Table 2 Summary of Relevant Literature Pertaining to Nutrient Timing and Exercise

Biolo et al. 1997[47]

6 untrained males

- Infusion of balanced AA mixture (0.15 g·kg^-1·h^-1 for 3 h)

Two conditions:

- REST

- Post-ex.

- Leg resistance exercise routine

- Muscle biopsies

- Arteriovenous blood samples for 3 h post-ex.

- PRO synthesis post-ex. > rest

- AA transport increased 30–100% post-ex. compared to rest- PRO intake immediately post-ex. may be more anabolic than other times

Kobayashi et al. 2003[30]

10 normal Yorkshire swine

Continuous infusion of a mixed AA solution

Infusion began 2 h into dialysis and for remaining 2 h

NONE

- A/V samples and biopsies were taken throughout entire protocol.

- Signal to change [AA] was plasma [AA]

- Decrease in PRO synthesis led to decrease in eIF2B activation

- Intramuscular [AA] did not change

Bohe et al. 2003[59]

- 21 healthy subjects (11 M, 10 F)

- 29 ± 2 yrs

- Mixed AA infusion at varying rates (44–261 mg AA·kg^-1·h^-1)

Study attempted to determine any dose-response relationship to PRO synthesis

NONE

- A/V blood samples pre-infusion and for next 6.5 h

- 4 biopsies at 30, 180, 240 and 390 min.

- Myofibrillar, sarcoplasmic, and mitochondrial PRO synthesis was similar

- PRO synthesis is regulated by extracellular [EAA] and becomes saturated at high concentrations.

- A dose-dependent relationship exists between [AA] and PRO synthesis.

Bohe et al. 2001[58]

6 (5 M, 1 F) normal, healthy adults

- Infusion (162 mg·kg^-1·h^-1) of mixed AA

6 h infusion period at constant rate

NONE

- A/V blood samples over 9 h

- Muscle biopsies to determine AA incorporation

- PRO synthesis increase ~2.8× basal value within 2 h of infusion

- PRO synthesis then declined rapidly

- AA availability may be limited by transport of AA into muscle

Paddon-Jones et al. 2003[45]

12 healthy male and females

Two conditions:

- Saline infusion + 15 g EAA solution

- 27 h cortisol infusion + 15 g EAA solution

- Measurements were taken pre- and post-consumption of EAA solution.

NONE

- A/V blood before and after EAA ingestion.

- 3 biopsies were taken (pre-/post-infusion, supplement consumption)

- Cortisol increased arterial, venous and muscle intracellular AA concentrations.

- EAAs improved muscle protein anabolism during acute hypercortisolemia and may help minimize muscle loss following debilitating injury.

Levenhagen et al. 2002[65]

5 M, 5 F tested 3× with 4 week wash-out

Oral doses of:

- Placebo (P)

- 8 g CHO + 3 g fat (SUPP)

- 8 g CHO + 3 g fat + 10 g PRO (SUPP+PRO)

Immediately after exercise

60-min. cycling @ 60% max VO₂ and 180 min recovery period.

- Blood every 15 min. before ex.

- Arterial and venous blood every 30 min. post-ex. for 180 min.

- In compared to NO or SUPP, SUPP + PRO resulted in a net uptake of EAA and increase in leg and whole-body protein synthesis

- AA are more important than energy for post-ex. repair and growth.

Levenhagen et al. 2001[56]

5 M, 5 F

10 g PRO + 8 g CHO + 3 g Fat

Oral administration immediate or 3 h post-ex.

60 min cycling @ 60% max VO₂

- Blood every 15 min. before ex.

- Arterial and venous blood every 30 min. post-ex. For 180 min.

- Early intake of a nutrient supplement enhances greater accretion of whole body and leg protein compared to late ingestion.

Tarnopolsky et al. 1997[66]

8 M, 8 F trained endurance athletes

3 groups:

- Placebo (PLA)

- CHO (1 g/kg)

- CHO (0.75 g/kg) + PRO (0.1 g/kg) + Fat (0.02 g/kg)

Two oral doses of each supplement:

- Immediately post-ex.

- 1 h post-ex.

- 90 min. cycle ergometer at 65% max VO₂

- Blood samples were given pre-ex., during ex. And 3 h and 4 h post-ex.

- 3 post-ex biopsies (immediate, 1 h 4 h)

- Glucose and insulin increased in both trials post-ex w/no gender effect

- Glycogen resynthesis increased in both trials vs. PLA w/no gender effect

Borsheim et al. 2004[52]

16 (10 M, 6 F) recreationally active subjects

Two conditions:

- 100 g CHO

- Placebo (PLA) solution

Oral ingestion at 1 h post-ex.

- Leg press (10 × 8 reps) @ 80% 1 Rmprior to 4 h bed rest

- 2 min. rest between sets

- Arteriovenous blood every ~20 min. for 4 h post-ex.

- 4 biopsies (1 pre/3 post-ex.)

- CHO ingestion improved PRO balance after RE

- Effect, however, was minor and delayed compared with ingestion of AA

Roy et al. 2000[67]

10 young (19–21 y), healthy males

- Placebo (PLC)

- CHO (1 g/kg)

- CHO/PRO/Fat (1 g/kg)

Immediately post-ex and 1 h post-ex.

