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Nutritional interventions in
sarcopenia and frailty
Dr Mary Hickson
Research Dietitian, Imperial College
Healthcare NHS Trust
Adjunct Professor, Imperial College
London
1
Impact of Nutrition
2
3
Nutrients implicated
• Protein and essential amino acids (EAA)
• Vitamin D
• Dietary fat - Alpha linoleic acid
• Alcohol
• Antioxidants
• Minerals
• Acid-base load
4
Welch A. Nutritional
influences on age-related
skeletal muscle loss.
Proceedings of the
Nutrition Society (2014),
73, 16–33
Dietary fat / α-linoleic acid
• Fatty acids source of energy for resting and working
muscle
• Integral component of myocellular membranes
• Influences inflammation and insulin resistance
• Different fatty acids could affect membrane function
• Animal models: high dietary fat muscle hypertrophy
• N-3 FA augments muscle protein anabolism
• PUFA: Associated with muscle mass
• α-linoleic acid (with resistance training): No effect on
muscle mass or performance
5
Alcohol
• Excess alcohol is related to muscle damage
– Reduced rates of protein synthesis and breakdown,
– Loss and redistribution of ribosomal RNA,
– Increased RNase activities
– Membrane damage
– Altered Ca2+ regulation
– Generation of free radicals
• Few studies looking at alcohol and sarcopenia
• Little evidence of association
6
Antioxidants
• Oxidative stress potentially muscle loss
• Antioxidant nutrients could oxidation in muscle
• Antioxidants = Vits C, E, Carotenoids, Cu, Mn, Se, Zn
• Some evidence that lack of these micronutrients (and
Fruit and Veg) are associated with functional
limitations
• Vit E and C supplementation (with resistance
exercise) improved lean mass more than resistance
exercise alone
7
Minerals
• Magnesium status has effects on muscle
performance
• Low serum Mg associated with lower
muscle strength
• Longitudinal study showed Mg, Fe, P, Zn
all associated positively with lean mass
8
Acid-base load
• Tendency for slight blood pH decrease with age
due to decreasing function of the kidneys (lower
excretion of H+)
• Diet can also influence metabolic acidosis
• Acidogenic foods:
– Meat, fish, eggs, cereals, dairy
• Alkalinogenic foods:
– Fruit and vegetables
• Overall balance is acid-base load
9
Acid-base load
• Metabolic acidosis potentially accelerates
protein breakdown
• Two studies: both showed alkaline diet favoured
muscle mass retention.
• The alkaline effect of diet was about half as
important as the effect of age on muscle loss
• Eat more fruit and veg!
10
What is the evidence?
• Systematic Reviews of RCT
• Cruz-Jentoft A et al. Prevalence of and
interventions for sarcopenia in ageing adults: a
systematic review. Report of the International
Sarcopenia Initiative. Age and Ageing 2014; 43:
748–759
• Bibas et al. Therapeutic Interventions for Frail
Elderly Patients: Part I. Published Randomized
Trials. Progress in cardivascular diseases 2014;
57: 134-143
11
Main findings
• Protein – 5 studies - no consistent effect
• EAA – 2 studies - very limited evidence –
some effect on muscle mass and function
• HMB – 4 studies - Limited evidence -
Some effects on muscle mass and
function
• Fatty acids – 1 study – no effect
12
Protein supplementation
• With and without resistance training
• With and without energy supplement
• With and without additional vitamins and
minerals
• Different populations
• Blinding mixed
• Adherence 44-98%
• Only some assessed dietary intake13
• Protein supplemented 13-40g/d
• Up to 1.4g/kg-bw/d
• Some evidence that supplements reduced
spontaneous food intake
• Difficulties recruiting; community dwelling
= 4-9% recruitment rate
14
Protein – no consistent effect?
