Although oral nutrient supplementation (ONS) appeared to improve redox status in trial patients included in the review, the authors note that results for other outcomes, such as inflammation, depression, and cognitive function, were “inadequate to suggest post-supplementation improvements”.
Writing in Dietetics, they comment: “ONS with saffron compounds may prove beneficial in improving antioxidant defence and oxidative stress in patients with MS; however, the evidence is scattered and inadequate in terms of making any suggestions regarding the direction of effect of other outcomes.”
The researchers assert that the non-standardised nature of these trials could multiply the probability of adverse events (AEs) and stressed the importance of implementing “specific standards of safety and efficacy”.
Symptoms and therapy
MS is an immune-mediated disease of the central nervous system (CNS), characterised by sensory loss, visual disturbance, muscle weakness and fatigue, cognitive impairment, chronic pain, and brain atrophy, among other symptoms, while disease pathogenesis is linked to environmental / lifestyle factors and genetic predisposition, the authors explain.
Clinicals often recommend natural alternative therapies as complementary treatment for patients - and particularly antioxidants that can reduce oxidative stress and improve anti-inflammatory response in MS.
Saffron contains active ingredients that demonstrate antidepressant, cardioprotective, neuroprotective, and neurocognitive activity, and as such it may prove to be a valuable treatment for managing several symptoms of the disease.
However, the “exact effect has not been weighed using evidence synthesis methods” that could inform clinical decisions.
“Given the frequent use of antioxidant supplements from patients with MS, it is important to understand which ones are efficient - and where further research is required,” the authors say.
Parameters and material
The review was designed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) with Synthesis Without Meta-analysis (SWiM) extension. Risk of bias was assessed using Cochrane’s RoB tool 2.0.
Trial material was sourced from the PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) database, clinicaltrials.gov website, and through gray literature searches.
Five randomised controlled trials (RCTs) were eligible for inclusion and included 225 patients with an MS diagnosis. Patient numbers per trial varied from 40 to 52.
Outcomes of interest were specific index/score for MS, including fatigue, disability, inflammation markers, redox status, cognition, physical function, anxiety, depression, and quality of life (QoL).
The authors note that most RCTs failed to provide information regarding saffron active ingredients or characteristics suggested by the Consolidated Standards of Reporting Trials (CONSORT) for herbal medicine.
“The exact composition of each intervention, the dose of active saffron ingredients, the type and concentration of extract solvent used, purity tests, and many more characteristics are missing from the RCTs,” they say.
Information relating to treatment adherence, and other biases was also missing in the majority of cases: the authors maintain that 60% of RCTs demonstrated an overall risk of bias and 40% a high RoB.
Moreover, three failed to disclose any information relating to adverse events. In fact, only one trial reported on adverse effects (AEs) – of which there were none - and one controlled for treatment adherence.
Given these protocol shortcomings and in spite of some proven benefits, the authors conclude: “Trials of better design and MS-specific outcomes are required to aid decision making regarding the efficacy of supplementation with saffron in MS.”
Published online, December 1, 2022: http://doi.org/10.3390/dietetics1030030
‘Supplementation with Crocus sativus L. (Saffron) against Placebo in Multiple Sclerosis: A Systematic Review and Synthesis without Meta-Analysis of Randomized Controlled Trials’
Authors: Grammatikopoulou, M.G., Tsiogkas, S.G., Gkiouras, K., Gioxari, A., Daskalou, E., Maraki. M.I., Dardiotis. E., and Bogdanos. D.P.,