Markers of Inflammatory Stress in Metabolic Meltdown
Mary D. Litchford PHD, RDN, LDN
mdlphd@casesoftware.com
Sl2 All rights reserved. No part of this presentation may be reproduced by any graphic, mechanical,
photographic or electronic process, or in the form of phonographic recording or otherwise copied for public or
private use without written permission from the publisher.
Sl 3 Non-Endorsement Statement
Sl 4 Points to Ponder
 Discuss the relationship between inflammatory stress, proinflammatory cytokines and nutritional
status.
 Examine the impact of proinflammatory cytokines on multiple organ systems.
 Explore emerging biomarkers of oxidative stress.
Sl 5 What do your patients want to see in the mirror?
Sl 6 What is the difference between inflammation & oxidative stress?
Sl 7 Which came first inflammation or oxidative stress?
Sl 8 Undernutrition-Malnourished Continuum
Litchford, M. Nutr Clin Prac. Aug 2014 29:428.
Poor Dietary Intake
• Fatigue, weakness, apathy
• Sedentary lifestyle  chronic disease
• Food insecurity
Increased nutrient needs
• Inflammatory Stress: d/t Illness, injury, infection or surgery
•  Protein utilization
• Frailty   ADLs
• Sarcopenia
Impaired nutrient transport
•  Organ function
•  Nutrient utilization
• Food-Meds Issues
Under nutrition & malnutrition
•  Muscle mass & strength
•  Ability to chew & swallow
•  Pro intake
•  Fat stores   Wt
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© CASE Software & Books, 2015
Markers of Inflammatory Stress in Metabolic Meltdown
Mary D. Litchford PHD, RDN, LDN
mdlphd@casesoftware.com
Sl 9 Nutrient Excess  Postprandial Inflammation
•  Glycemic Load
• Unhealthy Fats
•  Kcal Meal
 Inflammation +  Oxidative Stress Chronic Disease
Sl 10 Inflammatory response
Sl 11 Cycle of Adequate Protein
Diet provides IAA= 90-100 g protein/d + Body synthesizes DAA
Body breaks down about 200 g protein from LBM recycles AA into new body components  majority
protein reserved used each day is recycled to LBM reserves; small amount oxidized
Sl 12 Cycle of Protein Intake with Inflammatory Stress
Diet provides insufficient IAA + Body has less N to synthesizes DAA
Body breaks down about 300+ g protein from LBM recycles AA into new body components  2/3 protein
reserved used each day is recycled to LBM reserves; 1/3 oxidized
Sl 13 Neuroimmunoendocrine Response to Inflammatory Stress
Brain & CNS
• Sickness syndrome
Muscle
•  Mass
•  Strength
• Insulin resistance
Blood
•  Immunity
• Anemia
Blood Vessels
• Atherosclerosis
• Albumin loss
• Edema
Adipose
•  Lipolysis
•  TG
Glands
•  Norepinephrine
•  Cortisol
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© CASE Software & Books, 2015
Markers of Inflammatory Stress in Metabolic Meltdown
Mary D. Litchford PHD, RDN, LDN
mdlphd@casesoftware.com
Sl 13 continued Liver
•  -APR
•  +APR
•  LPL
Intestine
 Stomach emptying
 GI motility
Sl 14 Markers of Inflammation
Commonly Used Markers
Emerging Markers
Emerging Markers
Albumin
IL-1b, IL-6, IL-8
Haptoglobins
Prealbumin
Transferrin
Tumor Necrosis Factor TNF
Serum Amyloid A
Intercellular adhesion molecule-1
Vascular cell adhesion moelcule-1
Ferritin
Fibrinogen
Exhaled Nitric Oxide
C-Reactive Protein & hs-CRP
Plasminogen Activator Inhibitor
1 (PAI-1)
Erythrocyte Sedimentation Rate
Lp-PLA2 : PLAC
Sl 15 Albumin…Nutritional Marker or Inflammatory Marker???
