Chronic Fatigue

Fatigue is one of the most common presenting complaints in primary care and one of the most poorly served by the supplement industry, largely because the marketing promises energy while the actual problem is usually something specific and treatable. The clinically useful distinction is between tiredness, which improves with rest, and fatigue, which does not. Ordinary tiredness from a busy week resolves with a weekend. Fatigue that persists through adequate sleep, that is disproportionate to exertion, or that comes with new symptoms is a different phenomenon and worth working up. The differential is broad but front-loaded. Iron deficiency, with or without anaemia, is the single most common findable cause, particularly in menstruating women, and ferritin below 30 ug/L can cause fatigue with a completely normal haemoglobin. Hypothyroidism, obstructive sleep apnoea, depression, coeliac disease, vitamin B12 deficiency, poorly controlled diabetes and medication side effects — beta blockers, antihistamines, statins, antidepressants — make up most of the rest. A distinct condition, myalgic encephalomyelitis or chronic fatigue syndrome, involves at least six months of disabling fatigue, unrefreshing sleep, cognitive difficulty and, critically, post-exertional malaise: a disproportionate worsening of symptoms twelve to forty-eight hours after activity. That last feature is the diagnostic hallmark and matters enormously for management, because graded exercise can make it worse rather than better. Nutritional causes exist but are further down the list than supplement marketing suggests. Correcting a deficiency helps; supplementing an adequate level does not.

• •Exhaustion that is not relieved by sleep
• •Waking unrefreshed regardless of hours slept
• •Post-exertional worsening 12-48 hours after activity
• •Difficulty concentrating or word-finding
• •Muscle weakness or heaviness
• •Reduced tolerance for previously routine activity
• •Unrefreshing sleep alongside daytime sleepiness
• •Low mood or loss of motivation

• •Iron deficiency, with or without anaemia
• •Hypothyroidism
• •Obstructive sleep apnoea
• •Depression and anxiety disorders
• •Vitamin B12 or folate deficiency
• •Coeliac disease
• •Poorly controlled type 2 diabetes
• •Chronic kidney or liver disease
• •Medication effects including beta blockers, antihistamines and some antidepressants
• •Post-viral fatigue, including after COVID-19
• •Myalgic encephalomyelitis / chronic fatigue syndrome
• •Chronic insufficient sleep or shift work

Fatigue is a symptom, not a diagnosis, and the productive approach is systematic exclusion rather than symptomatic supplementation. The highest-yield explanations cluster in a few areas: oxygen and substrate delivery (iron deficiency, anaemia, hypothyroidism), sleep quality (apnoea, insomnia, shift work), mood (depression is a leading cause and frequently missed because patients present with tiredness rather than sadness), and iatrogenic effects from prescribed medication. Post-viral fatigue deserves separate mention. A substantial minority of people report persistent fatigue after infections including Epstein-Barr virus, influenza and SARS-CoV-2, and in some this evolves into ME/CFS. Where post-exertional malaise is present, the management priority shifts from building activity back up to pacing within an energy envelope, because pushing through reliably worsens the trajectory. Where no cause is found after a reasonable workup — which happens in a meaningful proportion of cases — the answer is not to keep testing indefinitely but to address sleep, activity pacing, mood and nutrition systematically.