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Nutrition in sickle cell disease: recent insights
This article was published in the following Dove Press journal:
Nutrition and Dietary Supplements
Kayellen Umeakunne
1
Jacqueline M Hibbert
2
1
Clinical Research Center, Bio-nutrition
Core, Morehouse School of Medicine,
Atlanta, GA, USA;
2
Morehouse School of
Medicine, Department of Microbiology,
Biochemistry and Immunology, Atlanta,
GA, USA
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Abstract: A cure for sickle cell anemia (SCA) is not available to all who have inherited this
devastating genetically inherited disease. However, increasing knowledge that nutritional
problems are fundamental to the severity of the disease, has produced interest in promoting
dietary supplementation for treating these patients. This review seeks to emphasize the
understanding that both children and adults with sickle cell disease require much higher
energy and protein consumption (more macronutrient intake) than healthy individuals and
tend to suffer from undernutrition if energy intake is consistently low. Shortages may also
exist for micronutrients, eg, Glutathione, which has both anti-inammatory and anti-oxidant
properties. Both chronic inammation and oxidant stress are central issues for increased
sickle cell disease severity. In conclusion, dedicating more effort and resources to establish-
ing recommended dietary reference intakes (DRIs)/recommended dietary allowances (RDAs)
for SCA patients is essential, and nutritional intervention should be included as an adjunct
treatment in tandem with standard practice.
Keywords: macronutrients, micronutrients, inammation, vaso-occlusive crisis (VOC)
Introduction
Sickle cell disease (SCD), involves widespread single-gene disorder hemoglobino-
pathies. The most common gene disorders are sickle cell anemia (HbSS or SCA),
hemoglobin SC (HbSC) and hemoglobin Sβthalassemia (HbSβ
thal
). Patients with
SCA suffer most severely, and these diseases represent a signicant global public
health concern, in endemic malaria environments. Over 100,000 people in the
United States, are affected. Estimates recorded by the United Nations for the year
2008, were 2025 million people worldwide living with SCD, with people of
African descent primarily affected.
1,2
This review addresses SCA with associated
high severity, and regular costly hospital stays. In 2004 approximately 113,000
hospitalizations for SCD were recorded in the United States. The estimated hospital
costs at that time were $488 million for the year.
3
Earlier estimates for 19891993
were $475 million per year,
4
indicating an approximate 3% increased hospitaliza-
tion cost between 1993 and 2004.
Hydroxyurea (HU), the rst drug approved by the FDA to treat SCD, has
provided the ability to extend life and reduce morbidity and mortality in individuals
affected by the disease.
5
However, average life expectancy is still approximately
30 years lower for individuals with sickle cell anemia (SCA) than for the general
population.
6
Increased use of HU has resulted in decreased attention to new studies
addressing nutritional deciencies, which still exist and contribute to slowed
growth, development, and reduced quality of life in this population. Nutrition is
reported to impact many chronic health conditions associated with SCD, including
chronic baseline inammation,
7
vaso-occlusive crisis (VOC), which is accompanied
Correspondence: Jacqueline M Hibbert
Morehouse School of Medicine, 720
Westview Drive, SW, Bldg. HG, Suite
309-D, Atlanta, GA 30310-1495, USA
Tel +1 404 752 1737
Fax +1 404 752 1179
Email jhibbert@msm.edu
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by frequent pain and greater occurrence of stroke, particu-
larly in young children.
8
Other severe manifestations of
SCD are pulmonary hypertension, cardiovascular and
renal disease.
Targeted evidence-based
recommendations for nutrition
therapy in sickle cell disease
It is becoming more apparent that current dietary recom-
mendations for SCD should include more emphasis on
adequate amounts of macronutrients.
8
Traditional supple-
mentation studies addressed only the association of SCA
with a variety of micronutrient deciencies, including zinc,
copper, folic acid, pyridoxine, vitamin E, and more recently
B6, B12, omega three fatty acids
9
and vitamin D.
10
The
standard treatment protocol provides these supplements.
One small study reported in 1985 demonstrated the efcacy
of including macronutrient supplementation. Compared
with only micronutrient supplements, intervention with
macronutrients, (proteins carbohydrates and fats) showed
measurable improvement in clinical condition, and reduced
hospital admissions in growth delayed children with SCA.
11
More recently, in a sickle cell mouse model, Manci et al,
conrmed diminished organ damage and vascular leakage
with a high protein to energy diet (35%) (Figure 1),
12
based
on a previous report by Archer et al, that macronutrient
supplementation reduced chronic inammation. Protein to
energy ratio is a signicant determinant of dietary ade-
quacy, and for optimal growth control mice require 20%
of energy from dietary protein. These studies showed
a trending increased weight gain for S35 versus S20 mice
(p<0.06). Also, inammatory proteins C-reactive protein
(CRP) and interleukin-6 (IL-6) decreased signicantly in
S35 versus S20 mice (P<0.05), suggesting that added
macronutrient intervention could reduce sickle cell disease-
associated inammation, which drives disease severity and
ultimate organ damage.
13
Energy and protein requirements
Adults and children with sickle cell anemia have a relative
energy shortage. Hibbert et al, and others have shown that
nutritional deciency in SCA is secondary to a marked
hypermetabolic state associated with higher energy
requirements. Investigations demonstrated increased urea
kinetics (a result of protein catabolism),
14
erythropoiesis,
myocardial energy expenditure,
15
and proinammatory
cytokines,
16
as signicant contributors to the increased
energy demands. In SCD patients, nutrients from the diet
and amino acids from body protein catabolism channeled
toward rapid red cell production, are replacing hemolyzed
sickle red cells being constantly removed from the circula-
tion. This metabolic irregularity drastically increases the
energy requirement and reduces the availability of nutri-
ents for growth and development in children and for main-
taining adequate muscle mass in adults. The primary
clinical manifestation of this relative nutrient deciency
is severe undernutrition. Singhal et al, measured the diet-
ary intakes and resting metabolic rates (RMR) of 41 chil-
dren with SCD and 31 control subjects with normal
hemoglobin, aged three to six years. Dietary intake was
assessed by weighed food consumption and RMR was
determined by indirect calorimetry. The children with
SCD had signicantly elevated RMR compared with the
healthy controls, after adjusting for gender and weight.
Energy intake was similar for both groups, but the ratio
of energy intake to RMR was signicantly lower for the
The high protein: energy diet (35%) prevented damage to spleen
& liver (P<0.001), kidney (P=0.06) and lung (P=0.006) in S35 mice
Vascular leak
(OD at 620 nm)
1.0
0.8
0.6
0.4
0.2
0.0
20%-diet 35%-diet
Lung
HEART
C20, control mice 20% diet; C35, C mice 35% diet
S20, sickle mice 20% diet; S35, S mice 35% diet
SPLEEN LIVER KIDNEY
C20
C35
S20
S35
P<0.0001
P<0.001
P=0.064
40
30
20
10
0
Organ damage score
Figure 1 High protein diet reduced organ damage in sickle cell mice.
