A Clinical Guide to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Author: Min Geraets | BNatMed | Naturopath & Medical Herbalist

Few conditions may test the clinical skills of practitioners as comprehensively as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).  Clients often present after years of consultations, multiple investigations and unsuccessful therapeutic strategies.  Many report feeling dismissed or misunderstood, while practitioners may find themselves navigating a condition with no definitive biomarker, no universally effective treatment and considerable clinical heterogeneity.

Over the past two decades, understanding of ME/CFS has shifted from a predominantly psychosocial model to recognising it as a complex, multisystem biomedical disease. During the 2000s and early 2010s, clinical management was strongly influenced by the biopsychosocial model and the 2011 PACE trial, which reported benefits from cognitive behavioural therapy (CBT) and graded exercise therapy (GET).  Although the 2011 PACE trial strongly influenced clinical practice by supporting CBT and GET, subsequent methodological criticisms and a growing body of evidence demonstrating immune, neurological, autonomic, and metabolic abnormalities have led to a fundamental change in the field’s understanding of ME/CFS.¹  This shift is reflected in the 2021 NICE guidelines, which no longer recommend GET and instead advocate personalised energy management (pacing), with CBT recommended only as supportive therapy rather than a treatment for the underlying disease.

The Covid-19 pandemic has accelerated research into these mechanisms.  A significant proportion of individuals with persistent post-viral symptoms fulfil diagnostic criteria for ME/CFS.  This provides impetus for understanding the biology of post-infectious illness and highlights shared pathways involving chronic inflammation, endothelial dysfunction, mitochondrial impairment and autonomic instability.

Why ME/CFS matters in clinical practice 

According to global epidemiological data, ME/CFS is estimated to affect 0.89% of the world’s population, with 1.5 to 2 times higher prevalence in women than in men.²  It is primarily diagnosed in people between 40 and 60 years of age.  However, the condition may develop in adolescence or later in life and increasing recognition has highlighted its impact across diverse populations.³⁴

The burden of disease extends well beyond fatigue.  Many individuals experience profound reductions in their ability to work, study, uphold family responsibilities and socialise.  The levels of disability associated with ME/CFS have been compared to multiple sclerosis, congestive heart failure and advanced kidney disease.  For some, the illness is mild and compatible with modified employment or study, while others may become housebound or bedbound.⁴

Understanding the pathophysiology

ME/CFS is best understood as a disorder of interconnected physiological systems rather than isolated organ pathology.  No single mechanism explains every case, and it is likely that multiple disease subtypes exist.  Current evidence suggests a convergence of neuro-immune-endocrine interactions, metabolic changes and genetic factors, often triggered by infection in genetically or environmentally susceptible individuals.³

The post-infectious model

Up to 80% of individuals with ME/CFS report the onset of symptoms following an acute infectious illness, often viral.  Epstein-Barr virus and other herpesviruses (HHV-6, HHV-7), cytomegalovirus, enterovirus and coronavirus infections including SARS-CoV-2, have all been implicated as potential triggers.⁴  Notably, most people recover uneventfully from these infections, suggesting that susceptibility to persistent illness depends on host factors rather than the infecting organism alone.  

The proposed mechanistic framework behind the post-infectious model suggests that an acute infection initiates persistent immune danger signalling that prevents normal recovery and maintains a chronic state of immune activation.  This sustained signalling is believed to facilitate mitochondrial and metabolic reprogramming, endothelial dysfunction, autonomic dysregulation and impaired physiological adaptability.⁵  This leaves individuals vulnerable to symptom exacerbation following minor physical or cognitive demands.

Clinical insight

A history of the Epstein-Barr virus and other herpesviruses (HHV-6, HHV-7), cytomegalovirus, enterovirus and coronavirus infections should prompt enquiry regarding the onset and progression of fatigue.  A distinct post-infectious onset often strengthens clinical suspicion of ME/CFS.

Neuroimmune dysregulation

Immune abnormalities represent one of the most consistently observed findings in ME/CFS, although no single laboratory marker has sufficient diagnostic accuracy for routine clinical use.

