Name: Souvenaid
Synonyms: FortasynTM Connect
Therapy Type: Dietary Supplement (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Not Regulated)
Status in Select Countries: Marketed


Souvenaid is a marketed product. It is a medical food designed to enhance the formation and function of synapses (Oct 2009 newsde Wilde et al., 2011). It contains a combination of nutrient precursors and co-factors known to be needed in the synthesis of neuronal membranes. Called Fortasyn Connect, this formulation includes docosahexaenoic acid, eicosapentaenoic acid, uridine-5'-mono-phosphate, choline, phospholipids, antioxidants, selenium, and B, C, and E vitamins. 

Preclinical data on this formulation, or its components, were reported from more than a dozen studies in various cell-based and animal models. For example, components of Fortasyn Connect were reported to increase the brain concentration of synaptic proteins and phospholipids, and to stimulate neurite outgrowth and improve performance on behavioral assays in rats and gerbils (e.g. Wang et al., 2005Wurtman et al., 2006Cansev et al., 2008Holguin et al., 2008).

One study, by researchers at Nutricia, claimed a protective effect against Aβ42-induced toxicity in rats (de Wilde et al., 2011).


Souvenaid is taken as a 125-ml breakfast drink. In clinical trials, it is being compared with a placebo of equal calories. 

In 2006, the first multicenter RCT, a 12-week study conducted in the Netherlands with 212 people with early AD, was reported to have yielded an efficacy signal on one delayed verbal memory test but not on the ADAS-cog 13 (see 2008 conference news).

Starting in 2009, the multicenter S-Connect study evaluated a six-month course of Souvenaid in 527 people with mild to moderate AD who were on standard Alzheimer's therapy. The primary outcome measure was the ADAS-cog 11. Souvenaid was safe, and compliance was high as reflected by blood concentration of Souvenaid nutrient components; however, the treatment and placebo groups declined equally, showing no efficacy on the primary endpoint (see Shah et al., 2013). 

Starting also in 2009, the Souvenir 1 and 2 trials respectively enrolled 225 and 255 patients with mild Alzheimer's disease who took no other AD medications. The former trial administered Souvenaid for three months and used the Wechsler Memory Scale test of delayed verbal recall, as well as the ADAS-cog 13, as its primary outcome; the latter trial ran for six months and used the z score on the neuropsychological test battery NTB as its primary outcome, with EEG measures of functional connectivity as a secondary outcome. The Souvenir 1 study reportedly showed a treatment benefit on a delayed verbal memory task, though the trial's other cognitive and functional outcome measures were unchanged (Scheltens et al., 2010). Souvenir 2 reported a trend toward benefit on the overall NTB, and a treatment benefit on the NTB's memory component. Secondary analysis of 179 Souvenir 1 and 2 participants showed that during the treatment phase, beta-band network measures of EEG differed between study groups in favor of the active group, indicating that Souvenaid might preserve synaptic brain networks, but the differences did not correlate with memory performance and their interpretation remains unclear. Souvenaid was again well-tolerated (Nov 2011 conference newsNov 2012 conference newsScheltens et al. 2012de Waal et al., 2014). In a six-month, open-label extension offered to patients in both trials, data from 201 participants confirmed high compliance and safety, as well as a treatment benefit on an exploratory NTB readout (Olde Rikkert et al., 2015). 

In 2009, the LipiDiDiet Trial began enrolling 300 people with prodromal Alzheimer's who do not take other AD medications for a two-year trial, with open-label extensions. The primary outcome is the NTB, and secondary outcomes include progression to dementia, as well as other cognitive and functional measures, blood markers, and brain atrophy. This trial has been completed but not yet published.

In 2012, an RCT in 30 people with mild to moderate AD used brain magnetic resonance spectroscopy to measure the effects of four weeks of once-daily Souvenaid on brain metabolism. This study is complete but not yet published. 

In 2013, the open-label AWARE study began to enroll 315 people with AD to evaluate the effect of Souvenaid in clinical practice settings against the Amsterdam version of the International Activities of Daily Living Questionnaire. 

In 2014, NL-ENIGMA, an RCT of 40 people with prodromal or mild AD, began. It will evaluate the effect of a six-month course of Souvenaid on glucose metabolism as assessed by FDG-PET of brain regions affected in Alzheimer's disease. 

Souvenaid has also been reported to reduce behavioral symptoms in a small, three-month crossover trial of frontotemporal dementia (see Pardini et al., 2015).

For a listing of trials, see International Clinical Trials Registry Platform.

Last Updated: 16 Oct 2015


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News Citations

  1. Chicago: Phase 2 News—Therapeutic Breakfast Food?
  2. Nutrient Formulation Appears to Grease Memory Function
  3. CTAD: EEG Gains Luster as More Trials Incorporate Biomarkers
  4. Medical Foods—Food for Thought, But Think Twice

Paper Citations

  1. . The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer's disease. Alzheimers Res Ther. 2013;5(6):59. Epub 2013 Nov 26 PubMed.
  2. . Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial. Alzheimers Dement. 2010 Jan;6(1):1-10.e1. PubMed.
  3. . Efficacy of Souvenaid in mild Alzheimer's disease: results from a randomized, controlled trial. J Alzheimers Dis. 2012;31(1):225-36. PubMed.
  4. . The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study. PLoS One. 2014;9(1):e86558. Epub 2014 Jan 27 PubMed.
  5. . Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study. J Alzheimers Dis. 2015;44(2):471-80. PubMed.
  6. . Souvenaid reduces behavioral deficits and improves social cognition skills in frontotemporal dementia: a proof-of-concept study. Neurodegener Dis. 2015;15(1):58-62. Epub 2015 Jan 15 PubMed.
  7. . Utility of imaging for nutritional intervention studies in Alzheimer's disease. Eur J Pharmacol. 2011 Sep;668 Suppl 1:S59-69. Epub 2011 Jul 27 PubMed.
  8. . Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci. 2005;27(1):137-45. PubMed.
  9. . Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res. 2006 May 9;1088(1):83-92. PubMed.
  10. . Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses. Alzheimers Dement. 2008 Jan;4(1 Suppl 1):S153-68. PubMed.
  11. . Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils. FASEB J. 2008 Nov;22(11):3938-46. PubMed.
  12. . Neuroprotective effects of a specific multi-nutrient intervention against Aβ42-induced toxicity in rats. J Alzheimers Dis. 2011;27(2):327-39. PubMed.

External Citations

  1. International Clinical Trials Registry Platform

Further Reading


  1. . A nutritional approach to ameliorate altered phospholipid metabolism in Alzheimer's disease. J Alzheimers Dis. 2014;41(3):715-7. PubMed.
  2. . Dietary long chain PUFAs differentially affect hippocampal muscarinic 1 and serotonergic 1A receptors in experimental cerebral hypoperfusion. Brain Res. 2002 Nov 1;954(1):32-41. PubMed.
  3. . Dietary supplementation with uridine-5'-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat. Brain Res. 2007 Feb 16;1133(1):42-8. Epub 2006 Dec 19 PubMed.
  4. . A specific multi-nutrient formulation enhances M1 muscarinic acetylcholine receptor responses in vitro. J Neurochem. 2012 Feb;120(4):631-40. PubMed.
  5. . Dietary fatty acids alter blood pressure, behavior and brain membrane composition of hypertensive rats. Brain Res. 2003 Oct 24;988(1-2):9-19. PubMed.
  6. . Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats. Neurobiol Learn Mem. 2003 Jul;80(1):63-79. PubMed.