• Clear well defined populations
• Four arm studies nutrition +/- exercise
• Standardised outcome measures
• Timing of nutritional supplement*
• Baseline nutritional status*
• Assessment of spontaneous food intake
• Protein in relation to requirement (g/kg-bw/d)
• Recruitment
• Adherence
15
Protein requirements
• 1.0-1.2g/kg bw/d
– 60kg person increase from 48g/d to 72g/d
• 1.2-1.5g/kg bw/d (risk of malnutrition, ill)
– 60kg person = 90g/d
• 25-30g/meal to stimulate anabolism
– suggests minimum of 75-90g/day
• Pulse feeding – majority (80%) of protein at one
meal to overcome effect of splanchnic
sequestration
16
17
The
Splanchnic
bed
Essential amino-acids
• Anabolic stimulus for muscle
• Only two studies
• One in healthy women and one in
sarcopenic women
• Different EAA supplements
18
EAA profiles
19
0
0.5
1
1.5
2
2.5
3
Dillon
Kim
20
40.7
43.5
41
45.2
38
39
40
41
42
43
44
45
46
placebo suppl
LeanBodyMass(kg)
baseline
3 months
p<0.05
Dillon EL et al. Amino Acid
Supplementation Increases Lean
Body Mass, Basal Muscle Protein
Synthesis, and Insulin-Like Growth
Factor-I Expression in Older
Women. J Clin Endocrinol Metab.
2009, 94(5):1630–1637
21
Kim et al. Effects of
Exercise and Amino Acid
Supplementation on Body
Composition and Physical
Function in Community-
Dwelling
Elderly Japanese
Sarcopenic Women: A
Randomized Controlled
Trial. JAGS 60:16-23, 2012
EAA future studies
• Agreement on EAA profile
• Adherence
• Acceptability
• Is leucine the key?
22
23
90-95%
conversion
5-10%
conversion
Essential Branched Chain AA
β-hydroxy β-methylbutyrate
(HMB)
24 Eley 2008
HMB dose
• 3g/d HMB
• = 60g leucine/d
• = >600g of high-quality protein sources
(eggs, dairy and meat) daily
25
Animal work
26
Wilson et al. Journal
of the International
Society of Sports
Nutrition 2012, 9:1
Changes in fat mass among control and HMB conditions in
young and older F344 rats.
HMB
• More consistent dose – 2-3g/d HMB (but
one with arginine and lysine)
• Generally free-living older adults
• One – bedrest study
• More consistent improvements in muscle
mass
• Less consistent improvements in strength
and function
27
Arginine and lysine
• Lysine requirement estimated at 30mg/kg
per day for maintenance in non-elderly
healthy adults (≈2g/d)
• Some evidence that older adults intake is
lower, particularly women.
• Key AA in muscle – needed for growth and
maintenance
• Arginine shown to stimulate whole-body
protein synthesis28
Protein seems important
• Amount - 1.2g/kg-bw/day (Bauer, 2013)
• Type - ? AA content
• Timing – even or pulse?
• Exercise
• Nutritional status
29
Vitamin D and muscle
• Deficiency: Symptoms = muscle weakness,
pain, and gait impairments.
• Vitamin D receptor on muscle tissue?
• Observational studies positive relationship
between vitamin D and muscle function.
• Vitamin D supplementation trials on muscle
function show effect on strength.
30
31
Effect of Vit D
supplementation
on global
muscle strength
(grip or lower limb)
Mean diff = 0.17
95% CI: 0.031, 0.31
P=0.017
I2=77.67%
Total subjects =
5533
Beaudart, J Clin
Endocrinol Metab
99: 4336–4345,
2014
32
Beaudart, J Clin
Endocrinol Metab
99: 4336–4345,
2014
Mean diff = 0.06 (P=0.52)
I2=3.34%
Effect of Vit D on muscle mass
33
Beaudart, J Clin
Endocrinol Metab
99: 4336–4345,
2014
Mean diff = 0.06 (P=0.66)
I2=0.0%
Effect of Vit D on muscle power
Vitamin D
• Modest but significant effect on muscle
strength
• Greatest effect in vit D deficient or
insufficient states
• Inconclusive data on power and mass
• Critical to assess baseline vit D status and
supplement vit D with other intervention.