Reported changes include:

·         Reduced natural killer (NK) cell cytotoxicity

·         Altered T-cell activation

·         Increased pro-inflammatory cytokines

·         Impaired antiviral responses

·         Reduced antioxidant levels

·         Evidence of chronic immune activation.⁶

These finding may help explain the characteristic ‘flu-like’ malaise reported by many with ME/CFS, particularly during periods of symptom exacerbation.

Mitochondrial dysfunction and impaired energy metabolism

One of the most compelling developments in ME/CFS research is the growing evidence for altered cellular bioenergetics.  Metabolomic studies have identified a reduced capacity for oxidative phosphorylation, altered fatty acid metabolism and impaired adenosine triphosphate (ATP) generation.  This limits cellular energy availability and contributes to the profound fatigue and reduced exercise tolerance that characterise the disease.  Rather than a complete failure of mitochondrial function, these changes appear to reflect reduced metabolic flexibility; the ability to adapt efficiently to increased energy demand.⁷

This evidence provides a plausible explanation for post-exertional malaise (PEM).  Activities that would normally require a modest increase in ATP production may exceed the individual’s metabolic capacity, resulting in delayed symptom exacerbation and prolonged recovery.  Although further research is needed to determine whether mitochondrial dysfunction is a primary cause or a downstream consequence of the disease, current findings support its important role in the pathophysiology of ME/CFS.

Clinical insight

Clients may often describe a delay of 12-48 hours between activity and deterioration.  Asking “What happens the day after you overexert yourself?” is often more informative than asking whether exercise makes them tired.

Autonomic nervous system dysfunction

Orthostatic intolerance is increasingly recognised as a key feature of ME/CFS.  Common manifestations include:

·         Dizziness on standing

·         Palpitations

·         Tachycardia

·         Exercise intolerance

·         Temperature dysregulation

·         Nausea

·         Cognitive impairment that improves on lying down.⁴

Other disorders of autonomic function such as postural orthostatic tachycardia syndrome (POTS) and mast-cell activation syndrome (MCAS) are common comorbidities.⁴

Clinical insight

Routine assessment of orthostatic symptoms and measurement of supine and standing heart rate and blood pressure can provide valuable clinical information and identify clients who may benefit from further evaluation.

Neuroinflammation

Functional neuroimaging studies have identified altered cerebral blood flow and evidence suggestive of neuroinflammation in people with ME/CFS.  Activation of glial cells, specifically microglia and astrocytes, has been proposed as a key mechanism linking peripheral immune activation with fatigue, cognitive impairment and sensory hypersensitivity.⁶

Cognitive dysfunction in ME/CFS may result from cytokines released during immune activation.  Pro-inflammatory cytokines are known to contribute to fatigue, cognitive impairment and mood disturbances.  For example, elevated peripheral levels of IL-6 have been shown to exert profound effects on mood, cognition and behaviour in human and animal models.⁸

Although the mechanisms underlying neuroinflammation in ME/CFS are unclear, evidence suggests a positive feedback loop between systemic inflammation and neuronal overactivation.  People with ME/CFS often need to exert significant effort to perform daily activities.  This increased neural activation may promote pro-inflammatory cytokine release, reactive oxidative species and nitrogen species, further amplifying neuroinflammation and symptom severity.⁸

Many people with ME/CFS also report heightened sensitivity to light, sound, odours, and medications.⁸  These symptoms are consistent with altered central nervous system processing rather than pathology confined to individual sensory organs.

HPA axis and stress physiology

Emerging evidence suggests dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis contributes to the pathogenesis of ME/CFS through an altered neuroendocrine stress response.  Studies indicate hypofunction of the HPA axis characterised by low circulating cortisol levels, reduced cortisol output and diminished responsiveness to physiological stressors are among the most consistently replicated biological abnormalities in ME/CFS.⁶ Unlike primary adrenal insufficiency, these changes appear to reflect altered regulation rather than irreversible glandular dysfunction.

Recognising the clinical picture

ME/CFS encompasses far more than persistent fatigue.  Individuals typically present with a collection of symptoms affecting multiple organ systems, and symptom severity often fluctuates over time.

