The importance of () protein for maintenance of muscle mass during aging & rehabilitation

METTE HANSEN, Associated Professor INSTITUTE OF PUBLIC HEALTH SECTION OF SPORT SCIENCE AARHUS UNIVERSITY DENMARK [email protected] AARHUS UNIVERSITY 2013

EU: THE PORPORTION OF ELDERLY GROW AARHUS UNIVERSITY 2013 SOCIETY: FOR HOW LONG CAN THEY REMAIN INDEPENDENT OF HELP ? $$$ INDIVIDUAL: CAN I DO WHAT I WANT TO DO? AARHUS UNIVERSITY 2013 DAILY ACTIVITIES WALKING STAIR CLIMBING CHAIR RISING

Physical function of the muscle skeletal system › Flexibility › Coordination / balance › Muscle endurance capacity

› Muscle strength › Muscle power

Muscle mass & Neural factors AARHUS UNIVERSITY 2013 REDUCTION IN: STRENGTH MUSCLE MASS Reduced by 0.5-2% /yr from 50-80 yrs Reduced by 1-1.5% /yr from 60-65 yrs Muscle fiber Maximal Isometric strength Loss of muscle fiber

Smaller muscle fiber

Vandervoort & McComas 1986, Spirdoso 1995 Spirduso, Physical dimensions of Ageing, 1995 Parise & Yarasheski, Curr Opin Clin Nutr Metab Care, 2000 AARHUS UNIVERSITY 2013

MUSCLE PROTEIN BALANCE

Muscle Muscle Synthesis Breakdown AARHUS UNIVERSITY 2013

MUSCLE PROTEIN BALANCE

Immobilization & disease

Muscle Muscle Synthesis Breakdown

Reduced energy & protein intake AARHUS UNIVERSITY 2013

ELECTIVE ABDOMINAL SURGERY DEPRESSES MUSCLE PROTEIN SYNTHESIS AND ACCELERATE MUSCLE LOSS

21 days, n=13 Body weight ↓11.8 kg

Fat free mass ↓11.5 kg

Arm- & leg muscles ↓5.3 kg

Heart muscle Dage

Petersson et al 1990 AARHUS It is difficult for elderly patients to UNIVERSITY 2013 regain muscle strength after Muscle strength immobilisation/disease (Sashika 1996, Aerobic Fitness Sherrington 1997, Trudelle-Jackson 2002) Functional capacity Immobilization Physically active /disease ageing Normal ageing Training

Diseased/Inactive ageing

Threshold for independence

Age N Beyer 2002 AARHUS UNIVERSITY 2013 STRENGTH TRAINING HAS AN ANABOLIC EFFECT ON MUSCLE GROWTH

AARHUS UNIVERSITY 2013

EFFECT OF ACUTE STRENGTH EXERCISE

Muscle protein synthesis * 8 sets of 0,12 %/hrs 8 rep 80% of 1RM 0,1 * 0,08 *

0,06 Fractional synthesis rate 0,04

0,02

0 Rest 3h 24h 48h

Philips et al, 1997 AARHUS UNIVERSITY 2013

EFFECT OF ACUTE STRENGTH EXERCISE

%/hrs * 8 sets of 0,16 %/hrs * 8 rep 80% of 1RM 0,14 * * * 0,12 * 0,1 * Fractional 0,08 * synthesis rate Fractional 0,06 breakdown rate 0,04 0,02 0 Rest 3 hrs 24 hrs 48 hrs

Philips et al, 1997 AARHUS UNIVERSITY 2013 MUSCLE PROTEIN BALANCE – EFFECT OF ENERGY & PROTEIN INTAKE Amino Acids Essential Acids (EAA) Energy

+ + - Muscle Muscle Synthesis Breakdown Carbohydrate

+ (?)

Insulin

BCAA AARHUS UNIVERSITY 2013

PROTEIN

. Protein quantity

. Protein quality (EAA, BCAA)

