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Moderate Evidence

Promising research with growing clinical support from multiple studies

Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME)

Chronic Fatigue Syndrome, also called Myalgic Encephalomyelitis (CFS/ME), is a complex, multi-system condition characterized by profound fatigue that is not improved by rest and is worsened by exertion. A defining, cardinal feature is post-exertional malaise (PEM): a delayed worsening of symptoms—fatigue, cognitive dysfunction (“brain fog”), pain, sleep disturbance, autonomic and flu-like symptoms—after physical, cognitive, or emotional stress. Many patients experience orthostatic intolerance (e.g., POTS or neurally mediated hypotension), unrefreshing sleep, and cognitive impairment, among other symptoms. The illness exists on a spectrum of severity, from reduced activity to housebound or bedbound states. There is currently no single diagnostic test or disease-modifying cure; care focuses on accurate diagnosis, energy management (pacing), treating comorbidities, and mitigating symptom burden. Western frameworks emphasize standardized diagnostic criteria and symptom-based management, with growing recognition of immune, autonomic, and metabolic abnormalities. The Fukuda criteria (1994) historically informed research but underweighted PEM. The Canadian Consensus Criteria (2003) and the U.S. Institute of Medicine/National Academy of Medicine report (2015) elevated PEM as essential and reframed the condition (SEID—systemic exertion intolerance disease). In 2021, the UK’s NICE guideline NG206 recognized PEM as central, reversed prior endorsements of graded exercise therapy (GET), and advised against any program that pushes patients to increase activity beyond their energy envelope. Evidence for GET was driven largely by the PACE trial (2011), which later drew substantial methodological criticism and reanalysis indicating far more limited benefits than originally claimed. Current best practice centers on pacing—patient-led activity regulation to prevent PEM. Pharmacologic strategies are symptom-targeted. Sleep aids (e.g., low-dose tricyclics like amitriptyline or doxepin

Neurology Updated February 19, 2026

This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication regimen.

Western Medicine

Diagnosis

Clinical diagnosis based on exclusion of alternative causes and fulfillment of accepted criteria. Commonly referenced: Fukuda (1994); Canadian Consensus Criteria (Carruthers et al., 2003) emphasizing PEM, pain, sleep disturbance, and neurocognitive/immune/autonomic features; IOM/NAM 2015 SEID criteria highlighting PEM, unrefreshing sleep, cognitive impairment and/or orthostatic intolerance of at least 6 months’ duration. No definitive biomarker yet; evaluation often includes screening for anemia, thyroid, adrenal, liver/kidney dysfunction, sleep apnea, autoimmune disease, infections, and assessment for orthostatic intolerance.

Treatments

  • Pacing/energy envelope management to prevent post-exertional malaise
  • Education on PEM triggers; activity diaries and heart-rate/threshold monitoring to stay below anaerobic threshold
  • Sleep optimization: sleep hygiene, circadian anchoring, cautious use of sleep aids
  • Autonomic dysfunction management: fluids, salt, compression garments, recumbent positioning; graded recumbent, symptom-titrated conditioning only within envelope
  • Pain management: non-opioid analgesics; neuropathic pain agents (e.g., gabapentin, pregabalin, duloxetine)
  • Cognitive symptom supports (task simplification, structured rest, sensory load reduction)
  • CBT for coping/adjustment (not as a cure or to increase activity beyond envelope)
  • Address comorbidities (migraine, mast cell activation symptoms, IBS, mood disorders)
  • Nutritional support; treatment of deficiencies (e.g., B12 if low, vitamin D)
  • Assistive devices, workplace/school accommodations, disability support when needed

Medications

  • Low-dose naltrexone (off-label) for pain/inflammation (emerging evidence)
  • Sleep aids: low-dose amitriptyline/doxepin, trazodone, melatonin
  • Pain/neuropathic agents: gabapentin, pregabalin, duloxetine, low-dose TCAs
  • Orthostatic intolerance: fludrocortisone, midodrine, beta-blockers, ivabradine (off-label), pyridostigmine
  • Stimulants (modafinil, methylphenidate) in carefully selected cases; monitor for PEM exacerbation
  • Antivirals/immunomodulators (e.g., valganciclovir, immunoglobulins) in select contexts—evidence limited

Limitations

Heterogeneous patient populations and absence of a validated biomarker limit trial consistency. No disease-modifying therapy has proven efficacy. Interventions that increase exertion can precipitate PEM and clinical decline; protocols must be individualized and symptom-titrated. Evidence for many medications is low-to-moderate quality and off-label. Immune-targeted therapies like rituximab failed in phase III trials. Microbiome findings are inconsistent across studies and interventional data are preliminary.

