Why is Protein Important?

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Hector Barton
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1 Title

2 Pearls

3 Protein

4 Why is Protein Important? Only nutrient containing nitrogen Responsible for synthesis of enzymes involved in wound healing and collagen synthesis Needed at every step of the healing process

5 Protein Energy Malnutrition (PEM) Most common form of malnutrition in the US Unintended weight loss is marker for PEM Is RDA for protein set too low?

6 Estimating Protein Needs Protein needs assessed as grams of protein per kilogram of body weight (g/kg bw) g/kg bw 140 # Pt. (g) 140# Pt. (oz) RDA Stressed, malnourished Critically ill or injured Evaluate renal function Provide adequate fluids

7 Protein Distribution Adapted from Paddon-Jones & Rassmussen. Curr Opin Clin Nutr Metab Care 2009, 12:

8 Interventions Food Eggs, beef, chicken Protein shakes Recipe modification Modular Protein Supplements Added to food Given between meals or with medications

9 Modular Protein Supplement Choices 1. Whey High biological protein source Formulated from cow s milk 2. Casein Milk protein extract Less bio-available than whey 3. Soy Good biological legume protein 4. Collagen Natural to the body Main component of cartilage, ligaments, tendons, bones and teeth

10 Deciding on a Protein Supplement Form Liquid or powder Final Volume Nutrient Density Palatability Ease of Administration Use in tube feedings Digestibility and tolerance Cost

11 Protein Pearls Protein needs are increased. Assure adequate protein intake at each meal. Modular protein is a good way to meet increased protein needs. You must find the right product for each patient.

13 Energy (or Calories) Insufficient caloric intake = weight loss Unintended weight loss tends to be loss of lean body mass

14 Relationship Between LBM Loss and Wound Healing <10% >10% Wound healing has priority for protein substrate The stimulus to restore LBM competes with the wound for protein >20% Correction of LBM takes precedence Wound healing stops

15 The Stress Response to Injury Psychological Pain Anxiety Threat Physical Wound Infection Acute Illness Neurophysiologic Activation System Pituitary-adrenal axis Sympathetic nervous system Corticotropin release Hypermetabolism Catabolism Immune Deficiency

16 Effect of Cytokines on Nutrition Anorexia Muscle wasting Decreased nitrogen retention Decreased albumin synthesis Decreased circulating levels of albumin and cholesterol

17 Nutrient Partitioning Normal Proteins Carbohydrate Fat Protein Synthesis (Lean body mass) Energy Production (ATP) Energy Depot (Fat) Defective 25% to 30% of the amino acids are misused Proteins Carbohydrate Fat Protein Synthesis (Lean body mass) Energy Production (ATP) Energy Depot (Fat) Demling, RH. Eplasty. 2009;9:e9. Epub 2009 Feb 3.

18 Interventions Favorite foods Diet order liberalization Culture change in LTC Assistance at meals Medical nutrition supplements Try varied forms including juices, puddings, bars, shakes, cookies, ice creams Appetite stimulants

19 Energy Pearls Without adequate calories, protein is used for energy. Try to encourage the foods Try to encourage the foods that give the most bang for the buck.

22 Categories of Amino Acids 1. Indispensable Amino Acids (IAA) Essential Amino Acids 2. Dispensable Amino Acids (DAA) Non-Essential Amino Acids 3. Conditionally Indispensable Amino Acids (CIAA) Conditionally Essential Amino Acids

23 Classification of Amino Acids IAA Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Valine DAA Alanine Aspartic acid Asparagine Glutamic acid Serine CIAA Arginine Cysteine Glutamine Glycine Proline Tyrosine Reeds, PJ. J. Nutr. 130: 1835S-1840S, 2000.

Nitrogen rich 32% nitrogen Helps support immune function Precursor to proline Improves IGF-1 Precursor to polyamines Substrate for nitric oxide synthesis Activates macrophages Improves vasodilation

24 Nitrogen rich 32% nitrogen Helps support immune function Precursor to proline Improves IGF-1 Precursor to polyamines Substrate for nitric oxide synthesis Activates macrophages Improves vasodilation Increases collagen formation Stimulates phosphorylation of mtor to activate downstream anabolic effects Barbul A, et al. Arginine enhances wound healing and lymphocyte immune responses in humans. Surgery.1990;108:

25 Cell Signaling TOR (target of rapamycin) protein kinase central element in a signaling pathway, which controls cell growth and proliferation mtor = mammalian target of rapamycin TOR signaling is activated by key functional amino acids: Arginine Glutamine Leucine Wullschleger, S. Loewith R, Hall MN. Cell. 2006;124: Jacinto E, Hall MN. Nat Rev Mol Cell Biol. 2003;4:

