NUTRITION – LEUCINE – INTAKE FOR THE AGING


16 RESEARCH ARTICLES + 1 GRAPHIC – CLICK ON IMAGE TO ENLARGE


Post-prandial means after your meal


LEUCINE, NOT TOTAL PROTEIN, IS THE PRIMARY DETERMINANT OF MUSCLE PROTEIN ANABOLIC RESPONSES IN HEALTHY OLDER WOMEN – 2018


Devries MC1McGlory C1Bolster DR2Kamil A2Rahn M2Harkness L2Baker SK3Phillips SM1.
BACKGROUND
– Older adults show a blunted muscle protein synthesis (MPS) response to meals relative to younger adults
– Evidence suggests that this anabolic resistance can be overcome by consuming greater quantities of Leucine
OBJECTIVE
– Determine whether adding Leucine to 10 g of milk proteins would, when compared with a larger dose (25 g) of whey protein isolate (WPI), result in similar increases in acute (hourly) and integrated (daily) myofibrillar protein synthesis (myoPS)
METHODS
Healthy older (age: 69 ± 1 y) women (n = 11/group)
2x daily consumption of either:
(1) WPI [25 g WPI (3 g l-leucine)]
(2) or Leucine (LEU; 10 g milk protein with 3 g total l-leucine) for 6 days
– Participants performed unilateral resistance exercise to allow assessment of the impact of the supplement alone and with resistance exercise
RESULTS
– Acute myoPS increased in both legs in response to LEU and WPI compared with fasting
– The increase was greater with LEU than with WPI in the exercised leg but not in the rested leg
– The acute myoPS response was greater in the exercised leg than in the rested leg for both WPI (63%) and LEU (58%)
– Integrated myoPS increased with WPI and LEU in the exercised leg during supplementation, and with WPI but not LEU in the rested leg compared with the basal state
CONCLUSIONS
– A lower-protein (10 compared with 25 g/dose), Leucine-matched beverage induced similar increases in acute and integrated myoPS
– Longer-term interventions are needed to substantiate these findings


PROTEIN LEUCINE CONTENT IS A DETERMINANT OF SHORTER AND LONGER TERM MUSCLE PROTEIN SYNTHETIC RESPONSES AT REST AND FOLLOWING RESISTANCE EXERCISE IN HEALTH OLDER WOMEN – 2018


Michaela C Devries Christopher McGlory Douglas R Bolster Alison Kamil Maike RahnLaura Harkness Steven K Baker Stuart M Phillips
OBJECTIVE
– We measured the acute (hourly) and integrated (daily) myofibrillar protein synthesis (myoPS) response to consumption of a high-quality mixed protein beverage compared with an isonitrogenous protein beverage with added leucine
DESIGN
– Healthy older women (aged 65–75 y, n = 11/group) consumed a fixed, weight-maintaining diet with protein at 1.0 g · kg–1 · d–1
– They were randomly assigned to twice-daily consumption of either:

a) 15 g milk protein beverage containing 4.2 g Leucine (LEU)
b) or 15 g mixed protein (milk and soy) beverage containing 1.3 g Leucine (CON)
– Unilateral leg resistance exercise allowed a determination of acute ([13C6]-phenylalanine infusion, hourly rate) and integrated (deuterated water ingestion, daily rate) exercised and rested myoPS responses.
RESULTS
– Acute myoPS increased in response to feeding in the rested (CON: 13% ± 4%; LEU: 53% ± 5%) and exercised (CON: 30% ± 4%; LEU: 87% ± 7%) leg in both groups, but the increase was greater in LEU
– Integrated myoPS increased during the supplementation period in both legs (rested: 9% ±1%; exercised: 17% ± 2%) in LEU, but in the exercised leg only (7% ± 2%) in CON
CONCLUSIONS
– A 15-g protein-containing beverage with ∼4 g Leucine induced greater increases in acute and integrated myoPS than did an isonitrogenous, isoenergetic mixed-protein beverage
– Declines in muscle mass in older women may be attenuated with habitual twice-daily consumption of a protein beverage providing 15 g protein and higher (4.2 g/serving) amounts of Leucine


EFFECTS OF LEUCINE-ENRICHED ESSENTIAL AMINO ACIDS AND WHEY PROTEIN UPON SKELETAL MPS AT REST AND AFTER EXERCISE IN OLDER WOMEN – 2017


