Role of nutrition in promoting muscle health for healthy aging

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1 Key highlights Role of nutrition in promoting muscle health for healthy aging Dieu Huynh Senior Lead, Clinical Research and Nutrition Science Abbott Nutrition R&D Asia-Pacific Center Importance of muscle mass and strength for healthy aging Nutritional factors to promote muscle health Enter title via "insert>header and footer>footer" November 15, Main functions of muscle SKELETAL MUSCLE Progressive Loss of Muscle With Age 100 STRUCTURAL FUNCTIONS Physical movement Maintenance of posture and balance METABOLIC FUNCTIONS Main reservoir of proteins Regulator of glucose levels % peak muscle mass Up to 8% loss per decade after age yrs 40 yrs 70 yrs 15% loss per decade after age Years Agriles J et al. JAMDA 2016: Enter title via "insert>header and footer>footer" November 15, Grimby G et al Clin Physiol. 1983;3: ; Flakoll P, et al. Nutrition. 2004;20: ; Baier S, et al. JPEN J Parenter Enteral Nutr. 2009;33:71 82; Janssen I, et al. J Appl Physiol. 2000;89: Enter title via "insert>header and footer>footer" November 15, 20174

2 Reduced physical activity and bed rest increase loss of muscle How does loss of lean mass affect patients? 0 Healthy Elders 14 days reduced activity 1 Healthy Elders 10 Days Inactivity kg (3.9%) loss of leg fat-free mass 2 kg (4.8%) loss of lean mass 1 Breen L et al. J Clin Endocrinol Metab. 2013; 98: Deutz NE, et al. Clinical nutrition (Edinburgh, Scotland). 2013;32(5): November 15, Loss of LBM approaching 40% increases the risk of death usually from pneumonia. Demling RH. Eplasty. 2009;9:65-94 Enter title Demling via "insert>header RH. Eplasty. and footer>footer" 2009;9:65-94 November 15, Why is muscle strength important? Ruiz JR et al. BMJ :a439 Prospective cohort study (n = 8762, y) with 18.9 y follow up showed significantly lower mortality rate in the upper third of muscular strength among individuals >60 y. Enter title via "insert>header and footer>footer" November 15, Sarcopenia = Low Muscle Mass + Low Strength &/or Function OR (95% CI) Mortality 3.59 ( ) Functional decline 3.03 ( Fall 3.45 ( ) Facture* 3.79 ( ) for men 2.27 ( ) for women Length of hospital stay* 1.84 ( ) *One study was included Beaudart C. PLoS One. 2017; 12(1): e Enter title via "insert>header and footer>footer" November 15, 20178

3 Strategies Towards Optimized Muscle Health Integrated approach to address muscle loss For optimal maintenance with aging, it is important to build muscle when young, maintain it in mid-life, and minimize loss in older adulthood Build Maintain Minimize Loss Protein, HMB, Vitamins (Vitamin D), Minerals Exercise 1 Sayer AA, et al. J Nutr Health Aging. 2008;12: Enter title via "insert>header and footer>footer" November 15, Pahor M. et al. JAMA; (2014): ; Enter title via "insert>header and footer>footer" November 15, Pahor M. et al. JAMA; (2014): ; Decline in muscle mass despite adequate protein intake according to RDA Protein intake at 0.8g/kg/day was associated with a decline in thigh muscle area after 14 weeks Protein 11 Campbell et al. J Gerotol A Biol Sci :M373-M380 12

4 Dietary protein intake evidence A prospective analysis including elderly adults in the health, aging, and body composition (Health ABC) study Overall lean body mass (LM) by quintile of protein intake Quintile 0 Change in LM (kg) p<0.05 for Quintile 1 vs 4 and 5 and Quintile 2 vs 5. Appendicular (ARM+LEG) lean mass (alm) by quintile of protein intake Change in alm (kg) Quintile p<0.05 for Quintiles 1 vs 4 and 5, and Quintiles 2 and 3 vs 5, and Quintile 4 vs 5 2RDA protein intake results in significantly greater protein synthesis a randomized controlled trial RCT (n = 20, y) showed significantly greater increase in NB and PS in those consuming 2RDA protein vs. 1 1RDA protein, regardless of distribution pattern. Subjects in the highest protein quintile lost 40% less lean mass (LM) than did those in the lowest protein quintile (p<0.01) Houston DK, et al. Am J Clin Nutr.: 2008:87: Kim IY. Et al. Am J Physiol Endocrinol Metab : E21 E28 2RDA protein intake has beneficial effects on lean body mass and leg power in elderly men 2RDA protein intake has beneficial effects on lean body mass and leg power in elderly men Mitchell CJ et al. Am J Clin Nutr Nov Mitchell CJ et al. Am J Clin Nutr Nov 1. 16