Core diagnostic features

·         Persistent, unexplained fatigue lasting more than six months

·         PEM

·         Unrefreshing sleep

·         Orthostatic intolerance

·         Cognitive impairment

·         Significant reduction in pre-illness functioning.⁴

Frequently associated symptoms

Neurological

·         Cognitive slowing

·         Difficulty with word retrieval

·         Impaired concentration and attention span

·         Short-term and working memory impairment

·         Inability to multitask

·         Headaches

·         Sleep disturbance; insomnia, unrefreshing sleep

·         Sensory hypersensitivity.^3,6

Musculoskeletal

·         Muscle pain

·         Joint pain without inflammatory arthritis

·         Muscle weakness

·         Delayed recovery following activity.⁶

Autonomic

·         Orthostatic intolerance

·         Palpitations

·         Cold extremities

·         Heat intolerance

·         Slow digestion.^3,6

Immune

·         Recurrent sore throat

·         Tender cervical lymph nodes

·         Flu-like malaise

·         Susceptibility to viral infections

·         New sensitivities to food or medications.^3,6

Gastrointestinal

·         Nausea

·         Bloating

·         Irritable bowel symptoms.³

Individuals with ME/CFS may also experience anxiety or low mood, although these are generally secondary to living with a chronic disabling illness rather than the primary cause of symptoms.

Post-exertional malaise: The hallmark feature

Among all clinical features of ME/CFS, PEM is the most distinctive and clinically useful.  PEM refers to a disproportionate worsening of symptoms following physical, cognitive, emotional or sensory exertion that would previously have been well tolerated.  Importantly, deterioration is often delayed by 12-48 hours and may persist for prolonged periods.⁴

Symptoms commonly aggravated during PEM include:

·         Energy: Profound exhaustion

·         Sensory: Heightened sensitivity to light, sounds, smell or temperature

·         Autonomic: Nausea, vertigo, dizziness, increased sighing and yawning, drop in core temperature, palpitations

·         Cognitive: Inability to process and retrieve words, trouble starting and changing tasks, thinking is effortful

·         Pain: Headache, aches, pains, pain where the skull meets the spine

·         Neuromuscular: Non-responsive muscles, painful muscles, feeling ‘heavy’

·         Metabolism: Feeling ‘poisoned or hungover’

·         Immune: Fever, sore throat, swollen lymph nodes.⁴

Recognition of PEM has transformed clinical management.  Earlier recommendations encouraging graded increases in exercises are no longer routinely advised for ME/CFS because they may exacerbate symptoms in individuals experiencing PEM.  Instead, contemporary guidelines advocate activity pacing, whereby individuals are advised to remain within their individual ‘energy envelope’ to reduce the frequency and severity of crashes.⁹

Assessment and diagnosis

A comprehensive clinical assessment should seek to confirm the characteristic symptom pattern, identify potential triggers, exclude alternative diagnoses and evaluate factors that may influence management.

Case history

Key questions include:

·         Was onset sudden or gradual?

·         Did symptoms begin after an infection, surgery or significant stressor?

·         What activities reliably trigger symptom worsening?

·         How long does recovery take?

·         What is the impact on work, study and daily activities?

·         Are there symptoms of orthostatic intolerance?

·         How restorative is sleep?

·         Are gastrointestinal symptoms present?

·         Has the client developed new food or chemical sensitivities?

·         What treatments have already been tried?

A detailed timeline is often invaluable, helping both practitioner and client identify patterns that may otherwise be overlooked.

Physical examination

Although examination findings may be subtle, assessment should include:

·         Vital signs, including orthostatic heart rate and blood pressure

·         General nutritional status

·         Thyroid examination

·         Lymph node assessment

·         Neurological assessment

·         Joint hypermobility where clinically indicated

·         Musculoskeletal examination

·         Cardiovascular assessment.

Findings inconsistent with ME/CFS—such as focal neurological deficits, inflammatory arthritis or significant weight loss—should prompt further investigation.

