Comparison of Different Weight Loss Diets With Different Protein Content
Condition: Weight Loss; Insulin Resistance
MeSH terms: Insulin Resistance; Body Weight; Weight Loss
Study type: Interventional

Summary: 
      High-protein diets better preserve lean mass than conventional low-fat diets. However, they
      are costly and have potential health risks. Preserving lean mass is important for sustaining
      high resting energy expenditure, leading to greater initial weight loss, better weight
      maintenance and improving blood sugar levels. Branched-chain amino acids (BCAA) supplements
      are known to preserve lean mass but their effects during weight loss have not been examined.
      Investigators want to investigate if a BCAA-supplemented diet is more effective than a
      standard hypocaloric diet in terms of the aforementioned benefits, and yet has less
      detrimental effects than a high-protein diet for weight loss. Using a 16-week weight loss and
      8-week weight maintenance intervention, overweight and obese men and women will be randomized
      to either a hypocaloric diet with BCAA or placebo supplements or a high-protein diet with
      placebo supplements. Participants' compliance to the diet versus supplements will be
      compared. Body composition, resting and diet-induced energy expenditure, insulin sensitivity
      will be measured and blood samples taken before and after weight loss. These findings will
      inform on the benefits of BCAA-supplementation during energy restriction and may offer an
      alternative cost-effective strategy for weight loss and maintenance, without the adverse
      health effects of a high-protein load.
    

Detailed description: 
      The prevalence of obesity globally and in Singapore continues to rise despite increased
      public awareness and efforts to control weight. Its association with chronic metabolic
      diseases, including diabetes, hypertension, cardiovascular diseases, signify the serious
      implications of obesity on public health. There remains, however, no scientific consensus on
      the optimal methods for weight loss and its maintenance over longer periods of time. The
      Atkins diet was introduced in the late 1990s and has since fuelled the popularity of using
      high-protein diets for weight loss. Scientific evidence have since shown high-protein diets
      to be more effective than conventional low-fat, high-carbohydrate diets in producing greater
      weight loss, at least in the short-term. More importantly, high-protein diets also reduce the
      amount of lean tissue lost during weight loss and may help to maintain weight loss to a
      greater extent than conventional diets. However, high-protein diets are also known to raise
      esterol, albeit improving TG and HDL-cholesterol levels. This could be due to the higher
      amounts of saturated fats that accompany foods rich in animal protein. In addition,
      high-protein diets may lower bone mineral density and impact on kidney function. High-protein
      diets are also more expensive than conventional low-fat, high carbohydrate foods , which is
      an important consideration for longer term compliance.

      Supplements containing branched-chain amino acids (BCAA:leucine, isoleucine and valine) are
      commonly used among muscle builders and athletic community. BCAAs have been shown to
      stimulate protein synthesis and preserve lean mass. While a few studies have examined BCAA
      supplementation with low protein diets for weight loss and found depletion of other essential
      amino acids, the effects of BCAA supplementation with moderate-protein hypocaloric diets on
      lean mass preservation during weight loss in energy-restricted obese patients has, to our
      knowledge, not been investigated. Compared to consuming a high (animal) protein diet, which
      is also rich in BCAAs, taking BCAA supplements would be a much more convenient and affordable
      way to obtain similar if not greater quantities of BCAA, without the adverse health effects
      of a high-protein load on the body.

      In this study investigators primarily aim to investigate in overweight/obese subjects,
      whether a BCAA-supplemented (moderate-protein) hypocaloric diet (BCAA) when compared to a
      standard (moderate-protein) hypocaloric diet (CT) will result in greater lean mass
      preservation, resting and diet-induced energy expenditure, and improved insulin sensitivity.
      Investigators will also examine the effects on lean mass preservation and insulin sensitivity
      changes between BCAA-supplemented diet and high-protein hypocaloric diet (HP). As a secondary
      aim, investigators have also powered the study to examine if the BCAA-supplemented diet has
      added advantage to the high-protein diet by incurring less negative effects on bone mineral
      density and renal function.

