RETRACTED: Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial

Abstract

Background: The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. Objective: To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. Methods: Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged > 60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-β peptide (Aβ) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. Results: A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (–6.51, –10.57 to –2.45) compared to placebo. DHA lower the Aβ40 levels (–40.57, –79.79 to –1.35) compared to placebo (p < 0.05), and folic acid + DHA reduced the Aβ42 (–95.59, –150.76 to –40.43) and Aβ40 levels (–45.75, –84.67 to –6.84) more than DHA (p < 0.05). Conclusion: Folic acid and DHA improve cognitive function and reduce blood Aβ production in MCI patients. Combination therapy may be more beneficial in reducing blood Aβ-related biomarkers.

Associations of Multidomain Interventions With Improvements in Cognition in Mild Cognitive Impairment

“…The publication period ranged from 2011 to 2021, as summarized in Table 1 . 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 Seventeen studies recruited participants from the community 31 , 32 , 36 , 37 , 39 , 40 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 whereas 11 recruited from memory clinics. 33 , 34 , 35 , 38 , 41 , 42 , 43 , 44 , 45 , 46 , 47 Total sample sizes ranged from 22 to 555, with a mean (SD) age of 71.6 (3.4) years.…”

“… 53 Eighteen studies conducted the intervention components sequentially, 31 , 33 , 34 , 36 , 37 , 38 , 40 , 41 , 42 , 43 , 44 , 46 , 47 , 48 , 49 , 54 , 57 , 58 whereas 10 studies conducted them simultaneously. 32 , 35 , 39 , 45 , 50 , 51 , 52 , 53 , 55 , 56 Interventions were also completed in a group setting in 19 studies 31 , 33 , 34 , 35 , 36 , 38 , 39 , 40 , 45 , 47 , 48 , 49 , 50 , 52 , 53 , 54 , 55 , 56 , 58 compared with the remaining 9, which were conducted individually. 32 , 37 , 41 , 42 , 43 , 44 , 46 , 51 , 57 Lastly, the active control in 21 studies contained 1 component of the multidomain int...…”

“… 32 , 35 , 39 , 45 , 50 , 51 , 52 , 53 , 55 , 56 Interventions were also completed in a group setting in 19 studies 31 , 33 , 34 , 35 , 36 , 38 , 39 , 40 , 45 , 47 , 48 , 49 , 50 , 52 , 53 , 54 , 55 , 56 , 58 compared with the remaining 9, which were conducted individually. 32 , 37 , 41 , 42 , 43 , 44 , 46 , 51 , 57 Lastly, the active control in 21 studies contained 1 component of the multidomain intervention, 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 51 , 53 , 54 , 57 , …”

The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer’s Disease

“…Additionally, experimental and theoretical evidence showed that FoA generates suppressing effects on Tau fibril formation through a spontaneous hydrophobic interaction leading to native state stabilization of tau followed by a decline in protein-protein interactions and Tau oligomerization [209]. In combination therapy with compounds such as docosahexaenoic acid [210], memantine [211], α-Tocopherol [212], and isoflavones [213], FoA was able to enhance cognitive improvement while preventing the pathological alterations caused by Aβ toxicity. The above results collectively suggest that FoA exerts numerous beneficial effects, being responsible for restoring antioxidant enzymes activity, offering protective effects against insulin impairment, and inhibiting amyloid fibrillization.…”

Effects of Supplementation with Folic Acid and Its Combinations with Other Nutrients on Cognitive Impairment and Alzheimer’s Disease: A Narrative Review

“…Both FA, DHA, and their combination improved cognitive function (measured by the full-scale intelligence quotient (FSIQ) and other arithmetic, picture complement and digit span scores) compared to placebo. Likewise, supplementation with either FA or the combination of FA with DHA led to a reduction in Hcy levels, whereas FA plus DHA treatment reduced levels of Aβ biomarkers (Aβ40 and Aβ42) [ 89 ]. According to the analyzed studies, further research is needed on the effects of nutrient combination to slow down the progression of cognitive impairment.…”