Differential diagnosis

ME/CFS remains a clinical diagnosis, but alternative causes of chronic fatigue must be considered.  Common differentials include:

·         Endocrine disorders (hypothyroidism, adrenal insufficiency, diabetes)

·         Nutritional deficiencies (iron, vitamin B12, folate)

·         Autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus, Multiple Sclerosis)

·         Lyme disease

·         Fibromyalgia

·         Sleep apnoea  

·         Respiratory disorders (chronic obstructive pulmonary disease, sarcoidosis)

·         Medication-induced fatigue

·         Neurological disorders (dementia, Parkinson’s disease, epilepsy)

·         Primary psychiatric illness.³

Importantly, the presence of depression or anxiety does not exclude ME/CFS, and these conditions frequently coexist.  The distinguishing feature remains PEM and the characteristic pattern of symptom exacerbation following activity.³

Recommended baseline investigations

Baseline investigations help exclude other conditions and identify modifiable contributors to fatigue.  Suggested tests include:

·         Full blood count

·         Comprehensive metabolic panel

·         Iron studies (including ferritin)

·         Vitamin B12 and folate

·         Vitamin D

·         Thyroid function tests

·         ESR and/or CRP

·         Cortisol

·         Liver and renal function

·         Coeliac serology where indicated.⁴

Herbal medicine in ME/CFS: A systems-based approach

The heterogeneity of ME/CFS means there is no single ‘best herb’ or universal protocol. Successful prescribing relies on identifying the dominant physiological disturbances in each client and selecting herbs that address these patterns.

Rather than targeting fatigue alone, herbal interventions should aim to:

·         Improve stress adaptation and recovery

·         Support mitochondrial energy production

·         Modulate immune function

·         Reduce oxidative stress and neuroinflammation

·         Improve sleep quality and restorative rest

·         Support autonomic nervous system regulation

·         Enhance cognitive function

·         Improve gastrointestinal integrity where relevant.

Clinical insight

People with ME/CFS commonly report sensitivity to medications, supplements and herbal medicines.  This heightened responsiveness may reflect altered autonomic regulation, central sensitisation or changes in hepatic metabolism.  Consider recommending one-quarter to one-half of the usual starting dose and titrate gradually over several weeks.

Adaptogens

·         Ashwagandha (Withania somnifera) is one of the most extensively studied adaptogenic herbs.  Its actions are particularly relevant where ME/CFS is accompanied by poor stress tolerance, sleep disturbance, anxiety or features suggestive of HPA-axis dysregulation.  Experimental studies indicate its withanolides influence inflammatory signalling, oxidative stress, mitochondrial function and neuroplasticity.¹⁰  Clinical trials have also demonstrated improvements in perceived stress, sleep quality and fatigue, although robust studies in ME/CFS remain limited.¹¹

·         Rhodiola (Rhodiola rosea) often benefits clients whose predominant complaint is impaired mental performance rather than sleep disturbance.  Its constituents, including rosavins and salidroside, appear to influence mitochondrial efficiency, monoamine signalling and antioxidant defence mechanisms.¹²  Several clinical studies outside ME/CFS suggest improvements in mental fatigue, concentration and work performance during periods of stress.¹³  Rhodiola may feel activating for some clients and therefore beginning at a low dose may help assess tolerance before gradual titration.

·         Siberian ginseng (Eleutherococcus senticosus) functions as both an adaptogen and immunomodulator, enhancing resilience during prolonged illness.  It supports mitochondrial function, improves endurance and reduces stress-induced immune suppression.¹²  In the context of ME/CFS, Siberian ginseng is best viewed as supporting physiological adaptation rather than increasing activity levels.

Mitochondrial support

·         Cordyceps (Cordyceps militaris) has attracted increasing interest because of its potential effects on cellular energy metabolism, which are predominantly attributed to its constituent cordycepin.  Experimental studies suggest cordycepin may enhance ATP production, improve mitochondrial efficiency, reduce oxidative stress, improve oxygen utilisation and support exercise recovery.¹⁴  Unlike stimulant herbs, Cordyceps generally supports energy without producing abrupt increases in sympathetic activation, making it suitable for clients with autonomic instability.

Neurocognitive support

·         Bacopa (Bacopa monnieri) has demonstrated improvements in memory, information processing and cognitive performance by enhancing cholinergic neurotransmission.  It also modulates neuroinflammation and supports mitochondrial function, helping to reduce neuronal apoptosis while promoting cellular resistance.¹⁵  Given that cognitive dysfunction is among the most disabling features of ME/CFS, Bacopa’s neuroprotective properties make it a valuable adjunct for clients experiencing brain fog.