Evidence: Moderate Evidence

Sources

  • Fukuda K et al. Ann Intern Med. 1994;121:953-959.
  • Carruthers BM et al. J Chronic Fatigue Syndr. 2003;11(1):7-115.
  • Institute of Medicine (NAM). Beyond ME/CFS: Redefining an Illness. 2015.
  • NICE Guideline NG206: Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome. 2021.
  • White PD et al. Lancet. 2011;377:823-836. (PACE trial)
  • Wilshire CE et al. BMC Psychol. 2018;6:6. (Reanalysis/critique of PACE)
  • Larun L et al. Cochrane Database Syst Rev. 2019;(10):CD003200. (Exercise therapy review, contested)
  • Fluge Ø et al. Ann Intern Med. 2019;170:585-593. (Rituximab phase III negative)
  • Giloteaux L et al. Microbiome. 2016;4:30. (Gut dysbiosis)

Eastern & Traditional Medicine

Traditional Chinese Medicine (TCM)

CFS/ME is often framed as qi and blood deficiency with involvement of Spleen (transforming/transporting), Lung (defensive qi), and Kidney (essence; yin/yang) systems. Overexertion, illness, and stress deplete qi and essence, leading to fatigue, cognitive fog, sleep disturbance, and increased susceptibility to illness. Treatment aims to tonify qi/blood, harmonize yin/yang, calm the shen, and gently restore function without provoking crashes (PEM).

Techniques

  • Acupuncture (body and auricular) with gentle protocols; electroacupuncture in select cases
  • Moxibustion and warming techniques for yang deficiency/Cold
  • Herbal formulas individualized to pattern, e.g., Bu Zhong Yi Qi Tang (qi tonification), Shi Quan Da Bu Tang (qi/blood), Liu Wei Di Huang Wan (Kidney yin), Jia Jian Xiao Yao San (Liver–Spleen disharmony)
  • Gentle qigong/taiji and breathing practices strictly within the energy envelope
Licensed acupuncturist (LAc) TCM herbalist Integrative physician with TCM training
Evidence: Emerging Research

Ayurveda (Rasayana/rejuvenation)

CFS/ME is interpreted as ojas depletion with vata aggravation (instability, insomnia, pain) and possible kapha involvement (heaviness, lethargy). Rasayana seeks to rebuild resilience, nourish tissues, improve digestion (agni), and calm the nervous system. Interventions emphasize restoration rather than exertion, aligning with pacing to avoid PEM.

Techniques

  • Rasayana botanicals: Withania somnifera (ashwagandha), Tinospora cordifolia (guduchi), Emblica officinalis (amla), Glycyrrhiza glabra (yashtimadhu)
  • Classical tonics such as chyawanprash (amla-based)
  • Gentle abhyanga (oil massage), shirodhara, yoga nidra, and pranayama within envelope
  • Dietary measures to support digestion and steady energy
Ayurvedic physician (BAMS/MD Ayurveda) Integrative clinician with Ayurvedic training
Evidence: Traditional Use

Adaptogenic herbal medicine (integrative/naturopathic)

Adaptogens are proposed to modulate stress-response systems (HPA axis, autonomic balance) and cellular energy pathways. In ME/CFS, they are used to support energy and resilience without forcing exertion. Evidence shows modest benefits for subjective fatigue and stress in heterogeneous populations; ME/CFS-specific data are limited.

Techniques

  • Ashwagandha root extract (standardized), typical 300–600 mg/day
  • Rhodiola rosea extract (e.g., SHR-5), 144–400 mg/day; avoid late dosing if activating
  • Eleutherococcus senticosus (Siberian ginseng), 300–1200 mg/day; monitor blood pressure and sleep
Naturopathic doctor (ND) Integrative/functional medicine physician Herbalist
Evidence: Moderate Evidence

Acupuncture (focused)

Applied to regulate autonomic function, improve sleep and pain, and reduce perceived fatigue. Protocols are typically low-intensity and individualized, with close monitoring for PEM.