Kwashiorkor
 Edema
  rates of infection
 Fatty liver
 Sparse subcutaneous fat
 Low albumin
 Diet: Adequate Kcal &   or no Pro
Sl 16 Albumin…Nutritional Marker or Inflammatory Marker???
 Marasmus
 Severe loss LBM
 Skeletal appearance
 Apathetic
 Listless
 Normal albumin
 Diet:   Kcal & Pro
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© CASE Software & Books, 2015
Markers of Inflammatory Stress in Metabolic Meltdown
Mary D. Litchford PHD, RDN, LDN
mdlphd@casesoftware.com
Sl 17 Minnesota Starvation Study, 1944
Parameter
Baseline
BMI
Body composition: LBM
Fat
Serum Albumin
6 mo semi-starvation diet
21.7
16.4
33.9%
29.2%
9.8%
4.3 g/dL
3.1%
3.9 g/dL
Sl 18 Can Nutrition Supplementation Raise Serum Albumin in Undernourished Patients?
 Most of studies are unblinded, small sample size , few randomized studies
Non-CKD populations:
 ~ half found no statistical improvement
CKD populations
 ~ half found no statistical improvement
Sl 19 Pre-Albumin…Nutritional Marker or Inflammatory Marker???
Changes in PAB, nutrient intake & systemic inflammation in elderly recuperative care patients
 111 M aged 64-93 yr
 PAB, CRP, TNF, IL-6 & their soluble receptors measured at admission & discharge
 Detailed calorie counts were performed daily; intake % of estimated requirements for protein
(1.5 g/kg body weight per day) & energy.
Protein intake accounted for only 6% of variance in prealbumin
Dennis, RA, JAGS, 2008;56:1270-5
Sl 20 Inflammatory Markers
Fibrinogen
200-400 mg/dL
th
Component in 4 rx of blood clotting
 Inflammation, CVD, cancer, renal diseases
Nonspecific marker used to monitor course of disease
Ferritin
F 10-150 ng/dL
M 12-300 ng/dL
Measure of iron stores in non-inflammatory state
Elevated in inflammatory states- does not reflect iron stores
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© CASE Software & Books, 2015
Markers of Inflammatory Stress in Metabolic Meltdown
Mary D. Litchford PHD, RDN, LDN
mdlphd@casesoftware.com
Sl 21-22 Iron utilization & Redistribution
Inflammatory stress triggers IL-1B body  synthesis ferritin and  synthesis transferrin
Sl 23 Inflammatory Markers
C-Reactive Protein & hs-C-Reactive Protein
CRP Adults: <1.0 mg/dL or < 10 mg/L;
hs-CRP 1.0-3.0 mg/dL High risk: > 3.0 mg/dL
18-20 hr half life
Positive acute phase protein
Up to 30% variation in day to day results in non sick person
Can increase 1000 X normal with inflammation
As inflammation wanes, levels fall and negative acute phase proteins may rise, BUT this is NOT indicative of
improved protein status
Sl 24-25 Inflammatory Markers
Erythrocyte Sedimentation Rate
M 0-15 mm/hr ( 50 yr+ 0-20 mm/hr) F 0-20 mm/hr (50+ 0-30 mm/hr)
Rate at which RBC clump or stack in a column
Inflammation  wt RBC
Nonspecific marker used to monitor course of disease
 infections, inflammatory diseases, thyroid disorders, anemias, MI, renal diseases
Lipoprotein-associated phospholipase A2 :Lp-PLA: PLAC
< 200 ng/mL
Enzyme circulating in blood attached to LDL
Inflammatory molecules build up in plaque
Marker for vascular diseases, not systemic inflammation
Zheng D,et al. Baseline elevated Lp-PLA2 is associated with increased risk for re-stenosis after stent
placement. Lipids in Health and Disease. 2014;13:41. doi:10.1186/1476-511X-13-41.
