Beta-sitosterol may relieve anxiety: Mouse study
Israeli researchers from the Weizmann Institute of Science found that a plant-derived substance may play a key role in reducing anxiety levels.
Beta-sitosterol is one of a many organic compounds found in plants that have a structure like that of body-produced cholesterol. It’s found in a number of foods such as avocado, nuts, and grains, and is also sold as a dietary supplement intended mainly to reduce cholesterol levels.
The research
The new study, published in Cell Reports Medicine, piggybacks off of research from several years ago, which examined international genomic databases to find existing drugs or compounds that mimicked a certain gene expression that would help induce “calmness.” The search led to a series of behavioral experiments which found that beta-sitosterol was able to produce a calming effect in mice both on its own and in tandem with antidepressant Prozac.
The current study was based off previous research from the lab of Professor Mike Fainzilber in Weizmann's Biomolecular Sciences Department, which studied the roles of proteins that transport cargoes into the nuclei of nerve cells. They found that in stressful situations, mice lacking a transporting protein (known as importin alpha-5) showed less anxiety than the control mice. The researchers then studied how these 'calmer' mice differed from the others in terms of gene expression. The team eventually identified a genetic signature for these chilled out mice, which is about 120 genes with a characteristic pattern of expression in the hippocampus, a region of the brain that regulates anxiety.
Nicolas Panayotis, PhD, who was part of the original research team is now a senior intern in Fainzilber's lab. In the current study, Panayotis and the other researchers identified five proteins and tested their effects on behavior in mice. That led to beta-sitosterol.
Side effects
In a series of behavioral experiments, mice given beta-sitosterol showed much less anxiety than the controls. The researchers noted that the mice were less fearful than the controls when placed in an illuminated enclosure, daring to walk into its brightly lit center, whereas regular mice were careful to stay on the darker periphery. The mice receiving beta-sitosterol did not exhibit any of the side effects that might be expected from antianxiety medications such as impaired mobility.
The research team also tested the effects of beta-sitosterol on mice in combination with fluoxetine, an antidepressant drug marketed as Prozac, which belongs to the class of selective serotonin reuptake inhibitors, or SSRIs. The report explained that both beta-sitosterol and fluoxetine reduced the anxiety of mice at lower doses when taken together, compared with the doses needed to produce the same effect when they were administered separately.
"One of the major problems with existing antianxiety medications is that they produce side effects, so if beta-sitosterol could help cut down the dosage of such medications, it might potentially also reduce the unwanted side effects," Panayotis said.
An avocado a day keeps anxiety away?
While beta-sitosterol is naturally present in plant-based foods, you can’t eat enough to experience the calming effects of the molecule.
"You'd need to eat avocado day and night to get the right dose—and you would be more likely to develop digestive problems than relieve your anxiety," explained Panayotis.
While beta-sitosterol's mechanism of action is still curious, the scientists did find that the expression of several genes known to be activated in stressful situations was reduced in mice given the supplement. They also found that these mice had changes in the levels of certain metabolites and neurotransmitters in brain areas involved in anxiety.
Human applicability
If these findings are confirmed in clinical trials, beta-sitosterol supplementation could help relieve anxiety in humans down the road.
According to the researchers, since the study focused on brain regions and neural pathways involved in regulating anxiety in both mice and humans, it is likely that these findings will also apply to humans.
"There's a need for a clinical trial to test the use of beta-sitosterol for reducing anxiety in humans. Until then, we recommend that people consult their physicians before taking the supplement for this purpose,” said Fainzilber.
Souce: Cell Reports Medicine
2021 DOI: 10.1016/j.xcrm.2021.100281
“β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice”
Authors: N. Panayotis et al.
