A 1‐year randomized controlled trial of a nutritional blend to improve nutritional biomarkers and prevent cognitive decline among community‐dwelling older adults: The Nolan Study

Abstract

Introduction This study aimed to test the efficacy of a nutritional blend (NB) in improving nutritional biomarkers and preventing cognitive decline among older adults. Methods A 1‐year randomized, double‐blind, multicenter, placebo‐controlled trial with 362 adults (58.6% female, mean 78.3 years, SD = 4.8) receiving an NB or placebo. Erythrocyte ω‐3 index and homocysteine concentrations were primary outcomes. Other outcomes included Patient‐Reported Outcomes Measurement Information System (PROMIS) Applied Cognition‐Abilities, composite cognitive score (CCS), Cognitive Function Instrument (CFI) self‐assessment and study partner, hippocampal volume (HV), and Alzheimer's disease signature cortical thickness (CT). Results A total of 305 subjects completed the follow‐up. Supplementation increased ω‐3 index and decreased homocysteine, but did not affect CCS, CFI self‐assessment, HV, and CT. Placebo improved and treatment did not change PROMIS at 1 month. Intervention showed a positive effect on CFI study partner. Discussion Although improving nutritional biomarkers, this 1‐year trial with a multi‐nutrient novel approach was not able to show effects on cognitive outcomes among older adults.

Effect of a 1-Year Nutritional Blend Supplementation on Plasma p-tau181 and GFAP Levels among Community-Dwelling Older Adults: A Secondary Analysis of the Nolan Trial

“…Although the supplementation tested in the present trial was able to improve omega-3 index and to reduce plasma Hcy levels (17), its 1-year duration may have been insufficient to affect plasma p-tau181 and GFAP, as also the given doses of each nutrient or compound. The fact that participants of the study were generally healthy individuals may also have exacerbated this relatively short follow-up.…”

“…The Nolan Study is a double-blind, multicenter, randomized, placebo-controlled trial (RCT) conducted Major exclusion criteria were: taking vitamin-B supplements in the past three months; taking ω-3 PUFA supplements containing >200 mg of DHA/day over six months before inclusion; basic activities of daily living (ADL) score <4; Mini-Mental State Examination (MMSE) score <24; confirmed diagnosis of dementia. Detailed inclusion and exclusion criteria has been described elsewhere (17). Treatment with anticoagulants or platelet aggregation inhibitors were accepted, but carefully monitored, considering that ω-3 PUFA can affect platelet function.…”

“…The Nolan Study was then designed to test this novel approach, through offering a nutritional blend (NB) developed to serve as a source of multiple nutrients to community dwelling older adults, and previously tested on cats (12) and dogs (13). In spite of not being able to affect cognitive function, as measured by clinical tests (except for a positive effect on the Cognitive Function Instrument -CFI study partner score), the nutritional blend positively improved two biomarkers that are believed to underlie an attenuation in cognitive decline during aging (14)(15)(16): plasma homocysteine (Hcy) levels decreased and erythrocyte omega-3 index increased after the 1-year intervention (17).…”

Does Nutritional Supplementation Have a Disease-Modifying Effect on the Alzheimer’s Disease Neurodegenerative Process?

“…The Nolan Study, in turn, tested the effect of a 1-year multi-nutrient supplementation (including omega-3 PUFA, vitamin C, vitamin D, vitamin E, thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, folic acid, biotin, cobalamin, selenium, choline and citrulline) on clinical tests, imaging and blood biomarkers related to the AD pathology among a sample of 362 community-dwelling older adults living in France ( 28 , 29 ). At the end of the follow-up, supplementation could not postpone the increase in plasma p-tau181 (observed in both intervention and placebo groups) ( 29 ), and neither showed an effect on cognitive function ( 28 ). Another randomized controlled trial (RCT) found no benefits of a 16-week supplementation of combined vitamin E (800IU/day), vitamin C (500mg/day) and α-lipoic acid (ALA) (900mg/day), or coenzyme Q alone (1200mg/day) on CSF Aβ42, t-tau or p-tau181 in a sample of 66 subjects with mild to moderate AD ( 30 ).…”

“…The Nolan Study, in turn, tested the effect of a 1-year multi-nutrient supplementation (including omega-3 PUFA, vitamin C, vitamin D, vitamin E, thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, folic acid, biotin, cobalamin, selenium, choline and citrulline) on clinical tests, imaging and blood biomarkers related to the AD pathology among a sample of 362 communitydwelling older adults living in France (28,29). At the end of the follow-up, supplementation could not postpone the increase in plasma p-tau181 (observed in both intervention and placebo groups) (29), and neither showed an effect on cognitive function (28).…”