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Changes in blood metabolite profile visible years before alcohol-related disease

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A new study has shown that the serum metabolite profile can be used to identify individuals likely at risk of developing an alcohol-related disease in the future, reports the University of Eastern Finland. The finding also opens up new avenues for preventing alcohol-related adverse effects.

The university reported on 19 October 2020 that the study is the first in the world to show that the serum metabolite profile can be used to identify individuals likely at risk of developing an alcohol-related disease in the future. The finding also opens up new avenues for preventing alcohol-related adverse effects.

The research was published in Alcoholism: Clinical and Experimental Research.

Alcohol is the cause underlying many severe diseases, such as alcohol dependence, liver cirrhosis and different types of cancer. It is estimated that alcohol accounts for approximately 5% of the global burden of disease, and the World Health Organization has listed the reduction of excessive consumption of alcohol as one of its most important priorities.

“However, it is challenging to identify individuals most in need of an intervention, that is, people who will go on to develop an alcohol-related disease,” Senior Researcher Olli Kärkkäinen says.

The study from the University of Eastern Finland discovered that changes in the serum metabolite profile are visible years before an individual is diagnosed with an alcohol-related disease.

The researchers used metabolomics methods to analyse serum samples collected from middle-aged Finnish men in the 1980s as part of a prospective study focusing on risk factors of coronary artery disease.

They analysed baseline serum samples from individuals who were diagnosed with an alcohol-related disease in the course of a 30-year a follow-up. On average, the diagnosis was made 13.6 years after the sample was taken.

The study had two control groups: one group consisted of individuals whose consumption of alcohol at baseline was equally heavy, but who were not diagnosed with an alcohol-related disease later on. The other control group consisted of individuals whose consumption of alcohol at baseline was moderate, allowing the researchers to analyse alcohol-related changes.

There were significant differences in the groups’ serum metabolite profiles. After controlling for self-reported alcohol use and gamma-glutamyl transferase levels, which is a biomarker of alcohol use, the researchers found that individuals who would later develop an alcohol-related disease had significantly lower serum levels of serotonin and asparagine than individuals in the control groups.

“Serotonin is an important mediator that regulates the function of the nervous system, and lower levels of asparagine may be related to an increased risk of alcohol-induced organ damage,” explains Kärkkäinen.

Heavy alcohol use in itself was associated with considerable changes in the blood metabolite profile, for example, in the levels of amino acids, steroid hormones and fatty acids.

“Our study is the first to show that the serum metabolite profile could be used to identify, already in advance, individuals who are likely to develop an alcohol-related disease in the future,” adds Kärkkäinen.

“This would have far-reaching consequences: if we can identify these individuals sufficiently early, we can target preventive measures at them. Successful prevention of alcohol-related adverse effects and diseases is highly significant both on the individual and societal levels.”

A limitation of the study is that it only analysed middle-aged Finnish men who belonged to a risk group for alcohol-related diseases.

“Future research should focus on analysing whether these findings can be generalised to other population groups, including women, younger people and people who are not Finnish,” Kärkkäinen concludes.

 

Changes in circulating metabolome precede alcohol‐related diseases in middle‐aged men: a prospective population‐based study with a 30‐year follow‐up

Alcoholism: Clinical and Experimental Research. Published on 17 October 2020.

Authors

Olli Kärkkäinen, Anton Klåvus, Ari Voutilainen, Jyrki Virtanen, Marko Lehtonen, Seppo Auriola, Jussi Kauhanen and Jaana Rysä

Abstract

Heavy alcohol use has been associated with altered circulating metabolome. We investigated whether changes in the circulating metabolome precede incident diagnoses of alcohol‐related diseases.

Methods

This is a prospective population‐based cohort study where the participants were 42‐60‐year‐old males at baseline (years 1984‐1989). Subjects who received a diagnosis for an alcohol‐related disease during the follow‐up were defined as cases (n = 92, mean follow‐up of 13.6 years before diagnosis). Diagnoses were obtained through linkage with national health registries.

We used two control groups: controls who self‐reported similar levels of alcohol use as compared to cases at baseline (alcohol‐controls, n = 92), and controls who self‐reported only light drinking at baseline (control‐controls, n = 90). A non‐targeted metabolomics analysis of baseline serum samples was performed.

Results

There were significant differences between the study groups in the baseline serum levels of 64 metabolites: in amino acids (e.g. glutamine [FDR corrected q‐value = 0.0012]), glycerophospholipids (e.g. lysophosphatidylcholine 16:1 [q = 0.0008]), steroids (e.g. cortisone [q = 0.00001]), and fatty acids (e.g. palmitoleic acid [q = 0.0031]). The main finding was that after controlling for baseline levels of self‐reported alcohol use and the biomarker of alcohol use, gamma‐glutamyl transferase, and when compared to both alcohol‐control and control‐control group, the alcohol‐case group had lower serum levels of asparagine (Cohen’s d = ‐0.48 [95% CI ‐0.78 to ‐0.19] and d = ‐0.49 [‐0.78 to ‐0.19], respectively) and serotonin (d = ‐0.45 [‐0.74 to ‐0.15], and d = ‐0.46 [‐0.75 to ‐0.16], respectively), with no difference between the two control groups (asparagine d = 0.00 [‐0.29 to 0.29], and serotonin d = ‐0.01 [‐0.30 to 0.29]).

Conclusions

Changes in the circulating metabolome, especially lower serum levels of asparagine and serotonin, are associated with later diagnoses of alcohol‐related diseases, even after adjustment for the baseline level of alcohol use.

 

Changes in blood metabolite profile are visible years before diagnosis of alcohol-related disease

 

Changes in circulating metabolome precede alcohol‐related diseases in middle‐aged men: a prospective population‐based study with a 30‐year follow‐up

 


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