assessment or nutritional status are we measuring · assessment or nutritional status ......
TRANSCRIPT
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Effects of inflammatory response on trace elements and minerals
H. Biesalski
ESPEN Congress Gothenburg 2011
Assessment or nutritional status – what are we measuring ?
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Effects of inflammatory response on trace elements and minerals
Assessment of nutritional status – what are we measuring
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What is Inflammation? How far are micronutrients involved ? Impact of trauma on micronutrients? Individual risk profile for low micronutrient status ? Therapeutic approach?
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Inflammation Activation of the innate immune system following environmental insults: pathogens, chemical-, physical injury Prevention of tissue damage, restoration of tissue homoeostasis, destruction of infectious agents Result of acute phase response with release of proinflammatory factors (TNFa, IL-1ß,IL-6) and subsequently secretion of CRP, PAI-1, etc.) Closely related to oxidative stress and NFkB
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Micronutrients involved in the inflammatory response
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Bacteria Inflammatory Cytokines
Oxidative Stress Mitogens
IKK
IkB IkB PP
Proteasome
NFkB
NFkB Transcription
Cell survival Stress response Immune response
The central role of NFkB in stress response: Balancing and directing the response
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Different pathways for activation of the NLRP3 inflammasome: Danger associated molecular patterns (DAMP) Or pathogen associated molecular patterns (PAMP) NLRP3 agonist ATP and DAMP/PAMP All together trigger ROS generation J.Tschoepp 2011 Cell
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Vitamins and trace elements are involved in the inflammatory process in two ways 1.Maintenance of the barrier function
2.Antioxidant activities
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1st. Line
2nd. Line
3rd. Line
4th. Line
Defense Lines against infections
Mucosa Barrier
MALT/BALT
Endothelial Function
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1st. Line
2nd. Line
3rd. Line
4th. Line
Defense Lines against infections: importance of micronutrients
Vitamin A, D
Vitamin E, C, Se
Vitamin E; n3 FA
Vitamin D, A, n3 FA
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Vitamin D acts via nuclear receptors together with the nuclear receptor of vitamin A (9 cis RA) Low vitamin A and/or D supply results in an impairment of the immune system
Immunmodulatory role of Vitamin D (Mora et al., Nat Rev Imm. 2008)
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Vitamins D and A play a major role in the protection against infections and in the control of chronic inflammatory response. Vitamin A controls mucosa barriers via a strong influence on cellular growth and differentiation
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Vitamins and trace elements are involved in the inflammatory process in two ways 1.Maintenance of the barrier function
2.Antioxidant activities
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Central role of NFkB in the regulation of stress response
OXIDATIVE STRESS
OXIDATIVE STRESS
NFkB
NFkB
Antioxidant Status
Antioxidant Status
A poor antioxidant status favours overexpression of NFkB and consequently overreaction of the stress response due to other factors
Enhanced response: Inflammation Apoptosis
Normal response
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Antioxidants form a network
E
E. LOOH C
C.
NAD
NADH
LH X.
L. XH LO2.
O2
Ascorbic acid bridges the intracellular and extracellular compartment
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Vitamins, Trace elements and Minerals are needed in adequate amount to ensure function of the innate and humoral immune system Open questions: Higher need during inflammation? Risk groups with low intake? Therapy?