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SCD compared with the control group. The authors con-
cluded that this observation indicates a relative energy
deciency in SCD.
17
These ndings support a hypothesis
for the increased need for energy from macronutrients (ie,
proteins, carbohydrates, and fats), for pre-pubertal children
with sickle cell disease. This condition is also likely to be
the case for adults with SCD, particularly those that inherit
the SCA genotype.
Macronutrients required to improve
nutritional status in SCD amino
acids
Arginine
The amino acid arginine plays a vital role in the synthesis
of nitric oxide in the endothelial cells. Nitric oxide stimu-
lates muscle cells to relax thereby regulating blood ow
and blood pressure through dilatation. Arginine metabo-
lism is impaired in SCD and contributes to endothelial
dysfunction, vaso-occlusive crises, and pulmonary hyper-
tension. Arginine deciency develops over time so that by
adulthood it achieves a low steady state. Due to the inter-
action between arginine availability and nitric oxide levels,
lack of adequate amounts of arginine leads to disruption of
vascular homeostasis and oxidative stress. Therefore, in
SCD arginine becomes an essential amino acid.
18
Kehinde et al, investigated twenty (20) normal non-sickle
cell anemia (NSCA) subjects and 20 SCA subjects receiving
supplementation with L-arginine (1 gm/day for six weeks) to
determine its effect on liver enzymes, lipid peroxidation, and
nitric oxide metabolites. Plasma arginine, liver enzymes ala-
nine aminotransferase (ALT), aspartate aminotransferase
(AST), alkaline phosphatase (ALP), plasma total bilirubin
concentration (TB), malondialdehyde concentration (MDA-a
marker of oxidative stress) and nitric oxide (NOx) metabolite
concentrations were estimated. ALT, AST, ALP (p<0.05 for
all) and TB (p<0.001) were signicantly higher for SCD
subjects than for healthy controls at baseline. Plasma arginine
and nitric oxide levels were signicantly higher for the con-
trols (p<0.001 and <0.05 respectively). Arginine supplemen-
tation caused a greater percentage increase in plasma
arginine and nitric oxide in SCD than in non-SCD subjects
(p<0.001).
19
This research provides evidence that a chronic,
oral low-dose supplementation with L-arginine improves
liver function, increases plasma arginine concentration and
nitric oxide metabolite levels in both non-SCD and SCD
subjects, thereby reducing oxidative stress with greater sen-
sitivity demonstrated in SCD subjects. A randomized,
double-blind study in children showed that supplementing
a ready-to-use food with arginine and citrulline resulted in
increased bioavailability of arginine and improvement in
endothelial function.
20
Dietary supplementation with argi-
nine and nitrates may help to alleviate endothelial dysfunc-
tion in SCD patients by maintaining ample substrate to
generate nitric oxide. Arginine supplementation has also
been shown to increase total antioxidant activity and erythro-
cyte integrity in SCA subjects.
21
Foods with high nitrate and
nitrite content include beets, spinach, radishes, celery, and
mustard greens.
22
Providing food sources of antioxidant
Vitamins E, C and A (beta-carotene) can also boost the
glutathione antioxidant defense system and work together
with arginine-derived nitric oxide to combat oxidative
stress.
23,24
Dietary sources of bioactive food components
that may be helpful for SCD associated chronic disease
management, as well as energy and macronutrient require-
ments, are found in (Table 1 ).
Glutamine
Glutamine is a non-essential amino acid whose synthesis is
ATP-dependent. Glutamine becomes conditionally essen-
tial in sickle cell disease due to its increased requirement.
Deciency for glutamine availability may result in meta-
bolic stress, increased resting energy expenditure (REE),
muscle wasting and decreased immune function. A study in
27 children and adolescents with SCD, supplemented with
600 mg/kg/day of oral glutamine resulted in decreased REE
by 6 percent indicative of reduced protein turnover and
improved glutamine nutritional status.
25
Glutamine is also
a precursor of NAD, and recent research indicates that
glutamine may make sickle RBCs less adhesive.
26
Evidence suggests that a pharmaceutical grade of
L-glutamine is benecial for decreasing the incidents of
SCD-related vaso-occlusive (VOC) pain events without
signicant safety concerns.
27
In 2017, the FDA approved
pharmaceutical grade L-glutamine for children and adults
with sickle cell disease. For individuals >5 years of age with
repeated VOC pain events, oral L-glutamine at a dose of
0.3 g/kg twice per day is recommended, with a maximum
daily dose of 30 g.
28
L-Histidine, leucine, valine, and
cysteine are also insufcient in SCD subjects.
29
Vitamin D and SCD
Vitamin D is vital for calcium homeostasis and essential
for bone mineralization. Deciency of Vitamin D is com-
mon in sickle cell disease due to dark skin pigmentation,
limited sun exposure, increased catabolism and decreased
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Table 1 Dietary reference intakes for healthy individuals and dietary sources of nutrients suggested for nutrition management of SCD*
Nutrient Increased
Need in
SCD
DRI (RDA)
Children
DRI (RDA)
Adults
Dietary Sources
Protein (g/d) 13y13
48y19
913 y 34
1418 y F 46
1418 y M 52
19 70+y F 46
19 70+y M 56
Pregnancy 71
Lactation 71
Beans, Peas, Lentils, Nuts, Seeds, Peanut, Butter, Whole Grains, Meat,
Fish, Poultry,
Carbohydrate (g/d) 118 y 130 1970+ y 130
