β-alanine Supplementation in Adults With Overweight/Obesity
Condition: Prediabetes; Hyperglycemia; Overweight or Obesity
MeSH terms: Obesity; Overweight; Hyperglycemia; Prediabetic State; Glucose Intolerance
Study type: Interventional

Summary: 
      The study will investigate the safety, feasibility, and efficacy of beta-alanine
      supplementation in adults with overweight or obesity. Beta-alanine is a widely used dietary
      supplement that can increase the amount of carnosine in skeletal muscle. Both carnosine and
      beta-alanine occur naturally in animal food products and previous research shows that
      supplementation with beta-alanine leads to an improvement in exercise performance; more
      recently, the present investigators have shown that increasing carnosine can also help to
      improve cardiometabolic health, detoxify skeletal muscle, and improve glucose (sugar) uptake
      into muscle cells.

      The investigators will recruit 30 participants (15 per arm) with overweight or obesity who
      meet the study criteria (this accounts for up to 20% attrition - a minimum of 12 participants
      per arm). Those who are eligible will be required to receive three short telephone calls and
      attend three laboratory sessions. Participants will be randomised to receive either
      beta-alanine or placebo (an inactive sugar pill) for the 3-month study period.

      To see whether beta-alanine supplementation is feasible in this population the investigators
      will measure recruitment, adherence (how well people can stick to the supplement regime), the
      number and nature of side effects, and blinding to the intervention. Markers of cardiac
      function, glycaemic control, and metabolic health will also be explored. All measurements
      will take place before and after a 3-month supplementation period. This will provide us with
      novel information of the role of beta-alanine and carnosine in cardiometabolic health; and
      will aid in the planning of a larger randomised controlled trial to assess the efficacy of
      beta-alanine supplementation as a therapeutic strategy.
    

Detailed description: 
      Overweight and obesity are major public health problems. Recent estimates show that 64.3% of
      people in the UK are living with overweight or obesity; this is projected to increase to 71%
      by 2040, which equates to approx. 42.2 million people (Cancer Research UK, 2022). Overweight
      and obesity are characterised by excess amounts of adiposity and systemic, chronic, low-grade
      inflammation, which is associated with a range of metabolic disorders including
      dyslipidaemia, hypertension, and hyperglycaemia (Calder et al., 2011). This confers an
      increased risk of developing prediabetes, type-2 diabetes, and cardiovascular disease, as
      well as associated microvascular complications such as retinopathy, neuropathy, and
      nephropathy (Brannick et al., 2016). Lifestyle interventions can help delay or prevent the
      progression of overweight or obesity, thereby reducing morbidity (Lin et al., 2017; Wing et
      al., 2021). Such interventions, however, can be challenging to implement and a lack of
      long-term adherence can limit their effectiveness (Fappa et al., 2008). It is therefore
      important to develop low-cost, novel adjunct therapies to improve cardiometabolic health and
      help delay or prevent disease progression.

      The multifunctional dipeptide carnosine has emerged as a candidate for improving glycaemic
      control and cardiometabolic health. A recent meta-analysis showed that supplementation with
      carnosine, or its rate-limiting precursor β-alanine, reduces fasting glucose and HbA1c in
      humans and rodents. Work from our Research Group shows that treatment with carnosine
      decreases highly toxic lipid peroxidation products in skeletal muscle cells, leading to an
      increase in insulin-stimulated glucose uptake under glucolipotoxic conditions. A similar role
      occurs in vivo, where supplementation with β-alanine leads to greater formation of
      carnosine-adducts in post-exercise skeletal muscle samples. Given that skeletal muscle
      insulin resistance is a key component of prediabetes and type 2 diabetes, and reactive
      aldehydes can directly interfere with insulin signalling, carnosine may exert its therapeutic
      actions in skeletal muscle. There is also emerging evidence that carnosine, and other
      histidine-containing dipeptides (HCDs), play an important role in Ca2+ handling and
      excitation-contraction coupling in cardiac muscle, which may have implications for
      cardiovascular health. A limitation of existing studies is that the low carnosine dose used
      is likely to have only a modest effect on tissue carnosine content. Supplementation with
      β-alanine, however, can increase skeletal muscle carnosine content by 60-80% in 4-10 weeks,
      but it has not yet been trialled in adults with overweight or obesity.

      Please note: a change was made to the study eligibility criteria, which was approved by the
      UK Health Research Authority Research Ethics Committee on 01/09/2022.
    

Intervention name(s): Beta-alanine; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Slow-release beta-alanine.; Taste and appearance-matched placebo (tapioca starch).
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A double-blinded, randomised, placebo-controlled, parallel group, feasibility trial. The allocation ratio of treatment to placebo will be 1:1.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Other
Keywords: Prediabetes; Hyperglycemia; Carnosine; Overweight; Obesity