Penny Kendall-Reed ND
Steven Reed MD, FRCP

Overtraining Syndrome – 2020 Update

Overtraining Syndrome (OTS) is becoming increasingly common in athletes at all levels.  Part of this increase relates to improved awareness and diagnosis, but a significant factor is the cumulative and synergistic impact of athletic stress and lifestyle stress.  The incidence of OTS in elite runners approaches 60% and even in non-elite competitive runners nearly a third will develop OTS at some point.  Preventative management and early recognition are essential to ensure the condition does not progress to a potentially dangerous and sport-ending stage.

Overtraining Syndrome (OTS) describes a combination of physical and mental abnormalities that results from cumulative high-level physical activity that is not accompanied by adequate recovery.  OTS is generally used to refer to an abnormal and persistent state characterized by physical, mental, hormonal and immunological dysfunction.  Older terms include “burnout” (more commonly used now for non-athletic stress), staleness, adaption failure, training stress syndrome and unexplained under performance syndrome.

“Over training” itself is not a diagnosis it is a verb.  It describes a process of intensified training, often sport-specific (as opposed to cross-training), completed with the purpose of achieving enhanced performance through what is often described as “super compensation” – the positively adaptive response of the body to physical stress.  Super compensation occurs during the period of rest immediately following a period of over training and is frequently incorporated into a program designed to culminate in a competitive event.  However, an imbalance between over training and rest/recovery can lead to progressive deterioration that does not resolve quickly and can be associated with more severe symptoms of maladaptive physiology.

OTS Symptoms

  • Decreased performance
  • Excessive fatigue
  • Muscle pain
  • Mental/Emotional disturbance (agitation, depression, poor concentration, poor motivation)
  • Insomnia
  • Appetite disruption/Thirst
  • Weight loss/gain
  • GI upset
  • Recurring or non-healing injuries
  • Recurrent colds/infections

There is often some confusion between the terms “Overreaching” and “Overtraining”.  Overreaching is an intensified program of sport-specific training that can, with the appropriate balance of rest and recovery AND in the right individual, result in a short-term decrease in capacity but an overall improvement in performance.  This is termed “Functional Overreaching (FOR)”.  It is a fine line and if recovery is incomplete the athlete can progress to the fist stage of OTS.

Figure 1: Think of Overreaching and Overtraining as part of a spectrum.  NFOR overlaps substantially with Stage 1 OTS.

Figure 2: OTS can be divided into 3 stages of severity.

As mentioned above, OTS affects a high percentage of athletes and is probably under-diagnosed due to poor education and under-reported due to fears about losing team positions or scholarships.

Prevalence or how many individuals are affected at one time, approaches 10% in elite collegiate endurance athletes (range 7-21%).  It should be noted, however, that the highest rates are likely inflated by the inclusion of FOR.

Incidence or how likely one individual is to develop OTS is 60% in elite runners.  Even among non-elite, competitive runners almost a third will develop some element of OTS during their running lifetime.  Outside of running, the incidence across all sports for high-level athletes is 30-40%.

One of the most important factors to recognize in OTS is its high recurrence rate.  In one study, 90% of athletes with one episode of OTS in their first collegiate year had at least one further episode during the next 3 years.  Those with no OTS in the first year maintained a 30% rate.  At least part of this high recurrence rate is due to inadequate treatment including an insufficient rest period.

So what causes OTS?  There are a number of theories but the Cytokine and Autonomic Dysfunction hypotheses are the most accepted and comprehensive in terms of identified symptoms and pathologies.  These two theories overlap as HPA dysfunction inevitably results in chronic inflammation.

Theories of OTS:

Glycogen Hypothesis – Depleted glycogen stores are associated with fatigue and poor performance.  Likely a contributing factor and associated with certain genotypes and poor nutrition but does not explain the majority of associated pathologies.

Glutamine Hypothesis – Glutamine is essential for immune cell function, DNA/RNA synthesis, nitrogen transport, gluconeogenesis and acid/base balance.  Prolonged or repeated bouts of high-intensity exercise are associated with a decrease in plasma glutamine.  Current evidence is inconclusive and shows only a weak association with OTS.  However, there is a possible role for glutamine supplementation.

