Manganese, Mussels, Clams, and the Glutamate-Glutamine Cycle
I am a caregiver for my wife who has been diagnosed with epilepsy for about a decade. Because when she seizes, the right side of her body convulses more strongly than the left, I suspect she has Temporal Lobe Epilepsy in the left side of her brain. In 2016, she was hospitalized for status epilepticus. She was in the ICU for four days and released after a ten-day hospital stay. She has been on significant dosages of Keppra, Vimpat, and Lamotrigine since then. Currently she is on Lacosamide (Vimpat) and Lamotrigine.
She seems to be having success with changes to her diet that have been made over the last year. She started by taking a manganese supplement and more recently has included Hazel nuts, mussels, and clams in her diet. All are rich in manganese. At the beginning of 2023, her seizures were between two and five weeks apart. Towards the end of 2023, her seizures are milder and appear to be between thirteen to eighteen weeks apart. This has occurred while her Lacosamide dosage has been reduced by 62.5%, from 400 mg per day to 150 mg per day. Her doctor has now approved a reduction in her Lamotrigine. We wonder if her improvement is related to the changes in her diet, the glutamate-glutamine cycle, an enzyme in her brain cells called glutamine synthetase (GS), and whether anyone has heard of this.
Glutamate is the major excitatory transmitter in the brain and spinal cord. In the glutamate-glutamine cycle, it is released into a synapse where it allows an action potential -- the electrochemical signal of the nervous system -- to move from one neuron to the next. To remove the glutamate from the synaptic cleft, cells called astrocytes have transporters in their cell membranes. They transport the glutamate out of the synapse and into the astrocyte. Once inside an astrocyte, the glutamate is processed by GS from glutamate into glutamine. This enzyme is an important constituent of mussel and clam physiology, reducing ammonia toxicity. The glutamine is then transported out of the astrocyte by glutamine transporters and into a neuron, where an enzyme known as glutaminase converts it back into glutamate. The glutamate is then transferred to the vicinity of that neuron’s synapses, where it is released into a synapse with the arrival of the next action potential. Then, this entire process is repeated. It is therefore called the glutamate-glutamine cycle.
The relationship between low blood levels of manganese and convulsions has been noted at least since 1978. And historically the Anglo-Saxons, who lived between 410 and 1066 AD, used lupine which is exceptionally high in manganese, to prevent seizures. The active sites of GS hold two manganese ions. If the body does not have enough manganese, it cannot make GS . If an astrocyte cell cannot make GS, it seems logical that the glutamate-glutamine cycle will not work. In that case, glutamate would accumulate in the astrocyte until this excitatory neurotransmitter is released by the cell into the extracellular space, flooding nearby synapses, leading to a seizure. Hyperammonemic Encephalopathy, a recognized medical condition which also involves the glutamate-glutamine cycle, would seem to be a closely analogous condition.
Since my wife has been getting plant- and animal-based manganese from Hazel nuts, mussels, and clams, together with the reduction in her anti-seizure medication, her cognition and memory have improved, and her seizures seem to be becoming less severe and farther apart.
Has anyone else had experience with these foods?
Note: The scientific references in the original document have been removed on this posting. Should you be interested, please contact me and I will be happy to forward them to you.
