Homovanillic Acid: What High and Low Levels Mean

Homovanillic acid (HVA) is the primary breakdown product of dopamine, and its levels in urine, blood, or spinal fluid serve as a rough gauge of how much dopamine your body is producing and using. High HVA can point toward catecholamine-secreting tumors, active psychosis, or recent stimulant use, while low HVA tends to show up in Parkinson’s disease, certain genetic disorders of dopamine production, and some forms of depression. The picture is more nuanced than a simple “high is bad, low is bad” framework, though, because HVA levels shift with age, sex, time of day, diet, and medication.

How HVA Ends Up in Your Body Fluids

Dopamine does not last long once it has done its job at a synapse. Two enzyme systems break it down: monoamine oxidase and catechol-O-methyltransferase. The end product of that breakdown is homovanillic acid. HVA was first described as a final product of dopamine metabolism found in urine, and researchers recognized early on that HVA levels in brain tissue reflect dopamine turnover, albeit with a slight delay.¹ Most HVA eventually makes its way out of the brain via a dedicated transporter at the blood-brain barrier and then gets filtered by the kidneys into urine.²

Clinicians can measure HVA in three places. A 24-hour urine collection is the most common and least invasive option, typically used to screen for catecholamine-secreting tumors. Plasma HVA is sometimes drawn in psychiatric research because it offers a snapshot of recent dopamine activity. Cerebrospinal fluid (CSF) HVA, collected by lumbar puncture, gives the closest window into what is happening inside the brain itself and is the gold standard when investigating rare genetic disorders of neurotransmitter metabolism. Where the sample comes from matters because each compartment reflects slightly different aspects of dopamine handling.

What Elevated HVA Can Mean

The most clinically urgent reason to check urinary HVA is to look for tumors that churn out catecholamines. Neuroblastoma, a childhood cancer of nerve tissue, is the classic example. Urinary HVA and another catecholamine metabolite called vanillylmandelic acid (VMA) are used together as markers for this disease.³ In a study of 408 children screened for neuroblastoma, 37 had elevated HVA or VMA and were subsequently diagnosed with the tumor, with no false-positive results at all.⁴ HVA tends to be the more sensitive of the two markers: only about one in forty children with neuroblastoma had elevated VMA but normal HVA, while roughly a quarter had elevated HVA but normal VMA.⁴

In adults, elevated urinary catecholamine metabolites raise suspicion for pheochromocytoma or paraganglioma, rare neuroendocrine tumors that arise from adrenal or extra-adrenal tissue. Biochemical confirmation of excessive catecholamines and their metabolites is considered essential for diagnosis and proper management of these tumors.⁵ While plasma-free metanephrines are now often the first-line screening test for pheochromocytoma, urinary HVA remains part of the workup in many clinical settings, especially alongside VMA and dopamine.

High HVA also appears in psychiatric contexts. Plasma HVA concentrations before treatment were found to be highly correlated with global severity of illness in people with schizophrenia.⁶ And CSF HVA levels were significantly higher in recently abstinent cocaine-dependent patients compared with healthy controls, consistent with the dopamine surge that stimulant use provokes.⁷

What Low HVA Can Mean

Low HVA generally signals that less dopamine is being made or turned over than expected. The most well-known example is Parkinson’s disease. As dopamine-producing neurons in the brain degenerate, HVA drops. Baseline CSF levels of HVA were lower in people with Parkinson’s compared with healthy controls, and those levels correlated with standardized measures of disease severity and with imaging markers of nigrostriatal pathway damage.⁸ Even after patients withdrew from levodopa therapy for five days, their mean CSF HVA remained significantly lower than in controls, reflecting the underlying loss of dopamine neurons rather than just a medication effect.⁹

Low CSF HVA also shows up in depression. In a comparison of patients with endogenous depression and neurological controls, the depressed group had significantly lower CSF HVA, supporting the idea that dopamine metabolism is involved in mood regulation, not just the serotonin story most people have heard.¹⁰ This is worth knowing because it hints that depression is not purely a “serotonin problem” and that dopamine-related motivation and reward circuits play a role too.

