The Future of Biomarkers in Sport and Exercise Medicine

The science and medicine team have a task to enhance an athletes health and resilience to injury and illness and maximize performance from physical conditioning and nutrition. Key variables are physical workload, diet, sleep and nutrition to promote health and recovery. Subjective tools are convenient, but can be inaccurate and prone to bias. Blood biomarkers offer objective data, but pre-sample approaches, sample timing and biomarker selection are keys to meaningful data.

The research evidence base supporting blood biomarkers in sport has developed over the past 30 years (Pedlar et al 2019).

The Future of Biomarkers in Sport and Exercise Medicine Athletes Nutrition

Biomarkers and Nutrition

Iron – underpins erythropoiesis and new red cell production. Essential for endurance training especially at altitude. Females at greater risk of iron store falls. Measure the total haemoglobin mass and ferritin for iron storage status. Hepcidin is a good biomarker of iron absorption.

Vitamin D – an important biomarker for athletes ( Owens et al 2018). Low vitamin D linked to reduced immune function, compromised bone health and muscle repair. Recent studies have shown a link with hamstring muscle injuries and low vitamin D levels with a 3 x increase risk of injury. The vitamin D assay ( 25-OHD) alone has limitations in the population and the biomarker vitamin D binding protein should be measured. Maintain normal vitamin D levels to reduce respiratory infection risk ( He et al 2016).

Fatty Acids – the Omega 3 index ( OM3I) is a validated marker of Omega 3 status. A good biomarkers – the Omega 3 index ( OM3I) is a validated marker of Omega 3 status. A good biomarker of the quality of the athletes diet in the previous 4 weeks. Various systems are influenced by fatty acid status – mood and cognition – muscle recovery – concussion and cardiovascular function. Measuring the biomarker allows for an early sports dietitian review.

Energy Availability – essential to monitor to prevent energy deficiency states ( Relative Energy Deficiency in Sport – RED-S ( Mountjoy et al 2018) ). Several peptide hormones and cytokines have been found to serve as indicators of energy monitors including IL6 , Leptin, Ghrelin and TNF alpha ( Jurimae et al 2011). Reduced total T3 has been found to relate to energy status and training adaptation in female swimmers and also responds to a reduced energy intake in males ( Friedl et al 2000). Testosterone declines with energy deficiency and is restored with a boost in dietary carbohydrates.

Biomarkers and Training Load

Point of Care blood biomarkers can be used to time athletes training loads both to increase and decrease the load. Rapid results from point of care in the training ground medical centre can inform decision making. The timing of these tests and consistency of measurements are important factors.

The most useful markers are :

  1. Oxidative Stress – lipid and protein hydroperoxides, isoprostanes and protein carbonyls.
  2. Inflammatory – IL6 and CRP
  3. Muscle damage – Creatine Kinase ( CK)
  4. Hormonal Drive – Testosterone and Cortisol.
  5. Hydration Status – Blood osmolality threshold ( 295mmol/kg), Haematocrit , Urea , Creatinine and Sodium.

Research evidence points to an increase in oxidative stress and a proportional increase in the risk of injury and illness ( Lewis et al 2020). Adaptation to aerobic training can be quantified by measuring blood lactate levels and can be used with oxidative stress biomarkers.

Hydration status can be measure pre-exercise / competition or post exercise in the recovery period

Athlete Injury and Illness

Low T3 and Testosterone levels have been linked with increased risk of injury, but population based clinical reference ranges for various hormones and biomarkers make injury predictions difficult. More research is needed in this area to establish biomarker patterns over the range of variables for oxidative stress, inflammation, energy and hormonal levels to determine a pattern that predicts injury or predicts a delay to return to sport or an early re-injury risk. Recent studies have shown a link with low vitamin D levels and a risk of hamstring muscle injuries.

Concussion

Traumatic brain injury affects 69 million people per year worldwide. The majority of brain injury is classified as mild, but even mild injury can have significant effects e.g cognitive impairment, memory loss, headaches, attention problems, mood disorders, depression and anxiety, poor sleep patterns and irritability. Most cases self resolve within 2 weeks. Long term problems lasting 6 months and longer develop in 12.5% of cases – termed post concussion syndrome.

Important biomarkers to watch in the future for head injury and concussion assessment , diagnosis and prognosis are:

  1. Neuronal damage markers NF-L, UCL-L1 and Tau
  2. Astrocyte damage markers GFAP, S100B
  3. Inflammatory markers IL6

Summary and Practical Applications

1.     Select appropriate biomarkers for an athlete profile at the start of the season using a baseline venous sample and laboratory test.

2.     Select appropriate biomarkers for a point of care capillary test for individual athletes.

3.     Remember that blood biomarkers provide a ‘window’ into the physiology at that point in time. Multiple point of care tests over the season give a pattern and trend.

4. Concussion biomarkers are likely to play a role in head injury decisions, concussion and return to play in the future.

5.     A multi-biomarker test platform is going to be more useful than individual biomarker tests to cover the range of physiological variables.

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