Modulation of muscle protein metabolism through amino acid supplementation and exercise in older women

Bukhari, Syed Shabbar Ijaz (2020) Modulation of muscle protein metabolism through amino acid supplementation and exercise in older women. PhD thesis, University of Nottingham.

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Skeletal muscle plays an important role in our body, not just in terms of locomotion but also for metabolic purposes. It itself is dependent on two main factors: an adequate diet of essential amino acids as well as regular exercise to keep it in functioning condition. As humans age, the ability of the skeletal muscle to function adequately declines, largely due to age-related muscle loss. This muscle loss has been studied in great detail mostly in men aged 60 and above. It is also well-known that leucine is the main driver of anabolic response to protein supplementation.


The aim of these studies was to quantify the anabolic response to two protein supplementations- Leucine enriched amino acids (LEAA) supplement at doses of 1.5 g, 3 g and 6 g, compared with “standard” whey protein 20 g & 40g, with and without resistance exercise in women aged 60-70 years. We also studied the effects of supplements and exercise on leg blood flow and muscle blood flow.


Forty-two acute studies were conducted, each lasting for just over 7 hours. Each study comprised of a fasting stage (with muscle biopsies) as well as supplementation followed by unilateral knee extension exercise (to allow for nutrition only vs. nutrition + exercise comparisons), thereby marking the post supplementation stage. In each experiment, the supplement was either a leucine enriched supplement or a standard whey protein supplement (doses mentioned above). Regular blood samples as well as muscle biopsies were taken to assess responses. Blood flow was measured in femoral artery (to assess leg blood flow) as well as contrast enhanced ultrasound (CEUS) to assess microvascular blood flow through the muscle vastus lateralis. The main strength of this design was that each volunteer was her own control (i.e. one side was protein supplement only and the other side was supplement + resistance exercise).


Plasma insulinemia and essential amino acidaemia was higher in whey protein groups compared to LEAA in all doses (P< 0.001). All the supplements resulted in an increase in muscle protein synthesis (MPS).

The LEAA at the dose of 3g showed a similar anabolic response compared to whey protein 20g (both P < 0.05vs. basal). However, this effect returned to baseline (fasting) levels at 4 hours. In the exercised leg, MPS also increased at 0–2 h but remained elevated at 4 h (both P < 0.05 compared to basal).

Similarly, in the study which explored the anabolic responses to LEAA 1.5g, LEAA 6g vs. Whey Protein 40g, MPS increased similarly in response to LEAA_1.5 (P < 0.05) and WP (P < 0.01) over 0-2 h, with MPS significantly greater than basal in the LEAA_6 and WP groups only over 0-4 h. However, in the FED-Ex leg, MPS significantly increased across all the groups from 0 to 4 h (LEAA-1.5P < 0.01; LEAA-6- P < 0.01 and WP- P < 0.001).

None of the supplements showed significant increases in leg blood flow or microvascular blood flow- only exercise groups showed an increase microvascular blood flow in LEAA 3g and WP 20g, reaching significance (P<0.05) Due to technical difficulties, only 6/group had their data used for LEAA 1.5g, LEAA6g and WP40, which didn’t show any difference.


The data generated from these studies suggest that smaller dose leucine enriched supplements may have a role to counteract sarcopenia, especially in elderly women, particularly when coupled with resistance exercise. Further studies in larger cohorts may be needed to confirm these results and if confirmed, these could form the basis for larger interventional trials in frail elderly patients suffering from mobility problems due to sarcopenia.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Atherton, Philip
Smith, Kenneth
Keywords: Skeletal muscle; Exercise; Protein supplementation; Anabolic response; Blood flow
Subjects: W Medicine and related subjects (NLM Classification) > WE Muscoskeletal system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 63556
Depositing User: Bukhari, Syed
Date Deposited: 07 Jan 2021 13:39
Last Modified: 07 Jan 2021 13:39

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