I'm waiting to have a pdf of the recent paper of Masino, but this is the abstract of a previous work:
Masino SA, Geiger JD. Are purines mediators of the anticonvulsant/neuroprotective effects of ketogenic diets? Trends Neurosci. 2008 Jun;31(6):273-8. Epub 2008 May 9.
Neuroscience Program/Psychology Department, Trinity College, Life Sciences
Center, 300 Summit Street, Hartford, CT 06106, USA.
susan.masino@trincoll.edu
Abnormal neuronal signaling caused by metabolic changes characterizes several
neurological disorders, and in some instances metabolic interventions provide
therapeutic benefits. Indeed, altering metabolism either by fasting or by
maintaining a low-carbohydrate (ketogenic) diet might reduce epileptic seizures
and offer neuroprotection in part because the diet increases mitochondrial
biogenesis and brain energy levels. Here we focus on a novel hypothesis that a
ketogenic diet-induced change in energy metabolism increases levels of ATP and
adenosine, purines that are critically involved in neuron-glia interactions,
neuromodulation and synaptic plasticity. Enhancing brain bioenergetics (ATP) and
increasing levels of adenosine, an endogenous anticonvulsant and neuroprotective
molecule, might help with understanding and treating a variety of neurological
disorders.
It's interesting to link this hypothesis to the increase in metabolism due to stressor.
ATP levels increase toghether NPY and noradrenalin levels showing a response of our body to an emergency. Then the neuroendocrine system play an important role.
SInce 1986 it's know the anticonvulsive effect of adenosine.
M. Dragunow, Adenosine: the brain's natural anticonvulsant?, Trends Pharmacol. Sci. 7 (1986), pp. 128–130
D. Boison, Adenosine kinase, epilepsy and stroke: mechanisms and therapies, Trends Pharmacol. Sci. 27 (2006), pp. 652–658
More recently the anticonvulsive effect of NPY and noradrenalin was shown, too.
NPY is named "endogenous anticonvulsant".
The stimuli to obtain this neuroendocrine response are: fasting, intestinal nutrients as: fats, medium chain triglycerids, tryptophan and serotonin.
The authors report KD increase ATP, then increase Krebs cycle,then peptide synthesis.
Neuropeptides are linked to neurogenesis and synapthogenesis, in this way they increase neuroprotective effects. In agreement with Jobe's theory (J neurochem 2005), neurogenesis and synapthogenesis allow to the brain to keep isolated bad function neurons, in this way there is not pathological manifestations.
Do you know KD carry out good clinical results in other pathologies than epilepsy?
I link the anticonvulsive effect of antidepressant SSRIs to the intestinal increasing of serotonin. It's reported for many AEDs carry out an intestinal increase in tryptophan and/or serotonin. The anticonvulsive effect showed by alpha-lactalbumin (ALAC) is due to intestinal tryptophan increase.
This paper suggest in our body there are endogenous systems to control brain. The acute phase reaction to an emergency start these systems. The basal mechanism of trasformation the food in energy are involved, i.e Krebs cycle, ATP, neuropeptide syntehesis. To study these systems could be very important to solve many pathologies.
Not only, the pathogenetic mechanisms of many diseases could be linked to nutritional aspects. In fact, ketogenic diet, MCT diet, ALAC diet are all diets. Can a diet to be more effective than drugs? Food better than drugs.
A too permeable intestinal membrane could be responsible of neurotoxic compunds in the blood. Surely it's responsible of an uncorrected metabolism of proteins, amino acids being decarbossiled to dangerous amine. For example tryptohan carry out to scatole and indole. In autism there is the theory of excess of opioid compunds...
A lot of studies have to be performed. Unfortunately multipharms are not interested to them.
Paolo Mainardi