Rare Genetic Disorders That Tank HVA

Some of the most dramatic low-HVA findings come from inherited disorders of neurotransmitter synthesis. Tyrosine hydroxylase (TH) deficiency is one. This enzyme catalyzes the rate-limiting step in making dopamine, so when it is genetically impaired, dopamine production collapses and CSF HVA drops accordingly. Low CSF HVA paired with low levels of a norepinephrine metabolite, but normal serotonin metabolite levels, is considered the biochemical hallmark of TH deficiency.¹¹¹² A consensus guideline confirms that the diagnosis is suggested by detecting low CSF HVA and confirmed through genetic testing.¹³

Aromatic L-amino acid decarboxylase (AADC) deficiency is another. Here, the enzyme one step downstream of tyrosine hydroxylase is impaired, blocking the conversion of L-dopa into dopamine. The result is again low CSF HVA, along with low serotonin metabolites and a distinctive buildup of L-dopa and other upstream compounds.¹⁴ In both TH and AADC deficiency, CSF HVA measurement is not just a research curiosity; it is a key step in reaching the correct diagnosis, which matters because some forms of TH deficiency respond well to levodopa treatment. In AADC deficiency, however, levodopa only helps a small subset of patients who carry specific mutations, and gene therapy is an emerging alternative.¹⁵ Early data on gene therapy for AADC deficiency show that CSF HVA increases in many but not all patients, and there is no clear-cut correlation between how much HVA rises and how much clinical improvement the patient experiences.¹⁶

HVA and Psychosis

The relationship between HVA and schizophrenia is one of the longer-running threads in psychiatric research. The key insight is that HVA levels in cerebrospinal fluid appear to track with the severity of psychotic symptoms rather than with the diagnosis of schizophrenia itself.¹⁷ In other words, a person with schizophrenia who is relatively stable may have normal or only mildly elevated HVA, while someone in the grip of active psychosis is more likely to show high levels.

When antipsychotic medications are stopped, a telling pattern emerges. Researchers found that the peak rise in plasma HVA after neuroleptic discontinuation correlated with the peak worsening of psychiatric symptoms.¹⁸ This supports the broader dopamine hypothesis of psychosis: that excessive dopamine signaling contributes to psychotic symptoms, and HVA reflects that signaling. Antipsychotic drugs like fluphenazine reduce plasma HVA and flatten its natural daily rhythm, consistent with their mechanism of blocking dopamine receptors and thereby reducing dopamine turnover.¹⁹

How Medications Shift HVA

Levodopa, the standard drug for Parkinson’s disease, has a predictable and large effect on HVA. When levodopa is given with carbidopa (which prevents levodopa from being broken down in the body before it reaches the brain), striatal HVA levels climb substantially in animal models.²⁰ In patients with Parkinsonism, CSF HVA measured after a standard oral dose of levodopa reflects how much of the drug actually made it into the brain and was metabolized there.²¹ Interestingly, though, the size of the HVA rise does not predict how well a patient responds clinically; patients with minimal CSF HVA increases improved just as much as those with larger elevations.²² That is a useful reminder that HVA is a metabolic byproduct, not a direct measure of dopamine signaling effectiveness.

Antipsychotics push HVA in the other direction. By blocking dopamine receptors, they initially trigger a compensatory increase in dopamine firing, which can briefly raise HVA. Over time, though, the system adjusts, and steady-state HVA tends to drop. The practical takeaway is that if you are on any medication that touches the dopamine system, your HVA results need to be interpreted in that context. A single HVA number is almost never interpreted in isolation.

The HVA-to-VMA Ratio in Neuroblastoma Prognosis

For families dealing with a neuroblastoma diagnosis, the ratio of HVA to VMA at diagnosis carries prognostic weight beyond what either marker shows alone. Children whose HVA-to-VMA ratio fell between 1 and 2 had a five-year survival rate of 80%. Those with a ratio above 2 had a survival rate of just over 5%, with most dying within 24 months. And those with a ratio below 1 had an intermediate but still poor survival of about 24%.²³ A high ratio suggests the tumor is producing an abundance of dopamine-pathway metabolites relative to norepinephrine-pathway metabolites, which tends to correlate with more aggressive biology, older age at diagnosis, and worse outcomes. This ratio has practical value because it helps oncologists gauge prognosis at the point of diagnosis.

Why Your Results Might Be Wrong

Diet is one of the more surprising confounders. A study that had healthy volunteers consume flavonol-rich foods found that dietary flavonols significantly increased urinary HVA excretion, with about one in five volunteers crossing the upper limit of normal and triggering a false-positive result.²⁴ Bananas also bump up urinary HVA.²⁵ These are plant compounds, not catecholamines, but older assays confuse them with HVA. That said, more modern liquid chromatography methods may be less susceptible. One group using newer techniques found that dietary interference did not push values past the twofold upper-limit-of-normal cutoff typically used to suspect a tumor, and concluded that a restrictive diet before urine collection may not always be essential for pheochromocytoma or neuroblastoma screening.²⁶ Still, if your lab uses an older assay, the instruction to avoid bananas, chocolate, and certain fruits before a 24-hour urine collection is not superstition.