Oxidative Stress Hypothesis – reactive oxygen species result from exercise and cause inflammation, muscle fatigue and soreness.  Higher levels are found in overstrained athletes.  It is unclear if this is a trigger or a result of OTS.

Cytokine Hypothesis – the repetitive micro-trauma occurring from vigorous exercise leads to the release of pro-inflammatory cytokines.  Inadequate recovery and failed resolution of the inflammatory cascade results in a chronic, systemic inflammatory response involving increased levels of IL-1-alpha and TNF-alpha.  This is an attractive hypothesis as it explains many features of OTS including reduced glycogen, low glutamine, reduced tryptophan/serotonin, decreased appetite, sleep disturbance and depression.  It also explains altered immunity.

Autonomic Nervous System and HPA Hypothesis – imbalance within the sympathetic/parasympathetic nervous system followed by alterations in HPA axis activity and feedback lead to numerous effects consistent with the exhaustion phase of Hans Seleye’s adaptation theory.  Dysregulation in HPA feedback leads to persistent cortisol secretion and cortisol resistance (similar to insulin resistance), which results in widespread neurochemical, hormonal and immune abnormalities.

Diagnosing OTS

One of the most important challenges in OTS is recognizing it early.  Once established, treatment becomes much harder and more prolonged.  Diagnosis relies on several areas of evaluation:

Rule out organic disease

A number of organic diseases can present in a similar way to OTS and are often overlooked as the population tends to be younger and disease uncommon.

  • Undiagnosed lung disease (asthma)
  • Hormonal Disease (Thyroid, Diabetes)
  • Anaemia
  • Infection (hepatitis, HIV, myocarditis, Lyme, EBV)
  • Malnutrition/Eating Disorder (RED-S)

(RED-S or Relative Energy Deficiency Sport is a low-energy state resulting from inadequate nutrition relative to the degree of training.  Originally known as the Female Athlete Triad (anorexia, amenorrhoea, osteoporosis) it is now known to affect both men and women equally.  Although similar in presentation, it can be distinguished from OTS.  RED-S is predominantly a low-energy rather than low-performance state; there are stronger food anxiety and body image issues; amenorrhea is more common as is low libido and erectile dysfunction; bone injury (stress fractures) occur rather than muscle injury; RED-S is easily reversed with appropriate nutrition.)


When taking a history look for potential triggers:

  • Increased training load without adequate rest
  • Training monotony
  • Excessive number of competitions
  • Sleep abnormalities
  • Additional stressors  – personal, work etc.
  • Recent illness
  • Environmental exposure – altitude, heat, cold


Symptoms are quite variable between individuals and can occur in any order.  However, even one or two can indicate early OTS and should not be ignored.  The more symptoms there are the more advanced the condition:

  • Inability to complete a training session
  • Tired but unable to sleep
  • Loss of “finishing kick”
  • Increased irritability
  • Depressed mood/Enhanced PMS
  • Weight loss/Weight Gain
  • Persistent thirst
  • Recurrent colds


Again, these are quite variable between individuals.  A high resting heart rate (10-30 bpm above normal) is the most reliable and often occurs in the early stages of OTS:

  • Increased resting heart rate
  • Fatigued/Sickly appearance
  • Muscle tenderness/tightness
  • Acne
  • Weak hair/nails

Blood tests

Blood Tests that have been used to diagnose OTS include blood sugar (often elevated due to the mild insulin resistance that occurs in some individuals), lactate, Glutamine, cortisol but are invasive, hard to interpret and often unreliable.  Oxidative stress biomarkers appear to be a promising test but only available in research centres.

Performance Testing

Physical and Mental testing appears to be the most reliable and useful method of assessing impending or established OTS.  Such tests include time-to fatigue tests, sport specific maximum aerobic function tests and strength or power tests in appropriate sports.  The Profile of Mood State questionnaire (or POMS) is a simple test with good reliability in diagnosing OTS.  By assigning values to self-perceived issues including fatigue, vigour, tension, anger, confusion and depression an overall emotional state score can be recorded and monitored.

Other tests include the MTDS, and REST-Q assessments, both available on-line.  They incorporate both mental and physical self-assessments of stress and recovery. The REST-Q questionnaire is more accessible and is available in a general version as well as specific versions for athletes and coaches.