- 9 resistance training exercises

- 3 sets @ 80% 1 RM

- Arterial/venous blood samples every ~20 min. post-ex.

- 24 h urine

- Nonoxidative leucine disposal (marker of protein synthesis) was increased 4 h for CHO/PRO/Fat and CHO immediately and 1 h following resistance training.

Tipton et al. 2001[3]

3 M, 3 F completed one PRE and POST session

EAC: 6 g EAA + 35 g CHO

PLA: Sweetened water

PRE: EAC solution pre-ex.

POST: EAC solution post-ex.

- Leg press and leg ext. 8–10 sets × 8 reps @ 80% 1 RM

- 2 min. rest between sets

- 16 venous and arterial blood samples pre-, during and post-ex. Over 180 min.

- Muscle biopsies @ -60, 0, 60 and 120 min.

- AA delivery increased w/ex. And 2 h post-ex. In both trials

- PRO synthesis increased compared to post

- PRE AA uptake was increased 160% more than in POST

- EAC promoted positive N balance in both trials

Borsheim et al. 2004[57]

8 subjects participated in both trials

Oral doses of:

- 77.4 g CHO + 17.5 g Whey + 4.9 g AA (PAAC)

- 100 g CHO (P)

1 h post-exercise

- Resistance exercise

- Femoral artery, vein and muscle biopsies were collected for 3 h post-ex.

- PAAC caused an immediate increase and a delayed increase in protein balance

- PAAC stimulated a greater increase in PRO synthesis vs. CHO after resistance training.

Tipton et al. 1999[54]

3 M, 3 F

Three solutions:

- 40 g CHO (PLA)

- 40 g mixed AA

- 40 g EAA

- Continual (100 mL) consumption every 15–20 min. from 1 h post-ex. To 4 h post-ex.

- Leg Press (5 × 10 reps @ 75% 1 RM)

- Squat, leg curls/ext. (4 × 8 reps @ 75% 1 RM

- Arteriovenous blood at -120, 30, 220, 260 and 270 min.

- Muscle biopsy was taken at 270 min.

- Both MAA and EAA increased net protein balance

- No difference in protein balance between MAA and EAA suggests no need for NEAA to cause protein synthesis

Tipton et al. 2003[60]

4 F, 3 M

Two conditions:

- REST

- REST + EAA+ EX

- 15 g EAA solution before and after exercise session

- 8 × 8 reps @ 80% 1 RM

- 2 min. rest between sets

- Five biopsies and A/V blood samples were taken throughout entire 24 h protocol.

- AA exchange (ES – REST) @ 3 h and 24 h was not different

- Acute response of muscle to EAA intake + EX is additive to rest and thus reflects 24 h response.

Tipton et al. 2004[62]

23 healthy untrained young males and females

Three conditions:

- Placebo (PLA)

- Casein (CAS)

- Whey protein (WP)

1 h post-ex.

- Leg ext. 10 × 8 reps @ 80% 1 RM

- 2 min. rest between sets

- Femoral A/V blood samples for 3 h post-ex.

- 4 biopsies (pre-, 1 h, 2 h, 5 h post-ex.)

- Both WP and CAS increased PRO balance to promote PRO synthesis

- AA uptake was increased after exercise in both groups

Ratamess et al. 2003[37]

17 resistance-trained men

Two conditions:

- Placebo (PLA)

- AA supplementation

- Immediately post-workout when training

- Mornings of no training

- 4 d/wk RE program for 4 wks

- 2 wk high-intensity phases

- Strength, power and endurance were determined at end of week

- Reduction in strength and power was attenuated by AA supplementation

- High intensity, moderate volume RE is effective to increase strength and power.

Rasmussen et al. 2000[51]

3 M, 3 F in postabsorptive state and recreationally active

- Placebo drink (PLA)

- EAA+CHO drink (35 g CHO+6 g EAA)

Two conditions:

- PLA 1 h post-ex + EAA+CHO 3 h post-ex

- EAA+CHO 1 h post-ex. + PLA 3 h post-ex.

- 8–10 sets × 8 reps @ 80% 1 RM

- 2 min. rest between sets

- 11 arteriovenous blood over 7 h time span.

- Muscle biopsies at 45 min, 2 h and 4 h post-ex.

- No change in PLA

- EAA+CHO increased PRO balance and PRO SYN 1 h and 3 h post-ex.

- No increase in PS and PRO balance at 3 h vs. 1 h with both > than pre-ex.

Miller et al. 2003[53]

6 M, 4 F

- CHO alone

- AA alone

- CHO + mixed AAs (MIX)*

*50% EAA according to wt.

- Two drinks at 1 h and 2 h post-ex.

- Infusion was started 1 h prior to exercise and continue 4 h post-ex.

- 8–10 sets × 10 reps of leg press and leg ext. @ 75% 1 RM

- 2 min. rest between sets

- Biopsies at 30, 90, 150 and 210 min. post-ex.

- Arteriovenous blood for 4 h post-ex.