·         Ginkgo (Ginkgo biloba) has been shown to support cerebral blood flow, endothelial function, antioxidant activity and microcirculation.¹⁶  Reduced cerebral perfusion has been proposed as one contributing factor to the cognitive dysfunction experienced in ME/CFS.  Clients whose cognitive symptoms worsen while standing or improve when supine may be particularly likely to benefit from Ginkgo.

Immunomodulators

·         Astragalus (Astragalus membranaceus) has a long history of traditional use during convalescence following infectious illness.  Modern clinical studies indicate effects on innate and adaptive immunity, inflammatory signalling and antioxidant pathways.  Its polysaccharides have also demonstrated significant anti-fatigue activity by modulating the composition of gut microbiota and increasing the production of short-chain fatty acids (SCFAs), particularly butyrate.  Butyrate can further regulate oxidative stress and neuroinflammation, contributing to Astragalus’s therapeutic role in ME/CFS.¹⁷  Supporting these findings, a clinical study in nurses experiencing post-Covid-19 CFS found that Astragalus root extract (500 mg 2x/day) significantly reduced chronic fatigue symptoms.¹⁸

·         Echinacea (Echinacea spp.) remains one of the most versatile immunomodulators in Western herbal medicine.  It exerts context-dependent immunomodulatory effects by downregulating pro-inflammatory mediators (TNF- α and IL-6) during states of hyperinflammation, while maintaining or enhancing innate surveillance mechanisms (such as phagocytosis) to protect against infection.¹⁹  Echinacea’s immunomodulatory effects make it particularly relevant for ME/CFS secondary to immune dysregulation.

·         Reishi (Ganoderma lucidum) occupies a unique position with ME/CFS management due to its broad actions across immune regulation, sleep quality, anxiety and inflammation.  Its polysaccharides (β-D-glucans) demonstrate immunomodulatory effects by stimulating IL-1, TNF-α, NK cells and T-lymphocytes, thereby enhancing protection against recurrent infections and helping to regulate chronic immune dysregulation.  Additionally, a clinical study in individuals with CFS found that Reishi extract (2 g/day) reduced fatigue and improved quality of life.  The study also reported an increase in serum cortisol levels toward the normal range, suggesting a regulating effect on the HPA axis.²⁰

Inflammation and oxidative stress

·         Baical skullcap (Scutellaria baicalensis) contains flavonoids including baicalin and baicalein, which have demonstrated significant effects on inflammatory signalling and oxidative stress pathways.¹²  Its relevance to ME/CFS lies particularly in presentations characterised by neuroinflammatory symptoms, sensory hypersensitivity, headaches and cognitive dysfunction.

·         Kawakawa (Macropiper excelsum) is widely recognised for its anti-inflammatory properties.  Experimental studies have demonstrated inhibition of inflammatory mediators and reductions in oxidative stress pathways.  Several of its constituents, including myristicin, piperine and isovetexin, exhibit cyclooxygenase-modulating, antioxidant and cytokine-regulating effects in both in vitro and animal studies.²¹  Additionally, although Kawakawa is not traditionally classified as an adaptogen, many practitioners report using it in clinical practice to improve energy levels and reduce fatigue, suggesting additional benefit for ME/CFS management.

·         Turmeric (Curcuma longa) contains curcuminoids that influence several inflammatory pathways relevant to ME/CFS including NF-κB signalling, cyclooxygenase and lipoxygenase pathways, oxidative stress regulation and inflammatory cytokine expression.²²  While direct clinical trials in ME/CFS remain limited, Turmeric may be useful where muscle pain, joint pain, headaches and metabolic dysfunction are prominent.

Nervine support and sleep restoration

·         Green oats (Avena sativa) are particularly suited to clients experiencing nervous system depletion following prolonged stress, illness or emotional strain.¹²  Green oats are a useful foundational nervine in ME/CFS formulations because it is generally well tolerated by highly sensitive presentations.

