Embed Size (px)
Citation preview
The Importance of Zinc
for Patients withThalassemia
Cooley’s Anemia Patient & Family ConferenceJune 21, 2014
Ellen B Fung, PhD RD
1958 Case Series (Iran & Egypt):40 young adult males
Severe anemia, hypogonadism, enlarged livers,severe growth retardation
Staff MD6 ft
21 yo4’ 11.5”
18 yo4’ 9”
18 yo4’ 6”
21 yo4’ 7”
NOT THALASSEMIA!
A Prasad et al. Am J Medicine 1961;31:532-546.
ZincDeficiency
H Sanstead et al Am J Clin Nutr 1967:422-442.
90 mg Zinc/dImproved
growth& pubertal
development
Zinc Deficiency is Common• Most common childhood nutritional deficiency world wide• Diarrhea & pneumonia related deaths <5 years• Zinc supplementation: adjunctive therapy (infectious diseases)
& preventative supplement in Developing Countries
• Clinical appreciation of zinc deficiency in individual patients is hindered: – non-specific signs of zinc deficiency
Poor growth, delayed puberty, night blindness, anorexia, hypogonadism, hair loss,
Zinc Deficiency is Common• Most common childhood nutritional deficiency world wide• Diarrhea & pneumonia related deaths <5 years• Zinc supplementation: adjunctive therapy (infectious diseases)
& preventative supplement in Developing Countries
• Clinical appreciation of zinc deficiency in individual patients is hindered: – non-specific signs of zinc deficiency – lack of sensitive biomarkers
Plasma Zinc- effected by hemolysis, inflammation, infection, food intake, time of day, hormones.
Are Patients with Thalassemia Zinc Deficient?
• Plasma zinc depressed (<70 ug/dL) in 10-80% of contemporary samples of patients with Thalassemia
• Transfused and non-transfused patients
• Children & Adults
How else can we tell?
If we give ZINC…
Zinc Improves Growth
Arcasoy et al Amer J Heme 1987;24:127-136
N=32 patientsB-Thal MajorTurkey
22 – 90 mg/d
1-7 years
n=21 n=11
p<0.01
Zinc Improves Bone Health in Thalassemia25 mg/d for 18 months
-20
-10
0
10
20
Who
le B
ody
BM
C, %
Cha
nge
fro
m B
ase
line
12 Months 18 Months
p=0.025C
Placebo Zinc Supplement
Absolute Difference 4.1%
*Data controlled for pubertal development and baseline BMC value
Fung EB et al AJCN 2013;98:960-71.
p=0.041
0.3 SD
Longitudinal Change in Spine BMD Z-scoreWB BMC % Change from Baseline
0.5
11
.52
2.5
33
.54
Cat
egor
ical
Sca
le o
f App
etite
PLACEBO ZINC
p=0.02p=NS
3mo 6mo 12mo 18mo 3mo 6mo 12mo 18mo
Not H
ungr
y
Ver
y Hu
ngry
Change in Appetite with Time of Study
by Group
Appetite improved more in the Zn Group
How hungry are you when it’s time to eat?
Fung EB et al AJCN 2013;98:960-71.
Altered Glucose Response Curve in Patients with Thalassemia
with Low Zn (n=13) vs. Normal Zn (n=23)
50
100
150
200
250
Glu
cose
, mg/
dL
Normal Zn LowZn
baseline 30 minute 60 minute 120 minute
Abnormal Fasting:>100 mg/dLDiabetic Fasting:>126 mg/dL
Abnormal 2 hr:>200 mg/dL
Models controlling for baseline p=0.048
Fung EB et al, unpublished data
100
150
200
250
Glu
cose
12
0 m
in P
ost
, mg/
dLBaseline 3 mo 6 mo
80
90
100
110
120
Fa
stin
g G
luco
se, m
g/dL
Baseline 3 mo 6 mo
Zinc Supplementation & Glucose Response
Fasting Glucose 120 min Glucose
Reduction in Fasting Glucose after 25 mg Zinc Supplementation
(p=0.03)
98.394.4
Reduction in 120 minute Glucose after 25 mg Zinc Supplementation
(p=0.02)
135.5
126.9
Fung EB et al, unpublished data
Why Are Patients with Thalassemia Zinc Deficient?
• Poor Dietary Intake
Best Sources of Zinc in Food
40
60
80
100
120
Pla
sma
Zin
c, u
g/dL
5 10 15 20 25Dietary Zinc Intake, mg/d
Dietary Zinc vs. Circulatory Zinc in Patients with Thalassemia
10 of 11With low PZnConsuming lowDietary Zn
Low PZn
Fung EB et al, unpublished data
Why Are Patients with Thalassemia Zinc Deficient?
• Poor Dietary Intake• Inadequate Absorption• Inadequate Intestinal reabsorption
Inside bodyInside body IntestinalLumen
Fe
Fe
FeFe
Fe
Fe
Fe
Fe
FeFe
Fe
FeZn
Zn
DFP
Exjade
Why Are Patients with Thalassemia Zinc Deficient?
• Poor Dietary Intake• Inadequate Absorption• Inadequate Intestinal reabsorption
Inside bodyInside body IntestinalLumen
FeFeFe
Fe
Fe
Fe
FeFe
FeFeFe
FeZn
Zn
Why Are Patients with Thalassemia Zinc Deficient?
• Poor Dietary Intake• Inadequate Absorption• Inadequate Intestinal reabsorption• Increased urinary excretion
Diabetics have Elevated Zn Excretion with Chelation Therapy
Al-Rafaie et al J Clin Pathol 1994
Elevated Zn Excretion withDeferiprone & Deferoxamine Therapy
0
200
400
600
800
1000
1200
24 h
r uri
nary
zin
c, u
g/d
None L1 Controls
0
50
100
150
200
250
Leukocy
te Z
n, ug/g
Grp1 Grp2 Grp3
Bartakke S et al 2005
Children w/ Tx-Thaln=28 no chelationn=30 LIn=29 controlsMumbai, India
0
50
100
150
200
250
300
24 h
r uri
nary
zin
c, u
g/d
Grp1 Grp2 Grp3
DeVirgiliis S et al 1988
Before & After 1 month DFO
Ferritin <1000 >2500 >2500
Many patients with thalassemia may be at risk for marginal zinc status- - Diabetics - Poor Growth
- Chelation Toxicity - Low dietary intake- High LIC
Zinc deficiency not always apparent from plasma/serum Zn analysis
Traditional theory that Iron Overload Co-morbidities is limiting—broaden our view
Daily supplementation with zinc has the potential to improve growth, bone health, and glucose homeostasis
Summary Take Home Message
Special Thanks To…
Elliott Vichinsky, MDJanet King, PhDAnnie LuiLisa CalvelliNancy Sweeters, PNPLisa Lavrisha, PNPBetty Flores, PNPLaurie Schumacher, PhDDru Haines, PNPAsh Lal, MDJanice HamerLeah Hagar
James Huang, MDLaura Quill, PNPJonah Todd-Geddes
CTSI Grants UL1 RR024131 (CHRCO) & UL1 RR024134 (CHOP)
Janet Kwiatkowski, MDBabette Zemel, PhD
Ginny Gildengorin. PHD
David Kilillea, PhD
