AMINOACIDI: OVERVIEW CLINICA
E
MECCANISMI FISIOPATOLOGICI
P rof. R oberto Aquilani
Fondazione Salvatore Maugeri
Clinica del Lavoro e della Riabilitazione
I.R.C.C.S.
Centro Medico Montescano (PV)
Torino, 30 Gennaio 2010
AREA NUTRIZIONE - CERVELLO
2- Stroke
“Protein supplementation may enhance the spontaneous recovery of
neurological in patients with ischaemic stroke”
(Aquilani R. et al., Clin Rehab 2008)
Controls
admission Δ (21days-admission)
NIHSS
0-30 scores
Supplemented
admission
Δ (21days-admission)
10.1±3.4
-3.±1.4
12.6±2.7
-4.4±1.5
CHO
g/day
204±84
11.6±56
145±44
34.3±39.7
Proteins
g/day
71.4±23
-1.24±22.5
50.8±18.3
+28.3±24.9
CHO/Prot
ratio
2.9±1
+0.06±1.2
3.2±1
-0.92±1.08
Dietary intakes
AREA NUTRIZIONE - CERVELLO
r=-0.50
p=0.001
B. Correlations of change (Δ in CHO
g/protein ratio between 21 days
and baseline versus change (Δ) in
NIH Stroke Scale. Open circles,
control group; filled circles,
supplemented group.
Δ Protein intake (g/day)
r=+0.40
p=0.01
Δ NIHSS
A. Correlation of change (Δ in
protein intake between 21 days
and baseline versus change) in
neurological test (NIH Stroke
Scale).
Δ NIHSS
2- Stroke
ΔCHO/Prot ratio
AREA NUTRIZIONE - CERVELLO
2- Stroke
“Effect of calorie-protein intake supplementation on the cognitive recovery
of patients with subacute stroke”
(Aquilani R. et al., Nutr Neuroscience 2008)
Controls
Supplemented
admission
21days
admission
21days
18.4±0.5
19±1.2
16.4±2.5
20.3±3.3
Proteins
g/kg
0.5±0.2
0.59±0.12
0.8±0.3
1.06±0.3
CHO
g/kg
2.3±0.4
2.5±0.5
2.4±0.7
2.8±0.7
Lipids
g/kg
0.71±0.25
0.68±0.4
0.8±0.18
0.96±0.51
MMSE
0-30 scores
Dietary intakes
AREA NUTRIZIONE - CERVELLO
2- Stroke
“Normalization of zinc intake enhances neurological retrieval of patients
suffering from ischemic strokes”
(Aquilani R. et al., Nutr Neuroscience 2009)
Controls
Dietary Zinc
mg
NIHSS
score
Supplemented (+10mg Zn)
admission
30 days
admission
30 days
5.36-6.52
3.43-6.97
2.77-5.93
12.67-16.22
12.1
8.8
13.5
8.8
RDA Zinc= 10 mg-15 mg day
AREA NUTRIZIONE - CERVELLO
2- Stroke
Change (D) in Zn 2+ intake between 30 days and baseline versus change (D) in neurological
test (NIH stroke scale): regression line and 95% CI.
30
r = 0.45
p = 0.06
20
NIHSS
NIHSS
AREA NUTRIZIONE - CERVELLO
2- Stroke
30
r = -0.47
p = 0.05
10
20
10
admission n=17
0
0
0
25
50
75
100
0
125
1
2
6
r = 0.48
p = 0.05
20
NIHSS
NIHSS
5
30
r = -0.52
p = 0.03
20
10
10
30 days n=17
0
0
0
25
50
75
100
0
125
1
2
30
30
r = - 0.41
p = 0.02
NIHSS
20
10
0
0
25
50
75
protein intake g/day
4
5
6
100
125
r = 0.37
p = 0.03
20
10
0
3
dietary CHO/prot ratio g/g
protein intake g/day
NIHSS
“Spontaneous neurocognitive
retrieval of patients with subacute
ischemic stroke is associated with
dietary protein intake”
(Aquilani R. et al., Nutr Neuroscience
2010, in press)
4
dietary CHO/prot ratio g/g
protein intake g/day
30
3
admission+30 days
n=34
0
1
2
3
4
dietary CHO/prot ratio g/g
5
6
30
30
25
25
20
20
MMSE
2- Stroke
MMSE
AREA NUTRIZIONE - CERVELLO
15
10
15
10
5 r = 0.77
5 r = -0.57
p = 0.0003
p =0.02
0
25
50
75
100
0
125
1
30
25
25
20
20
MMSE
MMSE
30
15
10
3
4
5
6
5
6
5
6
15
10
5 r =0.55
5 r = -0.24
p = 0.02
p =0.34
0
30 days n=17
0
0
25
50
75
100
125
0
1
protein intake g/day
2
3
4
dietary CHO/prot ratio g/g
30
30
25
25
20
MMSE
MMSE
2
dietary CHO/prot ratio g/g
protein intake g/day
“Spontaneous neurocognitive
retrieval of patients with subacute
ischemic stroke is associated with
dietary protein intake”
(Aquilani R. et al., Nutr Neuroscience
2010, in press)
admission n=17
0
0
15
20
15
10
10
r = 0.65
p = <0.0001
5
r = - 0.4
p =0.02
5
admission+30 days
n=34
0
0
0
25
50
75
protein intake g/day
100
125
0
1
2
3
4
dietary CHO/prot ratio g/g
AREA NUTRIZIONE - CERVELLO
2- Stroke
THE RATIONALE BEHIND USING EAAs/PROTEINS
1. to meet increased brain requirement in leucine activity in the
ischemic hemisphere
2. to limit/reverse inhibition of protein synthesis
3. to improve neurotransmitter synthesis
4. to reactivate hypometabolic areas
AREA NUTRIZIONE – Scompenso cardiaco cronico
a) Impairment in walking capacity and myocardial function in
the elderly: is there a role for non-pharmacologic therapy with
nutritional amino acid supplements?