Psychomotor speed tests are becoming increasingly useful.  They are simple, non-invasive and easily available through a computer.  They appear to have high validity in assessing athletic performance, combining mental and motor skills.  Examples include Zig-zag tracking, the Gibson Spiral Maze and the STROOP test.

Treatment of OTS

When it comes to managing OTS, if the diagnosis is made late then treatment becomes harder and more prolonged.  We have discussed early recognition, identifying OTS before it becomes OTS, as an important strategy.  This, along with risk reduction through appropriate training schedules and monitoring logs are key components of treatment.

Prevention includes maintaining adequate nutrition and hydration, getting adequate sleep, (often tough for those college athletes!), bodywork such a massage or individual stretching, and relaxation, particularly mindful meditation.  Keeping training logs can both ensure a training program is varied and give hints that performance is deteriorating.

The Rating of Perceived Exertion (RPE) scale assigns a difficulty value to a particular workout.  Weekly RPE totals should change to ensure varied intensity.  In addition, monitoring the RPE for a specific workout allows performance and fatigue to be followed.  If a certain routine is rated a 6 at the start of the season but becomes an 8 halfway through, then the individual may be showing signs of OTS.

Another performance monitor is the Maximum Aerobic Fitness test (MAF).

Treatment of Impending or Established OTS

Once an athlete shows signs of OTS then treatment needs to be instituted quickly and thoroughly in order to be effective.  Ignoring signs or taking half-measures will result in further deterioration and an even longer recovery.

Rest, rest and more rest is the key.  This is often incredibly difficult for an athlete to accept so involving a sports psychologist can be helpful.  Allowing cross training can overcome some of the inevitable despondency resulting from a halted season.  Restore sleep, one of the most essential factors in healing and improve nutrition ad hydration.  Consider the following supplements;

  • Glutamine – 5 grams per day
  • Liposomal Glutathione – 250mg twice a day
  • Resveratrol – 100mg twice a day

Reduction in activity and training needs to be quite profound and surprises most athletes.  However, failure to adhere to an appropriate rest and recovery protocol will result in a high likelihood of relapse.  Suggested time frames vary according to the Stage of OTS and are shown in the table below.  Note, however, that even though in Stage 1, participation in competition does not have to stop, the frequency of events should undoubtedly be minimized.

Stage 1 Stage 2 Stage 3
Reduce Training 50-70% YES YES YES
Eliminate High Intensity YES YES YES
Stop Competition NO YES YES
1-4 weeks 4-12 weeks 12-52 weeks

The Role of Genetics in OTS

All athletes are not created equal!  Certain individuals may be faster, stronger, show greater endurance or have better agility and coordination.  Part of this relates to training, diet and other external factors that might be termed “nurture”.   50-60%, however, is due to “nature”, essentially our genetic makeup.  There is increasing evidence that our coding for certain genes has a profound influence on everything from muscle fibre mass and composition to oxygen utilization and recovery from injury.  Knowledge of an athlete’s genetic profile can be tremendously important in terms of training and nutrition.  Tuning diet and fitness protocols to make them more suited to an individual’s “nature” will not only improve performance, but reduce risk of injury and OTS.

Genes and SNPs

Genes are defined sequences within our DNA that code for specific proteins. An “Allele” is a variant form of a gene.  Humans have two copies of each gene and the combination of the two is termed the “genotype”.  (The copy on one chromosome is called a “haplotype”).  If an individual has the same gene allele on each chromosome they are termed “homozygous”.  If the two genes have different alleles they are termed “heterozygous”.  Some gene alleles are dominant or recessive depending on how they influence the phenotype.  Dominant alleles “overpower” recessive alleles to exert their effect.  Thus, the phenotype coded by the gene will be present in those that are homozygous for the dominant gene or heterozygous (one dominant and one recessive).  Only those homozygous for the recessive allele will fail to show the trait or express the recessive allele trait.


There are two alleles of the hairline gene.  The allele for a straight hairline is recessive while the allele for a V-shaped hairline is dominant.  If we call the recessive allele “S” and the dominant allele “V” then individuals with the genotype VV, VS (or SV) will have a V-shaped hairline and only those with SS will have a straight hairline.

