Based on the summary of the findings presented here, it is clear that many malnourished children have low plasma a-tocopherol concentrations.
Moreover, in some cases low plasma a-tocopherol
concentrations have been demonstrated to be asso- ciated with the classic neurologic abnormalities seen in AVED subjects who have a genetic defect in the hepatic a-TTP. Thus, it is likely that if neuro-
logic testing were carried out in more children, then more children would be found with frank vitamin E deficiency. Although anemia was an early classic symptom of vitamin E deficiency in children (221), it is clear that neurologic abnormalities, especially ataxia, are now considered the first unequivocal symptom of vitamin E deficiency in humans (4).
This observation, however, does not negate the im- portance of a-tocopherol in maintaining erythrocyte
membranes and the susceptibility of a-tocopherol-
depleted membranes to rupture and hemolysis. “Antioxidant nutrients” is a rubric that covers a wide variety of dietary components in addition to vitamin E discussed in this review. Vitamin C and a range of dietary antioxidants are relatively abun- dant in a variety of fruits and vegetables. By con- trast, a-tocopherol is more difficult to acquire from
the diet because it is present in appreciable amounts only in foods such as nuts, some seeds, and vege- table oils. The complication in evaluating vitamin E status during malnutrition is the difficulty in evalu- ating a-tocopherol intakes. The quality of the diet
and the amounts of vitamin E consumed do not appear to have been studied in many investigations of kwashiorkor or marasmus. For example, one study noted that antioxidant intakes were limited based on their observation that few tomatoes were consumed (222). It is often difficult to assess the
a-tocopherol contents of diets because of the vari-
ability of vitamin E in oil, as well as the limitation in accurate food vitamin E measurements (4).
Moreover, it can be postulated that the product of low vitamin E status may not be solely due to a limitation in a-tocopherol intakes. For example,
severe PEM is associated not only with poor vitamin E status, but also with essential fatty acid deficiency (223). Also as was discussed previously, the expres- sion of the hepatic a-TTP may be sensitive to
dietary protein intake. It certainly would seem likely that if plasma albumin concentrations are not main- tained, then the hepatic a-TTP might be expendable
in the short term and thus not synthesized in the liver if protein intakes are inadequate. Additionally, a subject could consume a vitamin E-containing sup- plement, but if no dietary fat is consumed with the supplement, the vitamin E will not be absorbed (33). If the a-tocopherol were absorbed, and secreted
in chylomicrons, or if lipo-lysis is limiting (135),
a-tocopherol may not be available to the tissues.
175 Oxidative stress and vitamin E in anemia
a-tocopherol are taken up by the liver, the a-toco-
pherol may not be secreted by the hepatic a-TTP
into the plasma, if the a-TTP is limiting or perhaps
not even synthesized. These various steps in a-toco-
pherol absorption and deli-very to the liver all seem quite dependent upon dietary factors that are not likely to be available or functional during severe malnutrition. Thus, vitamin E deficiency at the RBC and tissue level may occur.
The formulation of a nutritional supplement containing a-tocopherol may be critical because
vitamin E is not well absorbed in the absence of dietary fat (33). Remarkably, Faber et al. (224) reported on anemia in infants aged 6–12 mo (n=361), who were randomly assigned to receive maize-meal porridge for 6 months that was either unfortified (control group) or fortified with b-
carotene, iron, zinc, ascorbic acid, copper, sele- nium, riboflavin, vitamin B6, vitamin B12, and
vitamin E. The proportion of infants with anemia decreased from 45% to 17% in the fortified-por- ridge group, whereas it remained >40% in the control group. These findings suggest that the
combination of nutrients as a supplement to food may be the best strategy for ameliorating anemia in at-risk children.
Taken together, many of the various types of anemia reported herein seem to be accompanied by low vitamin E status that may be also associ- ated with neurologic symptoms characteristic of
a-tocopherol deficiency. While the a-tocopherol
deficiency in malnutrition may be caused by inade- quate food intakes, other anemias related to genetic malfunctions or viral infections may result in a a-tocopherol deficiency caused either
by impaired vitamin E absorption or increased oxidative stress. In the latter cases, a-tocopherol
deficiency may occur in the absence of deficien- cies of other nutrients. In any case, the severity of the neurologic abnormalities that result from a-
tocopherol deficiency, as well as the immuno- logic dysregulation reported to occur with inade- quate a-tocopherol intakes, emphasizes the
critical need not only for vitamin E supplementa- tion but also adequate dietary support with respect to all nutrients.
A
BBREVIATIONS8- hydroxyguanine (80HG ar 8-oxoG) 8-hydroxy-2-deoxyguanosine (80HdG or 8- oxodG)
a-tocopherol (a-TOH)
a-tocopheroxyl radical (ac-TO·) a-tocopherol transfer protein (a-TTP)
ataxia with isolated vitamin E deficiency (AVED)
catalase (CAT)
carboxyethyl-6-hydroxychroman (CEHC) carbon centered radical (R·)
cytochrome P450 (CYP) erythrocyte (RBC) glutathione peroxidase (GSH-px) glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) hemoglobin (Hb)
high density lipoprotein (HDL)
human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) lipid hydroperoxides (ROOH)
low density lipoprotein (LDL) oxygen (02)
peroxyl radical (ROO·)
phospholipid transfer protein (PLTP) polyunsaturated fatty acids (PUFA, RH) protein energy malnutrition (PEM) reactive oxygen species (ROS) reactive nitrogen species (RNS) recommended daily allowance (RDA) reducing equivalents (NAD(P)H) scavenger receptor-B1 (SR-B1) superoxide dismutase (SOD)
thiobarbituric acid reactive substances (TBARS)
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