D2O Dosing Strategies to Assess Muscle Protein Synthesis

Skeletal muscle mass is regulated by the balance of muscle protein synthesis (MPS) and muscle protein breakdown (MPB). MPS is sensitive to exogenous stimuli, particularly exercise and protein ingestion. Much of what the investigators currently know about the impact of exercise and protein feeding on MPS has been derived from acute stable isotopic tracers in a controlled laboratory setting. However, recently, the field of skeletal muscle protein metabolism has moved towards the use of deuterium oxide (deuterated water (D2O)) to measure MPS. The ease of administration and the scope to measure turnover in a range of substrates whilst negating the need for strictly controlled laboratory settings makes D2O the ideal candidate to provide a more holistic view of in vivo skeletal muscle metabolism.

Currently, there is a lack of consensus amongst researchers regarding the dosing strategies of D2O provision for measuring fraction-specific (myofibrillar, mitochondrial and sarcoplasmic) protein synthetic rates. In addition, the analytical equipment (i.e., mass spectrometers) required to carry out the analysis of skeletal muscle-bound alanine are technically challenging, offer varying degrees of sensitivity that may drastically influence outcome measures and the expense of analysis differs greatly between the type of mass spectrometer required.Thus, this study will employ different D2O doses to assess basal and exercise plus protein feeding-induced rates of acute and integrated MPS in healthy young men and women. This will provide researchers with insight into the amount of D2O required to accurately assess MPS and the sensitivity of the analytical machine employed.

Eligibility Criteria:
Inclusion Criteria:

1. Men and women, between the ages of 18 - 35 years (inclusive)
2. Have a body mass index (BMI) between 18-30 kg·m2 (inclusive)
3. Be in general good health as assessed by a general health questionnaire
4. Non-smoking
5. Willing and able to provide informed consent

Exclusion Criteria:

1. Ingestion of deuterated water (D2O) in the previous \~6 months.
2. Routine/daily usage of non-steroidal anti-inflammatory drugs (NSAIDS, prescription use or daily use of over the counter medication), use of corticosteroids, testosterone replacement therapy (ingestion, injection, or transdermal), any anabolic steroid, creatine, whey protein supplements, casein or branched-chain amino acids (BCAAs) within 45 days prior to screening.
3. Use of tobacco or related products.
4. Veganism or vegetarianism
5. Any concurrent medical, orthopedic, or psychiatric condition that, in the opinion of the Investigator, would compromise his/her ability to comply with the study requirements.
6. Use assistive walking devices (e.g., cane or walker)
7. History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years.
8. Significant orthopedic, cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would preclude oral protein supplement ingestion and/or assessment of safety and study objectives.
9. Any cachexia-related condition (e.g., relating to cancer, tuberculosis or human immunodeficiency virus infection and acquired immune deficiency syndrome) or any genetic muscle diseases or disorders
10. Current illnesses which could interfere with the study (e.g. prolonged severe diarrhea, regurgitation, difficulty swallowing)
11. Hypersensitivity or known allergy to any of the components in the test formulations.
12. Excessive alcohol consumption (\>21 units/week)
13. History of bleeding diathesis, platelet or coagulation disorders, or antiplatelet/anticoagulation therapy (up to 81mg of baby aspirin per day taken as a prophylactic is permitted).
14. History of statin myalgia.
15. Personal or family history of clotting disorder or deep vein thrombosis.