Sl 26 Emerging Usage of Inflammatory Markers
Marker
Potential Use
Hs-CRP
Insulin resistance
IL-6 & IL-8 & TNF
Plasminogen Activator Inhibitor 1
Abdominal obesity
Visceral obesity
Exhaled Nitric Oxide
 upper respiratory tract infections, asthma & lung cancer,
 smoking, glucocorticoid steroids, pulmonary hypertension & cystic
fibrosis
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© CASE Software & Books, 2015
Markers of Inflammatory Stress in Metabolic Meltdown
Mary D. Litchford PHD, RDN, LDN
mdlphd@casesoftware.com
Sl 27 Oxidative Stress
Sl 28 Markers of Oxidative Stress
Biomarker
Specimen Type
Potential Use
IsoPs
MDA
Serum, urine
Serum
CVD risk
CVD risk
Nitrotyrosine
Serum & tissue
CVD risk
MPO
Serum
CVD risk
OxLDL
Serum
CVD risk
Vitamin C
Serum
Oxidant/antioxidant balance
Erythrocyte reduced glutathione (GSH)
Serum
Oxidant/antioxidant balance
Sl 29 Agents that Suppress Cytokines
Medications
Effect
Pentoxifylline, Thalidomide, Melatonin
 TFN production
Megestrol acetate
 TFN, IL6, CRP production
Corticosteroids
Monoclonal antibodies against specific cytokines
Anti-inflammatory
Specific cytokine inhibitors
Specific cytokine-receptor antagonists
Specific cytokine inhibitors
GH & IGF-1
Indirect cytokine inhibitor
Sl 30 Appetite Stimulants
Medications
Effect
Corticosteroids
Megestrol acetate
Cyproheptadine
Thalidomide
Cannabinoids
 appetite, but not weight
 appetite, but not weight in cancer , HIV, elderly pts
 appetite, but not weight in cancer pts
 appetite & weight in HIV pts
 appetite & weight in cancer, HIV, elderly pts
EPA
 appetite & weight in cancer pts
Grehlin
 appetite & weight in CHF, cancer pts
BCAA
 appetite, but not weight in cancer pts
Sl 31 Nutrition & Inflammation: Protein & energy supplementation in elderly at risk of malnutrition
Meta-analysis 3000+ patients, RCT
Mean wt gain 2.3%
26%  in relative risk of death Milne, AC. Cochrane Database of systemic reviews, 1, 2009.
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© CASE Software & Books, 2015
Markers of Inflammatory Stress in Metabolic Meltdown
Mary D. Litchford PHD, RDN, LDN
mdlphd@casesoftware.com
Sl 31 continued Protein & energy supplementation in Older Adults
Meta-analysis 3000+ patients, RCT
28%  in relative risk of death in malnourished Milne, AC. Ann Intern Med, 2006;144:37-48.
Sl 32 Anti-inflammatory foods Gunawardena, D. Eur J Nutr,2014 53:335-343.
 Onion
 Oyster & Button mushrooms
 Honey brown mushroom
 Red sweet potato
 Lime zest
 Oregano
 Cinnamon
 Cloves
 English breakfast tea leaves

Sl 33 Anti-inflammatory foods
 Walnuts
 Salmon
 Citrus fruits, Blueberries
 Cruciferous Vegetables:
 Broccoli, brussel sprouts, kale and cauliflower
 Olive Oil
 Spices
 ginger, turmeric, oregano, rosemary, cayenne, nutmeg & clove
Sl 34 High Risk Dietary & Lifestyle Practices
  consumption  calorie/ nutrient dense foods
 Eating away from home more often
 Changing to a different pattern on weekends
  dietary intake of saturated & trans fats
  fruit and vegetable intake





 portion size
Eat more  calorie/ fat/  sugar fast-foods
 intake of sweetened beverages
 intake of sugar and refined starches
Physical inactivity
Sl 35 Take Home Messages
 Inflammation & Oxidative Stress are implicated in weight loss, anorexia & many chronic diseases
 Know your accomplices…fat, sugar, obesity
 Selected anti-inflammatory medications may be helpful…or not
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© CASE Software & Books, 2015