Summary: A longitudinal study found that adolescents who drink at moderate to heavy levels show distinct changes in blood metabolite profiles. Some of these metabolite alterations—most notably elevated 1-methylhistamine—were associated with reduced brain grey matter volume, particularly in young women.
Source: University of Eastern Finland
A new 10-year follow-up study from the University of Eastern Finland and Kuopio University Hospital links adolescent alcohol use to measurable changes in serum metabolites and to decreases in brain grey matter volume. The research highlights biologically relevant changes even among young people who drink at levels often considered socially acceptable and who do not meet criteria for alcohol dependence.
Researcher Noora Heikkinen and colleagues report that moderate-to-heavy drinking during adolescence is associated with alterations in amino acid and energy metabolism detected in serum. In particular, the study found that serum concentrations of 1-methylhistamine were significantly higher in the moderate-to-heavy drinking group. The team also observed that higher levels of certain metabolites correlated with smaller brain grey matter volumes in female participants.
1-methylhistamine is a metabolite formed from histamine, a compound produced during immune responses in the brain and body. The elevated levels of 1-methylhistamine observed in heavy-drinking adolescents suggest increased histamine production or turnover in the brain, which may reflect inflammatory or immune-related processes related to alcohol exposure. According to the researchers, this biochemical signal could help identify early adverse effects of alcohol on the developing brain and potentially guide the development of interventions to reduce harm.
The study followed adolescents from eastern Finland over a decade. Participants were classified as moderate-to-heavy drinkers (n = 35) or light-drinking controls (n = 27) based on a 10-year history of alcohol use. The research combined targeted liquid chromatography–mass spectrometry (LC-MS) to quantify serum metabolites with 3.0 T magnetic resonance imaging (MRI) to measure brain grey matter volumes. Although prior studies have reported metabolite changes associated with heavy drinking, this investigation is notable for directly linking serum metabolite alterations with volumetric brain imaging in the same participants.
Key results included a statistically significant increase in serum 1-methylhistamine among moderate-to-heavy drinkers (p = 0.001, effect size d = 0.82). In female participants, higher concentrations of 1-methylhistamine (r = -0.48, p = 0.004) and creatine (r = -0.52, p = 0.001) were negatively correlated with total brain grey matter volume, suggesting sex-specific vulnerability in brain structure associated with these metabolic changes.
These findings carry several important implications. First, they suggest that metabolic markers detectable in blood can reflect brain-related consequences of alcohol exposure during adolescence. Second, even alcohol consumption that does not reach clinical dependence appears to be associated with biological changes that coincide with reductions in grey matter, especially among young women. Third, the identified metabolite signature—particularly elevated 1-methylhistamine—could serve as a biomarker for early detection of alcohol-related harm and as a potential target for therapeutic strategies aimed at mitigating the effects of alcohol on the developing brain.
Although average adolescent drinking rates have declined in some regions, the researchers note a polarization trend: a subgroup of adolescents continues to engage in heavy drinking and often uses other substances. Monitoring metabolite profiles alongside neuroimaging may offer a way to better understand and address the risks posed by heavy substance use in this vulnerable population.
Source: Noora Heikkinen – University of Eastern Finland
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Original research: Changes in the serum metabolite profile correlate with decreased brain grey matter volume in moderate-to-heavy-drinking young adults. Authors: Noora Heikkinen, Olli Kärkkäinen, Eila Laukkanen, Virve Kekkonen, Outi Kaarre, Petri Kivimäki, Mervi Könönen, Vidya Velagapud, Jatin Nandani, Soili M. Lehto, Eini Niskanen, Ritva Vanninen, Tommi Tolmunen. Published in Alcohol. DOI: 10.1016/j.alcohol.2018.05.010
Abstract (summarized)
The study investigated serum metabolite differences associated with moderate-to-heavy alcohol consumption in young adults and examined whether these metabolic changes relate to reduced brain grey matter volume. The sample included 35 moderate-to-heavy drinkers and 27 light-drinking controls with a ten-year history of alcohol use classification. Targeted LC-MS measured serum metabolite concentrations and 3.0 T MRI quantified brain grey matter volumes. Compared to controls, the moderate-to-heavy group showed alterations in amino acid and energy metabolism, including a significant increase in 1-methylhistamine. In females, higher 1-methylhistamine and creatine concentrations were negatively correlated with grey matter volume. Overall, the results indicate an association between moderate-to-heavy alcohol use and an altered serum metabolite profile in young adults, and suggest that some of these metabolite changes may be linked to reduced brain grey matter volume.