Pregnancy 175
Lactation 210
Wheat, Rice, Oats, Sorghum, Millet, Fonio Corn, Quinoa, Beans,
Lentils, Peas, Potatoes, Fruits, Vegetables, Breakfast Cereals, Breads,
Pasta
Omega 3 Fatty
Acids
α-Linolenic Acid
(g/d)
13 y 0.7
48 y 0.9
913 y F 1.0
913 y M 1.2
1418 y F 1.1
1418 y M 1.6
1970+y M 1.6
1970+y F 1.1
Pregnancy 1.4
Lactation 1.3
*α-Linolenic Acid sources;
Walnuts, Flaxseeds, Chia seeds, Black Walnuts, Edamame
Dietary Fiber (g/d) 13y19
48y25
913 y F 26
913 y M 31
1418 y F 26
1418 y M 38
1950 y M 38
1950 y F 25
5170+ M 30
5170+ F 21
Pregnancy 28
Lactation 29
Whole grains (wheat, millet, sorghum, fonio brown rice), lima beans,
kidney beans, black beans, pinto beans, black-eyed peas, sweet pota-
toes, greens pistachios, almonds, banana, apples, pears, berries, avo-
cado, yams
Vitamin B6 (mg/d) 13 y 0.5
48 y 0.6
913 y 1.0
1418 y F 1.2
1418 y M 1.3
1950 y 1.3
5170+ M 1.7
5170+ F 1.5
Pregnancy 1.9
Lactation 2.0
Chickpeas, Bananas, Potatoes, Fortied Breakfast Cereals, Tuna,
Salmon, Turkey
Vitamin B12(μg/d) 13 y 0.9
48 y 1.2
913 y 1.8
1418 y 2.4
1970+y 2.4
Pregnancy 2.6
Lactation 2.8
Clams, Liver, Fortied Cereals, Fortied Nutritional Yeast, Rainbow
Trout, Salmon, Tuna
Folate (μg/d) 13 y 150
48 y 200
913 y F 300
913 y M 400
1418 y 400
1970+y 400
Pregnancy 600
Lactation 500
Black-eyed Peas, Chickpeas, Asparagus, Avocado, Spinach, Broccoli,
Brussel Sprouts, Wheat Germ, Enriched Pasta, Mustard Greens,
Kidney Beans
Vitamin A (μg/d) 13 y 300
48 y 400
913 y 600
1418 y F 700
1418 y M 900
1970+y M 900
1970+y F 700
Pregnancy 770
Lactation 1,300
*Betacarotene sources
Sweet Potato, Carrots, Cantaloupe, Broccoli, Spinach, Pumpkin,
Mango, Red peppers, Sweet Potatoes, Papaya
Vitamin C (mg/d) 13y15
48y25
913 y 45
1418 y F 65
1418 y M 75
1970+y M 90
1970+y F 75
Pregnancy 85
Lactation 120
Broccoli, Oranges, Kiwi, Guava, Strawberries, Collard Greens,
Lemons, Brussel Sprouts, Cauliower, Bell Peppers, Tomatoes, Apples
Vitamin D (μg/d) 13y15
48y15
913 y 15
1418 y 15
1970 y 15
>70 y 20
Pregnancy 15
Lactation 15
Salmon, Tuna, Mackerel, Cod liver oil, Sardines, Fortied Cereals,
Fortied Milk & Yogurt, Fortied Soy Milk, Eggs, Fortied Orange
Juice, Mushrooms
(Continued)
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Table 1 (Continued).
Nutrient Increased
Need in
SCD
DRI (RDA)
Children
DRI (RDA)
Adults
Dietary Sources
Vitamin E (mg/d) 13y6
48y7
913 y 11
1418 y 15
1970+y 15
Pregnancy 15
Lactation 19
Wheat germ oil, Sunower Seeds, Almonds, Spinach, Broccoli, Plant
Oils, Peanut Butter, Spinach
Calcium(mg/d) 13 y 700
48 y 1,000
913 y 1,300
1418 y 1,300
1970 y M 1,000
1950 y F 1,000
5170+y F 1,200
>70 y M 1,200
Pregnancy 1,000
Lactation 1,000
Yogurt, Cheese, Sardines, Milk, Fortied Soymilk, Calcium-set Tofu,
Fortied Cereals, Turnip Greens, Kale, Fortied Orange Juice, Salmon
with bones, Frozen Yogurt, Ice Cream
Magnesium (mg/d) 13y80
48 y 130
913 y 240
1418 y F 360
1418 y M 410
1930 y M 400
3170+y M 420
1930 y F 310
3170+y F 320
Pregnancy 350
Lactation 320
Almonds, Cashews, Peanuts, Spinach, Whole Wheat Cereal, Soymilk,
Black Beans, Oatmeal, Avocado, Dark Chocolate, Edamame, Baked
Potato with Skin, Brown Rice, Kidney Beans
Potassium (mg/d) 13 y 3,000
48 y 3,800
913 y 4,500
1418 y 4,700
1970+y 4,700
Pregnancy 4,700
Lactation 5,100
Sweet Potato, Cantaloupe, Watermelon, Okra, Pineapple, Beans,
Banana, Orange, Collard Greens, Potatoes, Black-eyed Peas, Okra,
Peanuts, Peaches, Tomatoes, Beets
Zinc (mg/d) 13y3
48y5
913 y 8
1418 y F 9
1418 y M 11
1930 y M 400
3170+y M 420
1930 y F 310
3170+y F 320
Pregnancy 350
Lactation 320
Oysters, Crab, Beef, Fortied Cereals, Chickpeas Hummus,
Oatmeal, Beans, Lentils, Almonds, Cashews
Selenium (μg/d) 13y20
48y30
913 y 40
1418 y 55
1970+y 55
Pregnancy 60
Lactation 70
Brazil nuts, Tuna, Sardines, Shrimp, Brown Rice, Wheat Bread,
Oatmeal, Baked Beans, Oatmeal, Spinach
Dietary Flavanols *Quercetin sources
Cherries, Blueberries, Cranberries, Black currants, Elderberries, Goji
berries, Chokeberries, Juniper berries, Black-eyed Peas, Red Onions,
Okra, Watercress, Capers, Black Diamond Plums, Brussel Sprouts,
Cilantro, Fennel leaves, Ancho peppers, Radicchio, Chia seeds, Carob,
Buckwheat, Kale, Dill
Dietary Nitrates Spinach, Lettuce, Beetroot, Celery, Chinese Cabbage, Turnips, Endive,
Leeks, Kohlrabi, Fennel, Dill, Parsley
Dietary
Antioxidants and
Phytochemicals
Cloves, Cinnamon, Vanilla Beans, Oregano, Thyme, Sage,
Rosemary, Tumeric, Black Raspberries, Blueberries, Cranberries,
Black Currants, Elderberries, Blackberries, Strawberries,
Pomegranates, Apples
Notes: *DRIs provided for normal requirements.
Increased need for SCD.
References for Table 1:
1. Dietary Reference Intakes (DRIs): Recommended Dietary Allowances and Adequate Intakes. Food and Nutrition Board, Institute of Medicine, National Academies Press (2011).
2. USDA Database for the Flavonoid Content of Selected Foods, Release 3.3 (2018).
3. Hord NG. Dietary Nitrates, Nitrites, and Cardiovascular Disease. Curr Atheroscler Rep. 2011; 13:484492
Abbreviations: ALT, alanine am ino transferase; AST, aspartate amino transferase; ALP, alanine phosphatase; β
thal
, beta thalassem ia; CRP, c-reactive protein; DRI,
dietary refe rence intakes; HbSS/SCA, sickle cell anemia; HbSC, hemoglobin SC; HU, hydroxyurea; IL-6, interleukin-6; IU, international units ; RDA, recommended
dietary all owances; RMR, resting metabolic rate; REE, resting energy expenditure; SCD, sickle cell disease; S20, sickle mice fed 20% protein; S35, sickle mice fed 35%
protein; TB, tota l bilirubin; F, female, M, male.
