Clinical Evidence: Neuroaspis

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A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomized, double-blind, placebo-controlled proof-of-concept clinical trial

Marios C Pantzaris et al

Objective: To assess whether three novel interventions, formulated based on a systems medicine therapeutic concept, reduced disease activity in patients with relapsing–remitting multiple sclerosis (MS) who were either treated or not with disease modifying treatment.

Design: A 30-month randomized, double-blind, placebo-controlled, parallel design, phase II proof-of-concept clinical study.

Settings: Cyprus Institute of Neurology and Genetics.

Participants: Participants: 80 participants were randomized into four groups of 20 each. A total of 41 (51%) patients completed the 30-month trial. The eligibility criteria were an age of 18–65; a diagnosis of relapsing– remitting MS according to the McDonald criteria; a score of 0.0–5.5 on the Expanded Disability Status Scale (EDSS); MRI showing lesions consistent with MS; at least one documented clinical relapse and either receiving or not a disease-modifying treatment within the 24-month period before enrolment in the study. Patients were excluded because of a recent t (<30 days) relapse, prior immunosuppressant or monoclonal antibody therapy, pregnancy or nursing, other severe disease compromising organ function, progressive MS, history of recent drug or alcohol abuse, use of any additional food supplements, vitamins or any form of polyunsaturated fatty acids, and a history of severe allergic or anaphylactic reactions or known specific nutritional hypersensitivity.

Interventions: The first intervention (A) was composed of Ω-3 and Ω-6 polyunsaturated fatty acids at 1:1 wt/wt. Specifically, the Ω-3 fatty acids were docosahexaenoic acid and eicosapentaenoic acid at 3:1 wt/wt, and the Ω-6 fatty acids were linoleic acid and γ-linolenic acid at 2:1 wt/wt. This intervention also included minor quantities of other specific polyunsaturated, monounsaturated and saturated fatty acids as well as vitamin A and vitamin E (α-tocopherol). The second intervention (B, PLP10) was a combination of A and γ-tocopherol. The third intervention (C) was γ-tocopherol alone. The fourth group of 20 participants received placebo. The interventions were administered per os (by mouth) once daily, 30 min before dinner for 30 months.

Main outcome measures: The primary end point was the annualized relapse rate (ARR) of the three interventions versus the placebo at 2 years. The secondary end point was the time to confirmed disability progression at 2 years.

Results: A total of 41 (51%) patients completed the 30-month trial. Overall, for the per-protocol analysis of the 2-year primary end point, eight relapses were recorded in the PLP10 group (n=10; 0.40 ARR) versus 25 relapses in the placebo group (n=12; 1.04 ARR), representing a 64% adjusted relative rate reduction for the PLP10 group (RRR 0.36, 95% CI 0.15 to 0.87, p=0.024). In a subgroup analysis that excluded patients on monoclonal antibody (natalizumab) treatment, the observed adjusted RRR became stronger (72%) over the 2 years (RRR 0.28, 95% CI 0.10 to 0.79, p=0.016). The per-protocol analysis for the secondary outcome at 2 years, the time to disability progression, was significantly longer only for PLP10. The cumulative probability of disability progression at 2 years was 10% in the PLP10 group and 58% in the placebo group (unadjusted log-rank p=0.019). In a subgroup analysis that excluded patients on natalizumab, the cumulative probability of progression was 10% for the 10 patients in the PLP10 group and 70% for the 12 patients in the placebo group, representing a relative 86% decrease in the risk of the sustained progression of disability in the PLP10 group (unadjusted log-rank p=0.006; adjusted HR, 0.11; 95% CI 0.01 to 0.97, p=0.047). No adverse events were reported. Interventions A (10 patients) and C (9 patients) showed no significant efficacy.

Conclusions: In this small proof-of-concept, randomized, doubleblind clinical trial; the PLP10 treatment significantly reduced the ARR and the risk of sustained disability progression without any reported serious adverse events. Larger studies are needed to further assess the safety and efficacy of PLP10.