34
35
Fuller et al. Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 6, Nov 2011
HMB/Arg/Lys and Vit D
>30ng/mL
HMB/Arg/Lys and Vit D
<30ng/mL
control
Key points
• Protein and vitamin D seem to have the most
potential in treating and/or preventing sarcopenia
• Evidence is currently hampered by design issues
• Lack of agreement on the most appropriate
outcomes
• Baseline nutritional status is important
• Supplements need to be on top of recommended
requirements
• Other aspects of diet are under researched
36
37

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Nutrition interventions for frailty and sarcopenia

  • 1. Nutritional interventions in sarcopenia and frailty Dr Mary Hickson Research Dietitian, Imperial College Healthcare NHS Trust Adjunct Professor, Imperial College London 1
  • 3. 3
  • 4. Nutrients implicated • Protein and essential amino acids (EAA) • Vitamin D • Dietary fat - Alpha linoleic acid • Alcohol • Antioxidants • Minerals • Acid-base load 4 Welch A. Nutritional influences on age-related skeletal muscle loss. Proceedings of the Nutrition Society (2014), 73, 16–33
  • 5. Dietary fat / α-linoleic acid • Fatty acids source of energy for resting and working muscle • Integral component of myocellular membranes • Influences inflammation and insulin resistance • Different fatty acids could affect membrane function • Animal models: high dietary fat muscle hypertrophy • N-3 FA augments muscle protein anabolism • PUFA: Associated with muscle mass • α-linoleic acid (with resistance training): No effect on muscle mass or performance 5
  • 6. Alcohol • Excess alcohol is related to muscle damage – Reduced rates of protein synthesis and breakdown, – Loss and redistribution of ribosomal RNA, – Increased RNase activities – Membrane damage – Altered Ca2+ regulation – Generation of free radicals • Few studies looking at alcohol and sarcopenia • Little evidence of association 6
  • 7. Antioxidants • Oxidative stress potentially muscle loss • Antioxidant nutrients could oxidation in muscle • Antioxidants = Vits C, E, Carotenoids, Cu, Mn, Se, Zn • Some evidence that lack of these micronutrients (and Fruit and Veg) are associated with functional limitations • Vit E and C supplementation (with resistance exercise) improved lean mass more than resistance exercise alone 7
  • 8. Minerals • Magnesium status has effects on muscle performance • Low serum Mg associated with lower muscle strength • Longitudinal study showed Mg, Fe, P, Zn all associated positively with lean mass 8
  • 9. Acid-base load • Tendency for slight blood pH decrease with age due to decreasing function of the kidneys (lower excretion of H+) • Diet can also influence metabolic acidosis • Acidogenic foods: – Meat, fish, eggs, cereals, dairy • Alkalinogenic foods: – Fruit and vegetables • Overall balance is acid-base load 9
  • 10. Acid-base load • Metabolic acidosis potentially accelerates protein breakdown • Two studies: both showed alkaline diet favoured muscle mass retention. • The alkaline effect of diet was about half as important as the effect of age on muscle loss • Eat more fruit and veg! 10
  • 11. What is the evidence? • Systematic Reviews of RCT • Cruz-Jentoft A et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative. Age and Ageing 2014; 43: 748–759 • Bibas et al. Therapeutic Interventions for Frail Elderly Patients: Part I. Published Randomized Trials. Progress in cardivascular diseases 2014; 57: 134-143 11
  • 12. Main findings • Protein – 5 studies - no consistent effect • EAA – 2 studies - very limited evidence – some effect on muscle mass and function • HMB – 4 studies - Limited evidence - Some effects on muscle mass and function • Fatty acids – 1 study – no effect 12
  • 13. Protein supplementation • With and without resistance training • With and without energy supplement • With and without additional vitamins and minerals • Different populations • Blinding mixed • Adherence 44-98% • Only some assessed dietary intake13
  • 14. • Protein supplemented 13-40g/d • Up to 1.4g/kg-bw/d • Some evidence that supplements reduced spontaneous food intake • Difficulties recruiting; community dwelling = 4-9% recruitment rate 14