. Timing of protein intake

. Protein source AARHUS UNIVERSITY 2013

LOSS OF LEAN BODY MASS IN HEALTHY ELDERLY N=2066, 70-79 YRS, 3-YEAR PERIOD Houston DK, et al, 2008

11.2 12.7 14.1 15.8 18 Energy% 0.7 0.7 0.8 0.9 1.1 g protein/kg/day Among those who lost Gr 5 vs 1 weight over the 3-y period, lower 40% reduced protein intake was associated loss of LBM with greater loss of LM. Sammenhæng også signifikant ved vægtstigning Ingen sammenhæng med veg protein Scientific evidence suggests that a protein intake moderately higher than the current RDA of 0.8 g/kg/day may help support muscle and bone health in the elderly. Chaput et al, J. Nutr. Health Aging 11: 363, 2007. Meng, X., et al. J. Bone Miner. Res. 24: 1827, 2009. However, few studies have examined the effect of protein source on protein metabolism and body composition in older adults. In older women, protein breakdown in the absorptive state was inhibited in those consuming a highvegetable-protein diet to a lesser extent than in those consuming a high-animal-protein diet; the result was less net protein synthesis Animalsk protein gjorde udslaget among those in the former group than Veg NS – men ikke så stor among those in the latter group (22). In spredning i indtag studies contrasting the effect of a lactoovovegetarian diet and a meat- containing diet in combination with resistance training on changes in body composition in older men, results were mixed (23, 24). In the Health ABC Study cohort, we found significant associations between animal protein intake and changes in LM, but no such association with vegetable protein intake. However, the range of intake was much greater for animal protein than for vegetable protein, which may have limited our ability to detect a significant association between vegetable protein intake and changes in LM. There is some question regarding AARHUS UNIVERSITY 2013

PROTEIN

. Protein quantity seems to matter

. Protein quality (EAA, BCAA)

. Timing of protein intake

. Protein source AARHUS UNIVERSITY 2013 ENHANCED PROTEIN QUANTITY AND QUALITY DURING 60 DAYS BEDREST DO NOT REDUCE MUSCLE LOSS (healthy young women)

3 Meals a day C PRO Ex Gr 1: 1.6 g protein/kg/day (incl.7.2 g extra BCAA) Hypotese til forklaring af større tab af Gr 2: 1 g protein/kg/day (isocaloric to gr 1) muskel i kost-gruppen tilskrives Gr 3: 1 g protein/kg/day + Exercise in bed stimulering af muskelproteinnedbrydning. Quadriceps Isokalorisk C og kost, Ex mere energi

svarende til energiforbrug under exercise surae Fordelt på 3 måltider per dag. – i paddon jones studie fik de både flere måltider, mere protein og mere energi i interventionsgruppen Triceps Trappe et al, Acta Physiol (2007) AARHUS UNIVERSITY 2013

PROTEIN

. Protein quantity seem to matter

. Protein quality (EAA, BCAA)

. Timing of protein intake

. Protein source AARHUS UNIVERSITY 2013 ENHANCED PROTEIN QUANTITY AND QUALITY DURING 28 DAYS BEDREST DO REDUCE MUSCLE LOSS (healthy young men)

Paddon-Jones D et al, J Clin Endocrinol Metab (2004) 89: 4351–4358 AARHUS UNIVERSITY 2013 ENHANCED PROTEIN QUANTITY AND QUALITY DURING 28 DAYS BEDREST DO REDUCE MUSCLE LOSS (healthy young men)

Muscle mass Muscle strength

Paddon-Jones D et al, J Clin Endocrinol Metab (2004) 89: 4351–4358 AARHUS UNIVERSITY 2013 PROTEIN INGESTION DURING SLEEP IMPROVES WHOLE-BODY & MUSCLE PROTEIN BALANCE OVERNIGHT Res et al MSSE (2012) 44(8): 1560-9 40 g casein protein ½ hr before sleep

Whole body protein kinetic Muscle protein synthesis

Similar findings in elderly men after 40 g casein protein via nasogastric tupe during night sleep Groen BBL et al Am J physiol Endocrinol Metab (2012) 302: E52-60 AARHUS UNIVERSITY 2013

How much protein do we need to maximize muscle protein syntheis rate? AARHUS UNIVERSITY 2013

10 g EAA MAXIMIZE MYOFIBRILLAR PROTEIN SYNTHESIS

~20-25 g of high Cuthbertson et al, quality protein FASEB, 2005 (, eeg, meat, fish)

Cuthbertson et al, FASEB J (2005) 19(3): 422-4 AARHUS UNIVERSITY 2013 ?

+ PROTEIN = AARHUS UNIVERSITY 2013

RESISTANCE EXERCISE PROLONGED THE PERIOD OF ENHANCED MYOFIBRILLAR PROTEIN SYNTHESIS RATE

Moore DR et al, J Physiol (2009) 587(4): 897-904 AARHUS UNIVERSITY 2013

TIMING OF PROTEIN & TRAINING AARHUS UNIVERSITY 2013 TIMING OF POSTEXERCISE PROTEIN INTAKE IS IMPORTANT FOR MUSCLE HYPEORTROPHY (elderly men)

12 week of strength training (3 times per week)

10g protein + 7g CHO + 3.3g

Gr 1 (P0) Time = 0 hr after exercise Gr 2 (P2) Time = 2 hrs after exercise

Esmarck B et al, J Physiol (2001) 535(1): 301-311 AARHUS UNIVERSITY 2013

TIMING OF POSTEXERCISE PROTEIN INTAKE IS IMPORTANT FOR MUSCLE HYPEORTROPHY (elderly men) Muscle CSA Mean fiber areal

