Headache & Migraine Blood Test UK: The Biomarkers That Identify Treatable Causes Behind Chronic Head Pain

1. Ferritin

Ferritin is the primary storage form of iron in the body. Low ferritin indicates depleted iron stores and is one of the most common treatable causes of headache, particularly in women of reproductive age. Iron is essential for oxygen transport (via haemoglobin), energy metabolism (as a cofactor in the electron transport chain), and neurotransmitter synthesis (dopamine and serotonin pathways both require iron).

Multiple studies have demonstrated an association between low ferritin and increased headache frequency. A ferritin below 30 μg/L — technically within the NHS “normal” range for women — is associated with significantly increased migraine frequency in several observational studies. The mechanism involves reduced oxygen delivery to the brain and impaired serotonin metabolism, both of which lower the threshold for headache activation.

The NHS recognises headache as a symptom of iron deficiency anaemia. However, many people have iron depletion (low ferritin) without frank anaemia — their haemoglobin is still within range, but their iron stores are insufficient for optimal brain function. Ferritin testing catches this earlier stage that a haemoglobin check alone would miss.

2. FBC / Haemoglobin

The full blood count provides haemoglobin concentration, red cell indices (MCV, MCH, MCHC), and white cell and platelet counts. In headache investigation, its primary role is detecting anaemia. Headache is a cardinal symptom of anaemia regardless of the cause — the brain requires a disproportionate share of the body's oxygen (around 20% of total consumption despite being only 2% of body mass), so even mild anaemia can produce symptoms.

The red cell indices help identify the type of anaemia: microcytic (low MCV) suggests iron deficiency, macrocytic (high MCV) suggests B12 or folate deficiency, and normocytic anaemia may indicate chronic disease or renal causes. This distinction matters because the treatment differs fundamentally — iron for microcytic anaemia, B12 injections for pernicious anaemia, and folate supplementation for folate deficiency.

Even when haemoglobin is within the reference range, a value at the lower end (for example, 125 g/L in a woman with a reference range starting at 120 g/L) in someone with chronic headache warrants investigation of iron stores and B12 levels. The lower boundary of “normal” is not the same as optimal.

3. TSH (Thyroid-Stimulating Hormone)

TSH is the pituitary hormone that regulates thyroid function. An elevated TSH indicates the thyroid gland is underperforming (hypothyroidism), while a suppressed TSH suggests overactivity (hyperthyroidism). Both conditions cause headache, but hypothyroidism is the more common culprit in chronic headache presentations.

Headache affects up to 30% of people with hypothyroidism, and in some patients it is the presenting complaint before other classic symptoms (fatigue, weight gain, cold intolerance) become apparent. The mechanism involves thyroid hormone's role in regulating cerebral blood flow, neurotransmitter metabolism, and intracranial pressure. Hypothyroidism reduces cerebral blood flow and can cause a diffuse, pressure-type headache that is characteristically worse in the morning.

Subclinical hypothyroidism (TSH elevated above the upper reference limit, typically above 4.0–4.5 mU/L, with normal free T4) is particularly relevant because it is common, often undiagnosed, and can cause headache alongside fatigue and cognitive symptoms that are easily attributed to stress or poor sleep. The NICE CKS on headache assessment includes thyroid function tests in its investigation recommendations.

4. Free T4 (Thyroxine)

Free T4 is the unbound, biologically active form of the primary thyroid hormone. While TSH is the screening test, FT4 confirms the severity and nature of thyroid dysfunction. A low FT4 with elevated TSH confirms overt hypothyroidism; a normal FT4 with mildly elevated TSH indicates subclinical hypothyroidism.

In headache investigation, FT4 is essential because some patients have a TSH at the upper end of the reference range (for example 3.5–4.5 mU/L) with a FT4 at the lower end of its range — a combination that suggests the thyroid is working hard to maintain adequate hormone levels. These borderline patterns can produce symptoms, including headache, even when both values are technically “normal.”

