Discussion
Given its dual role, betaine has always been considered an important
nutrient for human physiology. But the evident growing literature
highlights a possible third role: the positive effects of betaine in CNS
disorders. The betaine in the liver and kidney has been well studied,
reviewed, and understood. Despite the reported benefits of betaine
supplementation in improving brain conditions, the mechanism of action
yet is not clear.
In this review, we highlight the positive role and therapeutic potential
of betaine in brain-associated diseases like AD, PD, dementia,
Schizophrenia, depression, PTSD, epilepsy, and anhedonia reported in
recent literature. Although BGT-1 can actively uptake betaine in the
brain, the little expression and lack of understanding around its role
in CNS raise questions over the mechanism behind accumulation and its
impact on the brain. Kunisawa et al showed that the interaction of
betaine with GABAergic pathway could not be limited to just
BGT-1[23 ]. Their results
indicate a possible betaine interaction with GABAA and
GABAB receptors. The work from
Ibi[57 ] et al supports this
hypothesis by showing that the prevention of cognitive impairment by
betaine is mediated by BGT-1, but not its antioxidant effects. Despite
the lower and questionable expression of BGT-1 in the
brain[19 ], the beneficial
effects of betaine appear to be asserted via active transport by BGT-1.
Although these effects are not solely driven by BGT-1 and involvement of
some other mechanisms is highly possible.
Under hyperosmotic conditions, betaine can significantly influence the
uptake of glycine and
glutamine[7 ]. Since glycine is
a precursor to GABA and glutamine to glutamate, a possible role for
betaine in maintaining the balance between inhibitory and excitatory
neurotransmission cannot be denied. Also, the effects of betaine against
stress-induced diseases and memory loss indicate a connection with the
GABAergic pathway in CNS.
Betaine certainly has neuroprotective properties that prevent the
progression of neurodegenerative diseases like AD, PD, and dementia.
Along with choline, folic acid, vitamin B6, and B12, betaine in the
maternal diet is correlated with early neuronal development and
attenuation of cognitive function at the later stage of
life[58 ]. One way betaine
helps is by reducing the Hcy levels in the neurons and promoting the
expression of memory-related
proteins[40 ,41 ].
Also, it can convert homocysteine to methionine and increase SAM, which
protects the brain against a variety of toxic agents causing oxidative
stress[59 ].
As a therapeutic, betaine is already in use as an FDA-approved drug to
treat homocystinuria. The reported side effects (for 6-9g/day) are
relatively mild such as gastrointestinal illness, mild body odour,
increased urination, feeling dry mouth, preference for salty food
etc[60 ]. The excess of betaine
is also associated with cardiovascular disease and pulmonary
hypertension[61 ,62 ].
While there are very few side effects recorded for
betaine[63 ,64 ],
there is still not enough information on the long-term effects of
regular betaine supplementation.