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How does Souvenaid work?

Souvenaid is designed to meet the specific nutritional needs of early Alzheimer's patients.

Souvenaid contains a unique, patented combination of nutrients designed to support synapse formation.
The nutrients work together to increase synthesis of phospholipids [9]. Phosphatidylcholine, the most abundant phospholipid in the brain, is generated primarily via a well-characterised pathway known as the Kennedy pathway [10].

The Kennedy pathway [10]: the formation of phosphatidylcholine involves three sequential enzymatic reactions. In the first, a monophosphate is transferred to choline, yielding phosphocholine. In the second, cytidine-5-monophosphate is transferred from cytidine triphosphate to phosphocholine, yielding cytidine diphosphate-choline (CDP-choline). Finally, cytidine diphosphate-choline and diacylglycerol (DAG) bond to yield phosphatidylcholine, the most abundant phospholipid in neuronal membranes. PUFAs = omega-3 polyunsaturated fatty acids; UMP = uridine monophosphate.

In Alzheimer’s disease, the levels of nutrients required to support this pathway seem not to be available in sufficient quantities. [11-13].

The production of phosphatidylcholine is positively affected by increasing the bioavailability of the nutrients omega-3 polyunsaturated fatty acids, uridine monophosphate and choline [9]. Furthermore, in preclinical experiments, enhancing the diet with certain nutrients was shown to increase dendritic spines, synaptic proteins and neurite outgrowth, all prerequisites for synapse formation [14-17]. The greatest effects were observed when combinations of nutrients were used [9, 17-19]. Administration of these nutrients was also shown to improve learning and memory in preclinical models [19-24]. These research findings provided the scientific rationale for the formulation of Souvenaid.

Souvenaid provides nutritional precursors and cofactors that work together to support synapse formation

  • Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), uridine monophosphate (UMP) and choline are precursors required to enhance neuronal membrane formation [25]
  • B vitamins and phospholipids serve as cofactors by enhancing bioavailability of the precursors

The specific combination of these nutrients can support the formation of neuronal membranes by increasing phosphatidylcholine synthesis and [9, 14-18].

 

References

  1. Wurtman RJ, Ulus IH, Cansev M, Watkins CJ, Wang L, Marzloff G. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res. 2006;1088:83-92.
  2. Kennedy EP, Weiss SB. The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem 1956;222:193-214.
  3. Igarashi M, Ma K, Gao F, Kim HW, Rapoport SI, Rao JS. Disturbed Choline Plasmalogen and Phospholipid Fatty Acid Concentrations in Alzheimer's Disease Prefrontal Cortex. JAD 2011; 24, 507-517.
  4. Pettegrew JW, Panchalingam K, Hamilton RL, McClure RJ. Brain membrane phospholipid alterations in Alzheimer's disease. Neurochem Res 2001 26, 771-782.
  5. Mulder C, Wahlund LO, Teerlink T, Blomberg M, Veerhuis R, van Kamp GJ, Scheltens P, Scheffer PG. Decreased lysophosphatidylcholine/phosphatidylcholine ratio in cerebrospinal fluid in Alzheimer's disease. J Neural Transm 2003; 110, 949-955.
  6. Sakamoto T, Cansev M, Wurtman RJ. Oral supplementation with docosahexaenoic acid and uridine-5'-monophosphate increases dendritic spine density in adult gerbil hippocampus. Brain Res. 2007;1182:50-9.
  7. Wang L, Pooler AM, Albrecht MA, Wurtman RJ. Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci. 2005;27:137-45.
  8. Pooler AM, Guez DH, Benedictus R, Wurtman RJ. Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12 [corrected]. Neuroscience. 2005;134(1):207-14.
  9. Cansev M, Marzloff G, Sakamoto T, Ulus IH, Wurtman RJ. Giving uridine and/or docosahexaenoic acid orally to rat dams during gestation and nursing increases synaptic elements in brains of weanling pups. Dev Neurosci. 2009;31:181-92.
  10. Savelkoul PJ, Janickova H, Kuipers AA, Hageman RJ, Kamphuis PJ, Dolezal V, Broersen LM. A specific multi-nutrient formulation enhances M1 muscarinic acetylcholine receptor responses in vitro. J Neurochem. 2012;120:631-40.
  11. Holguin S, Martinez J, Chow C, Wurtman R. Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils. FASEB J. 2008;22:3938-46.
  12. Teather LA, Wurtman RJ. Chronic administration of UMP ameliorates the impairment of hippocampal-dependent memory in impoverished rats. J Nutr. 2006;136:2834-7.
  13. de Wilde MC, Hogyes E, Kiliaan AJ, Farkas T, Luiten PG, Farkas E. Dietary fatty acids alter blood pressure, behavior and brain membrane composition of hypertensive rats. Brain Res. 2003;988:9-19.
  14. de Wilde MC, Farkas E, Gerrits M, Kiliaan AJ, Luiten PG. The effect of n-3 polyunsaturated fatty acid-rich diets on cognitive and cerebrovascular parameters in chronic cerebral hypoperfusion. Brain Res. 2002;94:166-73.
  15. De Bruin NM, Kiliaan AJ, De Wilde MC, Broersen LM. Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats. Neurobiol Learn Mem. 2003;80:63-79.
  16. de Wilde MC, Penke B, van der Beek EM, Kuipers AA, Kamphuis PJ, Broersen LM. Neuroprotective effects of a specific multi-nutrient intervention against Aβ42-induced toxicity in rats. J Alzheimers Dis. 2011;27:327-39.
  17. Scheltens P, Twisk JWR, Blesa R, Scarpini E, von Arnim CAF, Bongers A, Harrison J,  Swinkels SHN, Stam CJ, de Waal H, Wurtman RJ, Wieggers RL, Vellas B, Kamphuis PJGH. Efficacy of Souvenaid in mild Alzheimer’s disease – results from a randomised, controlled trial. J Alzheimers Dis (in press)