FT4 is also important for monitoring treatment response. In patients started on levothyroxine for hypothyroidism, resolution of headache typically correlates with normalisation of FT4 into the upper half of the reference range, which is the target for symptom relief rather than simply bringing TSH below the upper limit.

5. Vitamin B12

Vitamin B12 is essential for myelin synthesis, neuronal function, and DNA production. Deficiency causes a spectrum of neurological symptoms ranging from peripheral neuropathy and cognitive impairment to headache and fatigue. The NHS lists headache as a recognised symptom of B12 deficiency anaemia.

B12 deficiency is common in the UK, particularly among people over 60 (due to declining intrinsic factor production), vegetarians and vegans (B12 is found almost exclusively in animal products), people taking proton pump inhibitors (PPIs) or metformin (both reduce B12 absorption), and those with coeliac disease or Crohn's disease.

The mechanism linking B12 deficiency to headache involves both impaired oxygen transport (through macrocytic anaemia) and direct neurological effects. B12 is required for the conversion of homocysteine to methionine — when B12 is low, homocysteine accumulates. Elevated homocysteine is independently associated with migraine, particularly migraine with aura, and is thought to promote vascular endothelial dysfunction and cortical spreading depression.

6. Folate

Folate (vitamin B9) works in tandem with vitamin B12 in the one-carbon metabolism cycle. Deficiency causes macrocytic anaemia (identical to B12 deficiency on FBC) and contributes to elevated homocysteine. The combination of low folate and low B12 produces the highest homocysteine levels and is associated with the greatest increase in migraine risk.

Several studies have identified an association between low folate and migraine with aura specifically. The MTHFR gene polymorphism (particularly C677T), which is present in around 10% of the UK population in homozygous form, reduces folate metabolism efficiency and is associated with elevated homocysteine and increased migraine risk. While MTHFR testing itself is rarely clinically useful, measuring folate and homocysteine identifies the functional consequence regardless of genotype.

Folate deficiency is common in people with poor dietary variety, high alcohol intake, coeliac disease, and those taking certain medications (methotrexate, some anticonvulsants). Supplementation with methylfolate or folic acid, combined with B12 if also deficient, effectively reduces homocysteine and may reduce migraine frequency.

7. Vitamin D

Vitamin D deficiency is endemic in the UK — the SACN 2016 report found that a significant proportion of the UK population has levels below 25 nmol/L in winter. Multiple studies have demonstrated an association between low vitamin D (below 50 nmol/L) and increased headache frequency, including a large cross-sectional study in the journal Headache showing that individuals with vitamin D below 50 nmol/L had significantly more headache days per month.

The mechanism involves vitamin D's role in inflammation modulation (vitamin D receptors are present throughout the central nervous system), its influence on serotonin synthesis (which is directly relevant to migraine pathophysiology), and its effects on muscle function (low vitamin D causes tension in cervical and pericranial muscles, contributing to tension-type headache).

Vitamin D is also relevant to migraine specifically because it modulates nitric oxide and CGRP (calcitonin gene-related peptide) — the same pathway targeted by the newest class of migraine preventive medications (CGRP inhibitors such as erenumab, fremanezumab, and galcanezumab). Ensuring adequate vitamin D may therefore complement pharmacological migraine prophylaxis.

8. Magnesium

Magnesium is arguably the single most evidence-backed nutritional factor in migraine. It is required for over 300 enzymatic reactions, including neurotransmitter release, vascular tone regulation, and cortical excitability. Low magnesium lowers the threshold for cortical spreading depression (the electrophysiological event underlying migraine aura) and promotes vasospasm, platelet aggregation, and inflammatory mediator release.

Studies consistently show that people with migraine have lower intracellular magnesium than controls. The NICE CKS on headache mentions magnesium supplementation as an option for migraine prevention, and the American Headache Society and European Federation of Neurological Societies both recommend magnesium supplementation (typically 400–600 mg elemental magnesium daily, usually as magnesium citrate or glycinate) as a Level B evidence-based prophylactic for migraine.