·         Lemon balm (Melissa officinalis) may be particularly useful where ME/CFS includes anxiety, gastrointestinal symptoms, sleep disruption and post-viral recovery.  Its effects on GABAergic signalling may contribute to its calming and sleep-supportive actions.¹²

·         Passionflower (Passiflora incarnata) may support clients experiencing sympathetic nervous system dominance characterised by racing thoughts, difficulty winding down, nocturnal anxiety and sleep disruption.¹²

·         Skullcap (Scutellaria lateriflora) may be useful for ME/CFS clients experiencing muscle tension, sensory overload, sleep disturbance and hyperarousal of the nervous system.¹²

Autonomic dysfunction and orthostatic intolerance

·         Korean ginseng (Panax ginseng) may support physical endurance, cognition and immune resilience.  These effects are predominantly attributed to steroidal saponins, particularly ginsenosides, which have a corticosteroid-like action and inhibit re-uptake of several neurotransmitters (GABA, norepinephrine, dopamine, glutamate and serotonin).¹²  It is well-suited for convalescence, low motivation, physical weakness and older clients with reduced vitality. 

·         Liquorice (Glycyrrhiza glabra) may be particularly beneficial for clients with low blood pressure, poor stress tolerance, orthostatic symptoms and fatigue.  Its effects are partly attributed to inhibition of cortisol metabolism, leading to a subsequent increase in cortisol availability.¹²

Monitoring response to herbal therapy

Improvement in ME/CFS rarely follows a linear trajectory.  Rather than asking whether fatigue has disappeared, more meaningful questions include:

·         Is recovery after activity becoming faster?

·         Are PEM episodes less frequent?

·         Is cognitive clarity improving?

·         Is sleep more restorative?

·         Has orthostatic tolerance improved?

·         Is the client able to undertake slightly more activity without crashing?

Nutritional supplementation in ME/CFS

·         Coenzyme Q10 (100 – 300 mg/day) – Also known as ubiquinone, CoQ10 plays an essential role in mitochondrial electron transport and ATP generation.  It also functions as an intracellular antioxidant and is important for the health of all tissues and organs, particularly the heart.  A small clinical study in people with ME/CFS found that supplementation with CoQ10 (200 mg/day) combined with nicotinamide adenine dinucleotide (NADH; 20 mg/day) reduced cognitive fatigue and improved quality of life.²³  As the study evaluated the combination of both supplements, it is not possible to determine whether the observed benefits were due to CoQ10, NADH, or their combined effects.  The short duration of the study also means that the long-term sustainability of these benefits remains uncertain.

·         NADH (10 mg/day) – NADH is a coenzyme that plays a key role in cellular energy metabolism.  It helps replenish depleted ATP stores and participates in essential redox reactions involved in energy production.  A small clinical study in people with CFS found 10 mg/day of NADH produced a favourable response in approximately 31% of participants.²⁴  Another clinical study reported a 42% reduction in CFS symptoms following supplementation with 5-10 mg/day of NADH over 24 months.²⁵ 

·         Acetyl-l-carnitine (2000 mg/day) – Supports fatty acid transportation into mitochondria to produce cellular energy.  It can also cross the blood-brain barrier where it provides antioxidant and neuroprotective properties, helping improve cognition and memory.  A clinical study in people with CFS supplementing with acetyl-l-carnitine 2000 mg/day for 6 months improved general fatigue in up to 59% of participants.²⁶

·         D-ribose (5000 mg/day) – D-ribose is a naturally occurring pentose carbohydrate that serves as a direct substrate for several metabolic pathways essential to mitochondrial function and the maintenance of cellular energy homeostasis.  Clinical studies evaluating D-ribose supplementation (5000 mg/3x day) in people with CFS have demonstrated significant improvements in energy levels, sleep quality, mental clarity, pain intensity and overall well-being.^27,28

Clinical insight

As an ME/CFS diagnosis is defined by the absence of other medical conditions, fatigue resulting from iron, folate or vitamin B12 deficiency is not considered part of the condition.²⁹  There is currently no evidence that deficiencies in these nutrients are involved in the pathophysiology of ME/CFS.³⁰  Consequently, supplementation with iron, folate or vitamin B12 is unlikely to benefit people with ME/CFS unless a separate deficiency has been identified.