26 mtor Activation Supports Cell Growth Normal mtor function is vital for wound healing Amino acids Growth Signaling Arginine, glutamine and leucine activate mtor mtor Protein Synthesis Cyclin D HIF-1a Glut 1, LAT1 Buhaescu I, et al.ther Drug Monit. 2006;28:

27 Most abundant amino acid in the body > 20% total circulating AA > 60% free intracellular AA Increased needs in trauma and sepsis Benefits of supplemental glutamine include: Stimulates collagen synthesis Regulates nitrogen metabolism in catabolic states Supports immunity Supports gut integrity Buhaescu I, et al.ther Drug Monit. 2006;28: Escobar J, et al. Am J Physiol Endocrinol Metab 2005;288:

28 Branched chain amino acid Stimulates mtor signaling Inhibitor of protein degradation in incubated skeletal muscle and in perfused liver Stimulates muscle protein synthesis under both in vitro and in vivo experimental conditions 5% of leucine is converted to HMB Escobar J, et al. Am J Physiol Endocrinol Metab May; 288(5):E Epub 2005 Jan 11. Tischler ME, Desautels M, Goldberg AL. J Biol Chem. 1982, Feb 25;257 (4):

29 β-hydroxy- β-methylbutyrate (HMB) Metabolite of amino acid leucine Precursor for the manufacture of cholesterol Helps maintain muscle membrane integrity Slows muscle tissue breakdown Helps support immune function Anabolic Support Reduces the inflammatory response Decreases muscle breakdown Builds LBM Protects muscle from stress-related damage Williams JZ, Abumrad N, Barbul A. Ann Surg. Sep 2002;236(3): ; discussion Alon T, Bagchi D, Preuss HG. Res Commun Mol Pathol Pharmacol. 2002;111(1-4): Kuhls DA, Rathmacher JA, Musngi MD, et al. J Trauma. Jan 2007; 62(1): ; discussion Hsieh L, Chien S, Huang M, RTseng H, CHang C. Asia Pac J Clin Nurs. 2006;15:

30 Effect of HMB, glutamine and arginine on protein synthesis and degradation f=p<0.001 from Control degradation g=p<0.001 from Cachectic degradation h=p<0.001 from Glut+ Arg degradation, using one-way ANOVA with Tukey-Kramer Multiple Comparison Test (n=6) a=p<0.01 and b= p<0.001 from Control synthesis c=p<0.001 from cachectic synthesis d=p<0.05 e=p<0.01 from HMB, Arg + Glut synthesis using one-way ANOVA with Tukey-Kramer Multiple Comparison Test (n=6).) Source: Abbott on file.

31 Amino Acid Pearls Demand for CIAAs may be greater than supply. Arginine, glutamine and leucine needed to activate mtor. CIAA supplementation may be indicated.

33 RDAs/RDIs Offer vitamin and mineral supplements when dietary intake is poor or deficiencies are confirmed or suspected. - NPUAP How do you determine this? Deficiencies range from sub-clinical to severe NPUAP Pressure Ulcer Prevention & Treatment Clinical Practice Guideline 2009 p 60.

34 To Supplement or Not? Can meet needs with a healthy diet Elderly, sick, infirm may not have optimal diet Consider heavily draining wounds Reasonable to give MVI daily

35 Works with proline and lysine during collagen synthesis Needed for carnitine production for fatty acid metabolism Tensile strength Body does not store vitamin C

Vitamin C deficiency Scurvy Symptoms may develop rapidly but reverse quickly with treatment Interferes with fibroblast function Alters healing

36 Vitamin C deficiency Scurvy Symptoms may develop rapidly but reverse quickly with treatment Interferes with fibroblast function Alters healing process of collagen synthesis No secretion of procollagen chains Impaired polymerization Wrong amino acid sequence Increased blood cell fragility

37 Needed for all enzymatic reactions In deficiency state, may find low rate of epithelialization Deficiency causes decreased wound and collagen strength Urinary losses increase with stress and weight loss Body stores may be depleted in patients with malnutrition, chronic diarrhea and chronic corticosteroid use

38 Zinc Overload Above 40 mg day Excess zinc may interfere with wound healing via affecting lysyl oxidase, an enzyme involved in collagen synthesis Excess interferes with copper and iron absorption and metabolism NPUAP Pressure Ulcer Prevention & Treatment Clinical Practice Guideline 2009 p 60.

39 Cofactor for connective tissue production Collagen polymerization Formation of cross linkages to enhance scar strength Erythrocyte formation

40 RDA/RDI Pearls Reasonable to prescribe a daily MVI. Vitamin C is water soluble; needed daily. Zinc should not be given in excess. You cannot supplement in a vacuum!