The challenge with magnesium testing is that serum magnesium is a poor marker of total body magnesium — only 1% of body magnesium is in the blood, and serum levels are tightly regulated even when intracellular stores are depleted. RBC magnesium is a better indicator but is not routinely available. A serum magnesium at the lower end of the reference range in someone with migraine is clinically significant and warrants a trial of supplementation regardless.

9. HbA1c

HbA1c measures average blood glucose over three months. Its relevance to headache operates through two mechanisms. First, glucose is the brain's primary fuel source, and blood sugar dysregulation — both hyperglycaemia and hypoglycaemia — directly triggers headache. Second, pre-diabetes and insulin resistance drive chronic low-grade inflammation and endothelial dysfunction, both of which promote headache.

Metabolic headaches from blood sugar instability are characterised by a diffuse, bilateral, pressing quality that worsens with fasting and improves with eating. These headaches are extremely common and often attributed to “skipping meals” without recognising the underlying metabolic vulnerability. An HbA1c in the pre-diabetic range (42–47 mmol/mol) suggests impaired glucose regulation that could be contributing to headache frequency.

An HbA1c above 48 mmol/mol (6.5%) confirms diabetes, which is independently associated with increased headache prevalence and with migraine transformation (the progression from episodic to chronic migraine). For people with both diabetes and frequent headaches, optimising glycaemic control often reduces headache frequency as a secondary benefit.

10. CRP / ESR

C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are complementary markers of systemic inflammation. In headache investigation, they serve two distinct purposes: identifying chronic low-grade inflammation that may be contributing to headache frequency, and — critically in people over 50 — screening for giant cell arteritis (temporal arteritis).

Giant cell arteritis is a medical emergency that presents with new-onset headache (typically temporal), scalp tenderness, jaw claudication, and visual disturbance. It almost exclusively affects people over 50, and an ESR above 50 mm/hr in this context is a red flag that demands same-day assessment. NICE CG150 explicitly recommends ESR and CRP testing when giant cell arteritis is suspected. Untreated, it can cause irreversible blindness within days.

Beyond temporal arteritis, chronic low-grade elevation of CRP (above 3 mg/L but below the threshold for acute infection) is associated with increased migraine frequency in population studies. This inflammatory burden may reflect metabolic syndrome, obesity, chronic infection, or autoimmune activity — all of which can contribute to headache. ESR and CRP together provide a more complete inflammatory picture than either alone.

1. Iron Deficiency Headache

Iron deficiency is one of the most common nutritional deficiencies worldwide and a leading treatable cause of chronic headache, particularly in women of reproductive age. The NHS estimates that around 3 million people in the UK have iron deficiency. Headache occurs both with frank anaemia and with iron depletion alone (low ferritin, normal haemoglobin).

The blood test pattern is: low ferritin (below 30 μg/L), sometimes accompanied by low haemoglobin and low MCV (microcytic anaemia). Iron is required for cerebral oxygen delivery, dopamine synthesis, and mitochondrial energy production. When stores are depleted, the brain is among the first organs affected because of its extraordinarily high metabolic demand.

Treatment with oral iron supplementation typically produces improvement in headache frequency within 4–8 weeks, though full iron store repletion takes 3–6 months. Intravenous iron is considered for those who cannot tolerate oral iron or who have severe depletion. Importantly, the cause of iron deficiency should always be identified — heavy menstrual bleeding, coeliac disease, and gastrointestinal bleeding are the most common causes in the UK.

2. Hypothyroid Headache

Thyroid dysfunction is estimated to affect up to 2% of the UK population overtly, with subclinical hypothyroidism affecting an additional 5–10%. Both cause headache. The NHS notes that hypothyroidism causes a wide range of symptoms including fatigue, weight gain, constipation, and muscle aches — headache is often present alongside these but may be the dominant complaint.

The blood test pattern is: elevated TSH (above 4.5 mU/L) with low or low-normal FT4. In subclinical hypothyroidism, TSH is elevated but FT4 remains within the reference range. The headache mechanism involves reduced cerebral blood flow, impaired CSF absorption (which can cause mild intracranial hypertension), and altered serotonin metabolism.

