Protein Requirements for Optimal Health in Older Adults: Current Recommendations and New Evidence

DASPEN 2013 Aarhus, Denmark, May 3 2013 Protein Requirements for Optimal Health in Older Adults: Current Recommendations and New Evidence Elena Volpi, MD, PhD Claude D. Pepper Older Americans Independence Center Institute for Translational Sciences University of Texas Medical Branch at Galveston

Outline Current recommendations for protein intake Protein intake and physical function in older adults Anabolic resistance Importance of protein quantity and intake distribution pattern Special considerations for hospitalized older adults Conclusions

Current Recommendations Dietary Reference Intakes (DRI) for protein for healthy adults of any age: Estimated Average Requirement: 0.66 g/kg/day Minimum protein amount to avoid deficiency in 50% of the population Recommended Dietary Allowance: 0.8 g/kg/day Minimum amount to avoid deficiency in 97-98% of the population Acceptable Macronutrient Distribution Range (AMDR) for protein: 10-35 % of total energy (35 kcal/kg/day) 0.85-3 g/kg/day

Problems with Current Recommendations Applicable only to healthy people Based on nitrogen balance studies, mostly done in younger people Highly controlled with small number of subjects Difficult estimation of intake and losses Meaning of N balance Protein sparing effect of low protein diet 0 balance inadequate in people who already lost lean mass Lower end of AMDR range is higher than RDA Minimalistic approach Avoiding deficiency vs. optimal intake for health

Why is Dietary Protein So Important? Provides amino acids for general cell function, and is particularly important for: Muscle growth and homeostasis Immune function Skin integrity Gut function Neurotransmitters Unlike fat and glucose, there is no inactive storage for protein Skeletal muscle serves as storage for protein

Protein Intake and Muscle Loss with Aging Health ABC Cohort Energy-adjusted total protein intake Unadjusted 0.8±0.3 0.7±0.3 0.8±0.3 0.9±0.3 1.2±0.4 protein intake Houston DK et al. Am J Clin Nutr 2008

Sarcopenia Diagnostic Criteria of the European Working Group 1. Low muscle mass + 2. Low muscle strength or 3. Low physical performance Cruz-Jentoft AJ et al. Age & Ageing 2010 InChianti Cohort - Lauretani et al. J Appl Physiol 2003

Frailty and Sarcopenia Chronic undernutrition Aging Disease Medications Environment Energy expenditure CYCLE OF FRAILTY Sarcopenia Insulin sensitivity Resting metabolic rate Osteopenia Activity VO 2 max Walking speed Disability Dependency Immobilization Strength Power Falls Injuries Impaired balance Death Modified from Fried et al. Sci. Aging Knowl. Environ. 2005

Strength and Mortality in Older Adults Health ABC Study 2,292 healthy older adults, 70-79 yr at enrollment Men Women Newman et al. J Gerontol A Biol Sci Med Sci, 2006

Gait Speed Predicts Median Life Expectancy in Older Adults Pooled analysis of 9 cohort studies N = 34,485 Studenski S et al. JAMA 2011

Percent per hour Aging Attenuates the Meal Stimulated Increase in Muscle Protein Synthesis 0.12 0.10 * 0.08 0.06 0.04 0.02 0 Fasting Meal Young Adults Older Adults Volpi et al. J Clin Endocrinol Metab, 2000

What Are the Mechanisms of Anabolic Resistance to a Meal with Aging? Meal Nutrients Endogenous Hormones Fat Protein Carbohydrate Insulin Other Amino Acids Leucine Muscle Growth Amino Acid Storage

Percent per hour Muscle Protein Synthesis is Resistant to the Anabolic Effect of Insulin in Older Adults 0.12 * # 0.10 * # 0.08 0.06 0.04 0.02 0 Young Adults Prandial Dose Older Adults Prandial Dose Older Adults High Dose Fasting Insulin Rasmussen et al., FASEB J, 2006 Fujita et al. Diabetologia, 2009