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nutrient and energy intake. Deciencies in Vitamin
D contribute to osteopenia and osteoporosis which affect
up to 80% of SCD patients. Patients with low serum
Vitamin D (<14.1 ng/ml) have more crisis-related hospital
visits per year than those with 25 (OH)D
3
serum levels
>34 ng/ml. Dietary intake of sh correlated with these
ndings.
30
Vitamin D also functions to regulate immune
responses and inammation through its metabolite 1,25
dihydroxyvitamin D, which binds to the vitamin
D receptor to serve as a transcription factor, inducing
vitamin D-responsive genes present in cells of the immune
system.
31,32
A two year randomized clinical trial investi-
gating the effect of a high dose of 100,000 International
units (IU) (equivalent to 3,333 IU/day) versus the standard
treatment 12,000 IU (equivalent to 400 IU/day) of oral
vitamin D3 supplements for reducing risk of respiratory
infections, was studied in 62 children and adolescents with
SCD, aged 3-20 years. The results showed a signicant
reduction in respiratory events for both groups during the
two years. The group receiving 3,333 IU/day administered
as 100,000 IU once per month showed a decrease in
annual respiratory events from 4.34±0.35 at baseline to
1.49±0.37 at year 2. Similarly, the group receiving 400 IU/
day administered as 12,000 once monthly showed
a decrease in annual respiratory events from 3.91±0.35 to
1.54±0.37. Ninety-eight percent of the high-dose group
also stabilized at a mean serum 25-hydroxyvitamin
D concentration of 37.0 ng/ml. This study showed a pro-
tective effect of Vitamin D supplementation against
respiratory infections commonly found in children with
sickle cell disease.
33
Sources of dietary Vitamin D are
limited and include ergocalciferol (Vit. D
2
) from mush-
rooms, fortied milk, plant milk and yogurt, fortied
orange juice, fortied breakfast cereals, and as cholecalci-
ferol (Vit. D
3)
in fatty sh, cheese, egg yolks, and liver.
Importance of hydration and SCD
Hydration plays an essential role in sickle cell anemia.
Cells become sickled due to reduced hydration status and
hemolytic anemia. Poorly hydrated erythrocytes lead to
increased viscosity and may contribute to the vaso-
occlusive crisis in SCD.
34
It is crucial to promote proper
hydration by frequent intake of water and other uids, and
to avoid physical activity and extreme weather that result
in excessive sweating.
35
Even sickle cell trait carriers can
experience increased blood viscosity during strenuous
sports.
36
Avoiding dietary sodium intake can help to
maintain appropriate hydration status by preventing water
from leaving the erythrocytes.
37
Dietary recommendations
for maintaining good hydration status include limiting
high sodium, processed foods, and snacks while consum-
ing water and uids throughout the day.
The gut microbiome: considerations
in SCD
The gut microbiome contains trillions of bacteria, collec-
tively termed microbiota, that play a signicant role in
host immunity. While a balance of commensal and patho-
genic bacteria maintains the gut homeostasis,
a predominance of pathogenic bacteria in the gut may
arise from inadequate intake of the dietary substrate for
gut microbiota, physical damage, and antibiotic use. If the
prevalence of pathogenic bacteria compromises the intest-
inal barrier, disruption of the mucosal T-cell homeostasis
and inammation may result. There is a link between the
gut microbiome and many inammatory diseases. These
include type 2 diabetes, allergies and colorectal cancer.
38
Dietary intake of prebiotic substrates from legumes,
grains, fruit, and vegetables, as well as probiotics from
fermented dairy, soy, and grains, provide optimal sub-
strates for the gut microbiota that promotes the predomi-
nance of protective commensal bacteria such as
Lactobacillus and Bidobacterium. These foods also pro-
vide vitamins, minerals, phytochemicals and antioxidants
for the host.
39
Few studies have determined whether the gut microbiota
of SCD patients differs from those without SCD. In mouse
models, the gut microbiota has been shown to regulate
neutrophil aging via Toll-like receptors (TLRs) and myeloid
differentiation factor 88 (Myd88) mediated signaling path-
ways, leading to TNFα-induced VOC.
40
There is a notion
that VOC contributes to dysbiosis through the subclinical
intestinal ischemia it causes from its presence in the
splanchnic vasculature. Further exacerbation of this com-
promise may arise from dietary factors or medications. The
intestinal microbiome facilitates the synthesis of nitric
oxide (Figure 2)
41
in the gut through the arginine citrulline
pathway and in human endothelial cells from dietary ava-
nol derived gut metabolites. The impact of nutritional argi-
nine deciency in preventing adequate nitric oxide
production and resultant oxidative stress and inammation
may be due to both alterations of gut bacteria and impair-
ment of the gut microbial pathway. Gut modulation of
bioactive components of food sources of dietary
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phytochemicals, avanols and amino acids like arginine,
may aid in decreasing oxidative stress and improving both
endothelial function and blood pressure in SCD. Also,
studies through the Minority Coalition for Precision
Medicine and National Microbiome Initiative are currently
exploring the relationship between gut microbiota, circulat-
ing activated neutrophils and VOC.
42
Using 16SrRNA
sequencing studies individuals with SCD and no VOC or
antibiotic usage, are compared with sickle cell trait (AS)
carriers. Compared with AS, SCD had a lower relative
abundance of three species from Firmicutes phylum
(Pseudobutyrivibrio, Faecalibacterium, Subdoligranulum)
and two from Bacteriodetes phylum (Prevotella,
Alistipes). Relative abundance of Escherichia-Shigella
from Proteobacteria phylum was higher in SCD. When
further correlated with clinical parameters, lactate dehydro-
genase (LDH) correlated positively with the genera from
Firmicutes phylum. LDH is associated with hemolysis in
SCD patients.
43
Maintaining a healthy gut microbiota
through adequate dietary intake of fruits, vegetables,
whole grains, legumes, and fermented foods may aid the
SCD patient in optimizing host immunity.
Emerging medicinal plant derived
nutrients for SCD
Interest in natural products is gaining attention as an integra-
tive approach to management of sickle cell disease. Many of
these tropical plants are native to the countries where high
rates of sickle cell disease exist. Derivatives from plants have
been shown to contain antioxidant properties from bioactive
components such as phytochemicals and avanols.
44
Exploration for the use of extracts from the tropical plant
Moringa oleifera is in progress, to determine the antioxidant
capacity in the treatment of oxidative stress in sickle cell
disease. Ethanol extracts of Moringa oleifera showed anti-
oxidant values between 77 and 4,458 μg/ml.
45
Other plant
leaves known to contain phytochemicals, include Cajanus
cajan, Zanthoxylum zanthoxyloides, and Carica papaya.
Experiments using 2% sodium metabisulte to induce red
cell sickling in an in vitro model, demonstrated that these
plants could aid in the resistance of hemolysis and reduce the
number of sickled red blood cells.
