Nutris Cognitive
Basics Portfolio
OVERVIEW
Cytidine Monophosphate (CMP) and Uridine Monophosphate (UMP): neuronal membrane components. They act similarly enhancing ATP levels and reducing muscle fatigue [10] which is directly related to neurodegenerative diseases [7][8]. CMP & UMP contribute in a critical manner to:
1) Formation, regeneration, and growth of the axons and involving myelin [11].
2) Increase the brain´s cholinergic functions such as the cognitive response.
3) Increase the number of dopamine receptors.
Regarding brain function, UMP and citicoline increase phosphatidylcholine (PC) synthesis, which plays an essential role in brain activity and promoting new neuronal connections. Furthermore, it acts in a synergistic manner with both choline and DHA in the brain [1]. Citicoline is used extensively in cerebral and vascular disorders, conferring neuroprotective, neurostimulator and nootropic properties.
Since UMP is not directly cholinergic, it serves as a fantastic catalyst when combined with alpha-glycerylphosphorylcholine (alpha-GPC) [5]: a precursor of phosphatidylcholine. It is highly bioavailable due to that it crosses the blood-brain barrier and serves as a source of choline, critical for memory and cognitive function. It also provides cellular structural integrity, by promoting synthesis of neuronal membrane components (CMP & UMP).
Phosphatidylserine (PS) [6] is the main phospholipid found in the inner side of neuronal membranes. PS modulates synaptic receptors, helping to equilibrate neurotransmitter levels.
Inosine has a main neuroprotective role, acting as the urate precursor, a powerful antioxidant that reduces the mitochondrial oxidative stress levels [2][4]. Therefore, it prevents this energetic source disfunction and the progression of neurodegenerative diseases, also by downregulating the lactate levels [3].
Finally, Β-Hydroxy-β-Methylbutyrate (HMB) [9] and Palmitoylethanolamide (PEA) are critical to fight against neuroprotection and neuroinflammation, respectively. HMB not only has been used for the muscle recovery in neurodegeneration-related hospital patients, but also due to its neuroprotective effects, maintaining mitochondrial integrity and reducing oxidative stress. PEA has been incredibly well studied and used in humans for its analgesic-pain management and it ameliorates cognitive impairments. For instance, PEA is the key therapeutical agent to improve cognitive performance in Alzheimer´s Disease (AD) [12].
In conclusion, the MAIN FUNCTIONS of these actives are:
Neuroprotective & Neuroplasticity Benefits: protects your brain from oxidative stress through these antioxidant effects and improves the capacity to form new neural connections.
Healthy & Young Brain: maintenance of general brain homeostasis and activation of the Nerve Growth Factor (NGF) signaling.
REFERENCES
1) Wurtman R. J. (2014). A nutrient combination that can affect synapse formation. Nutrients, 6(4), 1701–1710. https://doi.org/10.3390/nu6041701
2) Kamatani, N., Kushiyama, A., Toyo-Oka, L., & Toyo-Oka, T. (2019). Treatment of two mitochondrial disease patients with a combination of febuxostat and inosine that enhances cellular ATP. Journal of human genetics, 64(4), 351–353. https://doi.org/10.1038/s10038-018-0558-0
3) Vadakkadath Meethal, S., & Atwood, C. S. (2012). Lactate dyscrasia: a novel explanation for amyotrophic lateral sclerosis. Neurobiology of aging, 33(3), 569–581. https://doi.org/10.1016/j.neurobiolaging.2010.04.012
4) Nicholson, K., Chan, J., Macklin, E. A., Levine-Weinberg, M., Breen, C., Bakshi, R., Grasso, D. L., Wills, A. M., Jahandideh, S., Taylor, A. A., Beaulieu, D., Ennist, D. L., Andronesi, O., Ratai, E. M., Schwarzschild, M. A., Cudkowicz, M., & Paganoni, S. (2018). Pilot trial of inosine to elevate urate levels in amyotrophic lateral sclerosis. Annals of clinical and translational neurology, 5(12), 1522–1533. https://doi.org/10.1002/acn3.671
5) Schettini, G., Ventra, C., Florio, T., Grimaldi, M., Meucci, O., Scorziello, A., Postiglione, A., & Marino, A. (1992). Molecular mechanisms mediating the effects of L-alpha-glycerylphosphorylcholine, a new cognition-enhancing drug, on behavioral and biochemical parameters in young and aged rats. Pharmacology, biochemistry, and behavior, 43(1), 139–151. https://doi.org/10.1016/0091-3057(92)90650-5
6) Zhou, M. M., Che, H. X., Huang, J. Q., Zhang, T. T., Xu, J., Xue, C. H., & Wang, Y. M. (2018). Comparative Study of Different Polar Groups of EPA-Enriched Phospholipids on Ameliorating Memory Loss and Cognitive Deficiency in Aged SAMP8 Mice. Molecular nutrition & food research, 62(7), e1700637. https://doi.org/10.1002/mnfr.201700637
7) Cansev M. (2006). Uridine and cytidine in the brain: their transport and utilization. Brain research reviews, 52(2), 389–397. https://doi.org/10.1016/j.brainresrev.2006.05.001
8) Dobolyi, A., Juhász, G., Kovács, Z., & Kardos, J. (2011). Uridine function in the central nervous system. Current topics in medicinal chemistry, 11(8), 1058–1067. https://doi.org/10.2174/156802611795347618
9) Deutz, N. E., Pereira, S. L., Hays, N. P., Oliver, J. S., Edens, N. K., Evans, C. M., & Wolfe, R. R. (2013). Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clinical nutrition (Edinburgh, Scotland), 32(5), 704–712. https://doi.org/10.1016/j.clnu.2013.02.011
10) Gella, A., Ponce, J., Cussó, R., & Durany, N. (2008). Effect of the nucleotides CMP and UMP on exhaustion in exercise rats. Journal of physiology and biochemistry, 64(1), 9–17. https://doi.org/10.1007/BF03168230
11) Wattig, B., Schalow, G., Heydenreich, F., Warzok, R., & Cervós-Navarro, J. (1992). Enhancement of nerve fibre regeneration by nucleotides after peripheral nerve crush damage. Electrophysiologic and morphometric investigations. Arzneimittel-Forschung, 42(9), 1075–1078.
12) Beggiato S, Tomasini MC and Ferraro L (2019) Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer’s Disease. Front. Pharmacol. 10:821. doi: 10.3389/fphar.2019.00821.https://doi.org/10.3389/fphar.2019.00821