Nutritional Strategy · AIDS/Cancer Protocols AIDS Lost >5% BW 36 subjects/8 wks Cancer Lost 10% BW...

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3/29/2002 Nutritional Strategy Protein break- down Metabolic Regulators Protein synthesis Energy and amino acids

Transcript of Nutritional Strategy · AIDS/Cancer Protocols AIDS Lost >5% BW 36 subjects/8 wks Cancer Lost 10% BW...

Page 1: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

3/29/2002

Nutritional Strategy

Protein break-down

Metabolic Regulators

Protein synthesis

Energy and amino acids

Page 2: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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CH2-CH2-C-O- Ca+

CH3

OHH3C

O

2

HMB- (����-hydroxy ����-methyl butyrate)

����

Page 3: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 4: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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Human Studies w/ HMB

Adjunct for muscle building (Comparisons)SafetyCombinationsOther effects

Page 5: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 6: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 7: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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Meta-Analysis:

Body composition Minimum 3-weeksMinimum trained 2x per weekPlacebo controlledStatistical information for ESProtein-(placebo issues)

Page 8: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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Meta-analysis: 250+ included

274Protein

242DHEA

323Androstenedione

3312Chromium

359HMB

3715Creatine

Quality score

Qualified studies

Page 9: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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*** ***

Page 10: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 11: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 12: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 13: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 14: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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Other observations

Less Protein turnover (muscle)Young and old: Men and womenEffect proportional to intensityImmune function improved

Page 15: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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Non exercising

Sedentary young people� HMB: No demonstrable effect� Creatine: No demonstrable effect

Wasting?

Page 16: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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WastingWastingNormalNormalProtein break-down

Protein synthesisProtein

synthesis

Protein break-down

Mechanism of wasting

Page 17: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 18: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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?

Page 19: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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Targeted Nutritional Strategy

Protein break-down

Slow

HMB

Protein synthesis

Enhance

Glutamine

Arginine

Page 20: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 21: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 22: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 23: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 24: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 25: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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HMB + amino acid

Targeted nutritional strategy validVery slight wasting can be reversedVery sever wasting can be reversedMulti-center studies underway

Page 26: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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

Page 27: Nutritional Strategy · 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. 3/29/2002 AIDS/Cancer

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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