46
Results in animal models
did not show acute toxicity of the Cajanus cajan leaf.
47
Conclusion
Management of SCD is complex and multifactorial.
Nutritional risks are high, and after more than 100 years
of following this disease, investigating the use of nutrition
as adjuvant therapy for addressing multiple diet-related
chronic disorders associated with SCD is still not
a priority for providing adequate treatment. The focus of
much of the research has been about increasing the red cell
count by various methods, without considering that the
changes in the form and function of the sickle red cells
may be associated with developing a nutrient deciency.
For example, individuals with sickle cell, experience var-
ied levels of hemolytic anemia, which reduces the oxygen-
carrying capacity of the blood. This is associated with
increased rates or red cell production and therefore
increasing amounts of young red cells (reticulocytes) in
the blood. Red cell production requires many substrates,
not the least of which is protein. Protein synthesis is
associated a with high energy cost and limits nutrient
availability for growth and maintenance of body mass.
The reticulocytes also readily stick to the blood vessel
endothelial cells due to increased availability of adhesion
sites. Therefore, the ow of nutrients for other essential
metabolic needs is limited. So, it is not surprising that a
sufcient diet for a healthy age, gender, and body-mass
matched individual will not cover the nutritional needs of
the person grappling with SCD. There has been no attempt
to calculate dietary requirements for these individuals, as
has been done for healthy people without the disease.
Frankly, developing recommended dietary intakes will be
a daunting task, as this involves gathering clinical infor-
mation (ie, body composition, anthropometry, energy
metabolism, measuring circulating nutrients by venipunc-
ture and food intakes by self-reported diet diaries, in
tandem with on-site compliance measurements, and
more). These investigations will require recruiting many
participants of different ages, followed prospectively for at
least six months. These data would then be used to calcu-
late the optimal nutritional requirements for different age
groups of individuals with varying types of sickle cell
disease, including HbSS, β-thallasemia and HbSC, the
NO3
NO2NO N2ON2
NH4
NO
Non-enzymatic
reaction at
pH < 5.5
gut
oral
cavity
CO2
OO
OPH2NO-Liver
Epithelial
cells
Arg
HbO
2
NOS Cit
Urea cycle
O-
Carbamoyl phosphate
Bacterial respiratory denitrification
DNRA
-
-
+
Figure 2 Nitrogen pathways in the human gut.
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most abundant and severe of this group of
hemoglobinopathies.
The protocol for this type of investigation has already
been developed for healthy individuals and is worth repeat-
ing for this health challenged group. Estimating dietary needs
for those affected by SCD can pave the way toward macro-
nutrient sufciency, ie, required energy and protein, which
are most decient in patients with SCD. Identifying and
recommending foods needed to supplement the elevated
metabolism of individuals with SCD will improve growth
and development, promote weight maintenance, conserve
muscle mass, and reduce inammation for these patients.
Finally, this paper addresses the need for the development
of a comprehensive Medical Nutrition Therapy approach to
treating SCD. This approach should include an emphasis on
high dietary requirements for macronutrients (protein carbo-
hydrate and fat) while incorporating evidence-based research
supporting the use of food sources of polyphenolic phyto-
chemicals, avanols and gut microbial required prebiotics.
We suggest that these components in combination with the
vitamins, minerals, and omega-3 fatty acids routinely used in
standard treatment, may provide adjuvant therapy for the
SCD-associated chronic disease burden, and promote sus-
tainable health, quality of life andincreased longevity for this
patient population.
Acknowledgments
Umeakunne K reports support from the Academy of
Nutrition and Dietetics Foundation and the National
Institute on Minority Health and Health Disparities
(NIMHD) and National Institute of Allergy and
Infectious Diseases (NIAID) Grant Number
U54MD007588. Hibbert JM reports support from the
Georgia Research Alliance (GRA) Phase I funding grant
number GRA.VL18.F1, the Department of Microbiology/
Biochemistry/Immunology microgrant fund #500061,
MSM, and Grant Number 8G12MD007602 from the
National Institute of Minority Health and Health
Disparities (NIMHD). The content is solely the responsi-
bility of the authors and does not necessarily represent the
ofcial views of the NIMHD or the NIH.
Disclosure
Jacqueline M Hibbert and Kayellen Umeakunne report
a patent US20110294727A1 issued to Hibbert JM, Stiles
JK, Hyacinth HI, Umeakunne K. The authors report no
other conicts of interest in this work.
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... Another functional food with antisickling properties is kiwi fruit (Figure 8b). Kiwi is rich in both vitamin C and E [92]. Dietary supplementation with Kiwi as given by [92], maybe an important adjunct during SCD therapy. ...
... Kiwi is rich in both vitamin C and E [92]. Dietary supplementation with Kiwi as given by [92], maybe an important adjunct during SCD therapy. Antioxidant vitamins C and E can boost the glutathione antioxidant defense system and exhibit an inhibitory role in red blood polymerization [2]. ...
... The effects of these vitamins have been shown to decrease arterial blood pressure, mean corpuscular hemoglobin levels, and irreversible sicklde cells [2]. Vegetable and fruit diets such as kiwi may contain vitamin C and E [92] with a great antisickling property and therapeutic benefits in sickle cell anemia management cases [95]. L-glutamine Targeting hemolysis-mediated endothelial dysfunction: boost the glutathione antioxidant defense system thereby promoting Antisickling and therapeutic properties [92] 6 Walnuts (Juglans regia); Flax seeds (Linum usitatissimum); Chia seeds (Salvia hispanica) ...
Article
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Sickle cell disease (SCD), also known as sickle cell anemia (SCA) is one of the structural hemoglobinopathies that occurs due to a single nucleotide mutation from GAG to GTG, which changes the amino acid of a β-globin chain of hemoglobin (Hb) from glutamate to valine. This singular mutation results to disorderliness in red blood cells (RBCs) with advent of changes in RBC morphology and other pathological conditions. In the 1980s, intermittent red blood cell transfusions, opioids, and penicillin prophylaxis were the only available therapy for SCA and were commonly reserved for acute, life threatening complications. So far, the US Food and Drug Administration (FDA) has granted a total of four drugs approval for the prophylaxis and treatment of the clinical complications of SCD. Due to limitations (adherence, safety, adverse effects) of existing therapies in the prophylaxis and treatment of SCD complications in Nigerian children and their inaccessibility to approved drugs, the present study discusses the therapeutic effects of readily available functional food as one of the therapies or an adjunct therapy to tackle the sickle cell crisis in Nigerian Children.
... Superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels in sickle cell disease patient in vaso-occlusive crisis are significantly lower compared to that of non-sickle cell controls [43]. There seems a justification to urgently develop dietary reference intakes (DRIs) and recommended dietary allowances (RDAs) for patients with SCD and integrate nutritional intervention as a vital adjunct in the prevention of VOC and the treatment of patients [44]. ...
