hydrates, fatty acids are broken down to beta-hydroxybutyrate
(BHB) and acetone in the liver.
BHB travels easily to the brain, where it’s taken up by nerve
cells. Here BHB is further broken down to molecules that can
enter into the energy production pathways downstream of the
point where energy metabolism breaks down in schizophrenia.
This metabolic pathway is a normal physiological process
that takes places during starvation, when the body accesses its
fat deposits to produce energy. In fact, it is likely that this could
have been a dominant metabolic process during most of human
evolution, when food was always scarce and carbohydrates
played a very small role as energy substrates.
My student, Ann Katrin Kraeuter, tested our hypothesis by
putting mice on a ketogenic diet for 3 weeks. She then admin-
istered a drug that has been known to induce psychosis in
humans and schizophrenia-like behaviours in mice.
Mice on the normal diet promptly exhibited a variety of
schizophrenia-like behaviours, such as hyperactivity, excessive
stereotyped behaviours, abnormal social interactions as well as
impaired working memory. The latter indicates that prefrontal
cortical functions are compromised.
Mice on the ketogenic diet, however, showed none of these
symptoms. They were lean, weighed less than mice on a normal
diet and had lower circulating blood glucose levels.
These results suggested that the ketogenic diet might be a
useful approach to manage schizophrenia, not only because it
normalised schizophrenia-like behaviours but also because of
its beneicial metabolic effects.
Antipsychotic drugs used in the treatment of schizophrenia
produce weight gain, elevated blood glucose, insulin resistance
and ultimately metabolic syndrome. These can contribute to the
patient’s early death due to cardiovascular disorders.
The ketogenic diet seems to counteract these deleterious
metabolic effects.Are These Findings Translatable to People?
We know that the ketogenic diet can be safely given to humans.
In fact, it has been used for the management of drug-resistant
epilepsy in children for a long time. The ketogenic diet has also
been used as a weight loss diet, and seems to be preferred by
bodybuilders who need a high energy intake that doesn’t
promote the conversion of fat from excess carbohydrates.
Long-term feeding trials of the ketogenic diet in mice showed
no deleterious consequences when used for up to a year, which
is about half of the life span of a mouse. This is encouraging, but
we need to demonstrate the eicacy of the ketogenic diet in
other animal models of schizophrenia before we can move to
clinical trials.
One might argue that the ketogenic diet is not easy to follow
and can be especially challenging for patients who are suffering
from schizophrenia. This prompts us to seek alternative ways to
deliver the diet, perhaps in the form of a supplement that mimics
its effects. This requires a better understanding of what is
happening in the body and brain of someone on a ketogenic diet.
Using dietary means to manage schizophrenia is not unheard
of. Recent pioneering work at The University of Melbourne has
shown that omega-3 fatty acids in ish oils decrease the devel-
opment of psychosis in individuals who have a high genetic
risk of developing schizophrenia.
Perhaps we are entering into the era of nutritional psychiatry.
Zoltán Sarnyai is Associate Professor and Head of the Laboratory of Psychiatric
Neuroscience at the Australian Institute of Tropical Health and Medicine, James Cook
University.MAY 2016|| 17