Loneliness has long been associated with ill health but researchers say they have fresh insights into the link between the two.
While poor health can result in people becoming isolated and lonely, studies have also suggested loneliness can itself lead to poorer health.
Now researchers say they have unpicked a mechanism for the latter relationship, finding loneliness can affect the levels of a handful of proteins associated with various diseases and even death.
Prof Barbara Sahakian, a co-author of the study at the University of Cambridge, said the World Health Organization had declared social isolation and loneliness a major problem in the world. “I think the message is that we’ve got to start to get people to realise that it’s part of a health thing, both for their mental health and their wellbeing but also for their physical health, that they have to remain connected with other people,” she said.
Writing in the journal Nature, the researchers describe how they used data from more than 42,000 participants in the UK Biobank project to explore whether the 9.3% who reported social isolation and 6.4% who reported loneliness had different levels of proteins in their blood compared with those who did not.
After taking into account factors including age, sex, education level, smoking and alcohol consumption, the team found 175 proteins associated with social isolation and 26 proteins associated with self-reported loneliness, many of which overlapped. Most of the proteins were found at higher levels in people who had reported social isolation or loneliness, and are involved in inflammation, antiviral responses and the immune system.
The researchers then studied data that tracked the health of participants over an average 14-year period. “We found around 90% of these proteins are linked to the risk of mortality,” said Dr Chun Shen, the first author of the research, from Fudan University in China. In addition, about 50% of the proteins were linked to cardiovascular disease, type 2 diabetes and stroke.
The researchers then used an approach known as Mendelian randomisation to look at whether people with genetic variants associated with loneliness or social isolation had a greater chance of having higher levels of the proteins of interest. They also looked at whether people with genetic variants that meant they had higher levels of these proteins were more likely to be socially isolated or lonely.
Assuming these variants are spread randomly throughout the population, the approach can shed light on whether levels of the proteins are a driver, or an effect, of social isolation or loneliness.
The researchers found none of the proteins appeared to cause social isolation or loneliness. However, loneliness influenced the levels of five proteins. “We found all these five proteins are related to numerous inflammation and metabolic markers,” Shen said.
Among other findings, these five proteins partly explained the association between loneliness and cardiovascular disease, stroke, and mortality, with four of the five associated with the volume of brain regions involved in emotional and social processes and the brain’s perception of the body’s state.
Shen said while the effects were not large, they were significant, noting that levels of one of the proteins, known as ADM, could explain, on average, about 7.5% of the association between loneliness and the risk of four diseases and mortality.
Prof Marko Elovainio, of the University of Helsinki, who was not involved in the work, said the study strongly supported previous research indicating that loneliness and – to some extent – social isolation were linked to numerous physical health problems, possibly as a result of systemic inflammatory processes induced by stress.
“A significant contribution of this study is that it now elucidates the biological mechanism – proteins – that may be responsible for the observed connections,” he said.
However, Elovainio suggested stress-related health behaviours, such as heavy alcohol consumption and low physical activity, might be an even more significant factor contributing to the health impacts of loneliness, and might also underlie some of the protein level changes flagged in the study.
“How society should … reduce the health risks related to loneliness is the interesting question, and if we want to focus on the mechanisms, the behaviour is probably [an] easier target than proteins,” he said.
