Why am I always tired? Causes, biomarkers and what to test

Iron deficiency and low ferritin

Iron deficiency is the most commonly overlooked cause of persistent fatigue in otherwise healthy adults, particularly in women of reproductive age. The problem is frequently missed because standard blood counts can appear normal even when ferritin, the storage protein that reflects how much iron is actually available in reserve, has dropped significantly. A person can have iron deficiency without anaemia, with normal haemoglobin but depleted stores, and experience debilitating tiredness as a result. Testing ferritin specifically, not just a full blood count, is the key distinction.

Thyroid dysfunction

The thyroid regulates the metabolic rate of every cell in the body. When thyroid hormone production falls, whether from Hashimoto's thyroiditis, nutrient depletion, or other causes, the body essentially slows down. Fatigue, cold sensitivity, weight changes and brain fog are classic hypothyroid symptoms. Standard NHS testing measures TSH alone, which can appear borderline-normal even when active thyroid hormone (Free T3) is low. Comprehensive thyroid testing, including Free T4, Free T3 and thyroid antibodies, gives a more complete picture than the single-marker screen most people receive.

Vitamin deficiencies affecting cellular energy

Vitamin B12 is required for the production of myelin (the insulating sheath around nerve fibres) and for red blood cell formation. When B12 falls, nerve signalling slows and oxygen delivery to tissues becomes less efficient, producing the specific combination of fatigue, brain fog and mood changes that people often attribute to stress or ageing. Vitamin D influences immune regulation, muscle function and mood, with deficiency strongly associated with fatigue, particularly in winter months. Folate works alongside B12 in the methylation cycle, and deficiency in either can elevate homocysteine, a marker linked to impaired energy metabolism and increased cardiovascular risk.

Blood sugar dysregulation

Unstable blood glucose creates energy swings throughout the day. A fasting glucose or HbA1c test provides a snapshot of long-term glucose regulation, while a full metabolic panel gives context around insulin sensitivity and metabolic efficiency. People with undiagnosed pre-diabetes frequently describe constant fatigue as a primary complaint, often attributed to lifestyle factors for years before the metabolic cause is identified.

Sleep quality and circadian disruption

Sleep architecture matters as much as total sleep duration. Conditions including sleep apnoea, restless legs syndrome and circadian rhythm disruption produce daytime fatigue regardless of hours in bed. Assessing sleep quality requires a different investigation pathway from blood testing, but blood biomarkers can still inform the picture: low ferritin is a specific risk factor for restless legs syndrome, thyroid dysfunction directly disrupts sleep architecture, and high cortisol from chronic stress shortens restorative sleep stages.

Chronic low-grade inflammation

Elevated CRP (C-reactive protein) and other inflammatory markers are associated with persistent fatigue through their effect on cytokine signalling, which directly modulates the brain's perception of energy. Inflammatory fatigue is often described as qualitatively different from tiredness caused by nutrient deficiency: heavy, flu-like, not relieved by sleep. Identifying an inflammatory driver, whether from gut dysbiosis, autoimmune activity or metabolic disease, is a necessary step toward resolution.

Methylation pathway dysfunction

Methylation is a core biochemical process that affects energy production, neurotransmitter synthesis and DNA repair. Variants in the MTHFR gene, which is present in some form in around half the population, can impair the conversion of folate into its active form and reduce the efficiency of the entire methylation cycle. This creates a downstream effect on B12 utilisation, homocysteine clearance and cellular energy that standard nutrient tests alone will not detect. DNA methylation testing reveals whether genetic variants are likely to be contributing to your specific fatigue pattern.

Most people who visit their GP with persistent fatigue receive a standard blood count, which checks haemoglobin but not ferritin, iron stores, thyroid function beyond TSH, or the nutrient markers most closely associated with energy. The result is a normal result that does not explain the symptoms.

A comprehensive approach to fatigue investigation tests the full range of relevant biomarkers in a single draw:

Ferritin is the most sensitive marker for iron status and directly correlates with fatigue severity at low levels. Standard blood counts miss early iron depletion entirely.

TSH, Free T4 and Free T3 assess the full thyroid axis. Free T3 is the active form of thyroid hormone and the marker most closely linked to how energy actually feels day to day.

Vitamin B12 and folate together assess the methylation pathway. Deficiency in either elevates homocysteine, a functional marker that reveals whether the methylation system is working effectively.

Vitamin D is the most common deficiency in the UK, particularly from October to March, and directly contributes to fatigue, immune dysfunction and mood changes.

HbA1c provides a 3-month average of blood glucose regulation, identifying metabolic drivers of fatigue that would otherwise be invisible on a one-off fasting glucose.

CRP identifies systemic inflammation, which is a major but frequently overlooked contributor to persistent tiredness.

Homocysteine reflects the integrated efficiency of B12, folate and methylation, giving a single-number view of how well this system is functioning.

If your GP has tested basic markers and they appear normal, a more comprehensive panel including ferritin, full thyroid axis, B12, vitamin D and homocysteine is the most logical next step before attributing ongoing fatigue to lifestyle or stress.

Addressing the root cause first

Lifestyle interventions for fatigue only work if the underlying physiology supports them. Sleep hygiene improvements will not resolve ferritin-driven tiredness. Exercise will not fix a thyroid that is underperforming. The most reliable path is identifying the specific drivers through testing, then applying targeted interventions, and using retesting to track whether those interventions are actually shifting the relevant biomarkers.

Nutrition and micronutrient foundations

Iron-rich foods alongside vitamin C improve absorption significantly: haem iron from red meat and fish is absorbed at around 25%, compared to 1-8% for non-haem iron from plant sources. B12 is found almost exclusively in animal products, making supplementation essential for vegans and vegetarians. Vitamin D has very few reliable dietary sources and cannot be produced through sun exposure in the UK from October to March for most people. Tracking ferritin, B12 and vitamin D levels over time is the only reliable way to confirm that dietary or supplementation approaches are working at your individual level.

Sleep architecture and circadian rhythm

Consistent sleep and wake times, regardless of total sleep duration, are among the most evidence-supported interventions for daytime fatigue. Reducing light exposure in the evening, particularly from screens, supports the natural rise in melatonin that precedes sleep. If fatigue persists despite adequate sleep, biomarker testing for thyroid and iron status is warranted before sleep aids or interventions are attempted.

Movement and metabolic health

Moderate-intensity exercise, particularly walking and resistance training, consistently improves self-reported energy levels through its effects on mitochondrial density, insulin sensitivity and cortisol regulation. The evidence suggests that consistent, moderate exercise outperforms intensive exercise for managing fatigue, particularly when inflammatory markers are elevated. Tracking HbA1c and CRP alongside any exercise programme shows whether metabolic and inflammatory drivers are actually responding.