(Scognamiglio R et al., Am J Cardiol 2008)
PLACEBO
L.V.E.F.
(%)
6-min W.T.
(m)
8 g AMINOTROFIC
basale
3 mesi
basale
3 mesi
62±8
55±8
63±6
p<0.01
67±7
212±36
212±40
212±34
p<0.001
269±35
AREA NUTRIZIONE – Scompenso cardiaco cronico
b) Oral amino acid supplements improve exercise capacities in
elderly patients with chronic heart failure
(Aquilani R et al., Am J Cardiol 2008)
PLACEBO
8 g AMINOTROFIC
basale
1 mese
basale
1 mese
Watts
83±23
87±22
70±21
p<0.03
86±21
50% Recupero
(sec)
330±65
327±65
315±79
p<0.005
161±52
AREA NUTRIZIONE – Scompenso cardiaco cronico
c) Adequate energy-protein intake is not enough to improve
nutritional and metabolic status in muscle-depleted patients
with chronic heart failure
(Aquilani R et al., Eur J Heart Failure 2008)
PLACEBO
8 g AMINOTROFIC
basale
2 mesi
basale
Weight (kg)
60.8±7
61.2±6.3
55.9±17
AMA (cm2)
34.2±5
TST (mm)
37.1±4
31.2±9.9
11.9±3.7
11.4±3.7
10.4±4.4
HOMA Index
4.77±1.8
5.08±2
4.3±3.2
PlasmaLactate
(µmol/l)
1.1±0.4
1.27±0.4
Watts
85±24
6 min WT (m)
298±142
p<0.02
p<0.01
2 mesi
p<0.01
p<0.02
58.2±7.2
34.9±10
10.3±3.9
p<0.06
3.7±2.5
1.2±0.3
p<0.01
0.9±0.35
88±22
80±28
p<0.01
95±25
310±155
331±124
p<0.001
405±130
AREA NUTRIZIONE – Scompenso cardiaco cronico
AAs e Scompenso cardiaco cronico: meccanismi
AMINO ACIDS
REACTIVATION OF AEROBIC METABOLISM
PROTEIN TURNOVER
Directly:
Indirectly:
protein synthesis
IGF-1 activity
Directly:
EAAs used as fuel in
Indirectly:
insulin resistance
citric acid cycle
for energy
proteolysis
increased protein
synthesis
pyruvate oxidation
lactate formation
energy formation
Increased protein synthesis/catabolism ratio
Tissue accrual
AREA NUTRIZIONE – BPCO
THERAPEUTIC INTERVENTIONS
Nutrition
Exercise
Oxygen
Anti-inflammatory drugs
Anabolic hormones
Other treatments (tested or suggested)
AREA NUTRIZIONE – BPCO
AMERICAN POSITION for NUTRITION in COPD
“Pulmonary rehabilitation: joint ACCP/AACVPR evidence-based clinical
practice guidelines”
Chest., 2007
summary data indicate that nutritional support/supplementation does not
have a clinically significant effects on lung function or functional abilities
recommendation
there is insufficient evidence to support the routine use of
nutritional supplementation in the pulmonary rehabilitation of
patients with COPD
no recommendation is provided
AREA NUTRIZIONE – BPCO
“Fat-free mass change after nutritional rehabilitation in weight loosing COPD:
role of insulin, C-reactive protein and tissue hypoxia”
(Baldi S. et al., Int J Chron Obstruct Pulmon Dis , 2009 in press)
EAAs +bike group
Bike group
baseline
12 weeks
baseline
12 weeks
Body weight (kg)
55.6±8.3
57.7±9.7
59.5±8.3
59.2±8.3
Fat-free mass (kg)
43.1±8
44.6±6.7
37.6±2.3
37.1±2.8
Bode (points)
8±2
5.8±2.3
6.4±2.1
5±2
FEV1 % (pred)
40.1±14.6
41.2±24.1
42.7±15.1
39.4±21.5
220.1±148.8