Treatment with levothyroxine typically resolves the headache within weeks to months of achieving euthyroid status. In subclinical hypothyroidism with symptoms, many endocrinologists advocate a trial of levothyroxine, particularly when TSH is above 7–10 mU/L or when thyroid antibodies (anti-TPO) are positive, indicating autoimmune thyroiditis (Hashimoto's disease).

3. Vitamin B12 and Folate Deficiency

B12 and folate deficiency, whether alone or combined, cause headache through two pathways: macrocytic anaemia (reducing oxygen delivery) and hyperhomocysteinaemia (promoting vascular endothelial dysfunction and cortical spreading depression). The NHS recognises headache as a symptom of both B12 and folate deficiency anaemia.

The blood test pattern is: low B12 (below 200 ng/L) and/or low folate (below 3.0 μg/L), often with raised MCV (above 100 fL) on FBC indicating macrocytosis. Homocysteine may be elevated as a consequence. The combination of low B12 and low folate is particularly significant for migraine with aura.

Treatment depends on the cause. B12 deficiency from pernicious anaemia requires lifelong intramuscular B12 injections. Dietary deficiency can be treated with oral supplements (1,000–2,000 μg cyanocobalamin or methylcobalamin daily). Folate deficiency responds to oral folic acid 5 mg daily, though B12 must always be checked and corrected first to avoid masking B12 deficiency with folate supplementation.

4. Vitamin D Deficiency

Vitamin D deficiency (below 50 nmol/L) affects an estimated one in five UK adults and is even more prevalent in winter. Multiple observational studies have found that people with chronic headache are significantly more likely to have low vitamin D than headache-free controls. A systematic review and meta-analysis published in Nutrients (2020) found a consistent inverse relationship between vitamin D levels and headache frequency.

The blood test pattern is: 25-hydroxyvitamin D below 50 nmol/L. Severe deficiency (below 25 nmol/L) is associated with the highest headache burden. Vitamin D's relevance to headache involves its anti- inflammatory properties (suppressing TNF-alpha and IL-6), its role in serotonin synthesis (vitamin D activates tryptophan hydroxylase, the rate-limiting enzyme), and its effects on CGRP modulation.

Supplementation with vitamin D to achieve levels above 75 nmol/L has shown promise in reducing headache frequency in several randomised controlled trials, though the SACN 2016 report notes that the evidence for headache-specific benefits is still accumulating. Given the established safety of supplementation at standard doses (800–2,000 IU daily) and the high prevalence of deficiency, correction is warranted regardless.

5. Pre-Diabetes and Metabolic Headache

Blood sugar dysregulation is an underrecognised driver of chronic headache. Pre-diabetes (HbA1c 42–47 mmol/mol) affects an estimated 13.6 million adults in England alone. The brain is exquisitely sensitive to glucose fluctuations — both drops (reactive hypoglycaemia after meals) and sustained elevation cause headache through distinct mechanisms.

The blood test pattern is: HbA1c in the pre-diabetic range (42–47 mmol/mol), sometimes accompanied by raised fasting glucose (above 5.5 mmol/L). Insulin resistance produces a characteristic postprandial pattern: headache 2–4 hours after carbohydrate-heavy meals as blood sugar overshoots then crashes below baseline.

Treatment is lifestyle-based: dietary modification (reducing refined carbohydrates, increasing protein and fibre at meals), regular physical activity (which improves insulin sensitivity within days), and weight management. These changes reliably reduce HbA1c and can substantially reduce headache frequency in people with metabolic headache. NICE NG28 (Type 2 diabetes prevention) recommends intensive lifestyle intervention for people with HbA1c in the pre-diabetic range.

1. Magnesium Supplementation (400–600 mg daily)

Magnesium is the most evidence-based nutritional supplement for migraine prevention. A Cochrane-level systematic review of randomised controlled trials found that magnesium supplementation at 400–600 mg daily reduces migraine frequency by approximately 40% over 12 weeks compared with placebo. The American Headache Society, European Federation of Neurological Societies, and BASH guidelines all recognise magnesium as a Level B evidence-based migraine prophylactic.

