Effects of a Multi-ingredient Supplement Study: a Randomized Controlled Trial in Men and Women
Condition: Skeletal Muscle Hypertrophy
MeSH terms: Hypertrophy
Study type: Interventional

Summary: 
      Resistance exercise training is a known stimulant for muscle protein synthesis (MPS) to
      occur, however the consumption of protein is also necessary to induce a shift towards a
      positive net protein balance. Other nutrients have been shown to be useful in the accretion
      of lean body mass and strength. Whey protein has been shown to improve muscle net protein
      balance after resistance exercise, more so when in conjunction with creatine. Furthermore,
      essential amino acids such as Leucine have been found to be important in moderating the shift
      towards a positive net protein balance, especially post-exercise and in combination with whey
      protein. Other vitamins and minerals have been shown to aid in permitting muscle protein
      synthesis rather than stimulating it, but are still necessary for optimal gains in
      hypertrophy. The effect of a multi-ingredient compound has rarely been investigated, and thus
      this study aims to combine whey protein, leucine, creatine, calcium citrate and vitamin D and
      test it in a resistance exercise training program over 12 weeks. Another novel aspect in this
      study will be testing this supplement against a placebo of equal amounts of protein and amino
      acids, the placebo will contain collagen protein and the non-essential amino acids alanine
      and glycine. Finally, this study will recruit both men and women (ages 18-30) to determine
      possible effects of the supplement on muscle hypertrophy in both sexes. We hypothesize that
      the synergistic effect of the ingredients in our supplement will induce hypertrophy to a
      larger degree than resistance exercise training with the placebo, and that these benefits
      will persist in both male and female participants.
    

Detailed description: 
      Supplementation in the form of whey protein, creatine and amino acids have all been shown to
      be a potent stimulus for muscle hypertrophy, when combined with resistance exercise. Burke et
      al. (2001) reported that males who supplemented with a combination of whey protein and
      creatine had greater increases in lean tissue mass and strength than those who supplemented
      with only whey protein or placebo. Hulmi at al. (2010) identified the most important
      component of whey to be its high concentration of the branched chain amino acid leucine, a
      critical amino acid for increasing muscle protein synthesis and suppressing muscle protein
      breakdown. The combination of leucine and whey protein has been shown to promote significant
      increases in muscle cross-sectional area. Vitamin D and calcium citrate have also been shown
      to enhance increases in muscle strength and lean mass, albeit in a permissive rather than
      stimulatory manner. Protein supplements have consistently been shown to promote greater gains
      in hypertrophy than their placebo counterparts, however these placebo supplements are often
      isoenergetic carbohydrate-based formulas. Few studies have compared two supplements with an
      equal amount of protein and amino acids, or have combined multiple beneficial ingredients to
      form a multicomponent supplement to promote greater gains in lean body mass and strength.
      Finally, sex differences in resistance training programs have rarely been studied, less so
      when testing a new supplement. Thus, the purpose of this study will be to determine whether
      there is an augmented effect of our nutritional supplement on the degree of hypertrophy in
      young male and female adults involved in a resistance training program. This nutritional
      supplement will be compared with a placebo containing an equivalent amount of collagen
      protein and non-essential amino acids. A secondary analysis will assess sex-based differences
      in strength and muscle size. Based on previous literature, we hypothesize that the
      combinatorial effect of whey protein, leucine, creatine, calcium citrate and vitamin D will
      induce hypertrophy to a larger degree than resistance exercise with the placebo in young
      adults.

      A synergistic combination of ingredients with known benefits will be given twice daily to
      healthy young men and women (18-30 years old), (n = 22) in conjunction with a 12-week
      undulating periodized resistance training protocol, in which the repetition number and
      intensity of the training sessions will vary. Notable ingredients in this supplement include
      whey protein isolate (20g), leucine (2g), creatine monohydrate (2.5g), calcium citrate
      (300mg) and vitamin D (1000IU). The placebo condition, also comprised of males and females
      (18-30 years old), (n=22) will ingest a formulation containing an equivalent amount of
      collagen protein (20g), as well as an equivalent amount of amino acids (alanine, 1.4g and
      glycine, 0.6g). Pre- and post- assessments will include dual-energy x-ray absorptiometry
      (DEXA), one-rep maximum (1RM), and an ultrasound of the quadriceps. Four muscle biopsies will
      be taken from the vastus lateralis: 1) at rest prior to training, 2) 48h after an acute bout
      of exercise prior to training, 3) at rest post-training, and 4) 48h after an acute bout
      post-training. This allows for comparisons of acute and trained effects of both conditions.
      Using novel immunohistochemical staining procedures we will examine the resistance
      exercise-induced changes in fibre type distribution and fibre cross-sectional area in the
      supplement and placebo conditions as well as perform sex-based comparisons.

      The novel aspect of this study will be the comparison of two isoenergetic, isonitrogenous
      supplements as stimulants for muscle protein accretion, as opposed to using carbohydrates as
      a placebo. The supplement will contain a new formulation of ingredients yet to be studied
      together. The synergistic effect of these ingredients will attempt to maximize muscle growth
      in both males and females, meaning that associations between sex and exercise can be
      assessed. This research will help us identify a new method to augment resistance exercise
      training through protein, amino acids, vitamins and minerals as well as expand the literature
      surrounding the effects of these ingredients on muscle hypertrophy.
    

Intervention name(s): Whey protein-based supplement; Collagen protein-based supplement
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): High quality protein supplement to be consumed twice daily; Lower quality protein supplement to be consumed daily
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel group design (with repeated measurements within each group)
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: Muscle Physiology; Nutrition