Effects of inflammatory response on trace elements and minerals

H. Biesalski

ESPEN Congress Gothenburg 2011

Assessment or nutritional status – what are we measuring ?

Effects of inflammatory response on trace elements and minerals

Assessment of nutritional status – what are we measuring

What is Inflammation? How far are micronutrients involved ? Impact of trauma on micronutrients? Individual risk profile for low micronutrient status ? Therapeutic approach?

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

Micronutrients involved in the inflammatory response

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

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

Vitamins and trace elements are involved in the inflammatory process in two ways 1.Maintenance of the barrier function

2.Antioxidant activities

1st. Line

2nd. Line

3rd. Line

4th. Line

Defense Lines against infections

Mucosa Barrier

MALT/BALT

Endothelial Function

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

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)

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

Vitamins and trace elements are involved in the inflammatory process in two ways 1.Maintenance of the barrier function

2.Antioxidant activities

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

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

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?

Leucocyte ascorbic acid and plasma vitamin D2 following surgery (Louw et al., AJCN 1992

Plasma vitamin E and total lipids following surgery (Louw et al., AJCN 1992

Plasma vitamin A and RBP following surgery (Louw et al., AJCN 1992

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

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

Ascorbic acid in plasma following cardiac bypass surgery (n= 30)

NW

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

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

Inverse correlation of inflammatory biomarker with plasma selenium (Sakr et al BJA 2007)

Initial (A) and minimum plasma selenium (B) and mortality (Sakr et al., BJA 2007

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

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

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?

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

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%

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

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

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.

Aasheim et al., AJCN 90: 2009

Vitamin plasma concentrations following gastric bypass or duodenal switch (> 90% supplemented)

Optimal plasma levels

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