Trial registration: International Standard Randomized Controlled Trial, number ISRCTN87818535

BMJ Open 2013;3:e002170. doi:10.1136/bmjopen-2012-002170

The Effects of Specific Omega-3 and Omega-6 Polyunsaturated Fatty Acids and Antioxidant Vitamins on Gait and Functional Capacity Parameters in Patients with Relapsing-Remitting Multiple Sclerosis

Panayiotis Aristotelous et al

 Patients with multiple sclerosis (MS) are characterized by, among other symptoms, impaired functional capacity and walking difficulties. Polyunsaturated fatty acids (PUFAs) have been found to improve MS patients’ clinical outcomes; however, their effect on other parameters associated with daily living activities need further investigation. The current study aimed to examine the effect of a 24-month supplementation with a cocktail dietary supplement formula, the Neuroaspis PLP10, containing specific omega-3 and omega-6 PUFAs and specific antioxidant vitamins on gait and functional capacity parameters of patients with MS. Fifty-one relapsing-remitting MS (RRMS) patients with low disability scores (age: 38.4 ± 7.1 years; 30 female) were randomized 1:1 to receive either a 20 mL daily dose of the dietary formula containing a mixture of omega-3 and omega-6 PUFAs (12,150 mg), vitamin A (0.6 mg), vitamin E (22 mg), and γ-tocopherol (760 mg), the OMEGA group (n = 27; age: 39 ± 8.3 years), or 20 mL placebo containing virgin olive oil, the placebo group (n = 24; age: 37.8 ± 5.3 years). The mean ± SD (standard deviation) Expanded Disability Status Scale (EDSS) score for the placebo group was 2.36 and for the OMEGA group 2.22. All enrolled patients in the study were on Interferon-β treatment. Spatiotemporal gait parameters and gait deviation index (GDI) were assessed using a motion capture system. Functional capacity was examined using various functional tests such as the six-minute walk test (6MWT), two sit-to-stand tests (STS-5 and STS-60), and the Timed Up and Go test (TUG). Isometric handgrip strength was assessed by a dynamometer. Leg strength was assessed using an isokinetic dynamometer. All assessments were performed at baseline and at 12 and 24 months of supplementation. A total of 36 patients completed the study (18 from each group). Six patients from the placebo group and 9 patients from the OMEGA group dropped out from the study or were lost to follow-up. The dietary supplement significantly improved the single support time and the step and stride time (p < 0.05), both spatiotemporal gait parameters. In addition, while GDI of the placebo group decreased by about 10% at 24 months, it increased by about 4% in the OMEGA group (p < 0.05). Moreover, performance in the STS-60 test improved in the OMEGA group (p < 0.05) and there was a tendency for improvement in the 6MWT and TUG tests. Long-term supplementation with high dosages of omega-3 and omega-6 PUFAs (compared to previous published clinical studies using PUFAs) and specific antioxidant vitamins improved some functional capacity and gait parameters in RRMS patients.

Nutrients 2021, 13, 3661.

The Effects of a 6-Month High Dose Omega-3 and Omega-6 Polyunsaturated Fatty Acids and Antioxidant Vitamins Supplementation on Cognitive Function and Functional Capacity in Older Adults with Mild Cognitive Impairment