- Combined effects of CHO Å after resistance exercise is equivalent to their independent effects.

- Prior intake of AA+CHO does not diminish metabolic response to a second comparable dose 1 h later.

Borsheim et al. 2002[1]

3 M, 3 F recreationally active

- 6 g Essential amino acids (EAA)

- Two oral doses of 6 g EAA at 1 h and 2 h post-ex

- 8–10 sets × 10 reps of leg press and leg ext. @ 80% 1 RM

- 2 min. rest between sets

- 4 muscle biopsies were provided post-ex

- Femoral artery and venous blood samples ~every 20 min. for 4 h post-ex

- PRO balance increased in response to both drinks and decreased when [AA] returned to basal levels

- Non-essential AA are not necessary for increasing PRO balance

- PRO synthesis is dose-dependent of [EAA]

Boirie et al. 1997[68]

16 young (24 ± 4 yrs) healthy subjects

Five conditions:

- 30 g whey

- 43 g casein (equal [Leu])

- 30 g unlabeled whey

- 43 g unlabeled casein

- 30 g unlabeled casein

- Feeding Trial

- No exercise

- All conditions were ingested at same time

NONE

- A/V blood samples for entire 7 h time period

- CAS had prolonged plateau of high [AA] inhibiting PRO breakdown by 34%

- WP caused dramatic increase in [AA] causing 68% increase in PRO synthesis

- Speed of PRO digestion and AA absorption have major effect on protein synthesis.

Dangin et al. 2003[69]

- 9 elderly (72 ± 1 yrs)

- 6 young (24 ± 1 yrs)

- Casein protein (CAS)

- Isonitrogenous whey w/CAS (WPiC)

- Isonitrogenous whey w/leucine (WPiL)

- Feeding Trial

- No exercise

NONE

- A/V blood samples

- Muscle biopsies

- Whey digested faster than CAS

- PRO breakdown was not different

- PRO synthesis was highest with WP vs. CAS irrespective of age

Dangin et al. 2001[70]

22 healthy young males (25 ± 1 yrs)

- 30 g casein

- 30 g free AA mimic casein

- 30 g whey

- Repeated small doses of whey

- Feeding Trial

- No exercise

NONE

- A/V blood samples for entire 7 h time period

- "Fast" meals (whey and free AA) caused strong, rapid increase of [AA]

- Moderate increase in [AA] with "slow" meals and stayed elevated longer

- 7 h Leu balance was higher after slow vs. fast meals

Volpi et al. 1998[71]

(71 ± 2 yrs)

- Infusion of an AA mixture

- Postabsorptive vs. Infusion state

NONE

- Muscle PRO synthesis and breakdown

- A/V blood

- Muscle biopsies

- Muscle PRO synthesis increased in response to AA infusion

- Muscle PRO breakdown did not change thus increasing PRO balance.

Paddon-Jones et al. 2004[72]

- 6 Young (34 ± 4 yrs)

- 7 Older (67 ± 2 yrs)

- One single oral dose of 15 g EAA solution

- Pre-/post-supplementation measures were taken.

NONE

- A/V blood samples and muscle biopsies were taken for 3 h pre- and 4 h post-supplementation

- EAA increased PRO synthesis in both young and old

- Increase in [AA] was slower in elderly subjects but remained elevated for a longer period.

- No overall diff. in PRO synthesis between young and old.

Esmarck et al. 2001[55]

13 M older individuals (74.1 ± 1 yr)

- Liquid supplement (10 g PRO + 7 g CHO + 3 g fat)

- Immediately post training session (P0)

- 2 h post training session (P2)

- 12 week RE program (3×/week)

- Body comp. (DEXA)

- Hypertrophy via MRI, and muscle biopsies

- Isokinetic strength

- P0 > P2 for cross-sect. area and mean fiber area

- Similar change in strength

- Immediate protein supplementation post-ex. promotes more growth in elderly males

Volpi et al. 2000[73]

4 M, 1 F young (30 ± 3 yrs)

4 M, 1 F elderly (72 ± 1 yrs)

- Resting or basal phase

- 40 g glucose + 40 g mixed AA

Subjects completed a:

- 300 min. resting period

- 180 min. supplement period

NONE

- AV samples every 10 min. last 60 min.

- 4 biopsies in 480 min.

- AA turnover was similar in young and old.

- PRO synthesis with high [AA] and [insulin] was blunted in elderly compared to young.

Volpi et al. 2003[74]

14 elderly adults (70 ± 2 yrs)

- 18 g EAA

- 40 g Mixed AA (18 g EAA+22 g NEAA)

Small oral boluses every 10 min. for 3 h

NONE

Protein metabolism was measured via:

- A/V blood

- Muscle biopsies

- AA balance increased in similar amounts from resting in both conditions

- EAA are responsible for PRO synthesis in elderly

Andersen et al. 2005[63]

- Isoenergetic CHO vs. PRO

- Before and after RE

- Morning on non-training days

14-week RE program

- Muscle cross-sectional area

- Strength

- PRO increased Type I/II fibers more than CHO

- Squat jump height increased in PRO vs. CHO