Cellular Mechanisms of Resistance to Anabolic Stimulation in Older Adults

Older Subject Young Subject Endothelial Dysfunction Contributes to Anabolic Resistance in Older adults Basal Insulin

VI/s Pharmacological Vasodilation Restores the Anabolic Response of Muscle to Insulin in Older Adults 30 25 20 15 10 5 Muscle Perfusion (Nutritive Flow) * nmol min -1 100 ml leg -1 180 160 140 120 100 80 60 40 20 Muscle Protein Synthesis * # 0 0 Fasting Insulin Fasting Insulin Older Control Older Sodium Nitroprusside Timmerman, Lee et al., Diabetes, 2010

VI/s Percent/hour Aerobic Exercise Restores the Muscle Protein Anabolic Response to a Mixed Meal in Elders Muscle Perfusion (Nutritive Flow) Muscle Protein Synthesis 1.5 * 120 100 * 1 80 60 0.5 40 20 0 Fasting Meal 0 Fasting Meal Control * P<0.05 vs. Basal Exercise P<0.05 vs. Control Timmerman et al., AJCN 2012

What Are the Mechanisms of Anabolic Resistance to a Meal with Aging? Meal Nutrients Endogenous Hormones Fat Protein Carbohydrate Insulin Other Amino Acids Leucine Muscle Growth Amino Acid Storage

Percent change from fasting Response of Muscle Protein Synthesis To Essential Amino Acids Depends on Leucine Dose 7 g Essential Amino Acids 18 g Essential Amino Acids 60 50 1.7 g Leucine (~15 g protein) 2.8 g Leucine (~30 g protein) * * 3.2 g Leucine (~40 g protein) * 40 30 * 20 10 0 Katsanos et al, AJP, 2006 Young adults Older adults Volpi et al, AJCN, 2003

Supplemental Leucine Optimizes Meal Protein Anabolism in Older Adults % / h 0.12 0.11 Muscle Protein Synthesis P=0.02 0.10 0.09 0.08 0.07 0.06 0.05 P=0.04 Post-absorptive Post-prandial 0 Day 1 (pre) Day 14 ( 2 weeks LEU) Casperson et al. Clin Nutr, 2012

What Are the Mechanisms of Anabolic Resistance to a Meal with Aging? Meal Nutrients Endogenous Hormones Fat Protein Carbohydrate Insulin Other = Amino Acids Muscle Growth Amino Acid Storage Leucine

Percent per hour Muscle Protein Synthesis in Older Adults: Protein Meal 0.14 0.12 30 g of Protein 4 oz beef patty (~320 kcal) * * 90 g of Protein 12 oz beef patty (~960 kcal) * * 0.1 0.08 0.06 0.04 0.02 50% 0 Fasting Meal Fasting Meal Symons et. al. AJCN, 2007 Young adults Older adults Symons et. al. J Am Diet Assoc, 2009

Percent of total daily intake Protein Intake Pattern Across Meals in Adults 70 yr and Older 50 Reported Distribution Average reported intake ~1 g/kg ~46% Ideal Distribution Max. Muscle Protein Synthesis Calculated ideal intake ~1.3 g/kg 40 ~33% ~33% ~33% 30 20 ~20% ~23% 10 0 14 g 16 g 32 g Breakfast Lunch Dinner 30 g 30 g 30 g Breakfast Lunch Dinner Source: NHANES 2007-2008 Paddon-Jones & Rasmussen, Curr Op Clin Nutr Metab Care 2009

Protein Intake Pattern Across Meals Significantly Impacts Muscle Protein Anabolism in Older Adults Breakfast Response 24-hour Response * * Mamerow, et.al. EB 2012

Function Patterns of Functional Loss and Disablement Independence Dependence 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 Age (yrs)

Hospitalized Older Adults Are Very Inactive Steps per Day Minutes Active per Day 6000 350 5000 300 4000 250 3000 200 150 2000 100 1000 50 0 Home Hospital 0 Home Hospital Fisher et al. JAGS 2011

