6-OH-Melatonin-Sulfate Test · Dried Urine

Your body runs on a 24-hour internal clock, and melatonin is the hormone that tells that clock when it is night. The trouble is that melatonin itself rises and falls in tight pulses overnight, making it hard to capture in a single blood draw. 6-OH-melatonin-sulfate (6-hydroxymelatonin sulfate, also called 6-sulfatoxymelatonin or aMT6s) solves that problem by accumulating in urine as your body breaks melatonin down, giving you a stable record of how much melatonin you actually produced while you slept.

This is a research-grade window into your circadian biology. Low levels have been linked to aging, Alzheimer's disease, advanced prostate cancer, and type 2 diabetes in human cohort studies. It is not yet a routine clinical test with standardized cutpoints, which is precisely why establishing your own baseline now gives you a head start on tracking one of the most under-measured aspects of your health.

What This Test Actually Measures

Your pineal gland (a tiny structure deep in your brain) releases melatonin into the bloodstream after dark. Your liver then breaks down roughly 80 to 85% of that melatonin into 6-hydroxymelatonin, attaches a sulfate group, and your kidneys excrete it in urine. By the time you wake up, your urine contains a chemical record of your overnight melatonin output.

This test does not measure melatonin in your blood. It measures the metabolite in your urine, which is a different molecule. The two are tightly correlated, which is why aMT6s has been used in human research for decades as a practical proxy for melatonin secretion. Most published studies use first-morning urine or overnight urine collected in the dried form that this test uses.

Aging and Cognitive Decline

Melatonin output drops as you get older. A meta-analysis of urinary 6-sulfatoxymelatonin reference values shows a gradual decline from childhood through roughly age 50 to 60, with a small uptick afterward. Adults in their 60s and 70s typically excrete a fraction of what they did in their 20s.

In Alzheimer's disease, the drop is steeper. A systematic review found that people across the Alzheimer's spectrum have lower total and nighttime melatonin output, measured as urinary aMT6s, compared with age-matched adults without the disease. The melatonin system appears to break down early in the disease process, which is one reason researchers are exploring this metabolite as a potential progression marker.

Cancer Risk

The most striking cancer signal comes from prostate research. In a case-cohort study of 928 elderly Icelandic men, those with morning aMT6s below the median had roughly four times the risk of advanced prostate cancer compared with men in the higher half (hazard ratio 4.04, 95% confidence interval 1.26 to 12.98). The association was strongest for aggressive disease, not for indolent cancers that might never cause harm.

The breast cancer story is more mixed. Some large nested case-control studies in postmenopausal women, including an Italian cohort of 3,966 women (ORDET), found that higher urinary melatonin was associated with lower risk of postmenopausal breast cancer. Other prospective studies and a meta-analysis found no significant association overall, and a premenopausal analysis within the same Italian cohort suggested the opposite direction. The signal appears to be real for some populations and weaker or absent in others.

Type 2 Diabetes

A prospective cohort study of 4,491 adults in the Malmö Offspring Study found that lower nocturnal melatonin output, measured as the urinary aMT6s-to-creatinine ratio in first-morning urine samples, was independently associated with a higher risk of developing type 2 diabetes. The association held after adjustment for standard risk factors, supporting a real biological link between circadian melatonin signaling and glucose metabolism rather than a confounded statistical artifact.

Mortality in Specific Populations

In a study of 701 stable kidney transplant recipients compared with 285 healthy controls, urinary 6-sulfatoxymelatonin levels were about 47% lower in the transplant group, and lower levels were linked to increased all-cause and cardiovascular mortality. This suggests that the melatonin system is suppressed in some chronic disease states and that the degree of suppression may carry prognostic information beyond standard markers.

Reference Ranges

There are no universally adopted clinical cutpoints for 6-OH-melatonin-sulfate. The most useful orientation comes from a meta-analysis of urinary aMT6s reference values that aggregated data across populations and ages. These are research-derived population values, not clinical targets, and your lab may report in different units or use a different normalization (e.g., per milligram of creatinine versus total excretion).

Use the table below as orientation only. Compare your result to your own previous results within the same lab and assay for the most meaningful interpretation.

Source: Braam and Spruyt (2022) meta-analysis of urinary 6-sulfatoxymelatonin reference intervals.

Why One Reading Is Not Enough

A single reading captures one night of melatonin output, which can be influenced by light exposure the evening before, screen use, alcohol, travel, or an unusually short sleep. The good news is that aMT6s is reasonably stable within the same person over time when conditions are consistent. A longitudinal study of 84 children and adolescents followed for up to 15 years showed that individual 24-hour aMT6s output stayed steady year after year, even as bodies grew. That stability makes serial measurements unusually informative: a real change in your level reflects a real change in your biology, not noise.

Get a baseline now. If you are making changes that target sleep or circadian health (cutting evening light exposure, supplementing melatonin, fixing a shift-work schedule), retest in 3 to 6 months. After that, at least annual testing lets you watch your trajectory against the expected age-related decline.

What an Abnormal Result Should Make You Do

A low result is most meaningful when interpreted alongside other circadian and metabolic markers. Pair it with a diurnal cortisol pattern to assess your full circadian axis, and with fasting glucose, HbA1c, and a lipid panel given the diabetes and cardiometabolic links. If your reading is low and you have sleep complaints, an evaluation for circadian rhythm disorder or sleep apnea is worth pursuing with a sleep medicine specialist. If your reading is low and you are an older adult with cognitive concerns or a strong family history of Alzheimer's, the result should reinforce, not replace, a broader cognitive workup.

A high result almost always reflects melatonin supplementation or unusually robust nocturnal output. It is not a cause for concern in itself.

When Results Can Be Misleading

• Evening light exposure: bright light at night, including phone and computer screens, suppresses melatonin production and will lower your overnight aMT6s. Your test reflects that single night, not your baseline biology.
• Melatonin supplements: any dose taken the night before will raise your urinary aMT6s sharply for hours. After a 20 to 100 mg oral dose, the major metabolite stays elevated for several hours and scales with the dose. If you supplement, decide whether you are testing your endogenous output (skip the dose) or your overall melatonin exposure (continue your normal regimen).
• Shift work and recent travel: night shift workers show significantly lower aMT6s than day workers in observational studies. Recent jet lag does the same. Test on a representative schedule.
• Age and body size: levels naturally decline with age and vary with body size. Compare your trajectory to your own past results, not to a reference range derived from a different age group.