329.5±117.3
209.5±106.1
257.8±114.8
63.1±7.6
63.5±9.9
59±5.7
59.5±7.1
6 MWD (m)
PaO2 ( mmHg)
Variables
pCO2 (mmHg)
pO2 (mmHg)
sO2
FEV1 (l/sec)
FEV% (%)
Lactate (µmol/l)
FFM (Kg)
BW (Kg)
LBMI (Kg/m2)
BMI (Kg/m2)
Steps (n°)
Serum total proteins (g/l)
Serum albumin (g/l)
MMT (score)
SGRQ (score)
Placebo group
EAA group
T2 vs T1
T3 vs T1
Interaction
T2 vs T1
T3 vs T1
T1
T2
T3
46.28±7.6
46.21±3.88
45.47±4.87
ns
ns
T1
T2
T3
45.32±6
46.32±5.22
46±3.74
ns
p=0.46
p=0.77
T1
T2
T3
60.15±4.88
58.12±4.58
57.14±4.14
ns
ns
T1
T2
T3
61.56±8.5
62.20±6.28
66.31±5.89
ns
p=0.01
p=0.039
T1
T2
T3
94.32±0.96
93.98±1.71
94±1.73
ns
ns
T1
T2
T3
94.6±1.86
92.75±2.76
94±2.42
ns
p=0.75
p=0.04
T1
T2
T3
0.84±0.15
0.78±0.16
0.75±0.15
ns
ns
T1
T2
T3
0.90±0.22
0.90±0.22
0.86±0.16
ns
p=0.46
p=0.58
T1
T2
T3
38±11.49
37.61±12.9
36.13±10.33
ns
ns
T1
T2
T3
39.62±7.35
39.5±7.20
39.19±7.5
ns
p=0.7
p=0.89
T1
T2
T3
1.73±0.27
1.8±0.35
1.95±0.36
ns
ns
T1
T2
T3
1.65±0.70
1.43±0.30
1.3±0.57
ns
p=0.023
p=0.07
T1
T2
T3
39.86±4.82
39.95±3
39.73±2.78
ns
ns
T1
T2
T3
40.41±4
41.56±4.51
44±4.53
ns
p=0.05
p=0.05
T1
T2
T3
54.38±6.95
54±6.82
53.31±5.77
ns
ns
T1
T2
T3
53.47±6.53
55.4±8.44
59±10
ns
p=0.002
p=0.006
T1
T2
T3
14.91±2
14.97±1.73
14.89±1.63
ns
ns
T1
T2
T3
15.34±2
15.7±1.51
16.68±2
ns
p=0.07
p=0.09
T1
T2
T3
20.21±1.80
20±1.65
19.9±1.69
ns
ns
T1
T2
T3
20.16±1.43
20.82±2.34
22.26±2.68
ns
p=0.002
p=0.006
T1
T2
T3
609.81±454.72
651.94±557.88
562.88±601.87
ns
ns
T1
T2
T3
638.8±661.8
880.20±836.60
1140.53±524.39
ns
p=0.01
p=0.0027
T1
T2
T3
61.57±5.15
60.35±5.17
60.94±5.12
ns
ns
T1
T2
T3
62.20±2.66
63.83±3.96
65±3.57
ns
p=0.041
p=0.12
T1
T2
T3
33.16±2.71
32.49±3.43
33.28±4.39
ns
ns
T1
T2
T3
32.94±3.67
35.14±3.51
37.22±2.86
p=0.001
p=0.001
p<.001
T1
T2
T3
20.19±3.52
19.62±3.59
19.44±3.68
ns
ns
T1
T2
T3
19.13±4.6
19±3.9
20.75±3.92
ns
p=0.011
p=0.011
T1
T2
T3
71.44±6.98
72.81±7
-
ns
ns
T1
T2
T3
72.25±8.52
69.56±9.41
-
p=0.01
-
p<0.001
AREA NUTRIZIONE – BPCO
Mean±SD and statistical analysis
between placebo and supplemented
group
Data are expressed as main±standard deviation
Statistical analysis: Anova test
T1= baseline; T2= after 1 months; T3= after 3 months
EAA group= essential amino acid supplemented group
pCO2= Partial pressure of carbon dioxide; pO2= partial pressure of
oxygen; sO2= oxygen saturation; FEV1= forced expiratory volume1;
FVC= forced vital capacity; FFM= fat-free mass; BW= body weight;
LBMI= Lean Body Mass Index; BMI= Body Mass Index; MMSE= Mini
Mental State Examination test; SGRQ= St.George’s Respiratory
Questionnaire
AREA NUTRIZIONE – BPCO
Trends over time of blood oxigen tension (PO2),
plasma lactate concentration, lean body mass (FFM),
body weight, serum albumin concentration,
neuropsychological test (MMSE) variables: Placebo
Group (―) vs Aminotrophic treated Group (−−).