5 Recommendations for higher protein intake in older adults 0.8g/kg=previous target intake level New target intake level 30% g/kg 88% g/kg 150% Up to 2.0 g/kg MORE THAN HEALTHY BONES Vitamin D Minimum protein intake* People with acute or chronic diseases* People with severe illness or injury or marked malnutrition* Caution needed among those with severe kidney disease [i.e. estimated Glomerular Filtration Rate <30mL/min/1.73 m 2, calculating their needs differently] Bauer J. et al. J Am Med Dir Assoc : Deutz NE et al. Clin Nutr : Effects of 1,25 vitamin D on muscle cells Older adults with low vitamin D level had lower appendicular lean mass and leg strength Halfon M. et al BioMed Research International Enter title via "insert>header and footer>footer" November 15, Tasmanian older adult cohort study including 686 community-dwelling older adults ~5% lower P< Appendicular lean mass (%) Leg strength (kg) ~9% lower p=0.014 low vitamin D normal vitamin D Scott D, et al. Clinical Endocrinology. 2010;73(5): November 15,

6 Vitamin D supplementation has a positive impact on muscle strength Meta analysis including 30 RCTs (n=5615) showed vitamin D supplementation had a small positive impact on muscle strength Vitamin D supplementation reduces the odds of falling High dose vitamin D (700 to 1000 IU vitamin D per day) reduced the odds of falling (OR=0.66 [ ] p=0.0002) Beaudart C, et al. The Journal of clinical endocrinology and metabolism. 2014;99(11): November 15, Bischoff-Ferrari HA. Geriatr Psychol Neuropsychiatr Vieil, vol. 15, n 1, mars 2017 Enter title via "insert>header and footer>footer" November 15, hydroxy- -methylbutyrate (HMB) HMB Active metabolite of amino acid leucine Occurs naturally in human muscle cells Found in small quantities in some foods 1.5 g CaHMB is equal to ~ 3,000 avocados QUICK FACTS 23 24

7 Leucine - HMB Metabolic Pathway 1 Mechanism of action of HMB on muscle Leucine (Diet Only) KIC ( - keto isocaproate) (Liver, Muscle) 5% Liver HMB Circulates Muscle: - Cholesterol Synthesis - NFkB - mtor Insulin HMB 95% Urine (10% 40%) Other Pathway 1. Nissen S, Abumrad N. J Nutr Biochem. 1997;8: Enter presentation title via "insert>header and footer>footer" November 15, November 15, Hydroxy- -methylbutyrate (HMB): Mechanisms of Action and Scientific Support 25 Adapted from Hoffman & Nader Nature Medicine (2004) 10, Eley HL et al. Am J Physiol Endocrinol Metab. 2008;295:E Giron et al (2015) PloS one, 10(2), e Wilkinson DJ et al. J. Physiol. 2013:591.11: Blood HMB Concentration Declines with Aging HMB contributes to preservation of muscle mass in older adults - Meta analysis of effectiveness of HMB HMB concentrations were significantly lower with increasing age groups -Could be one contributing factor of muscle loss with aging Greater muscle mass gain with HMB Kuriyan R, et al. Experimental gerontology. 2016;81: Wu et al, Arch Gerontol Geriatr. 2015;61(2):

8 Exercise! Summary Aging muscle does respond to exercise, especially resistance exercise Muscle mass and strength is vital for healthy aging. Loss of muscle mass and strength (sarcopenia) can de due to aging, physical inactivity and disease related, leading to loss of independence and poor quality of life ESPEN expert group encourage: continued participation in routine exercise or physical activities. Sarcopenia is preventable with exercise and adequate nutrition Regular exercise Adequate protein and vitamin D intake HMB supplementation Deutz NE, et al. Clinical nutrition (Edinburgh, Scotland). 2014;33(6): November 15,