New Research Links Systemic Inflammation, Liver Fibrosis, and Cognitive Impairment

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The bidirectional communication between the liver and the central nervous system is often referred to as the liver-brain axis. A recent study featured in The Lancet sheds new light on this important connection.

The researchers used data from the UK Biobank that included between 45,055 to 447,533 participants 37 years and older. Magnetic resonance imaging (MRI) was used to assess areas of brain atrophy using grey matter volumes for 38,244 participants aged 44 to 82 over a median nine-year follow-up.

“Immediately striking is the size and extent of the data used in the study,” commented Tina Kaczor, ND, FABNO, who is a naturopathic oncologist and the Editor-in-Chief of the Natural Medicine Journal. “There have been studies showing that there is brain atrophy with liver pathologies, but this study had so many participants that it allowed for the data to be parsed out to show specifically which areas of the brain were affected.”

The researchers also analyzed liver fibrosis and C-reactive protein (CRP) levels. They found significant associations between liver fibrosis and cognitive performance in reasoning, working memory, visual memory, prospective memory, executive function, and processing speed. Neuroimaging also revealed a significant association between liver fibrosis and reduced regional grey matter volumes. Atrophy was seen in the hippocampus, thalamus, ventral striatum, parahippocampal gyrus, brain stem, and cerebellum. CRP levels were significantly higher in the participants with advanced liver fibrosis than those without. 

 “This study was powered to provide confidence that the observed associations were not merely coincidental,” said Kaczor, who is the founder of Round Table Cancer Care and co-host of The Cancer Pod

The extent of liver fibrosis was associated with the level of systemic inflammation, which then correlated with cognitive impairment. The researchers concluded that their analysis helps illustrate the physiological role systemic inflammation has on the liver-brain axis.

Integrative Interventions

“This study implies that addressing systemic inflammation may be a means of limiting cognitive damage,” said Kaczor. “Reducing systemic inflammation, as reflected in CRP, is a fundamental concept in integrative medicine.”

In the United States, the most common cause of liver disease and high liver enzymes is nonalcoholic fatty liver disease (NAFLD). It’s estimated that about 24 percent of American adults have NAFLD, characterized by excess fat and inflammation in the liver.

“From an integrative medicine approach, prevention is key,” said Kaczor. “NAFLD is a condition that we can prevent through a balanced diet and active lifestyle.”

In addition to diet and lifestyle strategies, Kaczor uses herbal extracts such as ginger, turmeric, and Boswellia and targeted dietary supplements like fish oil and methylsulfonylmethane (MSM) to help lower inflammatory status. 

Liver-Brain-Inflammation Axis

This latest study further elucidates how the communication pathways between the liver and the brain influence inflammation and cognition. As the largest internal organ in the human body, it’s becoming clear that the liver exerts influence well beyond its borders, including the central nervous system. As the research in this area continues to grow, so will the ability to address the liver-brain-inflammation axis in clinical practice.

“While we may assume that any systemic inflammatory mediators may worsen cognition, this is the first study I’m aware of that clearly links systemic inflammation, liver fibrosis, and cognitive impairment together,” said Kaczor. “This information will help integrative practitioners formulate more effective interventions for their patients.”