Dymanic strength (5 RM) improved in both groups Isokinetic strength only improved in P0

Esmarck B et al, J Physiol (2001) 535(1): 301-311 AARHUS UNIVERSITY 2013

N=680 subjects, Resistance training > 6 weeks

FFM

<50 yr

>50 yr

~12 weeks resistance training + protein = +1 kg greater gain in FFM

Am J Clin Nutr (2012) 96:1454-64 AARHUS UNIVERSITY 2013

N=680 subjects, Resistance training > 6 weeks

FFMFFM

Am J Clin Nutr (2012) 96:1454-64 AARHUS UNIVERSITY 2013

Synthesis

Balance breakdown

Morning Morning Morning Morning before + protein + exercise + exercise (If no protein before bed) + protein AARHUS UNIVERSITY 20-25 G OF HIGH QUALITY PROTEIN 2013 MAXIMIZE MYOFIBRILLAR PROTEIN SYNTHESIS

AARHUS UNIVERSITY 2013

PROTEIN

. Protein quantity

. Protein quality (EAA, BCAA)

. Timing of protein intake

. Protein source AARHUS UNIVERSITY 2013

RESISTANCE TRAINING-INDUCED ΔLBM IN STUDIES OF SUBJECTS RECEIVING SUPPLEMENTAL PROTEIN SOURCES

11 weeks of training (range 8-16 weeks)

› Fra phillips 2012 All studies mean change (ci 95%)

3 studies 8 studies 3 studies 7 studies n=42 n=91 n=51 n=67

Phillips SM et al, J Am College Nutr (2009) 28(4): 343-354 AARHUS UNIVERSITY 2013 DIET PROTEIN  AA AVAILABLE FOR SKELETAL MUSCLE PROTEIN SYNTHESIS AARHUS UNIVERSITY 2013 PROTEIN SOURCES QUALITY 1,4 Determined by: - EAA composition 1,2 - Digestibility Maximum score of 1 for PDCAAS 1

0,8 PDCAAS 0,6 DIAAS

0,4 FAO (1) recommends that the DIAAS metod replaces 0,2 PDCAAS as the preferred method to evaluate protein 0 quality Milk Soy Barley Rice

1: Dietary protein quality evaluation in human nutrition. FAO FOOD AND NUTRITION PAPER 92. 2013. Data from Paul Moughan, Riddet Institute, Global Dairy Platform Workshop, San Francisco, USA, April 2012. AARHUS UNIVERSITY 2013

FAST OR SLOW DIGESTIBLE PROTEINS AA availability

Whey Casein

Milkprotein Myofibrillar protein synthesis in elderly men Oxidation 20% Whey 20 g whey or casein 80% casein Whey

Casein

Boirie Y, et al , 1997, Burd et al 2012 AARHUS Milkprotein UNIVERSITY 20% Whey2013 80%Casein FAST(WHEY) OR SLOW (CASEIN) DIGESTIBLE PROTEINS – MOST BENEFICIAL? Likely to depend on:

• Age Fast or a mix of slow/fast digestible proteins for elderly

Slow digestible protein • Time of the day ? before sleep ??

Slow digestible proteins for • Energy status? subject in a hypocaloric state Demling RH et al, 2000

• Sex ? AARHUS UNIVERSITY 2013 THE IMPORTANCE OF (DAIRY) PROTEIN FOR MAINTENANCE OF MUSCLE MASS DURING AGING & REHABILITATION - SUMMARY

› Protein quantity (recommendations) › Optimal dose for counteracting muscle loss in elderly is probably higher than 0.8 g/kg/day

› Protein quality (EAA, BCAA) › High content of EAA and BCAA reduce the total amount of protein needed for maximal stimulus of muscle protein synthesis

› Timing of protein intake › Important for muscle maintenance (between meals, before sleep?) › 20-25 g protein maximize muscle protein synthesis after/before hours of fasting

› Important for muscle growth combined with a training stimulus › 20-25 g proten maximize the effect of training on muscle mass

› Protein source › Animal protein have a high content of EAA and is well absorb from the intestine › As an example Bovine Milk is an effective post exercise beverage AARHUS UNIVERSITY 2013 20-25 G OF HIGH QUALITY PROTEIN TO MAXIMIZE MYOFIBRILLAR PROTEIN SYNTHESIS* AFTER OVERNIGHT FASTING AND WHEN TRAINING

~ 3 eggs

~ 100 g of Chicken/ Meat/ Turkey/ Fish

~ 0.6 L Milk or

~ 500 g Yoghurt

~ 200 g Skyr/ (yoghurt-like with high protein content)

~ 200 g Cottage

* 0.25-0.3 g protein/kg