Ashwagandha

• Adaptogen — HPA-axis and stress modulation. Ashwagandha (Withania somnifera) is classed as an adaptogen: compounds thought to help the body respond to stress by modulating the hypothalamic-pituitary-adrenal (HPA) axis and normalizing cortisol responses. Because dysregulated stress responses and elevated or blunted cortisol are implicated in fatigue syndromes, this mechanism plausibly reduces fatigue and improves energy. ScienceDirect
• Reduces perceived stress and improves sleep/energy. Randomized trials in stressed or fatigued adults report improvements in perceived stress, sleep quality and self-reported energy/fatigue scores after weeks of supplementation — effects that would be relevant to many CFS patients whose symptoms are worsened by poor sleep and chronic stress. SAGE Journals
• Anti-inflammatory & antioxidant effects. Ashwagandha contains withanolides and other constituents with anti-inflammatory and antioxidant activity; inflammation and oxidative stress are hypothesized contributors to CFS for some patients, so these properties provide an additional plausible pathway for benefit. ScienceDirect

Important caveat: Most clinical trials test people with generalized stress, fatigue, or poor sleep rather than strictly defined CFS populations. Direct, large-scale randomized trials specifically in patients meeting formal CFS diagnostic criteria are limited — so the biological rationale and the fatigue-reduction data are promising but not definitive proof for classic CFS. ScienceDirect

• Common clinical dosing range: Most randomized trials for stress/fatigue have used about 300–600 mg total daily of a standardized root extract (often 300 mg twice daily or 300 mg once daily) taken for 4–12 weeks. These doses are the best-supported range in clinical research for improving perceived stress and fatigue scores. Start at the lower end and assess tolerance. SAGE Journals
• Formulation: Use a standardized extract (marketed extracts include proprietary names such as the extracts used in clinical trials). Standardized root extracts ensure a measured content of withanolides; whole-root powder products vary more in potency. Clinical studies generally use standardized extracts rather than raw powder. SAGE Journals
• Timing & administration: Take with food if you experience GI upset. Some people take once daily (morning) for energy, others split the dose (morning + early evening). Because of possible mild sedative effects in some people, if you notice drowsiness start with the daytime dose or take in the evening if it helps sleep. Verywell Health
• Duration to expect effect: Trials commonly show measurable improvements over 4–8 weeks, with many protocols using 6–12 weeks for fuller benefit. If there is no improvement after about 8–12 weeks, re-evaluate with your clinician. SAGE Journals

Practical checklist before starting

• Discuss with your doctor (see warnings below).
• Confirm current medications (to check interactions).
• If pregnant, breastfeeding, autoimmune disease or on thyroid / diabetes / sedative drugs — discuss alternatives (contraindicated or caution with these groups). NCCIH

Systematic review / reviews

• Systematic review of ashwagandha trials (multiple outcomes including fatigue/stress). Reviews summarize many RCTs (tens of trials) showing benefit for stress, anxiety, sleep and fatigue metrics; these reviews note consistent positive signals but also heterogeneity in study quality and endpoints. ScienceDirect

Key randomized, placebo-controlled trials (examples)

• Journal of Psychopharmacology (2023) — randomized, double-blind, placebo-controlled trial of a standardized ashwagandha root extract (Witholytin®) in adults with high stress and fatigue showed reductions in perceived stress and fatigue vs placebo. This is a recent, well-designed trial supporting fatigue benefit in stressed adults. SAGE Journals
• Other RCTs of standardized extracts — multiple randomized trials have tested standardized root extracts (various proprietary extracts) and reported improvements in energy/fatigue scores, sleep quality and reduced cortisol at typical doses of 300–600 mg/day. (Examples and composites of these trials are discussed in nursing/clinical trial summaries and meta-analyses). Taylor & Francis Online

Clinical evidence specific to CFS

• Limited direct RCTs in strictly defined CFS cohorts. Some practitioner documents and small studies discuss use in CFS/fibromyalgia, and mechanistic/immunomodulatory data are supportive, but large, high-quality RCTs exclusively in CFS patients are sparse. That means evidence is stronger for general fatigue and stress than for CFS defined by formal diagnostic criteria. If you have classic CFS, the evidence is suggestive but not conclusive; clinical decisions should be individualized. collegeofmedicine.org.uk

Where to read the trials/reviews directly

• Trial/review pages and summaries (Journal of Psychopharmacology, ScienceDirect review, NCCIH summary) — see these for full trial methods and dosing. SAGE Journals