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


Souvenaid is a marketed product. For sale in Australia and some European countries but not the U.S., Souvenaid is a medical food designed to enhance the formation and function of synapses (Oct 2009 conference 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, 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). Since then, work by affiliated researchers has reported that diets containing the components of Fortasyn Connect are neuroprotective, improve cerebral blood flow, and reverse spatial learning defects in the APP/PS1 mouse model of AD (Jansen et al., 2013; Zerbi et al., 2014; Koivisto et al., 2014).


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 (Aug 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 (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, β-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 a meta-analysis of Souvenir 1, 2, and S-Connect data, scientists concluded that the supplement achieved a clinically detectable effect in patients with early AD (Cummings et al., 2017).

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 up to four additional years of optional, blinded extensions. The primary outcome was the NTB, and secondary outcomes included progression to dementia, other cognitive and functional measures, blood markers, and brain atrophy. This trial ran at sites in Finland, Germany, the Netherlands, and Sweden. It was completed in early 2019.

After two years of use, Souvenaid did not affect performance on the NTB, but did lead to slower decline on the CDR-sb and less hippocampal shrinkage (Mar 2016 conference news; Soininen et al., 2017). A post hoc analysis indicated that people on Souvenaid slowed their cognitive decline by one-third when measured on the ADCOMS (Hendrix et al., 2019).

At the 2020 AAT-AD/PD meeting, investigators reported results of a one-year extension including 45 treated and 36 placebo participants. After three years, the treatment effect widened. Those on Souvenaid showed a 45 percent slowing of decline on the CDR-sb compared with placebo, and a 33 percent decline in hippocampal atrophy. Both were significant (Apr 2020 conference news). A subsequent publication of the results reported improvement on additional endpoints, including a 60 percent slowing of decline on the NTB five-item composite, and 76 percent slowing on the NTB memory domain, compared to placebo. Whole brain atrophy slowed by 22 percent (Soininen et al., 2020).

In 2012, an RCT began to evaluate the effects of four weeks of once-daily Souvenaid on brain metabolism by way of brain magnetic resonance spectroscopy. It enrolled 34 people with mild to moderate AD. Compared with placebo controls, people on Souvenaid had changes in indices of phospholipid synthesis and breakdown, and choline metabolism; markers of neural integrity and gliosis were unchanged (Rijpma et al., 2017).

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. According to a poster presented at the 2020 AAIC conference, the study enrolled 116 people, who declined less on the IADL after six or 12 months of Souvenaid than a reference population (Ziere et al., 2020). 

In 2014, NL-ENIGMA began comparing six months of Souvenaid with placebo on the outcome of glucose metabolism as assessed by FDG-PET of brain regions affected in Alzheimer's disease (Scheltens et al., 2016). The trial enrolled 50 people with prodromal or mild AD; it found no change within treatment groups and no difference between treatment groups in glucose metabolism (Scheltens et al., 2019). A separate study reported that one year of Souvenaid significantly preserved glucose uptake on FDG-PET in people with MCI (Palomo et al., 2019).

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

In November 2019, a Phase 2 trial was registered that will compare one year of daily Souvenaid with a vitamin-only placebo on cognitive decline during normal aging. To be conducted at the University of Miami, this trial was originally scheduled to begin in December 2019 to enroll 120 participants aged 55 and 89 with age-related cognitive decline determined by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and a screen for subjective cognitive decline. Primary measures include a variety of cognitive tests. The study is now slated to begin in February 2021.

A trial will begin in April 2021 to study the feasibility of Souvenaid supplementation after acute traumatic brain injury. The primary outcome of the 50-person study will be retention rate after six months.

Souvenaid will be used in MIND-AD, a large, multimodal prevention trial planned for people with prodromal AD in Sweden, Finland, France, and Germany (see website). A pilot trial began in October 2017 to recruit 150 participants between 60 and 85 years old with biomarker-confirmed AD, low normal scores on memory tests, and potential for lifestyle improvements. Participants will follow one of three programs: regular health advice, a multidomain lifestyle intervention including nutritional guidance, exercise, cognitive training and management of vascular and metabolic risk factors, or the lifestyle intervention plus Souvenaid. The trial will run six months, with an optional six-month extension. The primary outcome is feasibility, assessed by recruitment time, overall adherence, and retention rate. The trial was set to end in November 2020.

