Stimulate the Brain’s Memory Neurotransmitters with NucleoCharged

Scientists nowadays accept that dietary nucleotides result in several health benefits, mostly to do with the immune system. However, some studies indicate that nucleotide supplements could have far more reaching benefits including the slowing down of the aging process, life extension, and slowing down age-related neurological degeneration. There is fascinating evidence that shows that exogenous nucleotides can significantly improve memory function in mice, and enhance at least one central nervous system neurotransmitter, acetylcholine.

Nucleotides are more commonly known as the building blocks of nucleic acids. DNA, which carries all our genetic information, and RNA, which transmits the information into protein sequences, are long polymers made up of nucleotides. There are five different types, which differ in the nucleic base, adenosine, guanine, cytosine, thymine and uracil. Thymine is only found in DNA and uracil only in RNA. When they are found in nucleic acids, nucleotides act as the ‘letters’ of the genetic information, with their sequence corresponding to the sequence of amino acids in the proteins they code for. However, individually they also have other separate roles, including as signaling molecules. This is especially true for the purines, adenosine and guanine, and especially for adenosine triphosphate, ATP, and its derivatives, ADP. AMP and cyclic AMP. It is most probably adenosine that is the active ingredient in nucleotide mixtures that produces the enhancement in cognition through its stimulation of neurotransmitter release.

Dr. Benjamin S. Frank, the pioneer of nucleotide supplementation, had already noticed the improvement of cognitive function as a result of a diet rich in nucleotides. As a physician Dr. Frank recommended a high nucleotide diet to his patients, and was able to notice its many benefits in humans. He ended up writing up his observations and recommendations in his book, ‘Dr. Frank’s No-Aging Diet’, and eating foods high in nucleic acids was the cornerstone of his recommendations. The problem is that although we can obtain nucleotides from foods, the type of foods that are particularly rich in them, red meat and especially offal, no longer feature heavily in our daily meals. Also many people avoid eating them altogether, or limit them, because of ethical, ecological, and health reasons. It is much simpler to obtain the multiple benefits of nucleotides from supplements rather than from the diet.

The effect of nucleotides on cognition and retarding neural aging was not just noticed in humans in a clinical setting, laboratory evidence in animals reinforces the same principles. Scientists in Japan writing in the Journal of Nutrition demonstrated that a nucleotide-rich diet reduced memory loss in sensescence-accelerated mice. They tested the mice with both passive avoidance and active avoidance tests. The mice fed on nucleotides performed significantly better than the mice not fed on supplements. The brains of the mice were also examinced histologically at 14 weeks of age. The mice that ate nucleotide supplemented diets had a lower number of vacuoles and lipofuscin –positive cells, a risk factor for degenerative diseases like Alzheimer’s or Parkinson’s, than control mice. This showed that even in senescence-accelerated mice, nucleotide supplements improve memory and slow down brain neurodegeneration. One of the mechanisms proposed by the authors was that dietary nucleotides increase the levels of phosphotidylcholine.

A study in rats showed that animals fed on a nucleotide-supplemented diet had a higher ratio of phosphatidylcholine in the plasma membranes of the cells in the central nervous system. The levels of the omega-3 fatty acid, DHA, and the omega-6 arachidonic acid was also higher in the brains of nucleotide-supplemented rats, although their diet did not differ from that of the control rats in other aspects. It is well known that polyunsaturated omega-3 and -6 fatty acids are very important for brain development and cognitive function. In the study, rats that had supplementary nucleotides performed better on memory and learning tests than control rats.

Phosphatidylcholine is, of course, used by the body to synthesise acetylcholine. Acetylcholine acts as a neurotransmitter both and neuromuscular junctions, where it is needed for skeletal muscle contractions and in the central nervous system where it affects synaptic plasticity, arousal and reward.

Neurotransmitters are chemicals that are needed to transmit nerve impulses across synapses. The ends of nerve axons do not contact the dendrites of other nerves directly. Instead there is a tiny gap between two nerves that make a connection known as a synapse. Electrical impulses cannot be transmitted across this gap. Instead the electrical nerve impulse must be converted into a chemical signal, which crosses the synapse and either excites or inhibits electrical impulses in the post synaptic neuron. There are many different types of neurotransmitters in the brain, different nerves employ different ones, with a variety of functions. Acetylcholine is used by cholinergic nerves, which are found in several parts of the brain. Amongst other functions it is found to be important for memory. The cholinergic nerve system is damaged in people with Alzheimer’s disease, and it is thought that this damage causes the memory deficits characteristic of the disease. The neurotransmitter also promotes REM sleep, potentially explaining one of the observations that nucleotides in their mothers’ milks are responsible for helping babies sleep. There is some evidence that the acetylcholine-using system in the brain is disrupted in clinical depression, and that this disruption could be the primary cause of the psychological disease.

Acetylcholine’s role as a modulator of synaptic plasticity is probably at the heart of its effect on improving memory. Synapses are far more than just gaps and obstacles to electric impulse transmissions that have to be overcome during nerve signaling. They are at the heart of learning and memory because of the ability of the strength of synaptic connections to be modulated. If neurons are stimulated at the same time, the connection between them is strengthened. This can be achieved throught increasing the number of neurotransmitter vesicles in the presynaptic neuron, or by increasing the number of receptors on the postsynaptic neuron. It is now generally accepted by neuroscientists that memories are ‘encoded’ in the central nervous system in the strengthened connections between neurons. Acetylcholine by modulating synaptic plasticity is at the centre of memory formation. Dietary nucleotides, by increasing the level of acetylcholine in the brain can improve memory and learning ability.

Nucleotides not only increase the levels of phosphatidylcholine, the acetylcholine precursor in the central nervous system, but also stimulate the release of the neurotransmitter at the synaptic level in the brain. This appears to occur through the activity of adenosine triphosphate (ATP) on the purinergic receptors. ATP is stored and appears to be released together with, or independently of, acetylcholine from the pre-synaptic neuron, into the synapse. In the extracellular space ATP might become hydrolysed to adenosine, although in some instansces where the enzyme iecto 5’-nucleotidase is not present, ATP itself exerts its modulatory effects on the purinergic receptors. Adenosine and ATP exert their effects through the A2a cholinergic receptors to enhance acetylcholine release.

Observations in people and studies in animals have shown that nucleotide supplements can enhance learning ability and protect the brain from the neurodegenerative effects of aging. Especially significant is the fact that nucleotide supplements have been shown to increase the levels of phosphatidylcholine, a precursor of the neurotransmitter acetylcholine in the central nervous system. In addition adenosine triphosphate (ATP), or the AMP and adenosine molecules derived from it, can lead to a stimulation of acetylcholine release in the central nervous system by acting on the A2a purinergic receptors. Since acetylcholine is a neurotransmitter required for memory, attention and mood, as well as affecting sleep, it is understandable that nucleotide supplementation can have such an important effect on cognitive brain function.

Further Reading:

Dietary nucleotides improve memory and slow down neurodegeneration in mice:

Effects of supplementary nucleotides on phospatidylcholine and PUFA content of brain plasma membranes, and learning ability in rats:

Acetylcholine is important for sustained attention performance in rats:

Purine nucleotides stimulate the release of acetylcholine through their actions on the purinergic receptors:

Image Attribution: The chemical structure of purine and pyrimidine nucleotides is by Boris and is in the public domain.The 3D structure of acetylcholine is in the public domain.The schematic picture of a synapse is by Curtis Neveu and is used here under the Creative Commons Attribution-Share Alike 3.0 (CC-BY-SA-3.0) licence.