Modulation of Muscle Protein Synthesis With Diet and Exercise in Old Aged Women

The Efficacy of Leucine Enriched-EAA Supplements vs. Whey Protein in the Modulation of Muscle Protein Synthesis, Albumin Synthesis and Leg/ Muscle Blood Flow in Older Women

In this study will measure differences in how muscle responds to both exercise and protein supplements in healthy women aged 60-69. We are studying two different protein supplements- a standard Whey Protein and a Leucine enriched supplement. Each patient would receive either one of these.

Study Overview

• Status: Completed
• Conditions: Sarcopenia

Detailed Description

One of the factors that plays an important role in the loss of functional performance and, as such, the capacity to maintain a healthy, active lifestyle is the progressive loss of skeletal muscle mass with ageing (i.e., sarcopenia). Indeed, sarcopenia is a more robust predictor of functional status and mortality in the elderly than chronological age or indeed, any other co-morbidity. Sarcopenia is an incipient process whereby lean muscle mass contributing up to ~50% of total body weight in young adults declines to ~25% when reaching the age of 75-80 y. Adequate nutritional intake, and in particular dietary protein, is important for offsetting age-related declines in muscle mass. The aim of this project is to seek the most effective nutrition with which to counteract sarcopenia, specifically in women.

• Study Type: Observational
• Enrollment (Actual): 48

Contacts and Locations

Study Locations

• United Kingdom
  • Derbyshire
    • Derby, Derbyshire, United Kingdom, DE22 3NE
      • University of Nottingham (Derby campus)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Healthy females aged 60-70

Description

Inclusion Criteria:

• Healthy post-menopausal females aged 60-70

Exclusion Criteria:

• • Obvious muscle wasting.

  • A body mass index (BMI) < 18 or > 40 kg•m2.
  • Active cardiovascular disease: uncontrolled high blood pressure, angina, heart failure (class III/IV), abnormal heart rhythm, right to left cardiac shunt or recent cardiac event.
  • Taking statin-based medication above 60mg•day-1.
  • Individuals taking beta-adrenergic blocking agents or Non-steroidal anti-inflammatory agents (NSAIDS)
  • Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial).
  • Respiratory disease including pulmonary hypertension, chronic obstructive pulmonary disease (COPD), asthma or a forced expiratory volume (FEV1) less than 1.5 litres.
  • Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, types 1 or 2 diabetes.
  • Active inflammatory bowel disease, renal disease, or malignancy.
  • Recent steroid treatment (within 6 months), or hormone replacement therapy.
  • Clotting dysfunction e.g. Deep vein thrombosis, pulmonary embolus, warfarin therapy and/ or haemophilia.
  • Musculoskeletal or neurological disorders.
  • Any leg amputated
  • Family history of early (<55y) death from cardiovascular disease.
  • Known sensitivity to SONOVUE (US contrast).

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle protein synthesis and muscle protein breakdown	Markers of muscle protein synthesis and breakdown are determined from muscle biopsy samples in form of myofibrillar Fractional Synthetic Rate (FSR) assessed by gas-chromatography-combustion-mass spectrometry, using incorporation of a stable isotope tracer (13-C-6 Phe)	7 Hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood flow (bulk and nutritive) and intramuscular cell signalling	Leg blood flow via Common femoral bulk flow (Doppler ultrasound); Microvascular blood flow via contrast enhanced ultrasound; Mammalian Target of Rapamycin-1 (mTORC1) and Protein Kinase B (PKB or AKT) phosphorylation via western immunoblotting	7 Hours

Collaborators and Investigators

• Sponsor: University of Nottingham
• Investigators: Principal Investigator: Kenneth Smith, PhD, University of Nottingham

Publications and helpful links

General Publications

• Wilkinson DJ, Bukhari SSI, Phillips BE, Limb MC, Cegielski J, Brook MS, Rankin D, Mitchell WK, Kobayashi H, Williams JP, Lund J, Greenhaff PL, Smith K, Atherton PJ. Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women. Clin Nutr. 2018 Dec;37(6 Pt A):2011-2021. doi: 10.1016/j.clnu.2017.09.008. Epub 2017 Sep 23.
• Bukhari SS, Phillips BE, Wilkinson DJ, Limb MC, Rankin D, Mitchell WK, Kobayashi H, Greenhaff PL, Smith K, Atherton PJ. Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise. Am J Physiol Endocrinol Metab. 2015 Jun 15;308(12):E1056-65. doi: 10.1152/ajpendo.00481.2014. Epub 2015 Mar 31.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: January 28, 2014
• First Submitted That Met QC Criteria: January 31, 2014
• First Posted (Estimate): February 3, 2014

Study Record Updates

• Last Update Posted (Actual): April 3, 2020
• Last Update Submitted That Met QC Criteria: March 31, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Muscle Protein Synthesis; Muscle Protein Breakdown
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia
• Other Study ID Numbers: C14082012