In December 2020, a Cochrane meta-analyses concluded that Souvenaid "probably does not reduce the risk of progression to dementia in people with prodromal AD." Also, that "There is no convincing evidence that Souvenaid affects other outcomes important to people with AD in the prodromal stage or mild to moderate stages of dementia. Conflicting evidence on combined cognitive-functional outcomes in prodromal AD and mild AD dementia warrants further investigation" (Burckhardt et al., 2020).

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

Last Updated: 17 Dec 2020


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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. Souvenaid Trial Missed Primary, Partially Met Secondary Endpoints
  5. Non-Aβ, Non-Tau Drugs Tweak Markers, Cognition in Alzheimer’s, Huntington’s
  6. 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. . Effect Size Analyses of Souvenaid in Patients with Alzheimer's Disease. J Alzheimers Dis. 2017;55(3):1131-1139. PubMed.
  7. . 24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial. Lancet Neurol. 2017 Dec;16(12):965-975. Epub 2017 Oct 30 PubMed.
  8. . Alzheimer's Disease Composite Score: A Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer's Disease. J Prev Alzheimers Dis. 2019;6(4):232-236. PubMed.
  9. . 36-month LipiDiDiet multinutrient clinical trial in prodromal Alzheimer's disease. Alzheimers Dement. 2021 Jan;17(1):29-40. Epub 2020 Sep 13 PubMed.
  10. . The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial. Alzheimers Res Ther. 2017 Jul 26;9(1):51. PubMed.
  11. . Design of the NL-ENIGMA study: Exploring the effect of Souvenaid on cerebral glucose metabolism in early Alzheimer's disease. Alzheimers Dement (N Y). 2016 Nov;2(4):233-240. Epub 2016 Sep 1 PubMed.
  12. . Exploring effects of Souvenaid on cerebral glucose metabolism in Alzheimer's disease. Alzheimers Dement (N Y). 2019;5:492-500. Epub 2019 Sep 27 PubMed.
  13. . Mild Cognitive Impairment with a High Risk of Progression to Alzheimer's Disease Dementia (MCI-HR-AD): Effect of Souvenaid® Treatment on Cognition and 18F-FDG PET Scans. J Alzheimers Dis Rep. 2019 May 3;3(1):95-102. PubMed.
  14. . 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.
  15. . Souvenaid for Alzheimer's disease. Cochrane Database Syst Rev. 2020 Dec 15;12:CD011679. PubMed.
  16. . 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.
  17. . 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.
  18. . 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.
  19. . 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.
  20. . Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils. FASEB J. 2008 Nov;22(11):3938-46. PubMed.
  21. . Neuroprotective effects of a specific multi-nutrient intervention against Aβ42-induced toxicity in rats. J Alzheimers Dis. 2011;27(2):327-39. PubMed.
  22. . Effects of Specific Multi-Nutrient Enriched Diets on Cerebral Metabolism, Cognition and Neuropathology in AβPPswe-PS1dE9 Mice. PLoS One. 2013;8(9):e75393. PubMed.
  23. . Multinutrient diets improve cerebral perfusion and neuroprotection in a murine model of Alzheimer's disease. Neurobiol Aging. 2014 Mar;35(3):600-13. Epub 2013 Oct 2 PubMed.
  24. . Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease independent of brain amyloid deposition. J Nutr Biochem. 2014 Feb;25(2):157-69. Epub 2013 Nov 6 PubMed.

External Citations

  1. Ziere et al., 2020
  2. website)
  3. 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.
  7. . Souvenaid in the management of mild cognitive impairment: an expert consensus opinion. Alzheimers Res Ther. 2019 Aug 17;11(1):73. PubMed.
  8. . Magnetoencephalography for the Detection of Intervention Effects of a Specific Nutrient Combination in Patients with Mild Alzheimer's Disease: Results from an Exploratory Double-Blind, Randomized, Controlled Study. Front Neurol. 2016;7:161. Epub 2016 Oct 17 PubMed.
  9. . Effects of Souvenaid on plasma micronutrient levels and fatty acid profiles in mild and mild-to-moderate Alzheimer's disease. Alzheimers Res Ther. 2015;7(1):51. Epub 2015 Jul 24 PubMed.
  10. . Economic evaluation of supplementing the diet with Souvenaid in patients with prodromal Alzheimer's disease. Alzheimers Res Ther. 2020 Dec 11;12(1):166. PubMed.
  11. . The LipiDiDiet trial: what does it add to the current evidence for Fortasyn Connect in early Alzheimer's disease?. Clin Interv Aging. 2019;14:1481-1492. Epub 2019 Aug 15 PubMed.