Chapter
Full-text available
Sickle cell disease (SCD) is a major public health challenge. It is a common cause of acute and chronic illness and death, which results from a single amino acid substitution (glutamic acid to valine) at position 6 of the beta (β) chain of the hemoglobin molecule. The pathophysiology is based on the polymerization of deoxygenated hemoglobin S (HbS) and production of irreversibly sickled red cells and vaso-occlusive crisis (VOC). The disease is associated with recurrent episodes of acute pain and organ damage. This chapter highlights the role of SES on the predisposition to VOC and mortality among SCD patients. Findings from this review will enable the development and implementation of policies that can facilitate the effective management of SCD in the region. More awareness and education of parents of children and adults living with SCD are needed to identify factors that predispose patients to VOC and common-sense measures to prevent these triggers. SCD patients should be protected against malaria. The need for nutritional intervention, proper hydration, avoidance of dietary intake of sodium, strenuous physical activity, and extreme weather to reduce the incidence of VOC cannot be overemphasized. Protective immunization and access to effective prophylactic and therapeutic agents should be implemented.
... A leading view is that the increased rate of red cell turnover, a primary feature of SCD patients, underlies a hypermetabolic state. The biochemical and physiological factors that contribute to hypermetabolism include increased protein turnover, increased myocardial activity, and production of proinflammatory cytokines [100][101][102][103][104]. The supposition is that the energy and nutrient requirements normally recommended are not adequate in patients with SCD given their increased energy expenditures and other unusual metabolic demands, which compete directly with energy needs required to sustain adequate growth. ...
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Full-text available
Background Sickle cell disease (SCD) is an inherited blood disorder that predominantly affects individuals in sub-Saharan Africa. However, research that elucidates links between SCD pathophysiology and nutritional status in African patients is lacking. This systematic review aimed to assess the landscape of studies in sub-Saharan Africa that focused on nutritional aspects of SCD, and highlights gaps in knowledge that could inform priority-setting for future research. Methods The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria comprised original, peer-reviewed research published between January 1995 and November 2020 involving individuals in Africa with any phenotypic variant of SCD and at least one nutritional status outcome. Nutritional status outcomes were defined as those that assessed dietary intakes, growth/anthropometry, or nutritional biomarkers. Databases used were Ovid Embase, Medline, Biosis and Web of Science. Results The search returned 526 articles, of which 76 were included in the final analyses. Most investigations (67%) were conducted in Nigeria. Studies were categorized into one of three main categories: descriptive studies of anthropometric characteristics (49%), descriptive studies of macro- or micronutrient status (41%), and interventional studies (11%). Findings consistently included growth impairment, especially among children and adolescents from sub-Saharan Africa. Studies assessing macro- and micronutrients generally had small sample sizes and were exploratory in nature. Only four randomized trials were identified, which measured the impact of lime juice, long-chain fatty acids supplementation, ready-to-use supplementary food (RUSF), and oral arginine on health outcomes. Conclusions The findings reveal a moderate number of descriptive studies, most with small sample sizes, that focused on various aspects of nutrition and SCD in African patients. There was a stark dearth of interventional studies that could be used to inform evidence-based changes in clinical practice. Findings from the investigations were generally consistent with data from other regional settings, describing a significant risk of growth faltering and malnutrition among individuals with SCD. There is an unmet need for clinical research to better understand the potential benefits of nutrition-related interventions for patients with SCD in sub-Saharan Africa to promote optimal growth and improve health outcomes.
... A leading view is that the increased rate of red cell turnover, a primary feature of SCD patients, underlies a hypermetabolic state. The biochemical and physiological factors that contribute to hypermetabolism include increased protein turnover, increased myocardial activity, and production of proin ammatory cytokines [89][90][91][92][93]. The supposition is that the energy and nutrient requirements normally recommended are not adequate in patients with SCD given their increased energy expenditures and other unusual metabolic demands, which compete directly with energy needs required to sustain adequate growth. ...
Preprint
Full-text available
Background: Sickle cell disease (SCD), an inherited blood disorder, predominantly affects individuals in sub-Saharan Africa. Research linking its pathophysiology and nutritional status in African patients has not been previously described. This systematic review aimed to assess the landscape of studies in sub-Saharan Africa focused on nutritional aspects of SCD and highlight gaps in knowledge that could inform priority-setting for future research. Methods: The study was conducted using the Preferred Reporting items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. All original studies involving individuals with any phenotypic variant of SCD and at least one nutritional status outcome; and were conducted between January 1995 and November 2020 in Africa were included. ‘Nutritional status’ was defined by studies on dietary intake, measurements of growth/anthropometry, or nutritional biomarkers. Studies were included if they involved Databases used were Ovid Embase, Medline, Biosis and Web of Science. Results: The search returned 526 articles with 76 studies included in the final analyses. Most investigations (67%) were conducted in Nigeria. Studies were categorized into one of three main categories: descriptive studies of anthropometric characteristics (49%), descriptive studies of macro- or micronutrient intakes (41%), and interventional studies (11%). Findings consistently found growth impairment, especially among children and adolescents from sub-Saharan Africa. Studies assessing macro- and micronutrients generally had small sample sizes and were exploratory in nature. Only four randomized trials were identified, which measured the impact of lime juice, long-chain fatty acids supplementation, ready-to-use supplementary food, and oral arginine on health outcomes. Conclusions: The findings reveal a moderate number of descriptive studies, most with small sample sizes, that focused on various aspects of nutrition and SCD in African patients. There was a stark lack of interventional studies that could be used to inform evidence-based changes in clinical practice. Findings of investigations were generally consistent with data from other regional settings, describing a significant risk of growth faltering and malnutrition among individuals with SCD. There is an unmet need for clinical research to better understand the potential benefits of nutritional-related interventions for patients with SCD in sub-Saharan Africa in order to promote optimal growth and improve health outcomes.
... Poor nutritional status is associated with impaired immune response to infections and, thus, drives infection-related mortality among children with SCD [4]. Nutritional status has also been implicated in the variability of SCD severity [6]. For instance, weight-for-age zscore (WAZ) has been shown to significantly predict hospitalization in SCD [7]. ...