Daniel J.WilkinsonPhilip J.Atherton
AIMS

– Impaired anabolic responses to nutrition and exercise contribute to loss of skeletal muscle mass with ageing (sarcopenia)
– We tested muscle protein synthesis (MPS) with Leucine-enriched essential amino acids (EAA) in comparison to a large bolus of whey protein (WP)
METHODS
– 24 older women (65 ± 1 y) received (N = 8/group):
(1) 1.5 g Leucine-enriched EAA supplements (LEAA 1.5)
(2) 6 g LEAA (LEAA 6)
(3) 40 g WP

CONCLUSIONS
– LEAA 1.5, despite only providing 0.6 g of Leucine, robustly stimulated MPS, with negligible trophic advantage of greater doses of LEAA or even to 40 g WP
– Highlighting that composition of EAA, in particular the presence of leucine rather than amount is most crucial for anabolism


ENRICHING A PROTEIN DRINK WITH LEUCINE AUGMENTS MPS AFTER RESISTANCE EXERCISE IN YOUNG AND OLDER MEN – 2016


Philip J Atherton, Kenneth Smith et al
PURPOSE/METHODS
– RE: 6 × 8 knee-extension repetitions at 75% of 1-RM
– Groups (n = 9) of young 24 ± 6 y and older men 70 ± 5 y
(i) RE followed by Slim-Fast Optima (SFO 10 g PRO; 24 g CHO) with 4.2 g of Leucine (LEU)
(ii) RE + SFO with 4.2 g of alanine (ALA; isonitrogenous control).
RESULTS
(1) In young men, area under the curve and peak FSR were greater in the SFO + Leucine than in the SFO + ALA group, after RE
(2) In older men, AUC post-exercise anabolic responses were greater in the SFO + Leucine than SFO + ALA group, after RE
(3) Irrespective of age, increases in p70S6K1 phosphorylation were evident in response to both SFO + Leucine and SFO + ALA, although greater with Leucine than alanine, specifically in the older men
CONCLUSION
– Addition of Leucine to a sub-maximal PRO bolus improves anabolic responses to RE in young and older men


LEUCINE ENHANCES MUSCLE PROTEIN SYNTHESIS IN OLDER MEN – 2016


Caoileann H Murphy2Stuart M Phillips2, et al
OBJECTIVE
– Examine Leucine taken with meals on MPS in older men who consumed higher protein (HP) or lower protein (LP) in rested and resistance exercise (REX) conditions
DESIGN
– 20 healthy older men [aged 65–85 y] were assigned to:
(1) LP (0.8 g · kg · d)
(2) HP diets (1.2 g · kg · d)
– They also ingested:
(1) a placebo (days 0–2)
(2) and Leucine supplement (5 g Leucine/meal; days 3–5) with their 3 main daily meals.
– A bout of unilateral REX was performed during the placebo and Leucine treatments.
CONCLUSIONS
Leucine co-ingestion with daily meals enhances MPS in free-living older men in rested and REX conditions
– It is equally effective in older men who consume daily protein intakes greater than or equal to the RDA


THE IMPACT OF POST-EXERCISE EAAs ON MUSCLE OF OLDER MEN – 2016


Dickinson JM1Reidy PT2Gundermann DM3Borack MS4Walker DK5D’Lugos AC6Volpi E4Rasmussen BB4.
METHOD
– Subjects (72±2yr) performed RE and 1h postexercise ingested:
(1) 10g of EAA containing a Leucine quantity similar to quality protein
(2) or enriched in leucine (Leucine, 3.5g Leucine, n=8)
(3) Control, 1.8g Leucine, n=7) 
CONCLUSIONS
– Ingesting a larger quantity of Leucine following RE may further reduce postexercise skeletal muscle autophagy in older men
– However it does not appear to influence the acute postexercise elevation in markers of the ubiquitin proteasome system or the breakdown of intact proteins


DETERMINATION OF THE SAFETY OF LEUCINE SUPPLEMENTATION IN ELDERLY MEN – 2016


Rasmussen B1Gilbert E1Turki A1Madden K2Elango R
INTRODUCTION

– The tolerable upper intake level (UL) for Leucine intake in young men has recently been determined to be 500 mg/kg/day
– Increases in blood ammonia concentrations were seen at intake levels above 500 mg/kg/day
– Ex: 80kg or 176lb = 40 grams of Leucine
OBJECTIVE
– Determine the safety of Leucine supplementation in healthy elderly men
METHOD
– 6 healthy elderly men (72.2 ± 3.5 yrs) received graded stepwise increases in Leucine intakes ranging from 50 to 750 mg/kg/day, on 8 separate study days
CONCLUSION
– Upper limit for leucine intake in healthy elderly could be set similar to young men at 500 mg/kg/day