Pinelopi S. Stavrinou et al

The aim of the present study was to examine the effects of a high-dose omega-3 and omega-6 fatty acids supplementation, in combination with antioxidant vitamins, on cognitive function and functional capacity of older adults with mild cognitive impairment (MCI), over a 6- month period in a randomized, double-blind, placebo-controlled trial. Forty-six older adults with MCI (age: 78.8 ± 7.3 years) were randomized 1:1 to receive either a 20 mL dose of a formula containing a mixture of omega-3 (810 mg Eicosapentaenoic acid and 4140 mg Docosahexaenoic acid) and omega-6 fatty acids (1800 mg gamma-Linolenic acid and 3150 mg Linoleic acid) (1:1 w/w), with 0.6 mg vitamin A, vitamin E (22 mg) plus pure γ-tocopherol (760 mg), or 20mL placebo containing olive oil. Participants completed assessments of cognitive function, functional capacity, body composition and various aspects of quality of life at baseline and following three and six months of supplementation. Thirty-six participants completed the study (eighteen from each group). A significant interaction between supplementation and time was found on cognitive function (Addenbrooke’s Cognitive Examination -Revised (ACE-R), Mini-Mental State Examination (MMSE) and Stroop Color and Word Test (STROOP) color test; p < 0.001, p = 0.011 and p = 0.037, respectively), functional capacity (6-min walk test and sit-to-stand-60; p = 0.028 and p = 0.032, respectively), fatigue (p < 0.001), physical health (p = 0.007), and daily sleepiness (p = 0.007)—showing a favorable improvement for the participants receiving the supplement. The results indicate that this nutritional modality could be promising for reducing cognitive and functional decline in the elderly with MCI.

Nutrients 2020, 12, 325; doi:10.3390/nu12020325

Effects of N-3 Polyunsaturated Fatty Acids on Dementia

Hidekatsu Yanai

N-3 polyunsaturated fatty acids (PUFAs) including α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory effects and neuronal protective functions and may benefit prevention of dementia; however, the epidemiological evidence is very limited. Therefore, the literature about the association between n-3 PUFA and dementia was searched, by using Pubmed. In the analyses of observational studies, n-3 PUFA has been reported to be beneficially associated with dementia in 17 studies; however, the beneficial association between n-3 PUFA and dementia was denied by three studies. In the analyses of intervention studies, n-3 PUFA supplementation was beneficially associated with dementia in eight studies; however, five studies reported the negligible effect of n-3 PUFA for dementia. N-3 PUFA may improve Alzheimer’s disease by increasing clearance of amyloid-β peptide, neurotrophic and neuroprotective factors, and by anti-inflammatory effects. In conclusion, patients with mild memory and/or cognitive impairment can be treated by a long-term and higher intake of n-3 PUFA.

J Clin Med Res. 2017;9(1):1-9

Impact of Omega-3 Fatty Acid Supplementation on Memory Functions in Healthy Older Adults

Nadine Kulzow et al

As the process of Alzheimer’s disease (AD) begins years before disease onset, searching for prevention strategies is of major medical and economic importance. Nutritional supplementation with long-chain polyunsaturated omega-3 fatty acids (LC-n3-FA) may exert beneficial effects on brain structure and function. However, experimental evidence in older adults without clinical dementia is inconsistent, possibly due to low sensitivity of previously employed test batteries for detecting subtle improvements in cognition in healthy individuals. Here we used LOCATO, recently described as a robust and sensitive tool for assessing object-location memory (OLM) in older adults, to evaluate the impact of LC-n3-FA supplementation on learning and memory formation. In a double-blind placebo-controlled proof-of-concept study, 44 (20 female) cognitively healthy individuals aged 50–75 years received either LC-n3-FA (2,200 mg/day, n = 22) or placebo (n = 22) for 26 weeks. Before and after intervention, memory performance in the OLM-task (primary) was tested. As secondary outcome parameters, performance in Rey Auditory Verbal Learning Test (AVLT), dietary habits, omega-3-index, and other blood-derived parameters were assessed. Omega-3 index increased significantly in the LC-n3-FA group compared with the placebo group. Moreover, recall of object locations was significantly better after LC-n3-FA supplementation compared with placebo. Performance in the AVLT was not significantly affected by LC-n3-FA. This double-blind placebo-controlled proof-of-concept study provides further experimental evidence that LC-n3-FA exert positive effects on memory functions in healthy older adults. Our findings suggest novel strategies to maintain cognitive functions into old age.

Journal of Alzheimer’s Disease 51 (2016) 713–725 DOI 10.3233/JAD-150886