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Background Malnutrition continues to affect under-five children in Africa to an overwhelming proportion. The situation is further compounded by the burden of sickle cell disease (SCD). However, association of SCD with stunting, wasting, and underweight in a nationally representative sample of under-five children remains unexplored. We aimed to describe prevalence of undernutrition by sickle cell status, to evaluate its association with growth faltering ascertained by anthropometric indices, and to explore mediating role of hemoglobin. Methods We availed data from the 2018 Nigeria Demographic and Health Survey (DHS) and the sample comprised 11,233 children aged 6–59 months who were successfully genotyped for SCD. The DHS employed a two-stage, stratified sampling strategy. SickleSCAN rapid diagnostic test was used for SCD genotyping. Z -scores of length/height-for-age (HAZ), weight-for-height (WHZ), and weight-for-age (WAZ) were computed against the 2006 World Health Organization Child Growth Standards. We fitted logistic regression models to evaluate association of SCD with stunting, wasting, and underweight. Mediation analysis was performed to capture the indirect effect of and proportion of total effect mediated through hemoglobin level in SCD-anthropometric indices association. Results Prevalences of stunting, wasting, and underweight among children with SCD were 55.4% (54.5–56.4), 9.1% (8.6–9.7), and 38.9% (38.0–39.8), respectively. The odds of stunting were 2.39 times higher (adjusted odds ratio (aOR) 2.39, 95% CI: 1.26–4.54) among sickle children than those with normal hemoglobin. SCD was also significantly associated with underweight (aOR 2.64, 95% CI: 1.25–5.98), but not with wasting (aOR: 1.60, 95% CI 0.85–3.02). Association of SCD with all three anthropometric indices was significantly mediated through hemoglobin level: for SCD-HAZ, the adjusted indirect effect (aIE) was − 0.328 (95% CI: − 0.387, − 0.270); for SCD-WHZ, the aIE was − 0.080 (95% CI: − 0.114, − 0.050); and for SCD-WAZ, the aIE was − 0.245 (95% CI: − 0.291, − 0.200). Conclusion We presented compelling evidence of the negative impact of SCD on anthropometric indices of nutritional status of under-five children. Integration of a nutrition-oriented approach into a definitive SCD care package and its nationwide implementation could bring promising results by mitigating the nutritional vulnerability of children with SCD.
... In contrast, caregivers should be advised against fried meals, especially the use of groundnut oil as it could precipitate crisis. 52 The detrimental effects of extreme emotions on VOC have been previously reported. 47 Psychological distress is known to release stress-related hormones, such as catecholamines and corticosteroids, which in turn increase the risk of sickle cell VOC by its adverse effects on blood cell count, plasma volume, and blood viscosity. ...
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Background The modulatory effects of psychosocial and biophysical environments on sickle cell disease (SCD) severity during childhood has not been well characterized in high burden settings, such as Nigeria. Objectives We identified socio‐demographic correlates and explored caregivers' perceptions on socio‐behavioral and environmental influences on hospitalization for pain and blood transfusion of children with SCD in Kano, Nigeria. Methods Using mixed methods, structured questionnaires were administered to a clinic‐based sample of caregivers of children with SCD (n = 372), complemented with eight focus group discussions. Binary logistic regression models and the framework approach were used to analyze the data. Results The majority (73.1%, n = 272) of the children had at least one vaso‐occlusive crisis (VOC), and 41.1% (n = 153) required hospitalization in the preceding year. A total of 170 children (45.7%) received blood transfusion. Hospitalization was predicted by the child's age (Adjusted Odds Ratio, AOR = 1.89; 95% Confidence Interval, CI: 1.18‐4.07, ≥10 vs <5 years), relationship with caregiver (AOR = 5.41; 95%CI: 1.17‐25.05, mother vs “others”), father's number of children (AOR = 2.21; 95%CI: 1.19‐5.31, ≥10 vs ≤4), and siblings with SCD (AOR = 2.36; 95%CI: 1.16‐8.80, 2 vs 0). Caregivers perceived maternal care, stable home environment, medication adherence, anti‐mosquito measures, and adequate nutrition as protective factors, whereas poverty, extreme emotions, physical exertion, and extreme temperatures were identified as detrimental to the health of the child. Conclusions Hospitalizations for VOC and transfusion rates among children with SCD were high. Understanding the modulatory effects of socio‐behavioral factors on SCD severity could inform preventive measures and enhance the quality of life of affected children.
... The biochemical and physiological factors that contribute to hypermetabolism include increased protein turnover, increased myocardial activity, and production of proin ammatory cytokines. [79][80][81][82][83] The supposition is that the energy and nutrient requirements normally recommended are not adequate in patients with SCD given their increased energy expenditures and other unusual metabolic demands, which compete directly with energy needs required to sustain adequate growth. ...
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Background: Sickle cell disease (SCD), an inherited blood disorder, predominantly affects individuals in sub-Saharan Africa. While there are established studies that links its pathophysiology and nutritional status, the extent of research in this area involving African patients has not been previously described. This systematic review aimed to assess the nutrition-focused landscape of SCD studies in Africa, summarize findings, and highlight gaps in knowledge that could inform priority-setting for future research. Methods: The study was conducted using the Preferred Reporting items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We included all original studies, conducted between 1995 and 2018, on nutritional status of individuals with SCD in Africa. ‘Nutritional status’ was defined by studies on dietary intake, measurements of growth/anthropometry, and nutritional biomarkers. Studies of anemia in non-SCD individuals and those with sickle cell traits were excluded. Databases used were Ovid Embase, Medline, Biosis and Web of Science. Results: The search returned 366 articles from which 62 studies were included in the final analyses. Seventy percent of the investigations were conducted in Nigeria. Studies were categorized into one of three main categories: descriptive studies of anthropometric characteristics (50%), descriptive studies of macro- or micronutrient levels (35%), and interventional studies (15%). Findings consistently found growth impairment, especially among children and adolescents. Studies assessing macro- and micro-nutrients generally had small sample sizes and were exploratory in nature. Only two randomized placebo-controlled trials were identified, which measured the impact of fatty acid supplementation and lime juice on health outcomes. Conclusions: The findings reveal a moderate number of descriptive studies, with small sample size, that focused on various aspects of nutrition and sickle cell disease in African patients. There was a stark lack of interventional studies that could be used to inform evidence-based changes in clinical practice. Findings of investigations were generally consistent with data from other regional settings, describing a significant risk of growth faltering and malnutrition among individuals with SCD. There is an unmet need for clinical research to better understand the potential benefits of nutritional-related interventions for patients with SCD in sub-Saharan Africa in order to promote optimal growth and improve health outcomes.
... Poor nutritional status is associated with impaired immune response to infections, and thus, drives infection-related mortality among children with SCD [4]. Nutritional status has also been implicated in the variability of SCD severity [6]. For instance, weight-for-age z-score (WAZ) has been shown to signi cantly predict hospitalization in SCD [7]. ...
