HbA1c, glycated hemoglobin; MDA, malondialdehyde; TBARS, thiobarbituric acid
reactive substances; t-BuOOH, tert-butyl hydroperoxide; TCA, trichloroacetic
acid; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus.
Effect of vitamin E supplementation
0022-3166/01 $3.00 © 2001 American Society for Nutritional Sciences.
Manuscript received 5 December 2000. Initial review completed 12 January 2001. Revision accepted 14 March 2001.
by guest on May 30, 2013
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