Homovanillic Acid (HVA)

Urinary HVA has an established role in evaluating neuroblastoma. This cancer develops from immature nerve cells and mostly affects young children. Many of these tumors produce dopamine and release more of its breakdown products into urine. HVA helps support the diagnosis alongside other findings, and it can contribute to follow-up.

For an adult without a suspected tumor, the evidence is much less developed. Urinary HVA hasn't been validated as a measure of brain dopamine, a guide to supplements, or a way to improve longevity. A result can describe what's in the sample without providing a useful treatment target.

Where This Molecule Comes From

Dopamine is a chemical messenger involved in movement and reward, but it's also made and used outside the brain. Your body breaks it down in several chemical steps, ending with HVA. Much of the HVA reaching urine comes from dopamine metabolism outside the brain, including the gut and other organs.

The urine result depends on both production and clearance. Your kidneys filter HVA from blood and also transport it into urine. That means a change in urinary HVA doesn't necessarily mean an equivalent change in how much dopamine your body produced. Findings about urinary dopamine itself also can't be assumed to describe HVA, even though the two are related.

How Your Result Is Measured and Reported

This test uses liquid chromatography-mass spectrometry, or LC-MS. The laboratory separates compounds in urine and identifies HVA using a characteristic mass signal. Many published studies use LC-MS/MS, which adds another stage of mass analysis. Those studies support this type of measurement, but their performance figures don't automatically apply to every laboratory's assay.

Results are reported in mcg/g, or micrograms per gram. Urinary HVA is commonly reported per gram of creatinine; your laboratory report should identify that denominator. Creatinine comes largely from muscle and is excreted in urine. Dividing by creatinine reduces the effect of urine dilution, but the resulting ratio still depends partly on creatinine production and kidney function. It isn't the same measurement as total HVA excreted over 24 hours.

Neuroblastoma in Children

HVA is usually evaluated with vanillylmandelic acid, or VMA. VMA is a breakdown product of noradrenaline and adrenaline. Dopamine, noradrenaline, and adrenaline belong to a family of chemical messengers called catecholamines. Tumors differ in which products they release, so the two markers provide complementary information. In a study of 1,209 spot urine samples from 357 children, HVA and VMA agreed on whether a result was raised about 89% of the time. That agreement figure describes the two tests, not their accuracy for diagnosing cancer.

A broader urine panel detected more tumors in one LC-MS/MS study, identifying about 94 of every 100 cases compared with 86 for HVA and VMA together. It also gave more false alarms, flagging about 25 of every 100 controls compared with 8. These are results for combinations of markers, not HVA alone.

A separate study detected more neuroblastomas using plasma 3-methoxytyramine and normetanephrine than urinary HVA and VMA, about 98% versus 82%. Those are different substances measured in blood. The blood combination studied included 3-methoxytyramine, which isn't usually part of a routine plasma free metanephrine panel.

Urine markers support an investigation, but some neuroblastomas produce little HVA or VMA. An unremarkable result cannot exclude the disease when symptoms or imaging are concerning. Diagnosis generally depends on tumor tissue, or on a qualifying combination of bone marrow findings and raised catecholamine breakdown products.

Using these markers to investigate a suspected tumor is different from screening healthy children. In a German program that screened about 1.5 million children around one year of age, urinary screening increased diagnoses without reducing neuroblastoma deaths. Some detected tumors would have regressed without causing illness.

What HVA Can Add During Follow-Up

HVA can add information during neuroblastoma follow-up, especially when it was raised at diagnosis. But its concentration isn't a direct measurement of tumor size. Remaining or recurrent disease can be present despite an unremarkable result, and a rise alone doesn't prove recurrence. Current international response criteria rely on imaging and bone marrow assessments where indicated, and do not include urinary catecholamines.

There is promising research on broader urine panels. A 2025 study of children with high-risk neuroblastoma found that an abnormal eight-marker panel when standard assessments showed no remaining disease was associated with greater relapse risk. That finding concerned the combined panel and doesn't establish that HVA alone can detect relapse early or determine whether treatment should change.

Adrenal and Related Tumors in Adults

Pheochromocytomas and paragangliomas can produce noradrenaline, adrenaline, or dopamine. HVA has limited value as an initial test for these tumors. Plasma free metanephrines or urinary fractionated metanephrines are the established initial biochemical tests, and an unremarkable HVA result cannot substitute for them.

Brain Dopamine and Neurological Disease

Urinary HVA combines contributions from several organs and doesn't reliably show dopamine activity in the brain. A low result cannot diagnose Parkinson's disease, depression, or a brain dopamine deficiency. A high result doesn't establish that your brain has excess dopamine.

Some neurological research measures HVA in the fluid surrounding the brain and spinal cord. In one early Parkinson's disease cohort, lower baseline HVA in that fluid was associated with faster cognitive decline over six years. This was a different specimen, despite use of a related mass spectrometry method, and the finding doesn't validate urine testing for that purpose. Specialized spinal fluid testing can also contribute to diagnosing rare inherited dopamine disorders, alongside clinical and genetic assessment. In selected inherited metabolic disorders, urine HVA can also contribute to a broader biochemical and genetic workup.

Gut and Stress Research in Adults

One study compared 40 women with functional constipation with 40 women without it. The constipation group had about a quarter more creatinine-adjusted urinary HVA, measured by LC-MS/MS. The groups also differed in gut bacteria. This association doesn't establish that HVA causes constipation or that an individual's result identifies an imbalance of gut bacteria.

In a study of 100 workers, the group reporting more job stress had lower urinary HVA. That analysis reported HVA concentration per volume of urine, which is affected by dilution and differs from a creatinine-adjusted result. It doesn't establish how to interpret this test as a measure of stress.

These studies suggest that urinary HVA may reflect changes outside the nervous system. They haven't established a beneficial direction to aim for or shown that treatment guided by HVA improves constipation, stress, or long-term health.

When Results Can Be Misleading

• Age and creatinine: creatinine-adjusted HVA changes substantially through childhood. Interpretation needs to account for age. Low muscle mass can reduce urine creatinine and make an HVA-to-creatinine ratio appear higher even without increased HVA production.
• Medicines that change biology: levodopa can markedly increase urinary HVA because it supplies material for dopamine production and breakdown. Other drugs that affect dopamine metabolism can also alter the result. These changes don't by themselves indicate a tumor.
• Kidney handling: changes in kidney function or transport can affect how HVA moves from blood into urine. Blood HVA and urinary HVA aren't interchangeable measures of this process.
• Diet: a small LC-MS/MS study found generally modest HVA changes or departures from laboratory limits after amine-rich foods. Its results don't establish one preparation rule for every assay or collection protocol.
• Assay interference: LC-MS reduces many problems seen with older detection methods, but urine constituents can still weaken the instrument's signal. Some LC-MS/MS HVA assays also warn of interference from trimethoprim-sulfamethoxazole. Whether a drug interferes depends on the laboratory's specific assay.
• Comparability: laboratories can differ in sample preparation, calibration, reporting units, and creatinine adjustment. Results from older electrochemical methods, LC-MS methods, dried urine, blood, and spinal fluid shouldn't be treated as one continuous series.

Interpreting a Trend

The meaning of a change depends on the clinical setting, the starting result, age, medicines, and measurement conditions. There is no universal percentage change that distinguishes ordinary variation from disease. Variability measured in blood or in a single infant cannot establish that rule for adult urine.