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Leucocyte ascorbic acid and plasma vitamin D2 following surgery (Louw et al., AJCN 1992
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Plasma vitamin E and total lipids following surgery (Louw et al., AJCN 1992
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Plasma vitamin A and RBP following surgery (Louw et al., AJCN 1992
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Plasma vitamin C and beta-carotene concentrations of patients at
baseline and weeks 1 through 3 after burn injury
● indicate values for placebo group (n=14), and ■ indicate values for group provided 30 mg/day supplemental beta-carotene (n=12)
1 2 3 0 weeks
Vit
amin
C (
µm
ol/
L)
0
20
40
60
1 2 3 0 0.0
0.1
0.2
0.3
0.4
0.5
weeks B
eta-
caro
ten
e (µ
mo
l/L)
p < 0.02 p < 0.003
80
100
0.6
0.8
0.7
Rock et al J Burn Care Rehab 18: 1997
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Plasma retinol and alpha-tocopherol concentrations of
patients at baseline and weeks 1 through 3 after burn injury
● indicate values for placebo group (n=14), and ■ indicate values for group
provided 30 mg/day supplemental beta-carotene (n=12)
1 2 3 0 weeks
Retin
ol (
µm
ol/L
)
0
1
2
3
1 2 3 0 5
10
15
20
25
30
weeks A
lph
a-t
oco
ph
ero
l (µ
mo
l/L
)
p < 0.04 p < 0.0001
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Ascorbic acid in plasma following cardiac bypass surgery (n= 30)
NW
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O2
- H2O2
Cu/ZnSOD
MnSOD
OH
Fe 2+
catalase Se-GPx
H2O + O2
SOD as a prominent antioxidative System
In case of inadequate concentration of co-factors (dysbalance) the „detoxification“ is inadequate
Chronic Inflammation results in upregulation of SOD- and GPX-activity
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Low initial plasma selenium levels in patients with later SIRS or Sepsis and significant decrease of plasma selenium in patients with SIRS or severe sepsis. ----- lower boundary of normal reference values. Sakr et al., BJA 2007
Low selenium increases risk for SIRS and Sepsis
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Inverse correlation of inflammatory biomarker with plasma selenium (Sakr et al BJA 2007)
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Initial (A) and minimum plasma selenium (B) and mortality (Sakr et al., BJA 2007
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Micronutrients
Effects of acute phase response
Plasma Fe, Se, Zn
Vitamins B1, C, A, E,
Carotenoids
Cu, Mn
Liver, spleen Zn
Urine Vitamin A, RBP
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100 80 60 40 20 10 00
33%
67%
89%
11%
AOX intake between 66% to 100% of RDA
AOX intake below 66% of RDA
In case of insufficient supply prior hospital admission low AOX status results in a greater oxidative stress. Oxidative stress may have a negative impact on disease development.
Abiles et al. Crit Care 2006
Higher ox.stress
Lower ox.stress
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Vitamins, Trace elements and Minerals are needed in adequate amount to ensure function of the innate and humoral immune system Open questions: Higher need during inflammation? Risk groups with low intake or higher need? Therapy?
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100%
90
80
70
60
50
40
30
20
10
00
VD FA VE Ca VA Mg Zn B1 B2
% not reaching recommendations in
the German nutrition survey 2008
(age: 18 - >65)
Male
Female
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0 10 20 30 40 50 60 70
gynecology
surgery
urology
cardiology
other medical
gastroenterology
oncology
geriatrics 172 / 306
38 / 100
89 / 273
81 / 305
44 / 201
15 / 102
70 / 512
7 / 87
The german hospital malnutrition study
Prevalenz of Malnutrition (allways associated with inadequate micronutrient supply)
% SGA B+C
Patients: n = 1886 Hospitals : n = 13 Malnutrition: 27,4%; SGA B: 17,6% SGA C: 9,8% Maligne vs benigne disease: 30,9 vs 26,2 %; p<0,05
Overweight: n = 677 = 36,5% Obesity: n = 286 = 15,4%
Pirlich et al.Clin Nutrition 2006 submitted
46,2%
37,6%
38%
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0 100 200 300
0
100
200
300 19
patients
399 patients
557 patients
417 patients
Food intake in 1707 hospitalised patients : a prospective comprehensive hospital survey
Dupertuis YM. Clin Nutr 2003, 22: 115-23
Energy % recommended needs
Protein % recommended needs
Independant from energy low protein intake is associated with low micronutrient intake
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Major groups at risk for hidden hunger
(inadequate micronutrient intake despite
adequate energy)
Low socio-economic level
Low educational level
Low mobility
Obesity
Diabetes
Pregnancy
Old age
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Aasheim et al., AJCN 87: 2008 Vitamin Status in morbidly obese patients (76 female, 34 male, 30 female controls) Green line: mean levels, black line: lower limit of reference values.
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Aasheim et al., AJCN 90: 2009
Vitamin plasma concentrations following gastric bypass or duodenal switch (> 90% supplemented)
Optimal plasma levels
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Assessment of micronutrient status 1. Biochemical data (with exceptions) give only limited
information 2. Nutrition status including micronutrients needs to
be determined at hospitalisation 3. A short questionnaire (balanced diet?) including risk
profile examination (age, social status, co-morbidities) may produce better results
4. Trauma and injury are frequently associated with a low micronutrient status
5. If possible deliver a multi-micronutrient supplement (1-3xRDA).
6. Do not use single micronutrients in high doses
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