*Anti-sickling
effect of dietary thyocyanate in prophylactic control of sickle
cell anemia
Agbai, O
J Natl Med Assoc 1986 Nov;78(11):1053-6
*Sickle
cell anemia and dietary precursors of cyanate
Houston RG
Am J Clin Nutr 1973 Nov;26(11):1261-4
Oral
glutamine supplementation decreases resting energy expenditure
in children and adolescents with sickle cell anemia.
Williams R, Olivi S, Li CS, Storm M, Cremer L, Mackert P, Wang
W.
J Pediatr Hematol Oncol. 2004 Oct;26(10):619-25.
CONCLUSIONS: After 24 weeks of orally administered
glutamine, children and adolescents with sickle cell anemia
had a decrease in REE and improvement in nutritional parameters.
Those who were underweight had a greater decrease in REE than
those of normal body weight. Lowering REE may be an effective
way to improve the growth of these children and adolescents...
Arginine
therapy: a new treatment for pulmonary hypertension in sickle
cell disease?
Morris CR, Morris SM Jr, Hagar W, Van Warmerdam J, Claster S,
Kepka-Lenhart D, Machado L, Kuypers FA, Vichinsky EP.
Am J Respir Crit Care Med. 2003 Jul 1;168(1):63-9. Epub 2003
Mar 05.
With limited treatment options and a
high mortality rate for patients with sickle cell disease who
develop pulmonary hypertension, arginine is a promising new
therapy that warrants further investigation.
Oral
citrulline as arginine precursor may be beneficial in sickle cell
disease: early phase two results.
Waugh WH, Daeschner CW 3rd, Files BA, McConnell ME, Strandjord SE.
J Natl Med Assoc. 2001 Oct;93(10):363-71.
Continued L-citrulline supplementation in compliant
subjects continued to lessen symptomatology, to maintain plasma
arginine concentrations greater than control levels, and to
maintain nearly normal total leukocyte and neutrophil counts.
Side effects or toxicity from citrulline were not experienced.
Oral L-citrulline may portend very useful for palliative therapy
in sickle cell disease. Placebo-controlled, long-term trials
are now indicated.
In
Vitro Effects of Aged Garlic Extract and Other Nutritional Supplements
on Sickle Erythrocytes
Ohnishi ST, Ohnishi T.
J Nutr. 2001 Mar;131(3s):1085S-92S.
On the basis of these in vivo and ex vivo studies,
we propose that a cocktail of antioxidants would have beneficial
effects in lessening the incidence and severity of crisis and
reducing anemia in sickle cell disease
Body
composition in children with sickle cell disease.
Barden EM, Kawchak DA, Ohene-Frempong K, Stallings VA, Zemel BS.
Am J Hematol. 2002 Apr;69(4):239-46.
CONCLUSIONS: Children with SCD have impaired
growth, delayed puberty, and poor nutritional status. Low z
scores for upper arm fat area indicate deficits in fat (energy)
stores, and low FFM coupled with low upper arm muscle area indicate
muscle wasting and low protein stores. These body-composition
abnormalities suggest that the nutritional needs of the African
American children with SCD were not being met.
Optimization
of folic acid, vitamin B(12), and vitamin B(6) supplements in pediatric
patients with sickle cell disease.
van der Dijs FP, Fokkema MR, Dijck-Brouwer DA, Niessink B, van der
Wal TI, Schnog JJ, Duits AJ, Muskiet FD, Muskiet FA.
Am J Hematol. 2002 Apr;69(4):239-46.
Using homocysteine as a functional marker, we
determined optimal folic acid, vitamin B(12), and vitamin B(6)
dosages in 21 pediatric sickle cell disease (SCD) patients (11
HbSS, 10 HbSC; 7-16 years). Optimal dosages are as follows:
700 microg folic acid (3.5-7 U.S. 1989 RDA), 3 U.S. 1989 RDA
vitamin B(12) (4.2-6.0 microg), and 3 U.S. 1989 RDA vitamin
B(6) (4.2-6.0 mg). A practical daily combination is 1 mg folic
acid (4.3-8.5 U.S. 1998 RDA when taken with meals), 6 microg
vitamin B(12) (2.5-5 U.S. 1998 RDA), and 6 mg vitamin B(6) (4.6-10
U.S. 1998 RDA). This combination may by simple and relatively
inexpensive means reduce these patients' inherently high risk
of endothelial damage. Copyright 2002 Wiley-Liss, Inc.
