《Frontiers》 Molecular Neuroscience Journal | Long term oral administration of β - hydroxybutyric acid can reduce anxiety and may even help lower the risk of depression and suicide
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Date:2024-03-27

《Frontiers》 Molecular Neuroscience Journal | Long term oral administration of β - hydroxybutyric acid can reduce anxiety and may even help lower the risk of depression and suicide

As is well known, there is an inseparable relationship between anxiety, depression, and suicidal tendencies. In fact, many patients with severe depression often have suicidal thoughts due to severe mental anxiety problems.

Therefore, reducing anxiety symptoms may play a crucial role in improving depression and reducing the risk of suicide.

In recent years, a research team from the University of South Florida in the United States has published results in the Frontiers journal (Impact Factor=5.6) showing that long-term feeding with feed supplemented with β - hydroxybutyric acid (3HB) significantly reduced anxiety behavior in rats. And this breakthrough also demonstrates for the first time that exogenous ketone body supplementation may be a novel non pharmacological treatment for combating anxiety and improving depression.


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In animal experiments, researchers found that the anxiety state of rats in the group that consumed 3HB for a long time was significantly reduced (Figure 1).


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Figure 1: Behavior and changes in blood ketone and blood glucose levels of animals in the elevated cross maze test

(After 13 weeks of 3HB diet feeding)


Behavioral performance in A/B/C-maze test; D-blood ketone levels; E-blood glucose level; F - Weight

Simply put, researchers determine the level of anxiety in animals by their performance in the elevated cross maze test (Figure 2). As a result, it was found that the number of times and duration of animals in the experimental group entered the closed arm decreased, while the number of times, duration of stay, and distance of movement in the open arm increased significantly.

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Figure 2: The basic form of the elevated cross maze test and the terminal indicators used to determine anxiety levels - the time and distance animals spend on open arms are negatively correlated with their own anxiety state.

It is worth mentioning that researchers also found that in another experimental group that received 3HB orally continuously for a short period of time (7 days), the anxiety level of rats was similarly relieved (Figure 3).


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Figure 3: Behavior and changes in blood ketone and blood glucose levels of animals in the elevated cross maze test

(Oral gavage of 3HB for 7 consecutive days)

Behavioral performance in A/B-maze test; C-blood ketone levels; D-blood glucose level; E-weight


It seems that exogenous β - hydroxybutyric acid may really be effective in helping people with depression or anxiety to combat anxiety - in layman's terms, 3HB may become the natural neuronal nutrient that can help people let go of anxiety and gradually "get out of the haze and see the light again"!

reference material:

1 Ari C et al., Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats. Front Mol Neurosci 2016, 9: 137. doi: 10.3389/fnmol.2016.00137.

2 Walf A and Frye C, The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2007, 2: 322–328. https://doi.org/10.1038/nprot.2007.44