Citrus supplementation in subjective cognitive decline: results of a 36-week, randomized, placebo-controlled trial.
Interleukin-8
Nutraceutical
Placebo response
Randomized clinical trial
Subjective cognitive decline
Journal
Nutrition journal
ISSN: 1475-2891
Titre abrégé: Nutr J
Pays: England
ID NLM: 101152213
Informations de publication
Date de publication:
01 Nov 2024
01 Nov 2024
Historique:
received:
29
06
2024
accepted:
23
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
epublish
Résumé
Developing interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD. Eighty participants were randomly assigned to active treatment (400 mg of Citrus peel extract containing 3.0 mg of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) levels over the 36-week trial period in a subsample of 60 consecutive participants. An Intention-to-treat approach with generalized linear mixed models was used for data analysis. The RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time < .001, d = 0.36, p time x treatment = .910). Significant time effects were also found in cognitive domains of short- and long-term verbal memory (p < .001) and scales of subjective memory (p < .01), with no significant time x treatment interaction. The largest effect sizes were observed in verbal memory in the placebo group (d = 0.69 in short-term, and d = 0.78 in long-term verbal memory). Increased IL-8 levels were found at 36-week follow-up in both Citrus peel extract and placebo groups (p for time = .010, d = 0.21, p time x treatment = .772). Adverse events were balanced between groups. In this randomized clinical trial, long-term Citrus peel extract supplementation did not show cognitive benefits over placebo in participants with SCD, possibly due to high placebo response. These findings might have specific implications for designing future nutraceutical trials in individuals experiencing SCD. The trial has been registered at the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 ( https://www. gov/ct2/show/NCT04744922 ).
Sections du résumé
BACKGROUND
BACKGROUND
Developing interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD.
METHODS
METHODS
Eighty participants were randomly assigned to active treatment (400 mg of Citrus peel extract containing 3.0 mg of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) levels over the 36-week trial period in a subsample of 60 consecutive participants. An Intention-to-treat approach with generalized linear mixed models was used for data analysis.
RESULTS
RESULTS
The RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time < .001, d = 0.36, p time x treatment = .910). Significant time effects were also found in cognitive domains of short- and long-term verbal memory (p < .001) and scales of subjective memory (p < .01), with no significant time x treatment interaction. The largest effect sizes were observed in verbal memory in the placebo group (d = 0.69 in short-term, and d = 0.78 in long-term verbal memory). Increased IL-8 levels were found at 36-week follow-up in both Citrus peel extract and placebo groups (p for time = .010, d = 0.21, p time x treatment = .772). Adverse events were balanced between groups.
CONCLUSIONS
CONCLUSIONS
In this randomized clinical trial, long-term Citrus peel extract supplementation did not show cognitive benefits over placebo in participants with SCD, possibly due to high placebo response. These findings might have specific implications for designing future nutraceutical trials in individuals experiencing SCD.
TRIAL REGISTRATION
BACKGROUND
The trial has been registered at the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 ( https://www.
CLINICALTRIALS
RESULTS
gov/ct2/show/NCT04744922 ).
Identifiants
pubmed: 39482712
doi: 10.1186/s12937-024-01039-8
pii: 10.1186/s12937-024-01039-8
doi:
Substances chimiques
Plant Extracts
0
Interleukin-8
0
Flavanones
0
naringenin
HN5425SBF2
Banques de données
ClinicalTrials.gov
['NCT04744922']
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
135Informations de copyright
© 2024. The Author(s).
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