AREA NUTRIZIONE – Long-term care (RSA)
“La supplementazione con aminoacidi essenziali induce un recupero psicofisico
dell’anziano istituzionalizzato”
(Rondanelli M. et al., 36° Congresso SIMFER, 2008)
Placebo
8 g Aminotrofic
basale
2 mesi
basale
2 mesi
Età
79.8±4.2
-
83.5±7.7
-
BMI (kg/m2)
22.2±2.6
22.2±2.6
21.8±2.3
21.8±2.3
MNA
22.5±1.7
22.8±1.5
21.8±1.6
p<0.005
22.6±1.5
Grip strenght (kg)
55.4±3.4
55.5±3.1
56±4
p<0.001
59±5
MMSE
27.1±2.0
-
Albumina (g/dl)
3.89±0.4
3.84±0.4
3.89±0.3
p<0.01
4.05±0.3
Prealbumina (mg/dl)
17.9±3.1
18.2±3
17.1±4.6
p<0.005
19.4±3.0
GDS
14.8±4.6
15.8±5.7
13.8±3.4
p<0.000
10.3±1.7
37.6±9.4
41.4±12
36.5±9.9
p<0.005
42.1±9.3
52±9.4
50.6±14
55±16
26±2.1
-
SF-36:
Vitalità
Salute mentale
p<0.02
63±13
AREA NUTRIZIONE – INFEZIONE
“Effects of essential amino acids on long-term care acquired infections in elderly
patients”
(Aquilani R et al., 2010 Arch Gerontol Geriatr)
Durante il 1° mese di
ospedalizzazione: totale infezioni
54/80 pazienti (=67.5%)
PLACEBO
82.5% (=33/40 pz)
8 g AMINOTROFIC
52.5% (=21/40 pz)
L’incidente di infezione è stato inferiore del 30% nel gruppo trattato con aminoacidi essenziali
AREA NUTRIZIONE - DIABETE 2° TIPO DELL’ANZIANO

“Improvement of blood glucose control and insulin sensitivity
during a long-term (60 weeks) randomized study with amino acid
dietary supplements in elderly subjects with type 2 diabetes
mellitus”
(Solerte SB et al., Am J Cardiol, 2008)
Nel gruppo trattato con 8 g AMINOTROFIC sono stati ottenuti:
1.
Miglioramento della glicemia a digiuno e postprandiale (1 ora e 2 ore)
2.
Riduzione dell’insulinemia
3.
Riduzione di HOMA index
4.
Riduzione di HbA1c
AREA NUTRIZIONE - DIABETE
Meccanismi aminoacidi e diabete
AMINOACIDI
aumento sintesi del
recettore dell’insulina
increased protein anabolism
muscle tissue synthesis
autofosforilazione
Improvement in insulin
sensitivity
aumento dell’attività
dell’insulina
improvement of blood
glucose control
NUTRITIONAL INTERVENTION
Creutzberg
(Nutrition, 2003)
Dal Negro
(Monaldi Arch. Chest.
Med., 2010)
Baldi
(Int.J.COPD, 2010)
Rondanelli
(Clin.Nutr., 2011)
Population
Weight-losing
COPD
SarcopenicCOPD
Cachetic-COPD
Institutionalized
elderly patients
Rehabilitation
8-weeks
No rehab
No rehab
No rehab
Supplementation
2-3 daily oral
liquid nutrition
8g EAAs
(Aminotrofic)
8g EAAs
(Aminotrofic)
8g EAAs
(Aminotrofic)
-2.7 score SGRQ
nd
+5.5 score SF36
Outcomes:
HRQoL
body weight
+2.1±2.1 Kg
+5.5±3.2 Kg
+3.8±2.6 Kg
No change
FFM
+1.1±2 Kg
+3.6±3.5 Kg
+1.5±2.6 Kg
+0.8 score MNA
MIP
+4±10 cmH2O
nd
nd
nd
handgrip
strength
+1.2±3.1 Kg
nd
nd
+1.1 Kg
peak overload
+7±11 W
( bycycle)
+502±490
(steps)
+109±98
m WT
+0.2 score ADL
cognition
nd
nd
No change
depression
nd
nd
-4 score GDS 23
nd