Improving natural product research translation: From source to clinical trial

Abstract

While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a Septe mber, 2018 trans disci plina ry workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research. K E Y W O R D S clinical predictive validity, dietary supplements, model systems, rigor and replicability, value of information | 43 SORKIN et al.still provide invaluable guidance, the results of such trials are often met with concerns that different design choiceswhether of product, dose, timing, participant eligibility criteria, outcomes, etc.-might have yielded a substantially different result. Each interventional trial represents a substantial investment, with well-powered Phase III CTs typically consuming more than $10 million and many person-years. 9,10 Additionally, as time and funds are limited, and participant pools may also be constrained, a decision to invest in a CT often precludes pursuing other research questions, 11 which may provide more useful public health-relevant knowledge than an RCT with an insufficient evidence base.

Antitumor effect and molecular mechanism of fucoidan in NSCLC

“…Recently, great interest has been raised in developing natural molecules as potential anticancer agents [ 22 ]. Many recent studies have have been investigated to discover the potential anti-tumor natural products using in vitro and in vivo systems.…”

West meets east: open up a dialogue on phytomedicine

“…The development of health products of phytomedicine has often stemmed from traditional or historical use, or from long-term evidence that consumption of phytomedicine is associated with better health outcomes [ 1 ]. Phytomedicine represent a collection of therapeutic knowledge that deeply rooted in a culture and formed the basis of early version of pharmacopoeias, which was based in large part on natural products originated from botanicals, animals, fungi, and minerals.…”

Omega-7 Mixed Fatty Acid Supplementation Fails to Reduce Serum Inflammatory Biomarkers: A Placebo-Controlled, Double-Blind Randomized Crossover Trial

“…Our study showed a decreased trend for the cytokines TNFα and IL-6 with MCT and an increased trend with n7FA. It is a well-described phenomenon that most natural product clinical trials have failed to show statistical significance beyond placebo [ 4 ]. CAM clinical trials, including vitamins, minerals, and other dietary supplements are likely to have low effect sizes because the underlying purpose of using CAM is most often to assist the inherent healing process of the individual and this may be easily confounded by the placebo effect.…”

“…Essential fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been extensively studied for their potential anti-inflammatory effects [ 2 ]. Omega-7-rich mixed fatty acid (n7FA) supplements have also been proposed to modulate serum inflammatory biomarkers [ 3 , 4 ]. The principal active constituent of n7FA is palmitoleate, which is a 16-carbon monounsaturated (16:1) fatty acid with a double bond occurring at the 7th carbon atom away from the methyl group.…”