Nutritional Strategy · AIDS/Cancer Protocols AIDS Lost >5% BW 36 subjects/8 wks Cancer Lost 10% BW...
Transcript of Nutritional Strategy · AIDS/Cancer Protocols AIDS Lost >5% BW 36 subjects/8 wks Cancer Lost 10% BW...
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Nutritional Strategy
Protein break-down
Metabolic Regulators
Protein synthesis
Energy and amino acids
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CH2-CH2-C-O- Ca+
CH3
OHH3C
O
2
HMB- (����-hydroxy ����-methyl butyrate)
����
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HMB:
Theory: Cholesterol synthesis may limit cell growth/repair at certain times
HMB β-hydroxy-β-methylbutyrate
Leucine KIC CO2
Cholesterol
HMG-CoA
Cell membrane
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Human Studies w/ HMB
Adjunct for muscle building (Comparisons)SafetyCombinationsOther effects
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HMB and Resistance training
00.050.1
0.150.2
0.250.3
0.350.4
Net g
ain
lean
(%/w
k)
Nissen et al. 1996
Nissen et al. 1996
Panton 2000
Panton et al. 2000
Kreider et al. 1999
Jowko et al. 2001
Gallagher et al 2000
Slater et al. 2001
Vukovich et al 2001
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No adverse changes *Less negative moodEmotional
No adverse changesBlood hematology
No adverse changes*Lower cholesterol
Blood chemistry
No Adverse effects *Decreased BP Physical
Safety: 3-12 weeks
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Meta-Analysis:
Body composition Minimum 3-weeksMinimum trained 2x per weekPlacebo controlledStatistical information for ESProtein-(placebo issues)
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Meta-analysis: 250+ included
274Protein
242DHEA
323Androstenedione
3312Chromium
359HMB
3715Creatine
Quality score
Qualified studies
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Lean Tissue Gain
0
0.1
0.2
0.3
0.4
0.5
0.6
% g
ain
per
wee
k
CreatineHMB Chromium
Androstene...
DHEA Protein
Placebo Treatment*** ***
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Meta-Analysis
-0.10
0.00
0.10
0.20
0.30
Effe
ct S
ize
CreatineHMB
Chromium
Androstenedione
DHEAProtein
0.00
0.05
0.10
0.15
0.20
0.25
Effe
ct S
ize Lean Tissue
Gain
Strength Gain
Significant Effect size
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HMB and Creatine
+++Fat loss(weight training)
++-(risk of muscle
damage)
++(protect muscle)
Runner benefit
+-++++ (BP and cholesterol
lowered)
Health benefits
+++++++Lean gain (weight training)
CreatineHMB
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Minimizing Muscle damage
0
50
100
150
200
250
CPK
cha
nge
(%)
Pre Post Day 1 Day 2 Day 3 Day 4
Placebo
HMB
CPK after a 10K race
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Muscle stress results in tears in cell membrane
Muscle CPK leaks into the blood
CPK is 30-80% lowerLess muscle breakdown� Lower 3-
methylhistidine� Lower proteases
Less soreness
HMB effects on Damage
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Other observations
Less Protein turnover (muscle)Young and old: Men and womenEffect proportional to intensityImmune function improved
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Non exercising
Sedentary young people� HMB: No demonstrable effect� Creatine: No demonstrable effect
Wasting?
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WastingWastingNormalNormalProtein break-down
Protein synthesisProtein
synthesis
Protein break-down
Mechanism of wasting
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Age-related muscle mass
Age
Mus
cle
mas
s
100% of max
80% of max
70% of max
25 y 50 y
75 y<70%: Zone where Risk of Death is high
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Disease-related wasting
Most AIDS patients wasteNearly all stage 2-4 lung, pancreas, colon and upper GI cancers >10% muscle loss=risk
Question: Can targeted nutrition reverse wasting?
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Targeted Nutritional Strategy
Protein break-down
Slow
HMB
Protein synthesis
Enhance
Glutamine
Arginine
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Elderly protocol
Age ~78 yearsTwo replicate experimentsMostly women12 week studyEndpoints: lean tissue/mobilityAssisted living 2 g HMB/5 g Arg/ 1.5 g LysineOnce per day
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Body Composition changes
Body lean: +1 kg
-1.5-1
-0.50
0.51
1.52
2.53
% C
hang
e ov
er 1
2 w
ks
Iowa TN
Lean change
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Function(Get-Up & Go)
4 6 8 10 12
Get-Up & Go time (sec)
***+12 wks
Start
Start
+12 wks
PlaceboPlacebo
HMB/ HMB/ Arg /LysArg /Lys
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AIDS/Cancer Protocols
AIDS� Lost >5% BW� 36 subjects/8 wks
Cancer� Lost 10% BW� 40 subjects/8+wks
Mixture� 3 g HMB� 15 g Arginine� 15 g Glutamine
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AIDS/Cancer comparison
-0.7-1.1
2.5
1.4
-2.5
-1.5
-0.5
0.5
1.5
2.5
3.5Le
an g
ain
or lo
ss (
Kg)
AIDSsubjects
Cancer subjects
**
**
Placebo
HMB/Arg/Gln
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HMB + amino acid
Targeted nutritional strategy validVery slight wasting can be reversedVery sever wasting can be reversedMulti-center studies underway
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Muscle-Immune connection
-3
-2
-1
0
1
2
3
Placebo
HMB/Arg/Gln
Placebo vs HMB/Arg/Gln significantly different p<.01
Log changein viral titer
Viral titers in AIDS subjects treated for wasting
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Summary
250+ nutrition supplements marketed: � Only creatine and HMB meet scientific
threshold for resistance exercise~Double effectShort-term safetyNew applications: � Rational Combinations� Targeted