Some diseases are caused by recessive alleles, such as sickle cell disease.  Those related to genes not on the X or Y sex chromosomes are called “autosomal” while those on the X or Y-chromosomes are called “sex-linked” or “X” or “Y” linked.  X-linked traits are more common and include diseases such as colour blindness, haemophilia A and B, and Duchenne muscular dystrophy.

Most traits and diseases, however, are polygenic, influenced by a number of genes.  Eye colour is an example and explains why we can have green and hazel eyes, caused by a mixture of blue and brown alleles even though the blue allele is recessive.

SNPs (Single Nucleotide Polymorphisms) are single DNA points in a gene where variations occur.  As opposed to mutations, these variations are extremely common in the population.  They do not cause serious disease but can impact the way a gene works, often altering its expression or potency.  This altered function results in changes to an individual’s physiology that can affect performance or health.

The vast majority of personal genetic analysis involves the detection of these SNP’s in which there is a difference in a single nucleotide of one base pair of a DNA sequence.  For example:

At a specific locus in a gene the population might show two different sequences:


In this case there would be a SNP at position 4.  (In reality of course, gene sequences are far longer and a SNP may occur at position 12 or 972 for example.)

When performing SNP analysis and describing variants, an individual’s coding is compared to a “baseline” or “standard” allele.  This baseline allele is also called the “Ancestral Allele” (and sometimes the “Wild Allele”) and refers to the original evolutionary haplotype.  Subsequent mutations that occurred during human evolution have produced “Derived Alleles” and represent the SNP variation between individuals that we use to analyse personal traits.  For a given SNP, the alleles will be defined according to the amino acid base variation and are often labelled as ancestral or baseline (the “normal” or original allele) and derived or variant (the “mutated” allele).  Alleles may also be labelled “major” or “minor” according to their population frequency.  The minor allele is most often (but not always) the derived or variant allele and may also be the “risk” allele as it usually confers an adverse health effect.

For example, if the ancestral allele is C then the original or baseline “normal” coding for a particular gene, might include the following sequence;

…GTGCAT.. where “C” is the SNP.

As there are 2 copies (one on each chromosome) of the gene there would be two SNP’s and these would both be ancestral, thus CC.

If the variant (derived or risk allele) is T then the gene sequence would read;


The individual may only have this on one of their two chromosomes and have the ancestral allele on the other.  Their coding would therefore be CT (the order does not matter) and they would be termed heterozygous.  If both genes have the variant then they would be TT and termed homozygous.

SNPs are relevant as they impart identifiable morphologic traits or are found to be associated with certain physiologic states or diseases on analysis with genome-wide association studies.  It is a new, highly important and rapidly expanding field and this article only touches the surface of its depth and intricacy.  However, the following SNP descriptions are presented for their relevance to OTS.

ACTN3 – gene for speed

The ACTN3 gene codes for the muscle protein Actin-3, a vital component of fast-twitch muscle fibres.  Individuals with the variant T-allele (C is the normal allele) of this SNP produce no Actin-3.  As there are two copies (one on each chromosome), heterozygotes (C/T) produce some, but less than C/Cs.  Homozygote variants (T/T) produce none.

T-allele associated with:

  • Fewer fast-twitch fibers, higher slow-twitch
  • Smaller muscle volume/Lower Strength + Sprint Times
  • Better endurance + oxidative metabolism
  • Higher VO2 max
  • More prone to muscle damage especially with ECCENTRIC loading
  • Increased DOMS with HIIT
  • Profound effect on stretch-shortening exercise performance (running vs. swimming)

T/T athletes in endurance sports are at much higher risk of OTS.

ACE – gene for endurance

ACE codes for angiotensin converting enzyme, which affects blood vessel contractility and electrolyte balance.  The G allele is the normal allele while the A allele is variant and, in this case, actually confers benefit in terms of endurance exercise.

A-allele associated with:

  • Lower ACE activity
  • Better with endurance, especially at altitude
  • Lower muscle capillary density
  • Increased CK with eccentric exercise
  • Greater susceptibility to muscle damage

These individuals will be more prone to injury and OTS with explosive strength-dominant exercise, while those with the G allele will be at risk with endurance exercise.