Magnesium citrate and magnesium glycinate are the best- tolerated oral forms. Magnesium oxide has the highest elemental magnesium per tablet but lower bioavailability and more gastrointestinal side effects. Allow 8–12 weeks for the full prophylactic effect. Magnesium is safe at supplemental doses and is one of the few migraine interventions recommended before pharmacological prophylaxis in many headache guidelines.

2. Riboflavin (Vitamin B2) 400 mg Daily

Riboflavin at 400 mg daily is a well-established migraine prophylactic with Level B evidence. A pivotal randomised controlled trial published in Neurology (Schoenen et al. 1998) found that riboflavin 400 mg daily reduced migraine frequency by 50% in 59% of participants over three months, compared with 15% on placebo. The mechanism involves riboflavin's role as a precursor to FAD and FMN, which are essential cofactors in the mitochondrial electron transport chain.

Migraine is increasingly recognised as a mitochondrial energy disorder, with impaired mitochondrial function in the cortex lowering the threshold for cortical spreading depression. Riboflavin supplementation supports mitochondrial energy production. It has essentially no side effects at 400 mg daily (urine turns bright yellow, which is harmless) and is safe in pregnancy, making it suitable for women who cannot take pharmacological prophylaxis.

3. Coenzyme Q10 (100–300 mg Daily)

CoQ10 is another mitochondrial cofactor with evidence for migraine prevention. A randomised double-blind trial published in Neurology (2005) found that CoQ10 100 mg three times daily reduced migraine frequency by 48% over three months. Like riboflavin, CoQ10 supports mitochondrial energy production in the brain.

CoQ10 supplementation is particularly worth considering in people who take statins, as statins reduce CoQ10 synthesis. Statin-associated headache (a recognised side effect) may partially reflect CoQ10 depletion. CoQ10 is well tolerated, with gastrointestinal upset being the only common side effect at higher doses. The combination of CoQ10, riboflavin, and magnesium has been studied as a triple supplement approach and shows additive benefit in some trials.

4. Vitamin D Optimisation

Where deficiency is confirmed (below 50 nmol/L), vitamin D supplementation to achieve levels above 75 nmol/L has shown benefit in reducing headache frequency in several randomised controlled trials. The SACN 2016 report recommends 400 IU daily for the general population, with higher doses (up to 4,000 IU daily) considered safe for correcting deficiency.

Vitamin D's relevance extends beyond headache: it supports immune regulation, bone health, and muscle function. In someone with chronic headache and confirmed vitamin D deficiency, supplementation addresses a modifiable risk factor with an excellent safety profile. Vitamin D3 (cholecalciferol) is more effective than D2 (ergocalciferol) at raising and maintaining serum levels.

5. Iron Repletion

Where iron deficiency is confirmed (ferritin below 30 μg/L), iron supplementation is both a treatment for anaemia and a specific headache intervention. The NHS recommends oral ferrous sulphate as first-line treatment for iron deficiency anaemia, with treatment continuing for three months after haemoglobin normalises to replete iron stores.

For headache, the benefit is measurable: iron repletion to ferritin above 50 μg/L is associated with reduced headache frequency in observational studies. Oral iron should be taken on an empty stomach with vitamin C to improve absorption. Common side effects (constipation, nausea) can be managed by taking iron every other day, which recent evidence suggests produces equivalent repletion with fewer side effects.

6. Mediterranean Diet

A Mediterranean dietary pattern reduces systemic inflammation (including CRP) and provides natural dietary sources of magnesium, B vitamins, and omega-3 fatty acids. A BMJ-published meta-analysis found significant reductions in CRP and other inflammatory markers with Mediterranean dietary adherence.

For migraine specifically, a dietary pattern rich in leafy greens (magnesium, folate), oily fish (omega-3, vitamin D), nuts and seeds (magnesium, CoQ10), and olive oil (anti-inflammatory polyphenols) addresses multiple headache mechanisms simultaneously. Reducing processed foods, refined sugars, and alcohol supports blood sugar stability and reduces the inflammatory burden that promotes migraine.