Note: 176 lbs or 80 kg would equal 40 grams of Leucine per day from ALL sources


IMPACT OF THE MACRONUTRIENT COMPOSITION OF A NUTRIENT SUPPLEMENT ON MUSCLE PROTEIN SYNTHESIS RATES IN OLDER MEN – 2015


Fleur Kramer, van Loon LJ et al
METHODS
– A total of 45 non-sarcopenic older men (age: 69±1) were assigned to ingest:
(1) 21 g of Leucine-enriched whey protein with carbohydrate (9 g) and fat (3 g) (Pro-En)
(2) an isonitrogenous amount of 21 g of Leucine-enriched whey protein without carbohydrate and fat (Pro)
(3) or an isocaloric mixture (628 kJ) containing carbohydrate and fat only (En)
CONCLUSION
– 21 g of leucine-enriched whey protein significantly raises muscle protein synthesis rates in non-sarcopenic older men


INTAKE OF LOW-DOSE LEUCINE-RICH ESSENTIAL AMINO ACIDS STIMULATES MUSCLE ANABOLISM EQUIVALENT TO BOLUS WHEY PROTEIN IN OLDER WOMEN AT REST AND AFTER EXERCISE – 2015


Syed S. I. Bukhari, Philip J. Atherton et al
METHOD
– We determined the effects of two feeding regimes in older women (66 ± 2.5 yr; n = 8/group):
(1) bolus whey protein (WP-20 g)
(2) or low-dose Leucine-enriched essential amino acids (EAA) [LEAA; 3 g (40% leucine)].
– Quantify muscle (MPS) and albumin (APS) protein synthesis at baseline and in response to feeding (FED) and feeding plus exercise (FED-EX)
– Exercise: 6 × 8 knee extensions at 75% 1-repetition maximum
RESULTS
(1) Plasma insulinemia and EAA/aemia were markedly greater after WP than LEAA
(2) Neither LEAA nor WP modified LBF in response to FED or FED-EX, whereas MBF increased to a similar extent in both groups only after FED-EX
(3) In response to FED, both WP and LEAA equally stimulated MPS 0–2 h, abating thereafter (0–4 h)
(4) In contrast, after FED-EX, MPS increased at 0–2 h and remained elevated at 0–4 h with both WP and LEAA
(5) No anabolic signals quantifiably increased after FED, but p70 S6K1 Thr389 increased after FED-EX (2 h)
(6) APS increased similarly after WP and LEAA.
CONCLUSION
– Older women remain subtly responsive to nutrition ± exercise.
– Intriguingly though, bolus WP offers no trophic advantage over LEAA


4 MONTH COURSE OF SOLUBLE MILK PROTEINS INTERACTS WITH EXERCISE TO IMPROVE MUSCLE STRENGTH AND DELAY FATIGUE IN THE ELDERLY – 2014


Gryson C1, Ratel S2, Rance M2, Penando S3, Bonhomme C4, Le Ruyet P5, Duclos M3, Boirie Y6, Walrand S7.
DESIGN
– 48 healthy sedentary men 60.8 ± 0.4 yrs; 16-wk multicomponent exercise training program with a milk-based supplement:
(1) total milk proteins 4g/day
(2) total milk proteins 10 g/day
(3) soluble milk proteins rich in Leucine (PRO) 10 g/day
RESULTS
(1) Body fat mass was reduced after the 4-month training program in groups receiving 10 g/day of protein supplementation
(2) The training program sustained with the daily 10 g/day PRO was associated with a significant increase in dominant fat free mass (+5.4%) and in appendicular muscle mass (+4.5%)
(3) Blood cholesterol was decreased in the trained group receiving 10 g/day PRO
(4) The index of insulin resistance and blood creatine phosphokinase were reduced in the groups receiving 10 g/day PRO, irrespective of exercise
(5) The inflammatory and endothelial markers were not different between the groups
(6) Training caused a significant improvement (+10.6% to 19.4%) in the maximal oxygen uptake
(7) Increased maximum voluntary contraction force was seen in the trained groups receiving 10 g/day of proteins (about 3%)
(8) Time to task failure was improved in the trained participants receiving a 10 g/day supplementation with PRO
CONCLUSIONS
– Soluble milk proteins rich in Leucine, after prolonged multicomponent exercise training in healthy older men, improved time to:
(1) muscle failure
(2) increase in skeletal muscle mass
(3) strength 


