Zeitzer · The American journal of medicine 1999 · cross-sectional comparative study · n=132

Do plasma melatonin concentrations decline with age?

Cited 240 times in the scientific literature.

Level 4 - case-series / case-control

Cross-sectional comparative physiological study comparing two age cohorts

PubMed 10569297 · doi:10.1016/s0002-9343(99)00266-1 · record verified 2026-08-28

What was done

Researchers evaluated plasma melatonin profiles under a constant routine protocol in 34 healthy, drug-free older adults (20 women and 14 men, aged 65 to 81 years) and compared them with 98 healthy, drug-free young men (aged 18 to 30 years) to assess whether endogenous circadian melatonin concentrations change with age.

What was found

No statistically significant differences were found between healthy older subjects and young men in 24-hour average melatonin concentration (70 pmol/L vs 73 pmol/L, P = 0.97), nocturnal peak duration (9.3 hours vs 9.1 hours, P = 0.43), nocturnal peak mean (162 pmol/L vs 161 pmol/L, P = 0.63), or integrated nocturnal area (85,800 pmol x min/L vs 86,700 pmol x min/L, P = 0.66).

Why it matters

This study challenges the common assumption that melatonin secretion inevitably declines with healthy aging, suggesting that age alone should not justify melatonin replacement therapy without documented deficiency.

Limits

The comparison group of young subjects consisted entirely of men, creating a sex imbalance against the mixed-sex older group. The design was cross-sectional rather than longitudinal, the older sample size was modest (n = 34), and the strict exclusion of disease or medication limits generalizability to typical older populations.

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