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Background: Malnutrition continues to affect under-five children in Africa to an overwhelming proportion. The situation is further compounded by the burden of sickle cell disease (SCD). However, association of SCD with stunting, wasting, and underweight in a nationally representative sample of under-five children remains unexplored. We aimed to describe prevalence of undernutrition by sickle cell status, to evaluate its association with growth faltering ascertained with anthropometric indices, and to explore mediating role of hemoglobin. Methods: We availed data from the 2018 Nigeria Demographic and Health Survey (DHS) and the sample comprised 11233 children aged 6–59 months who were successfully genotyped for SCD. The DHS employed a two-stage stratified sampling strategy. SickleSCAN rapid diagnostic test was used for SCD genotyping. Z-scores of length/height-for-age (HAZ), weight-for-height (WHZ), and weight-for-age (WAZ) were computed against the 2006 World Health Organization Child Growth Standards. We fitted logistic regression models to evaluate association of SCD with stunting, wasting, and underweight. Mediation analysis was performed to capture the indirect effect of, and proportion of total effect mediated through hemoglobin level in SCD-anthropometric indices association. Results: Prevalences of stunting, wasting, and underweight among children with SCD were 55.4% (54.5–56.4), 9.1% (8.6–9.7), and 38.9% (38.0-39.8), respectively. The odds of stunting were 2.39 times higher (adjusted odds ratio (aOR) 2.39, 95% CI: 1.26–4.54) among sickle children than those with normal hemoglobin. SCD was also significantly associated with underweight (aOR 2.64, 95% CI: 1.25–5.98), but not with wasting (aOR 1.60, 95% CI: 0.85–3.02). Hemoglobin level significantly mediated SCD-HAZ (adjusted indirect effect (aIE) -0.328, 95% CI: -0.387, -0.270), SCD-WHZ (aIE − 0.080, 95% CI: -0.114, -0.050), and WAZ (aIE − 0.245, 95% CI: -0.291, -0.200) associations. The extent of mediation was highest for SCD-HAZ association (adjusted proportion mediated 0.928, 95% CI: 0.535–2.770). Conclusion: We presented compelling evidence of the negative impact of SCD on nutritional status of under-five children. Integration of a nutrition-oriented approach into a definitive SCD care package and its nation-wide implementation could bring promising results by mitigating the nutritional vulnerability of children with SCD.
... 6. SCD is associated with chronic protein energy and nutrient deficiencies. Nutritional supplementation including folic acid and macro-and micronutrients to mitigate these deficiencies, as well as parent education on the value of optimal nutrition and hydration in health maintenance, is considered an essential part of preventive SCD care [50]. 7. Blood transfusion to mitigate sickle cell crises, as well as transcranial Doppler ultrasound to assess the risk of stroke, both require higher levels of equipment and training than available at primary centers. ...
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Background: Most of the world's sickle cell disease (SCD) burden is in Africa, where it is a major contributor to child morbidity and mortality. Despite the low cost of many preventive SCD interventions, insufficient resources have been allocated, and progress in alleviating the SCD burden has lagged behind other public-health efforts in Africa. The recent announcement of massive new funding for research into curative SCD therapies is encouraging in the long term, but over the next few decades, it is unlikely to help Africa's SCD children substantially. Main discussion: A major barrier to progress has been the absence of large-scale early-life screening. Most SCD deaths in Africa probably occur before cases are even diagnosed. In the last few years, novel inexpensive SCD point-of-care test kits have become widely available and have been deployed successfully in African field settings. These kits could potentially enable universal early SCD screening. Other recent developments are the expansion of the pneumococcal conjugate vaccine towards near-universal coverage, and the demonstrated safety, efficacy, and increasing availability and affordability of hydroxyurea across the continent. Most elements of standard healthcare for SCD children that are already proven to work in the West, could and should now be implemented at scale in Africa. National and continental SCD research and care networks in Africa have also made substantial progress, assembling care guidelines and enabling the deployment and scale-up of SCD public-health systems. Substantial logistical, cultural, and awareness barriers remain, but with sufficient financial and political will, similar barriers have already been overcome in efforts to control other diseases in Africa. Conclusion and recommendations: Despite remaining challenges, several high-SCD-burden African countries have the political will and infrastructure for the rapid implementation and scale-up of comprehensive SCD childcare programs. A globally funded effort starting with these countries and expanding elsewhere in Africa and to other high-burden countries, including India, could transform the lives of SCD children worldwide and help countries to attain their Sustainable Development Goals. This endeavor would also require ongoing research focused on the unique needs and challenges of SCD patients, and children in particular, in regions of high prevalence.
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Sickle cell anaemia (SCA) is a chronic haemolytic anaemia associated with vaso-occlusive painful crises which may affect several systems including the gastro-intestinal system, resulting in abdominal pain. The concurrence of inflammatory bowel disease and haemoglobinopathy is rare. No previously reported concurrent cases of both SCA and ulcerative colitis (UC) in sub-Saharan Africa were found in the literature. A 16-year-old girl with concurrent SCA and UC is presented. She was admitted to University College Hospital, Ibadan with a 1-year history of recurrent peri-umbilical pain and bloody stools. These symptoms were mainly attributed to SCA at the referring hospital, and she was managed for chronic tropical diarrhoea without a remarkable clinical response. This case illustrates the concurrent presentation of SCA and ulcerative colitis which led to the missed and delayed diagnosis of ulcerative colitis.
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Sickle cell disease (SCD) is a genetic disorder resulting from the presence of mutated hemoglobin S (HbS). Homozygous carriers will present with early manifestations of painful vaso-occlusive crises. SCD patients have been reported to be severely deficient in vitamin D (<20 ng/mL). Four years (2010–2014) of individual de-identified Sickle Cell Clinic of Southern Louisiana (SCCSL-SCD) patient records were analyzed for vitamin D status and the level of crisis-related ER/hospital utilization. To determine the dietary, and behavioral mediators of SCD-crisis in our study population, a cohort of 102 SCCSL-SCD patients were administered a survey that evaluated sun exposure, dietary behaviors, and pain frequency and severity. Patients with circulating levels of 25(OH)D3 less than 14.1 ng/mL reported having more crisis-related hospital visits per year (10) than patients with 25(OH)D3 serum levels >34 ng/mL. The result of the dietary survey detailed a relationship between patients who reported to have “Almost Never” consumed fish or milk in their diets and more frequent hospital stays and ER visits than those who reported consuming these products on a daily basis. Those who consumed these foods in their diet several times a month also had fewer ER visits when compared to the “Almost Never” category.
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In 2017, the Food and Drug Administration (FDA) approved two medications for sickle cell anemia (SCA): hydroxyurea for children (≥2 years of age) and L-glutamine for children and adults (≥5 years). The approval of hydroxyurea for children was long overdue, having been authorized by the FDA for adults in 1998 and by the European Medicines Agency for adults and children in 2007, but the approval of L-glutamine was a surprise to many in the field. There are few published studies of L-glutamine as a treatment for SCA, so all can be reviewed in this brief manuscript. Accordingly, there are many unanswered questions about L-glutamine and its role in current therapy for SCA.
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Key Points Annual rates of respiratory illness in sickle cell disease decreased by >50% during the second year of monthly doses of oral vitamin D3. Reduction in rates was similar with high-dose (100 000 IU/mo) and standard-dose (12 000 IU/mo) treatment.
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