42 Lab or Biochemical Data Look at the date labs were drawn - Too old = doesn t reflect current situation - Too frequent = no true change If patient had recent blood transfusion, labs reflect donor Labs should be used in context with a nutrition focused physical assessment

43 Evaluating Protein Lab Data Protein Half-Life Other Albumin 20 days Low sensitivity for acute changes in protein nutrition Transferrin 10 days Intermediate sensitivity for acute protein deficiency Prealbumin 48 hours Sensitive for acute dietary deprivation and refeeding Retinol-binding protein 12 hours Sensitive for acute dietary deprivation and refeeding

44 Serum Albumin Accounts for over 50% of the serum proteins Slow to reflect changes because of the large serum pool and long half-life Reflects inflammatory processes and probably not current nutritional status

45 Interpreting Serum Albumin (g/100 ml) Normal = greater than 3.5 Mild depletion = Moderate depletion = Severe depletion = less than 2.1

46 Serum transferrin Iron transport protein Half-life is quicker than albumin but still slow to respond to refeeding Concentrations reflect both iron and protein status Thus, transferrin as an indicator of protein status is difficult when iron deficiency is also present

47 Transferrin and Iron Transferrin rises as iron deficiency grows worse Transferrin falls as iron status improves In mild to moderate PEM, transferrin levels may vary Markedly low transferrin levels are correlated with severe PEM

48 Prealbumin Also known as transthyretin and thyroxin-binding prealbumin Responds quicker to refeeding May also reflect inflammatory process May be elevated with the use of corticosteroids and in renal disease

49 Hepatic Proteins Useful as indicators of severity of illness Help to identify those who are the most likely to develop malnutrition Do not accurately measure nutritional repletion

50 Lab Pearl Hepatic proteins are not indicators of nutritional status but rather indicators of morbidity and mortality and recovery from acute and chronic disease. Changes in albumin, prealbumin or transferrin should not be used to suggest changes in protein status in individuals with acute or chronic inflammatory states. Fuhrman MP, et al. Hepatic Proteins and Nutrition Assessment. J Am Diet Assoc. 2004;104:

52 Sarcopenia vs. Cachexia vs. Starvation Sarcopenia is loss of muscle mass and strength with age Driven by the normal aging process in everyone, even athletes Cachexia is involuntary loss of LBM Driven by hypercatabolism and hypermetabolism Starvation is involuntary loss of of weight Driven by inadequate nutrition and anorexia

53 Sarcopenia Greek: poverty of flesh Age-related shift in body composition Major cause of frailty and loss of independence in the elderly Sarcopenic obesity Seen mainly with inactivity but also in physically active people Roubenoff Curr Opin Clin Nutr Metab Care 2003;6: Roubenoff Obesity Res 2004;12:

54 Main Causes of Sarcopenia Motor-unit remodeling Protein deficiency Decreased hormone Decreased hormone levels/anabolic stimuli

55 Motor Unit Restructuring Motor units = motor neurons + muscle fibers they control Fast twitch (FT) and slow twitch (ST) FT die sooner and ST innervate the muscle fibers to keep it alive (atrophy) Change in command is called motor unit restructuring Imperfect because ST are less precise than FT

56 Protein Deficiency Elderly lost fat-free mass even when meeting protein RDA RDA may not be adequate Subtle physiologic accommodation responses 1.5 g/kg bw or 15% - 20% of total calories may be a reasonable target Campbell W. Synergistic Use of Higher-Protein Diets or Nutritional Supplements with Resistance Training to Counter Sarcopenia. Nutrition Reviews [serial online]. September 2007;65(9): Wolfe R, Miller S, Miller K. Optimal protein intake in the elderly. Clinical Nutrition, Volume 27, Issue 5, Pages

57 Hormones Decreases in GH, testosterone, IGF-1 Changes in female estrogen may also play a role during menopause No consensus on hormone replacements to rebuild muscle mass in elderly GH is most studied

58 Interventions Progressive resistance exercise Provision of adequate high quality protein at each meal Arginine, glutamine and leucine to activate mtor Studies on creatine, DHEA, HMB, essential amino acids, protein and more Cosmeceuticals!

59 Sarcopenia Pearls Sarcopenia, cachexia and starvation are different mechanisms of weight loss but all contribute to poor healing. Aim to prevent atrophy. Keep exercising and eat protein to maintain LBM.

60 Give your patients protein, energy and amino acids. Meet the RDAs/RDIs and monitor labs, but remember, there is no magic supplement or number. Sarcopenia doesn t have to be inevitable. Keep moving!

Nutrition and Pressure Ulcers: Current Thinking

Nutrition and Pressure Ulcers: Current Thinking Lynn Carpenter Moore, RD, LD Faculty Disclosure Lynn Carpenter Moore, RD, LD Mrs. Moore has listed no financial interest/arrangement that would be considered