The Effects of Whey vs. Collagen on MPS
Condition: Aging
Study type: Interventional

Summary: 
      With aging there is a natural loss of muscle mass and strength called sarcopenia, which
      increases the risk of falls and metabolic disease (i.e. Type II diabetes) and decreases the
      ability to perform activities of daily living. Eating protein and doing resistance exercise
      both increase the body's ability to make muscle protein, which is important to offset losses
      in muscle mass; however, older adults have a lower appetite and do not consume enough
      calories or protein to crease muscle and as such investigations in this population are
      needed. The amino acid (the building blocks of proteins) leucine is known to increase the
      ability of protein to make muscle. In this study we will investigate the ability of beverages
      with different types of protein and leucine to create muscle in older men and women whoa re
      particularly vulnerable to muscle losses and do not eat enough protein and are understudied
      in this area.
    

Detailed description: 
      The age-related decline in skeletal muscle mass and strength, termed sarcopenia, is
      associated with a host of metabolic disease states including, but not limited to, cancer,
      stroke, microvascular disease, type 2 diabetes, Parkinson's and Alzheimer's. Moreover,
      declines in skeletal muscle mass also are accompanied by an even more precipitous reduction
      in skeletal muscle strength, known as dynapenia, which is a predisposition for disability and
      falls. Sarcopenia begins in the 5th decade of life and proceeds, at least based on
      population-derived estimates, at a ~0.8% loss annually, with strength losses being greater
      and more variable at 2-5% year past the age of 50. Strategies to offset the loss of muscle
      mass with aging are imperative for the maintenance of quality of life and ability to perform
      activities of daily living in an older population.

      Losses of skeletal muscle mass are underpinned by an imbalance between rates of muscle
      protein synthesis (MPS) and muscle protein breakdown (MPB). In healthy humans it is known
      that the change in the rate of MPS in response to contractile activity and protein feeding is
      the primary locus of control for human muscle mass. With aging, basal levels of MPS do not
      change in comparison to younger adults, however elevation in MPS response following an
      anabolic stimulus such as resistance exercise or protein ingestion are blunted when
      participants are exposed to the same stimulus, termed anabolic resistance. For example, older
      adults require 3-6 times the amount of resistance exercise volume and a 0.4 g/kg compared to
      0.24 g/kg dose of high quality protein into order to stimulate basal rates of muscle protein
      synthesis.

      Protein quality and dose are also critical when targeting maximal increases in MPS. The
      importance of amino acid digestibility is crucial as undigested dietary proteins may be
      unabsorbed and excreted rather than being absorbed in the small intestine or contributions to
      lean mass. The Food and Agriculture Organization has endorsed the digestible indispensable
      amino acid score (DIAAS) to assess protein quality as it is able to distinguish between
      proteins that were previously classed at an equivalent value. Using the DIAAS, proteins with
      the highest digestibility and quality scores are the two main milk proteins casein and whey,
      which have scores of 1.18 and 1.09, respectively whereas hydrolyzed collagen peptides
      (derived from bones and cartilaginous tissues) has a score of 0 as it lacks the amino acid
      tryptophan. Importantly, casein and whey have higher leucine contents than collagen peptides,
      including more of other essential amino acids. This is particularly important as data from
      our own laboratory has demonstrated that increasing the leucine concentration of a low
      protein mixed macronutrient beverage rescues rates of postprandial MPS to those seen with
      higher protein content. Moreover, leucine is a key trigger of the mechanistic target of
      rapamycin complex 1 (mTORC1), a 280-kDa serine/threonine kinase known to activate key
      translation initiation factors involved in MPS. Thus, protein doses of lower quality such as
      hydrolyzed collagen would in theory require a greater dose in order to elicit a similar
      response to whey or casein.

      The use of hydrolyzed collagen as a supplement to enhance skeletal muscle anabolism has been
      scarcely examined previously literature with most studies in humans involving the use of
      collagen peptide supplementation to enhance collagen-containing tissues such as hair, skin
      and cartilaginous joints. Of the current literature, supplementation with collagen peptides
      in combination with resistance exercise was found to have remarkable effects on the accrual
      of lean mass in older men with a concomitant remarkable decrease in fat mass within a 12-week
      training period. It was also found to have remarkable effects on nitrogen balance in older
      women in comparison to whey protein despite a leucine content in collagen that is 1/16th of
      that found in whey protein isolate. If the anabolic potential of hydrolyzed collagen is able
      to match that of whey protein, it may provide an important, cost effective, and feasible
      method by which older adults are able to achieve suggested protein recommendations.

      Protein ingestion following resistance exercise provides a potent and additive stimulus over
      either anabolic influence alone. A resistance exercise bout has been shown to sensitize the
      muscle to the effects of protein. Our lab has previously shown that older adults achieve the
      greatest increase in MPS following a resistance exercise bout when consuming 40 g of whey
      protein and that this effect was greater than consuming 40 g of protein without exercise. It
      will be crucial to our understanding of the protein needs of older adults to determine
      whether consumption of whey protein and collagen peptides are indeed equivalent and can be
      used to augment the muscle protein synthetic response following resistance exercise in older
      adults.

      Many studies that assess acute changes in rates of MPS in response to protein intake do so by
      infusing a labeled amino acid tracer and calculating the incorporation of that tracer into
      skeletal muscle over a period of hours. While this approach provides important information,
      especially when coupled with quantitative measures of changes in muscle mass such a MRI, the
      assessment of tracer-infusion measured MPS is limited to ~5-6 h. Thus, recent developments of
      analytical techniques have enabled the use of a deuterated water methodology that enables
      assessment of MPS with much longer periods of incorporation i.e., days-to-weeks. Indeed, this
      method has been recently validated and its use is now becoming the interest of many
      researchers. However, only a few laboratories have demonstrated the ability to competently
      perform this measurement. In fact, we have recently conducted two studies using this
      methodology, and the MPS values that we obtained are entirely consistent with published
      reports. We propose that the use of the deuterated water methodology in combination with the
      use of stable isotope tracers, will provide us with measurements of MPS in both a
      controlled-acute and a free-living situation and would be a substantial advance in
      determining mechanisms underpinning protein ingestion and aging.
    

Intervention name(s): Collagen peptide; Whey protein isolate
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Low leucine content protein supplement to be consumed twice daily; High quality protein (DIAAS score), high leucine supplement, to be consumed twice daily
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel group design (with repeated measurements within each group)
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Other
Keywords: Skeletal muscle; Protein synthesis; Protein ingestion; Resistance exercise