Nutritional Strategy AIDS/Cancer Protocols AIDS Lost >5% BW 36 subjects/8 wks Cancer Lost 10% BW 40

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Transcript of Nutritional Strategy AIDS/Cancer Protocols AIDS Lost >5% BW 36 subjects/8 wks Cancer Lost 10% BW 40

  • 3/29/2002

    Nutritional Strategy

    Protein break- down

    Metabolic Regulators

    Protein synthesis

    Energy and amino acids

  • 3/29/2002

    CH2-CH2-C-O- Ca+

    CH3

    OH H3C

    O

    2

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

    ����

  • 3/29/2002

    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

  • 3/29/2002

    Human Studies w/ HMB

    Adjunct for muscle building (Comparisons) Safety Combinations Other effects

  • 3/29/2002

    HMB and Resistance training

    0 0.05 0.1

    0.15 0.2

    0.25 0.3

    0.35 0.4

    Ne t g

    ai n

    le an

    (% /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

  • 3/29/2002

    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

  • 3/29/2002

    Meta-Analysis:

    Body composition Minimum 3-weeks Minimum trained 2x per week Placebo controlled Statistical information for ES Protein-(placebo issues)

  • 3/29/2002

    Meta-analysis: 250+ included

    274Protein

    242DHEA

    323Androstenedione

    3312Chromium

    359HMB

    3715Creatine

    Quality score

    Qualified studies

  • 3/29/2002

    Lean Tissue Gain

    0

    0.1

    0.2

    0.3

    0.4

    0.5

    0.6

    % g

    ai n

    pe r

    w ee

    k

    Creatine HMB Chromium

    Androstene...

    DHEA Protein

    Placebo Treatment *** ***

  • 3/29/2002

    Meta-Analysis

    -0.10

    0.00

    0.10

    0.20

    0.30

    Ef fe

    ct S

    iz e

    Creatine HMB

    Chromium

    Androstenedione

    DHEA Protein

    0.00

    0.05

    0.10

    0.15

    0.20

    0.25

    Ef fe

    ct S

    iz e Lean Tissue

    Gain

    Strength Gain

    Significant Effect size

  • 3/29/2002

    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

  • 3/29/2002

    Minimizing Muscle damage

    0

    50

    100

    150

    200

    250

    C PK

    c ha

    ng e

    (% )

    Pre Post Day 1 Day 2 Day 3 Day 4

    Placebo

    HMB

    CPK after a 10K race

  • 3/29/2002

    Muscle stress results in tears in cell membrane

    Muscle CPK leaks into the blood

    CPK is 30-80% lower Less muscle breakdown � Lower 3-

    methylhistidine � Lower proteases

    Less soreness

    HMB effects on Damage

  • 3/29/2002

    Other observations

    Less Protein turnover (muscle) Young and old: Men and women Effect proportional to intensity Immune function improved

  • 3/29/2002

    Non exercising

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

    Wasting?

  • 3/29/2002

    WastingWastingNormalNormal Protein break- down

    Protein synthesisProtein

    synthesis

    Protein break- down

    Mechanism of wasting

  • 3/29/2002

    Age-related muscle mass

    Age

    M us

    cl e

    m as

    s

    100% of max

    80% of max

    70% of max

    25 y 50 y

    75 y

  • 3/29/2002

    Disease-related wasting

    Most AIDS patients waste Nearly all stage 2-4 lung, pancreas, colon and upper GI cancers >10% muscle loss=risk

    Question: Can targeted nutrition reverse wasting?

  • 3/29/2002

    Targeted Nutritional Strategy

    Protein break- down

    Slow

    HMB

    Protein synthesis

    Enhance

    Glutamine

    Arginine

  • 3/29/2002

    Elderly protocol

    Age ~78 years Two replicate experiments Mostly women 12 week study Endpoints: lean tissue/mobility Assisted living 2 g HMB/5 g Arg/ 1.5 g Lysine Once per day

  • 3/29/2002

    Body Composition changes

    Body lean: +1 kg

    -1.5 -1

    -0.5 0

    0.5 1

    1.5 2

    2.5 3

    % C

    ha ng

    e ov

    er 1

    2 w

    ks

    Iowa TN

    Lean change

  • 3/29/2002

    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

  • 3/29/2002

    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 comparison

    -0.7 -1.1

    2.5

    1.4

    -2.5

    -1.5

    -0.5

    0.5

    1.5

    2.5

    3.5 Le

    an g

    ai n

    or lo

    ss (

    Kg )

    AIDS subjects

    Cancer subjects

    **

    **

    Placebo

    HMB/Arg /Gln

  • 3/29/2002

    HMB + amino acid

    Targeted nutritional strategy valid Very slight wasting can be reversed Very sever wasting can be reversed Multi-center studies underway

  • 3/29/2002

    Muscle-Immune connection

    -3

    -2

    -1

    0

    1

    2

    3

    Placebo

    HMB/Arg/Gln

    Placebo vs HMB/Arg/Gln significantly different p

  • 3/29/2002

    Summary

    250+ nutrition supplements marketed: � Only creatine and HMB meet scientific

    threshold for resistance exercise ~Double effect Short-term safety New applications: � Rational Combinations � Targeted