7. Hydration

Dehydration is one of the most commonly reported migraine triggers and is easily underestimated. A randomised controlled trial published in European Journal of Neurology (2005) found that increasing water intake by 1.5 litres per day reduced total headache hours and headache intensity over a two-week period.

The NHS headache guidance includes drinking plenty of fluids as a first-line recommendation. The mechanism involves cerebral blood flow regulation — mild dehydration reduces blood volume, which the brain compensates for through vasoconstriction, triggering headache. For migraine, dehydration also increases cortical excitability by altering electrolyte balance. Aiming for 2–2.5 litres of water daily (more in warm weather or with exercise) is a simple, cost-free intervention that many headache sufferers overlook.

What blood tests should I ask my GP for if I have chronic headaches?

As a minimum, ask for a full blood count, ferritin, thyroid function (TSH and free T4), and vitamin D. If migraines are the primary pattern, add vitamin B12, folate, and magnesium. If you are over 50 with a new headache, ESR and CRP are essential to screen for giant cell arteritis. HbA1c is worth including if you suspect blood sugar is contributing to your headache pattern.

Can low iron cause migraines?

Yes. Low iron stores (ferritin below 30 µg/L) are associated with increased migraine frequency, even when haemoglobin is still within the normal range. Iron is required for oxygen transport to the brain, dopamine synthesis, and serotonin metabolism. Iron repletion to ferritin above 50 µg/L has been shown to reduce headache frequency in several observational studies. If you have frequent migraines, checking ferritin is one of the most important first steps.

I take magnesium for migraines — how long should it take to work?

Magnesium supplementation for migraine prevention typically takes 8–12 weeks to reach its full effect. The evidence supports a dose of 400–600 mg of elemental magnesium daily, usually as magnesium citrate or glycinate. If you have not noticed any improvement after 12 weeks of consistent supplementation at an adequate dose, it is reasonable to conclude that magnesium alone is insufficient and discuss additional prophylactic options with your GP.

My thyroid tests are ‘normal’ but I have headaches and fatigue — could it still be thyroid-related?

Possibly. A TSH at the upper end of the reference range (3.5–4.5 mU/L) with a free T4 at the lower end is technically ‘normal’ but may indicate suboptimal thyroid function. This is sometimes called subclinical hypothyroidism and can cause headache, fatigue, and cognitive symptoms. Ask your GP about the actual values (not just whether they are ‘normal’) and whether thyroid antibodies (anti-TPO) should be checked. If anti-TPO is positive, it suggests autoimmune thyroiditis and a trial of levothyroxine may be considered.

Should I be worried about an elevated ESR?

An elevated ESR has different significance depending on your age and the degree of elevation. In someone over 50 with a new-onset headache, an ESR above 50 mm/hr is a red flag for giant cell arteritis and requires same-day medical assessment — do not wait for a routine appointment. A mildly elevated ESR (15–30 mm/hr) can reflect chronic low-grade inflammation from many causes including obesity, infection, or autoimmune conditions, and warrants clinical review but is less urgent.

Can vitamin D deficiency cause headaches?

Yes. Multiple studies have found an association between vitamin D levels below 50 nmol/L and increased headache frequency. Vitamin D is involved in inflammation modulation, serotonin synthesis, and CGRP regulation — all relevant to headache and migraine pathophysiology. Supplementation to achieve levels above 75 nmol/L has shown benefit in several randomised controlled trials. Given the high prevalence of vitamin D deficiency in the UK, it is one of the most common and easily correctable headache contributors.

Will my GP accept private blood test results for headache investigation?

Most GPs will review private blood test results and use them to inform clinical decisions. UKAS-accredited private labs, which Helvy uses, meet the same quality standards as NHS laboratories. Present your results clearly, explain your headache history, and ask specifically about any abnormal values. Some GPs may wish to repeat a confirmatory test through their own lab before initiating treatment, particularly for thyroid function or vitamin B12.