LEUCINE AFTER RESISTANCE EXERCISE PROLONGS PROTEIN SYNTHESIS IN OLDER MEN – 2014


Jared M. Dickinson and Blake B. Rasmussen4
OBJECTIVE
– Determine role of increased post-exercise Leucine ingestion on older men over 24-h post–resistance exercise (RE) time course
METHOD
– Older men performed RE and at 1h after exercise ingested:
(1) 10g of essential amino acids (EAAs) containing Leucine content similar to quality protein (control, 1.85 g of Leu, n = 7)
(2) 10g of essential amino acids (EAAs) containing enriched Leucine (LEU; 3.5 g of Leu, n = 8)
CONCLUSIONS
Leucine-enriched EAA after RE may prolong the anabolic response and sensitivity of skeletal muscle to amino acids in older adults


PROTEIN CONSIDERATIONS TO SUPPORT ACTIVE AGING – 2014


Benjamin T. Wall1, Naomi M. Cermak1 and Luc J. C. van Loon
SUMMARY
(1) Evidence suggests 30–40g protein represents optimal dose to best promote (post-exercise) muscle protein synthesis in older adults
(2) Sub-optimal doses of protein can be optimized by selecting proteins with rapid digestion and absorption rich in Leucine (e.g. whey), and/or enriched protein with Leucine
(3) Emerging evidence suggests oral creatine and/or fish oil-derived fatty acid supplementation may be effective as a means to enhance training adaptations in the older population


MILK PROTEINS WITH EXERCISE IMPROVES STRENGTH & DELAYS FATIGUE IN THE ELDERLY – 2014


Gryson C1Ratel S2Rance M2Penando S3Bonhomme C4Le Ruyet P5Duclos M3Boirie Y6Walrand S7.
DESIGN
:
– 48 healthy sedentary men aged 60.8 ± 0.4 yrs
– 16-wk multicomponent exercise training program
– supplement total milk proteins 4 or 10 g/day or soluble milk proteins rich in Leucine (PRO) 10 g/day
CONCLUSIONS:
– Soluble milk proteins rich in Leucine improved time to muscle failure and increase in skeletal muscle mass and strength


WHEY PROTEIN FOLLOWING EXERCISE IN OLDER MEN – 2014


Randall Souza; David Cameron-Smith
METHOD
:
– 46 healthy men 60–75 yrs (~86kg, ~176cm) did a single bout of unaccustomed lower body resistance exercise immediately followed by:
(1) a noncaloric placebo beverage
(2) or supplement containing 10, 20, 30, or 40 g whey protein concentrate (WPC).
RESULTS:
(1) Resistance exercise alone reduced intramuscular branch chain amino acid (BCAA; leucine, isoleucine, and valine) content
(2) Supplementation with increasing doses of whey protein prevented this fall in muscle BCAAs during postexercise recovery
(3) Larger doses (30 g and 40 g) significantly augmented postexercise muscle BCAA content
CONCLUSIONS:
– Intramuscular BCAAs, and Leucine in particular, appear to be important regulators of anabolic signaling in aged human muscle during postexercise recovery via reversal of exercise-induced declines in intramuscular BCAAs


LEUCINE SUPPLEMENTATION IMPROVES MUSCLE PROTEIN SYNTHESIS IN OLDER ADULTS CONSUMING THE RDA PROTEIN – 2012


Casperson SL1Sheffield-Moore MHewlings SJPaddon-Jones D.
METHODS

– 8 healthy but sedentary older adults participated in this project
– For 2-weeks we supplemented meals of older individuals with Leucine (4 g/meal; 3 meals/day; days 2-14)
RESULTS
(1) The meal modestly increased mixed muscle fractional synthesis rate (FSR) on Day 1
(2) However, 2 wks of Leucine increased postabsorptive FSR and response to the meal
CONCLUSION
– In older adults, Leucine supplementation may improve muscle protein synthesis in response to lower protein meals


A HIGH PROPORTION OF LEUCINE IS REQUIRED FOR OPTIMAL STIMULATION OF THE RATE OF MUSCLE PROTEIN SYNTHESIS IN THE ELDERLY – 2006


Katsanos CS1Kobayashi HSheffield-Moore MAarsland AWolfe RR.
AIM

– Evaluate effects of enriching an essential amino acid (EAA) mixture with Leucine on muscle protein metabolism in elderly and young
METHODS
– Four (2 elderly and 2 young) groups were studied before and after ingestion of 6.7 g of EAAs. EAAs were based on:
(1) the composition of whey protein 26% Leucine
(2) or were enriched in leucine 41% Leucine
RESULTS
(1) Fractional Synthetic Rate FSR increased following amino acid ingestion in both the 26% and the 41% Leu young groups
(2) In the elderly, FSR did not increase following ingestion of 26% Leucine EAA but did increase following ingestion of 41% Leucine EAA
(3) Similar to the FSR responses, the mean response of muscle phenylalanine net balance, a reflection of muscle protein balance, was improved in all groups, with the exception of the 26% Leu elderly group


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