      In addition, investigators will determine the participant's compliance to the diet versus
      supplements as a weight loss and maintenance strategy. The findings of this study will
      provide us novel insight on BCAA-supplementation in the hypocaloric diet. If this study is
      successful, BCAA-supplementation on a hypocaloric diet could provide an alternative to a
      standard (moderate-protein) hypocaloric diet for weight reduction strategy without the
      attending potential health risks of a high protein load e.g. reduced bone mineral density and
      detrimental effects on renal function.

      There are three main hypotheses which investigators propose to examine.

      Hypothesis 1: A BCAA-supplemented hypocaloric diet (BCAA) would lead to greater lean mass
      preservation during weight loss compared to a standard (moderate-protein) hypocaloric diet
      (CT).

      Diets with varying diet composition, including low-fat, high-carbohydrate diets to
      high-protein, low-carbohydrate diets have been tested in search of the optimal macronutrient
      composition for weight loss. High-protein diets have been highly favored for their ability to
      initiate greater initial weight loss. However, accumulative data from recent studies has
      shown no significant differences in amount of weight loss between high-protein diets and
      other traditional (normally low-fat, high-carbohydrate) energy-restricted diets in the longer
      term (16 weeks to 1 year). It appears that total energy intake, rather than diet composition,
      is the most important determinant of longer term weight loss.

      However, an overriding advantage of high-protein diets is their favorable effects on body
      composition, that is preserving greater lean mass, compared to high-carbohydrate diets,
      during weight loss in adult obese patients, independent of energy intake. A recent
      meta-analysis demonstrated that high protein diets (protein > 1.05g/kg body weight) are
      associated with up to 1.21 kg additional fat-free mass retention compared with diets of lower
      protein intake. Lean mass or fat-free mass is a main determinant of basal (resting) energy
      expenditure. Its greater preservation would reduce the weight loss-induced decreased in
      energy expenditure, which might have two important implications. Firstly, higher basal energy
      expenditure during weight loss could lead to greater weight loss for the same amount of
      calories consumed. Secondly, the amount of lean mass preserved at the end of weight loss
      might mitigate weight regain during maintenance phase of weight loss, i.e. success of weight
      maintenance.

      Branched-chain amino acids like leucine, isoleucine and valine are substrates for protein
      synthesis and also potent nutrients that regulate protein metabolism. Supplementation with
      leucine or leucine-rich protein sources have been suggested to develop muscle mass or prevent
      protein loss in conditions characterized by muscle protein wasting. In human studies, the use
      of leucine or leucine-rich protein sources supplementation have been well-investigated to
      optimize the effects of exercise on body composition.Several studies have examined the impact
      of chronic (average of 3 months) leucine-rich amino acid supplementation in healthy elderly
      humans, and have demonstrated significant improvement in lean body mass, muscle strength and
      physical capacity.

      Whether the lean mass preservation during high-protein hypocaloric diet is due to the
      presence of the higher amounts of BCAA content is less clear. Two studies have examined the
      use of whey protein (rich in BCAA) in weight loss but it was uncertain if the benefits of
      enhanced weight loss with less lean muscle loss can be attributed to the BCAA alone or due to
      the enrichment of other nutrients like calcium and bioactive peptides in the whey protein
      fraction. It is also not clear whether animal sources of protein (rich in BCAAs) are more
      beneficial than plant sources of protein on energy expenditure, body composition , satiety
      and fat loss.

      To investigators' knowledge, no studies have specifically examined the beneficial effect of
      BCAA supplementation with a moderate-protein diet on lean mass preservation during weight
      loss in energy-restricted obese patients. Investigators hypothesize that similar to a
      high-protein diet (as shown in literature), a BCAA-supplemented hypocaloric diet would also
      lead to greater lean mass preservation than a standard (moderate-protein) hypocaloric diet
      during weight loss. In addition, investigators want to examine the effects on lean mass
      preservation between BCAA-supplemented hypocaloric diet and high protein hypocaloric diet.

