fasting.pdf (application/pdf Object)
Summary Anecdotal evidence links the initial phase of fasting or a low-carbohydrate diet with feelings of well-being
and mild euphoria. These feelings have often been attributed to ketosis, the production of ketone bodies which can
replace glucose as an energy source for the brain. One of these ketone bodies, b-hydroxybutyrate (BHB), is an isomer of
the notorious drug of abuse, GHB (c-hydroxybutyrate). GHB is also of interest in relation to its potential as a treatment
for alcohol and opiate dependence and narcolepsy-associated cataplexy. Here I hypothesize that, the mild euphoria
often noted with fasting or low-carbohydrate diets may be due to shared actions of BHB and GHB on the brain.
Specifically, I propose that BHB, like GHB, induces mild euphoria by being a weak partial agonist for GABA
I outline several approaches that would test the hypothesis, including receptor binding studies in cultured cells,
perception studies in trained rodents, and psychometric testing and functional magnetic resonance imaging in humans.
These and other studies investigating whether BHB and GHB share common effects on brain chemistry and mood are
timely and warranted, especially when considering their structural similarities and the popularity of ketogenic diets
and GHB as a drug of abuse.
Since recorded time, across many cultures, fasting
has been used in rituals aimed at attaining a higher
state of being. Fasting for religious and spiritual
reasons has been mentioned in the Bible, both
Old and New Testaments, the Koran and the Mahabharata
. Anecdotal feelings of well-being and
mild euphoria also litter the popular literature on
low-carbohydrate diets. For example, one diarist
wrote after 2–3 days on the Atkin’s Diet: ‘‘It is
not an unpleasant feeling, a sort of mild, foggy
euphoria’’. . From an evolutionary perspective,
mild euphoria associated with short-term fasting
may ease anxiety and aid the search for food. Ketosis
occurs during the first few days of fasting or a
low-carbohydrate diet, when breakdown of fat (boxidation)
outstrips breakdown of carbohydrate
(glycolysis). Three ketone bodies are produced by
After 2–3 days of fasting BHB reaches
millimolar levels in the blood and brain , and together
with acetoacetate provides the brain with
an alternative energy source to glucose. Several
biochemical explanations have been proposed for
the feelings of euphoria often associated with
short-term total fasting or low-carbohydrate diets.
Bloom  postulated that accumulation of acetoacetate
produces a mild intoxication similar to ethanol.
Phillips  speculated from his studies in
dairy cows that the accumulation of isopropyl alcohol
(a byproduct of acetone metabolism) in neural
tissue might be responsible for fasting-induced religious,
mystical or hallucinatory experiences.
Here I propose that diet-induced euphoria may involve
production of BHB, and may be at least partially
explained by the well-known psychological
effects of its isomer, c-hydroxybutyrate (GHB)
(Fig. 1). Considering their structural similarities,
it is perhaps surprising that no one has linked BHB
and GHB before.