title: Effects of Souvenaid on plasma micronutrient levels and fatty acid profiles in mild and mild-to-moderate Alzheimer's disease.
abstract: BACKGROUND
  Circulating levels of uridine, selenium, vitamins B12, E and C, folate, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been shown to be lower in patients with Alzheimer's disease (AD) than in healthy individuals. These low levels may affect disease pathways involved in synapse formation and neural functioning. Here, we investigated whether, and to what extent, circulating levels of micronutrients and fatty acids can be affected by oral supplementation with Souvenaid (containing a specific nutrient combination), using data derived from three randomized clinical trials (RCT) and an open-label extension (OLE) study with follow-up data from 12 to 48 weeks.
  
  
  METHODS
  Subjects with mild (RCT1, RCT2) or mild-to-moderate AD (RCT3) received active or control product once daily for 12-24 weeks or active product during the 24-week OLE following RCT2 (n = 212-527). Measurements included plasma levels of B vitamins, choline, vitamin E, selenium, uridine and homocysteine and proportions of DHA, EPA and total n-3 long-chain polyunsaturated fatty acids in plasma and erythrocytes. Between-group comparisons were made using t tests or non-parametric alternatives.
  
  
  RESULTS
  We found that 12-24-week active product intake increased plasma and/or erythrocyte micronutrients: uridine; choline; selenium; folate; vitamins B6, B12 and E; and fatty acid levels of DHA and EPA (all p < 0.001). In the OLE study, similar levels were reached in former control product/initial active product users, whereas 24-week continued active product intake showed no suggestion of a further increase in nutrient levels.
  
  
  CONCLUSIONS
  These data show that circulating levels of nutrients known to be decreased in the AD population can be increased in patients with mild and mild-tomoderate AD by 24-48-week oral supplementation with Souvenaid. In addition, to our knowledge, this is the first report of the effects of sustained dietary intake of uridine monophosphate on plasma uridine levels in humans. Uptake of nutrients is observed within 6 weeks, and a plateau phase is reached for most nutrients during prolonged intake, thus increasing the availability of precursors and cofactors in the circulation that may be used for the formation and function of neuronal membranes and synapses in the brain.
authors.affiliation: Radboud Alzheimer Center, Department of Geriatric Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: Rijpma
authors.affiliation: Radboud Alzheimer Center, Department of Geriatric Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Olga
authors.initials: O
authors.lastname: Meulenbroek
authors.affiliation: Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands.
authors.forename: Anneke M J
authors.initials: AM
authors.lastname: van Hees
authors.affiliation: Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands.
authors.forename: John W C
authors.initials: JW
authors.lastname: Sijben
authors.affiliation: Gerontopole, INSERM U1027, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL USA.
authors.forename: Raj C
authors.initials: RC
authors.lastname: Shah
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Radboud Alzheimer Center, Department of Geriatric Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Marcel G M
authors.initials: MG
authors.lastname: Olde Rikkert
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000178:diet therapy*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D005526:Food, Formulated; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D018977:Micronutrients / Q000097:blood*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress / Q000502:physiology; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D005227:Fatty Acids; D018977:Micronutrients; D018696:Neuroprotective Agents