Effect
of zinc supplementation on growth and body composition in children
with sickle cell disease.
Zemel BS, Kawchak DA, Fung EB, Ohene-Frempong K, Stallings VA.
Biochem Med Metab Biol. 1988 Feb;39(1):64-8.
CONCLUSIONS: Prepubertal children with SCD-SS
may have zinc deficiency and may benefit from zinc supplementation
to improve linear growth and weight gain.
Carbamylation
of hemoglobin in vivo with chronic sublethal dietary cyanide: implications
for hemoglobin S.
Jackson LC, Oseguera M, Medrano S, Kim YL.
Biochem Med Metab Biol. 1988 Feb;39(1):64-8.
Carbamylation of the hemoglobin in sickle cell
anemia has been demonstrated to improve the status of this hemoglobinopathy.
Using an animal model of West African human patterns of chronic
sublethal dietary cyanide ingestion, 12 miniature swine consuming
either 0, 0.4, 0.7, or 1.2 mg of cyanide/kg body weight/day
were studied for 24 weeks to determine if this dietary regime
could produce irreversible carbamylated hemoglobin. Throughout
the study, the hematological status of all animals remained
similar; however, the levels of carbamylated hemoglobin as measured
by nanomoles of valine hydantoin varied proportionally to dietary
sublethal cyanide intakes, indicating that these natural dietary
levels could effect an important and presumably permanent modification
of the hemoglobin's beta chain. Serum thiocyanate levels were
also positively correlated with cyanide ingestion loads (r =
0.83, P less than 0.01). The implications of these findings
in swine are important for the millions of humans with hemoglobin
S who regularly consume similar levels of dietary cyanide and
for our assessments of the biochemical and medical status of
hemoglobin S under natural conditions.
Interaction
of Antioxidants and Their Implication in Genetic Anemia
Chan AC, Chow CK, Chiu D.
Proc Soc Exp Biol Med. 1999 Dec;222(3):274-82.
The generation of reactive oxygen species (ROS)
is a steady-state cellular event in respiring cells. Their production
can be grossly amplified in response to a variety of pathophysiological
conditions such as inflammation, immunologic disorders, hypoxia,
hyperoxia, metabolism of drug or alcohol, exposure to UV or
therapeutic radiation, and deficiency in antioxidant vitamins.
Uncontrolled production of ROS often leads to damage of cellular
macromolecules (DNA, protein, and lipids) and other small antioxidant
molecules. A number of major cellular defense mechanisms exist
to neutralize and combat the damaging effects of these reactive
substances. The enzymic system functions by direct or sequential
removal of ROS (superoxide dismutase, catalase, and glutathione
peroxidase), thereby terminating their activities. Metal binding
proteins, targeted to bind iron and copper ions, ensure that
these Fenton metals are cryptic. Nonenzymic defense consists
of scavenging molecules that are endogenously produced (GSH,
ubiquinols, uric acid) or those derived from the diet (vitamins
C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids).
These antioxidant nutrients occupy distinct cellular compartments
and among them, there are active recycling. For example, oxidized
vitamin E (tocopheroxy radical) has been shown to be regenerated
by ascorbate, GSH, lipoic acid, or ubiquinols. GSH disulfides
(GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent
protein), and enzymic pathways have been identified for the
recycling of ascorbate radical and dehydroascorbate. The electrons
that are used to fuel these recycling reactions (NADH and NADPH)
are ultimately derived from the oxidation of foods. Sickle cell
anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency
are all hereditary disorders with higher potential for oxidative
damage due to chronic redox imbalance in red cells that often
results in clinical manifestation of mild to serve hemolysis
in patients with these disorders. The release of hemoglobin
during hemolysis and the subsequent therapeutic transfusion
in some cases lead to systemic iron overloading that further
potentiates the generation of ROS. Antioxidant status in anemia
will be examined, and the potential application of antioxidant
treatment as an adjunct therapy under these conditions will
be discussed.