Techniques

  • Manual acupuncture and electroacupuncture with conservative dosing
  • Ear acupuncture for autonomic modulation
  • Adjunct moxibustion for cold/yang deficiency patterns
Licensed acupuncturist (LAc) Medical acupuncturist
Evidence: Emerging Research

Sources

  • Zhang W et al. Acupunct Med. 2019;37:211-222. (Systematic review/meta-analysis, limited-quality trials)
  • Chen R et al. J Altern Complement Med. 2010;16:1211-1216. (Acupuncture RCTs—mixed quality)
  • Lee MS et al. Eur J Integr Med. 2011;3:e245-e252. (Herbal formula reviews; low–moderate quality)
  • Ng QX et al. Complement Ther Med. 2020;52:102456. (Ashwagandha for stress/anxiety; extrapolated to fatigue)
  • Rastogi S. J Ayurveda Integr Med. 2011;2:199-204. (Rasayana concepts; traditional evidence)
  • Ishaque S et al. BMC Complement Altern Med. 2012;12:70. (Rhodiola systematic review)
  • Panossian A, Wikman G. Phytomedicine. 2010;17:435-449. (Adaptogen mechanisms/review)
  • Davydov M, Krikorian AD. J Ethnopharmacol. 2000;72:345-393. (Eleutherococcus review)
  • Ng QX et al. Nutrients. 2020;12:2152. (Ashwagandha review)
  • Zhang W et al. Acupunct Med. 2019;37:211-222. (Systematic review/meta-analysis)
  • Kim JE et al. J Altern Complement Med. 2013;19:111-121. (Small RCTs—variable quality)

Integrative Perspective

Across both paradigms, pacing is paramount: avoid pushing through fatigue, as exceeding one’s energy envelope can trigger post-exertional malaise and prolonged setbacks. Start low and go slow with any intervention—physical therapy, breathwork, acupuncture, herbs, or medications—and titrate to tolerance. Favor recumbent or seated activities; prioritize rest and symptom-contingent activity rather than time-contingent progression. Screen and manage orthostatic intolerance early (fluids, salt, compression; medications when appropriate). Coordinate care across disciplines, and monitor for herb–drug interactions (e.g., rhodiola may be activating; ashwagandha may affect thyroid/autoimmunity; CoQ10 may interact with anticoagulants). Interventions aimed at “conditioning” should be symptom-guided and never force incremental increases that provoke PEM. Gentle mind–body work (qigong, pranayama, yoga nidra) can support regulation if kept within the envelope. Nutraceuticals like CoQ10 and NADH have small RCT signals in ME/CFS and broader fatigue literature; benefits are individualized.

Sources

  1. Fukuda K et al. Ann Intern Med. 1994;121:953-959.
  2. Carruthers BM et al. J Chronic Fatigue Syndr. 2003;11(1):7-115.
  3. Institute of Medicine (National Academy of Medicine). Beyond ME/CFS: Redefining an Illness. 2015.
  4. NICE Guideline NG206. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. 2021.
  5. White PD et al. Lancet. 2011;377:823-836. (PACE)
  6. Wilshire CE et al. BMC Psychol. 2018;6:6. (PACE reanalysis/critique)
  7. Larun L et al. Cochrane Database Syst Rev. 2019;(10):CD003200. (Exercise therapy—contested)
  8. Fluge Ø et al. Ann Intern Med. 2019;170:585-593. (Rituximab phase III negative)
  9. Giloteaux L et al. Microbiome. 2016;4:30. (Gut dysbiosis in ME/CFS)
  10. Castro-Marrero J et al. Nutrients. 2021;13:394. (Review of nutritional/interventional strategies)
  11. Castro-Marrero J et al. Antioxid Redox Signal. 2015;22:679-685. (CoQ10+NADH pilot RCT in CFS)
  12. Forsyth LM et al. Ann Allergy Asthma Immunol. 1999;82:185-191. (NADH RCT)
  13. Ishaque S et al. BMC Complement Altern Med. 2012;12:70. (Rhodiola review)
  14. Panossian A, Wikman G. Phytomedicine. 2010;17:435-449. (Adaptogens)
  15. Zhang W et al. Acupunct Med. 2019;37:211-222. (Acupuncture for CFS)

Health Disclaimer

This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication regimen.