Time of day matters too. Plasma HVA follows a circadian rhythm, peaking in the early morning hours and dipping to its lowest point in the afternoon.¹⁹ Serum measurements confirm similar daily swings, paralleling urinary data from other investigators.²⁷ A 24-hour urine collection averages this out, which is one reason it remains the standard clinical specimen. But if someone is measuring spot plasma HVA for research purposes, an afternoon draw and a morning draw will give different numbers from the same person.

Normal Variation by Age and Sex

If you are comparing your HVA result to a reference range, the range itself depends on who you are. In children and adolescents, urinary HVA (adjusted for creatinine to account for body size) declines steadily from birth through about age 15 to 18, when it reaches adult levels.²⁸ This means a toddler’s HVA would look alarmingly high by adult standards, which is perfectly normal. Reference ranges for children are separately dependent on age, sex, and weight.²⁹

Sex differences persist into adulthood. Plasma HVA levels are lower in men than in women. In one study, elderly men had a geometric mean plasma HVA of about 25 nmol/L compared with about 39 nmol/L in postmenopausal women, and a similar gap existed in younger adults.³⁰ The researchers also found that cross-sex hormone therapy in transgender individuals did not eliminate this difference, suggesting the gap is not driven by circulating sex hormones but by some other factor, possibly differences in dopamine neuron density or transporter expression established during development.³⁰

Exercise and HVA

Physical activity acutely raises HVA. In people with Parkinson’s disease, both moderate-intensity continuous exercise and high-intensity interval exercise produced significant increases in HVA concentrations, with moderate-intensity exercise having a greater impact on HVA than high-intensity exercise.³¹ This aligns with the common experience that exercise improves mood and motor symptoms in Parkinson’s, and it gives a concrete biochemical marker for something most people sense intuitively. It also means that a urine collection or blood draw done right after a hard workout could show higher HVA than one collected after a sedentary day.

Gut Bacteria and Dopamine Metabolism

One of the more surprising recent findings is that gut bacteria can produce HVA. Research published in 2024 found that certain gut species, particularly Bifidobacterium longum, generate HVA, and that another species, Roseburia intestinalis, boosts HVA indirectly by promoting the growth of B. longum. Both bacterial species were depleted in people with depression and in mouse models of depression.³² Separately, other researchers confirmed that Bifidobacterium scardovii can produce HVA in culture, and that treating stressed mice with these bacteria raised HVA concentrations in both plasma and brain.³³

This opens up a dimension of HVA biology that was barely on the radar a few years ago. If gut bacteria contribute meaningfully to the body’s HVA pool, then factors affecting the microbiome (antibiotics, diet, probiotics, illness) could influence HVA levels and potentially mood and neurological function. The research is still at an early stage, largely in animal models and small human observational studies, so it would be premature to start taking probiotics specifically to raise HVA. But it does challenge the traditional assumption that HVA is purely a readout of brain dopamine, and it may eventually explain some of the person-to-person variability in HVA levels that has puzzled researchers for decades.

When Doctors Actually Order an HVA Test

Despite its connections to psychiatry, neurology, and oncology, HVA testing is not routine. In practice, the most common scenarios where a clinician orders it are:

Suspected neuroblastoma: A pediatrician investigating an abdominal mass, unexplained bone pain, or certain paraneoplastic signs in a child will order urinary HVA and VMA. Combined determination of HVA and VMA with another metabolite can achieve near-perfect sensitivity and specificity depending on the child’s age group.³⁴
Suspected pheochromocytoma or paraganglioma: An adult with episodic hypertension, headaches, and sweating may have urinary catecholamine metabolites checked as part of a biochemical workup.
Neurotransmitter disorders in infants: A child with unexplained movement problems, hypotonia, or developmental delay may undergo CSF neurotransmitter analysis. Low HVA in that setting triggers further genetic testing for TH or AADC deficiency.
Research protocols: Psychiatric and neurological studies continue to measure HVA in plasma and CSF to investigate dopamine-related hypotheses, but this rarely translates into a test ordered for an individual patient outside of a study.

For most people, HVA is not something you will see on a standard blood panel. If your doctor has ordered it, the clinical question is usually specific, and the result will be interpreted alongside imaging, other lab values, and your symptoms rather than as a standalone number. A mildly elevated urinary HVA on its own is not a diagnosis of anything; context and follow-up testing determine what it means for you.