  • 15. Protein – no consistent effect? • Clear well defined populations • Four arm studies nutrition +/- exercise • Standardised outcome measures • Timing of nutritional supplement* • Baseline nutritional status* • Assessment of spontaneous food intake • Protein in relation to requirement (g/kg-bw/d) • Recruitment • Adherence 15
  • 16. Protein requirements • 1.0-1.2g/kg bw/d – 60kg person increase from 48g/d to 72g/d • 1.2-1.5g/kg bw/d (risk of malnutrition, ill) – 60kg person = 90g/d • 25-30g/meal to stimulate anabolism – suggests minimum of 75-90g/day • Pulse feeding – majority (80%) of protein at one meal to overcome effect of splanchnic sequestration 16
  • 18. Essential amino-acids • Anabolic stimulus for muscle • Only two studies • One in healthy women and one in sarcopenic women • Different EAA supplements 18
  • 20. 20 40.7 43.5 41 45.2 38 39 40 41 42 43 44 45 46 placebo suppl LeanBodyMass(kg) baseline 3 months p<0.05 Dillon EL et al. Amino Acid Supplementation Increases Lean Body Mass, Basal Muscle Protein Synthesis, and Insulin-Like Growth Factor-I Expression in Older Women. J Clin Endocrinol Metab. 2009, 94(5):1630–1637
  • 21. 21 Kim et al. Effects of Exercise and Amino Acid Supplementation on Body Composition and Physical Function in Community- Dwelling Elderly Japanese Sarcopenic Women: A Randomized Controlled Trial. JAGS 60:16-23, 2012
  • 22. EAA future studies • Agreement on EAA profile • Adherence • Acceptability • Is leucine the key? 22
  • 25. HMB dose • 3g/d HMB • = 60g leucine/d • = >600g of high-quality protein sources (eggs, dairy and meat) daily 25
  • 26. Animal work 26 Wilson et al. Journal of the International Society of Sports Nutrition 2012, 9:1 Changes in fat mass among control and HMB conditions in young and older F344 rats.
  • 27. HMB • More consistent dose – 2-3g/d HMB (but one with arginine and lysine) • Generally free-living older adults • One – bedrest study • More consistent improvements in muscle mass • Less consistent improvements in strength and function 27
  • 28. Arginine and lysine • Lysine requirement estimated at 30mg/kg per day for maintenance in non-elderly healthy adults (≈2g/d) • Some evidence that older adults intake is lower, particularly women. • Key AA in muscle – needed for growth and maintenance • Arginine shown to stimulate whole-body protein synthesis28
  • 29. Protein seems important • Amount - 1.2g/kg-bw/day (Bauer, 2013) • Type - ? AA content • Timing – even or pulse? • Exercise • Nutritional status 29
  • 30. Vitamin D and muscle • Deficiency: Symptoms = muscle weakness, pain, and gait impairments. • Vitamin D receptor on muscle tissue? • Observational studies positive relationship between vitamin D and muscle function. • Vitamin D supplementation trials on muscle function show effect on strength. 30
  • 31. 31 Effect of Vit D supplementation on global muscle strength (grip or lower limb) Mean diff = 0.17 95% CI: 0.031, 0.31 P=0.017 I2=77.67% Total subjects = 5533 Beaudart, J Clin Endocrinol Metab 99: 4336–4345, 2014
  • 32. 32 Beaudart, J Clin Endocrinol Metab 99: 4336–4345, 2014 Mean diff = 0.06 (P=0.52) I2=3.34% Effect of Vit D on muscle mass
  • 33. 33 Beaudart, J Clin Endocrinol Metab 99: 4336–4345, 2014 Mean diff = 0.06 (P=0.66) I2=0.0% Effect of Vit D on muscle power
  • 34. Vitamin D • Modest but significant effect on muscle strength • Greatest effect in vit D deficient or insufficient states • Inconclusive data on power and mass • Critical to assess baseline vit D status and supplement vit D with other intervention. 34
  • 35. 35 Fuller et al. Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 6, Nov 2011 HMB/Arg/Lys and Vit D >30ng/mL HMB/Arg/Lys and Vit D <30ng/mL control
  • 36. Key points • Protein and vitamin D seem to have the most potential in treating and/or preventing sarcopenia • Evidence is currently hampered by design issues • Lack of agreement on the most appropriate outcomes • Baseline nutritional status is important • Supplements need to be on top of recommended requirements • Other aspects of diet are under researched 36
  • 37. 37