      Hypothesis 2: Improvement in insulin sensitivity with a BCAA-supplemented hypocaloric diet
      (BCAA) is greater than a standard (moderate-protein) hypocaloric diet (CT).

      The insulin stimulating effects of proteins maybe mediated through specific amino acids,
      making them potent modulators of insulin action and glucose metabolism. In animal models,
      BCAA supplementation has been found to improve glucose tolerance and stimulate glucose uptake
      in skeletal muscle by mechanisms involving glycogen synthase activity. While energy
      restriction and weight loss have positive effects on insulin sensitivity , whether diet
      composition further impacts on insulin sensitivity is still inconclusive. Several studies
      found significant improvement in insulin sensitivity after high-protein diets compared to
      control diets, independent of weight loss, while others did not. As skeletal muscle mass is a
      major determinate of insulin sensitivity, investigators postulate that due to greater lean
      mass preservation, the BCAA diet would result in greater improvement in insulin sensitivity
      compared to CT diet.

      Hypothesis 3: The BCAA-supplementation diet (BCAA) would be easier to adhere to and has less
      detrimental effects on bone mineral density and renal function than the high-protein diet
      (HP), leading to better (short-term) weight maintenance and less weight regain.

      Maintaining weight loss is a greater challenge than the weight loss process and may not be as
      easily achieved. Studies have shown that weight regain is significantly lesser in subjects in
      the high-protein group compared to control group after six months to a year on a
      weight-maintenance diet. In these studies, study foods are provided and may not reflect
      real-life free-living situations during weight maintenance phase. Achieving a high-protein
      diet long term can be costly and requires careful planning of meals. To what extent subjects
      can continue to maintain the same diet composition as their weight loss diet on their own
      accord at energy balance during weight maintenance has not been well-investigated The
      effectiveness of longer term BCAA supplementation in hypocaloric diet has also not been fully
      investigated. If BCAA supplementation could induce similar metabolic improvement as of a
      high-protein diet during the weight loss phase, it might help to maintain body weight through
      easy administration and greater compliance in the longer term.

      In this study, investigators proposed to provide BCAA supplements to the BCAA group and
      placebo supplements provided to the HP and CT groups throughout the entire study (weight loss
      and maintenance phases).

      Study foods will, however, only be provided during the weight loss phase. Investigators
      speculate that overall, adherence to supplementation would be better than adherence to the
      respective diet compositions at the end of the weight maintenance phase for subjects in all
      three groups. Investigators hypothesize that while subjects on the HP and BCAA diets will
      have less weight regain in the initial weight maintenance phase (due to greater lean mass)
      than the CT group, the BCAA group will have the least weight regain at the end of weight
      maintenance phase due to better compliance.

      Concerns have been raised over the safety of high-protein diets. Studies have indicated that
      increase protein intake is associated with increased renal calcium excretion, negative
      calcium balance, bone resorption and causes hyperfiltration. At the same time, it is also
      known that loss of bone mass often accompanies weight loss induced by calorie restriction.
      Whether high-protein diets have a detrimental impact on bone mineral density and renal
      function is still inconclusive. In this study, investigators hypothesize that the
      BCAA-supplemented diet would result in lesser detrimental effects on bone mineral density and
      renal function than the high-protein diet.

      Other secondary hypotheses:

      The three dietary interventions may lead to significant differences in markers of
      cardiometabolic outcomes including inflammatory markers

      The resting/basal metabolic rate change with time, and diet induced thermogenesis, may differ
      between the three groups

      The resting basal metabolic rate change in the subjects with weight loss at 16 weeks predicts
      the weight gain/rebound at 24 weeks.
    

Intervention name(s): BCAA; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Branched chain amino acid(BCAA) pills will be provided to subjects 0.15g/kg of body weight per day for six months; Placebo will be provided to the other two arms for six months
Other intervention name(s): AST BCAA 4500; Starch pill manufactured to mimic AST BCAA 4500
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Other
Keywords: Branched chain amino acid, high protein diet, weight loss