Dietary strategies in ME/CFS

Currently, there is no specific recommended dietary intervention for ME/CFS.⁹  The most accepted ‘best practice’ diet that lays the foundation for recovery in ME/CFS is one that is balanced and has a variety of foods and macro-and micro-nutrients.  The following structure provides a general guide for supporting nutrition in those with MF/CFS:

1.      Assess current nutritional intake – A thorough assessment of the client's current dietary intake provides the foundation for any nutritional intervention.  Begin by evaluating whether they are consuming sufficient energy, protein, healthy fats and carbohydrates to meet their individual needs.  Many people with ME/CFS experience reduced appetite, difficulties preparing meals, food sensitivities, or gastrointestinal symptoms that can inadvertently lead to inadequate nutritional intake.³¹  Identifying these barriers early allows you to develop practical, realistic strategies that fit within the client's available energy envelope.

2.      Identify micronutrient gaps – Once overall dietary adequacy has been established, assess micronutrient intake and identify potential nutritional gaps.  Where possible, prioritise food-first strategies to improve nutrient status, reserving supplementation for situations where dietary intake is insufficient, deficiencies are identified, or clinical circumstances warrant additional support.³¹  This approach encourages long-term dietary improvements while avoiding unnecessary supplementation.

3.      Support sustained energy throughout the day – Rather than focusing on restrictive or highly prescriptive diets, encourage clients to establish regular eating patterns that help maintain stable energy availability throughout the day.  Long periods without eating may contribute to fluctuations in blood glucose and leave some individuals feeling more fatigued.  Small, balanced meals and snacks that combine protein, complex carbohydrates and healthy fats are often better tolerated than large meals, particularly for clients experiencing post-prandial fatigue or digestive discomfort.³¹

4.      Consider gastrointestinal disturbances – Given the high prevalence of gastrointestinal symptoms in ME/CFS, it is worthwhile screening for co-existing digestive conditions such as irritable bowel syndrome, gastro-oesophageal reflux, food intolerances or coeliac disease where clinically indicated.  Addressing these conditions may improve gastrointestinal comfort, nutritional intake and overall wellbeing.  However, restrictive elimination diets should only be implemented when there is a clear clinical rationale, as unnecessary dietary restriction can increase the risk of malnutrition and add to the burden of managing a chronic illness.³¹

5.      Implement changes gradually – As practitioners, it can be tempting to explore multiple dietary interventions in search of symptom improvement.  However, clients with ME/CFS often have limited physical, cognitive and emotional resources.  Introducing dietary changes gradually and prioritising interventions with the greatest potential benefit can improve adherence while minimising additional stress.  

Pacing: The lifestyle foundation of ME/CFS management

Pacing is one of the most important management strategies for preventing deterioration.  It aims to balance activity and recovery so the person with ME/CFS remains within their available energy capacity.  Pacing requires individuals with ME/CFS to determine the level at which they can function, which does not lead to a marked increase in fatigue and other symptoms.³²

Understanding the energy envelope

Every person with ME/CFS has a variable physiological limit.  Exceeding this limit may result in delayed symptom worsening, prolonged recovery and reduced baseline function.³²

The energy envelope theory suggests that people with ME/CFS should aim to moderate, not increase or decrease their activity levels while practising energy conservation.³¹  A successful pacing strategy helps clients recognise early warning signs, energy expenditure patterns and activities most likely to trigger PEM.³²

Practical pacing strategies

·         Activity monitoring – People with ME/CFS may benefit tracking physical activity, cognitive demands, socialisation, emotional stressors and symptom changes.  Keeping a diary or log can identify personal limits or triggers that may not be obvious during daily life.³²

·         Avoid the ‘push and crash’ cycle – Breaking this cycle is often the first therapeutic goal.  This cycle involves feeling slight improvement, increasing activity substantially, experiencing PEM, requiring prolonged rest and experiencing a decline in baseline function.  The primary method to avoid this cycle is not overdoing activity on good days.³²

·         Cognitive pacing – Mental exertion can trigger PEM.  Important considerations include computer use, reading, conversations, decision making and sensory stimulation.  Cognitive rest should be recognised as legitimate physiological rest.³¹