IL-6 is an inflammatory cytokine and an individual’s SNP coding will have a profound impact on exercise tolerance, injury and OTS.

G-allele associated with:

  • Faster recovery and muscle repair
  • Reduced fatigue post exercise
  • Reduced injury risk post eccentric exercise (lower CK)
  • Better with power sports/HIIT
  • Lower VO2 max
  • Increased risk of D2M
  • Increased cardiovascular disease, especially when performing the wrong kind of exercise.
  • Increased susceptibility to over training syndrome.


The gene coding for the cytokine tumour necrosis factor alpha has a significant influence on inflammation and impacts musculoskeletal injury, recovery and ultimately the likelihood of OTS.  There is a strong association with tendinopathy.

A-allele associated with:

  • Increased expression of TNFa.
  • Higher CRP post exercise
  • Reduced repair and regeneration after muscle injury
  • Impaired response to physical activity in older individuals
  • Increased inflammatory conditions – tendinopathies, arthritis, allergies, bowel inflammation and heart disease.
  • Increased risk of OTS

Nutrition and metabolic genes

There are innumerable genes affecting the absorption and metabolism of proteins, fats and carbohydrates.  They interact extensively making interpretation difficult.  However, accurate analysis is essential when providing dietary advice to athletes in terms of adequate nutrition (a keystone for OTS), managing weight and controlling inflammation.

  • FTO – gene that determines the required amount of protein/meal.
    • Normal (T)– require the least amount of protein – excess will increase inflammation.
    • Variant (A) – require the highest amount of protein – insufficient intake prevents healing and increases weight gain.
  • TCF7L2 – a gene that responds to carbohydrates via inflammation and insulin.
    • Normal (C) – produce less insulin and cytokines for the same carb content. Handle carbs well and need to incorporate them into their diet.
    • Variant (T) – produce a great deal of insulin and cytokines for the same carb.   Need to limit carb intake.
  • APOA2 – a gene that determines the body’s response to saturated fats.
    • Normal (A) – decreased inflammation and weight gain with saturated fats.  Handle fats well.
    • Variant (G) – increased inflammation and weight gain with saturated fats. Need to limit them in their diet.

The above examples serve to illustrate how genetic SNP information can be a useful part of the prevention and treatment of OTS.  It’s use has been valuable performance tool in high level athletes for many years but the increasing availability of home kits such as 23andMe means the science is now accessible by everyone.  Unfortunately, while the DNA SNP raw data produced by such companies is extensive, the interpretation and application of the data into useable recommendations remains limited. is one of the few on-line data-analysis platforms that interprets and integrates raw data into a practical and useable format.

Case Report

Cameron is a 25-year-old competitive middle-distance runner who has completed a vigorous off-season schedule and pre-event training camp.  He has adopted a low-carbohydrate Keto-type diet hoping to improve energy and performance.  Unfortunately, he begins to experience fatigue and poor performance, increasing muscle pain and Achilles tendonitis, insomnia, irritability and recurrent colds.  All consistent with OTS.

SNP analysis:

  • ACTN3– C/T – better with middle distance
  • ACE– G/G – Better with longer distances
  • IL6–G/G – Increased inflammation and OTS risk
  • TNF – A/G – Slight increase in inflammation
  • MMP3– G/G – increased collagenases, tendinopathies
  • TCF7L2 – C/C good control with carbohydrates
  • APOA2 – A/G – increased inflammation and weight with saturated fats


  • Reduce training by 70%, stop high-intensity and competition (10-12 weeks)
  • Increase carbohydrates and hydration
  • Reduce saturated fats (<28g/day)
  • Bodywork, relaxation, cross-training
  • Ice, K-tape, heel-raise
  • Consider sports psychologist

After 10-12 weeks re-start training

  • Less sprints and more endurance (modified intervals)
  • Lower weight, higher rep conditioning
  • Continue dietary changes
  • Performance monitoring (RPE/MAF)
  • Consider shift to longer distance is an on-line program that uses your raw 23andMe data to create a personalized report. It is accessible by your doctor, naturopath or other health professional, or by your personal trainer.