High-dose
vitamin C: a risk for persons with high iron stores?
Gerster H.
Int J Vitam Nutr Res. 1999 Mar;69(2):67-82.£
The contribution of vitamin C (ascorbic acid)
to the prevention of iron deficiency anemia by promoting the
absorption of dietary non-heme iron-especially in persons with
low iron stores--is well established. But the question has been
raised whether high-dose intakes of vitamin C might unduly enhance
the absorption of dietary iron in persons with high iron stores
or in patients with iron overload, possibly increasing the potential
risk of iron toxicity. Extensive studies have shown that overall
the uptake and storage of iron in humans is efficiently controlled
by a network of regulatory mechanisms. Even high vitamin C intakes
do not cause iron imbalance in healthy persons and probably
in persons who are heterozygous for hemochromatosis. The uptake,
renal tubular reabsorption and storage of vitamin C itself are
also strictly limited after high-dose intake so that no excessive
plasma and tissue concentrations of vitamin C are produced.
The effect of high-dose vitamin C on iron absorption in patients
with iron overload due to homozygous hemochromatosis has not
been studied. Of special importance is the early identification
of hemochromatosis patients, which is assisted by the newly
developed PCR test for hereditary hemochromatosis. Specific
treatment consists of regular phlebotomy and possibly iron-chelating
therapy. These patients should moreover avoid any possibility
of facilitated absorption of iron and need to limit their intake
of iron. Patients with beta-thalassemia major and sickle cell
anemia who suffer from iron overload due to regular blood transfusions
or excessive destruction of red blood cells need specialized
medical treatment with iron chelators and should also control
their intake of iron. The serum of patients with pathological
iron overload can contain non-transferrin-bound iron inducing
lipid peroxidation with subsequent consumption of antioxidants
such as vitamin E and vitamin C. The role of iron in coronary
heart disease and cancer is controversial. Early suggestions
that moderately elevated iron stores are associated with an
increased risk of CHD have not been confirmed by later studies.
In vitro, ascorbic acid can act as a prooxidant in the presence
of transition metals such as iron or copper, but in the living
organism its major functions are as an antioxidant. High intakes
of vitamin C have thus not been found to increase oxidative
damage in humans. Accordingly, the risk of CHD or cancer is
not elevated. On the contrary, most studies have shown that
diets rich in vitamin C are inversely related to the incidence
of these diseases.
A
decrease in irreversibly sickled erythrocytes in sickle cell anemia
patients given vitamin E.
Natta CL, Machlin LJ, Brin M.
Am J Clin Nutr. 1980 May;33(5):968-71.
Patients with sickle cell anemia were given 450
IU of vitamin E (as alpha-tocopherol) per day for 6 to 35 weeks.
Plasma tocopherol levels increased from 0.7 +/- 0.2 mg/g lipid
pretreatment, to 2.3 +/- 0.3 mg/g lipid. The percentage of circulating
irreversibly sickled red cells decreased from 25 +/- 3% pretreatment
to 11 +/- 1% after vitamin E administration (P less than 0.001).
The percentage of irreversibly sickled red cells remained below
pretreatment levels as long as the vitamin was administered
(up to 35 weeks). The biochemical and clinical implications
of these observations are discussed.
Zinc
deficiency in patients with sickle cell disease
Prasad AS.
Am J Clin Nutr. 2002 Feb;75(2):181-2.
Zinc deficiency is relatively common in adult
patients with SCD, affecting 60–70% of the adult SCD patients
in our center (2, 6). Our diagnosis of zinc deficiency is based
on zinc concentrations in lymphocytes and granulocytes in SCD
patients. Hyperzincuria and a high protein turnover due to increased
hemolysis significantly increase the daily zinc requirement
in SCD patients, which is not met by the usual dietary intake.
The role of intestinal absorption and endogenous zinc loss is
not known.