·         Activity-rest balancing – Alternate periods of activity with planned rest before symptoms worsen.³²

·         Prioritise and plan activities – Focus on essential tasks and spread activities across the day or week.³²

·         Adjust activity based on symptoms – Increase or decrease activity according to day-to-day symptom severity rather than following a fixed exercise progression. ³²

Autonomic dysfunction and POTS

Autonomic dysfunction requires specific attention.  Clinical features suggesting orthostatic intolerance include:

·         Symptoms worse on standing

·         Improvement lying down

·         Rapid heart rate increase on standing

·         Dizziness

·         Faintness

·         Temperature regulation issues.³³

Supportive strategies include:

·         Hydration – Aim for 2-3 L of fluid daily.³⁴  Adequate hydration is vital for keeping blood volume high, which helps maintain healthy blood pressure.

·         Salt supplementation – An additional 6-10 g of salt daily is recommended for individuals with orthostatic intolerance.³⁴  Sodium helps the body retain water, which increases blood volume, improves blood circulation and helps maintain healthy blood pressure.

·         Compression – Compression garments may reduce venous pooling and improve orthostatic tolerance.³³

^·          Gentle vagus nerve stimulation – Humming, gargling, singing and massaging the outer ear are all effective methods for stimulating the vagus nerve.  Vagus nerve stimulation activates the parasympathetic nervous system, which supports autonomic regulation and may help improve POTS symptoms. ³⁵

Key takeaways

• ME/CFS is a complex, multisystem condition characterised by impaired energy production, neuroimmune dysregulation and autonomic dysfunction.
• Post-exertional malaise (PEM) is the hallmark clinical feature and distinguishes ME/CFS from most other causes of chronic fatigue.
• Current evidence supports a biopsychosocial model in which immune activation, mitochondrial dysfunction, autonomic imbalance and altered central nervous system signalling interact to perpetuate symptoms.
• Management should prioritise symptom stabilisation, prevention of PEM and restoration of function rather than aggressive attempts to increase activity.
• Herbal and nutritional medicines have an important role in supporting physiological resilience when prescribed as part of an individualised, multidisciplinary management plan.
• Sensitive clients often respond best to conservative herbal dosing that is carefully monitored.
• Recovery is usually gradual and measured through improved function rather than complete symptom resolution.

References

1.      Weir, W., & Speight, N. (2021). ME/CFS: Past, present and future. Healthcare, 9(8), 984. https://doi.org/10.3390/healthcare9080984

2.      Lim, E.-J., Ahn, Y.-C., Jang, E.-S., Lee, S.-W., Lee, S.-H., & Son, C.-G. (2020). Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Journal of Translational Medicine, 18(1). https://doi.org/10.1186/s12967-020-02269-0

3.      Graves, B. S., Patel, M., Newgent, H., Gauri Parvathy, Nasri, A., Moxam, J., Gill, G. S., Sawhney, V., & Gupta, M. (2024). Chronic fatigue syndrome: Diagnosis, treatment, and future direction. Cureus, 16(10). https://doi.org/10.7759/cureus.70616

4.      Grach, S. L., Seltzer, J., Chon, T. Y., & Ganesh, R. (2023). Diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome. Mayo Clinic Proceedings, 98(10), 1544–1551. https://doi.org/10.1016/j.mayocp.2023.07.032

5.      Watton, P., & Prusty, B. K. (2026). Reframing ME/CFS: Toward a unified mechanistic model of chronic post-infectious diseases. Journal of Translational Medicine, 24(1). https://doi.org/10.1186/s12967-026-08319-3

6.      Cortes Rivera, M., Mastronardi, C., Silva-Aldana, C., Arcos-Burgos, M., & Lidbury, B. (2019). Myalgic encephalomyelitis/chronic fatigue syndrome: A comprehensive review. Diagnostics, 9(3), 91. https://doi.org/10.3390/diagnostics9030091

7.      Missailidis, D., Annesley, S. J., & Fisher, P. R. (2019). Pathological mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome. Diagnostics, 9(3), 80. https://doi.org/10.3390/diagnostics9030080

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