Total Steps (median) Length of Stay Total Daily Steps and Early Mobilization Predict Hospital Length of Stay in Older Adults Number of Steps and LOS Early Mobilization and LOS 700 600 500 n=77 400 n=58 300 200 100 n=19 n=38 n=47 n=34 n=28 0 0 1 2 3 4 5 6 7 Complete Hospital Days Step Change from 1 st to 2 nd Hospital Day Fisher et al. JAGS 2011 Fisher et al. Arch Int Med 2010

Loss of lean leg mass (g) Inactivity Induces Significant Muscle Loss in Older Adults 250 0 Young Control 28 Days Older Adults 10 Days Young Stress model 28 Days -250-500 -750 2% -1000-1500 -2000 9% While consuming the protein RDA 6% Paddon-Jones et al. J Clin Endcrinol Metab, 2004 Kortebein et al. J Gerontology, 2008

Percent loss Shorter (7-Day) Bed Rest Induces Muscle Loss in Older Adults 0,0 Total Lean Mass Leg Lean Mass -1,0-1.6 kg -0.8 kg -2,0-3,0-4,0-5,0-6,0 Drummond et al. AJP Endo Metab 2012

Percent/hour Bed Rest Reduces the Response of Muscle Protein Synthesis to Amino Acids in Older Adults 0,12 0,09 * 0,06 0,03 0,00 Postabsorptive Fasting 12g EAA Essential period Amino (3h) Acids Pre-bed rest Post-bed rest Drummond et al. AJP Endo Metab 2012

Fold Change Bed Rest Reduces the Response of Amino Acid Transporters to Amino Acids in Older Adults Fold Change LAT1 protein SNAT2 protein 2,0 1,5 * # * # 2,0 1,5 * # * # 1,0 1,0 0,5 0,5 0,0 Baseline Fasting 1h-EAA 3h-EAA 0,0 Baseline Fasting 1h-EAA 3h-EAA Pre-Bed Rest Post-Bed Rest * P<0.05 vs. Fasting # P<0.05 vs. Pre-Bed Rest Drummond et al. AJP Endo Metab 2012

Grams per meal Hospitalized Older Patients May Not Eat Adequate Amounts of Protein 100 Presented Consumed 80 60 40 20 0 Protein Carbohydrate Fat Paddon-Jones, ACE Unit pilot data

24 hr Protein Synthesis (%/h) Excess Dietary Amino Acids Can Prevent Inactivity- Induced Reductions in Muscle Protein Synthesis 0.1 0.09 0.08 # 0.07 0.06 * 30% 0.05 0.04 0.03 0.02 0.01 0 Normal Diet Normal Diet + Amino Acids Normal Diet Normal Diet + Amino Acids Day 1 Day 10 Normal diet protein content: 0.8 g/kg/day Ferrando et al. Clin Nutr 2010

Summary In older adults: Total daily protein intake is a predictor of sarcopenia Response to mixed nutrient is impaired due to: Insulin resistance and endothelial dysfunction Reduced response of muscle protein synthesis to amino acids at lower intakes Aerobic exercise can reduce anabolic resistance Maximal stimulation of muscle protein synthesis is achieved at intakes of ~3 g of leucine corresponding to ~30 g of whole protein Immobilization reduces appetite, protein/energy intake and the response of muscle to anabolic stimulation by nutrients Supplementation with amino acids can improve muscle protein anabolism in response to feeding and during immobilization

Conclusions Adequate protein intake is essential to maintain muscle mass and function in older adults Protein is the only macronutrient that has no inactive reservoir (i.e. it is stored in active tissues, mainly muscle, or converted to energy) The current DRI for protein is often inadequate to maintain muscle mass and function in older adults. Data in the literature support higher intakes (1-1.2 g/kg/day) Protein intake distribution over meals should be considered Protein intake should be adjusted according to health status and activity level What is the optimal protein intake for hospitalized/inactive older adults? What is the optimal protein intake for active older persons?

Grow old along with me! The best is yet to be, the last of life, for which the first was made Robert Browning evolpi@utmb.edu www.utmb.edu/scoa/pepper/index.asp