Posted by Introduction: Sulforaphane (SFN) is a naturally occurring isothiocyanate (Fig.1) associated with various health benefits, including reduced cancer risk, and has been extensively explored as a potential therapeutic. However, its inherent instability presents challenges in formulation, storage, and administration as a medicinal product. To make this compound „druggable”, scientists prepared a cyclodextrin inclusion complex with alpha-cyclodextrin. (cavity size matters!) The complex, termed SFX-01 (Sulforadex®) is a patented synthetic form of racemic d,l sulforaphane stabilized within a biologically inert alpha-cyclodextrin complex. (1)
Figure 1. Structre of S/R sulforaphane (1-Isothiocyanato-4-(methanesulfinyl)butane)
Sulforaphane, a naturally occurring isothiocyanate derived from glucoraphanin (Fig.2) found in cruciferous vegetables (mainly in broccoli sprouts) and is associated with various health benefits.
Figure 2. Glucoraphanin, the glucosinolate precursor to sulforaphane
A recently published study (2) evaluated for the first time the human safety, tolerability and pharmacokinetic behaviour of sulforaphane (SFX-01) alpha-cyclodextrin complex (Fig 3) in a novel, enteric-coated tablet formulation in healthy male participants.
Fig. 3. Structure of sulforaphane (SFX-01) alpha-cyclodextrin complex (source patent WO2013179057A1)
From this study it was learned that SFX-01 was well tolerated over 7 days at the doses evaluated, with most side effects being mild and transient in nature. The pharmacokinetic properties of the SFX-01 tablet formulation were in line with expectations, suggesting that an enteric coating and stabilization of sulforaphane delivers levels of sulforaphane and metabolites in the range where biological activity is observed.
Why does the complexed sulphorafane have health benefits? Upon oral administration of sulforaphane/alpha-cyclodextrin complex SFX-01, sulforaphane activates the transcription factor so called NF-E2-related factor 2 (Nrf2; NFE2L2).This is Nuclear factor erythroid 2-related factor 2 (NRF2), is a transcription factor that in humans regulates the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation. Sulforaphane is the most potent known natural activator of the Nrf2 antioxidant pathway. So, sulforaphane/alpha-cyclodextrin complex is currently being tested in clinical trials for breast cancer and subarachnoid hemorrhage following stroke. (3)
Other expected benefits of sulforaphane/alpha-cyclodextrin complex:
Neuroprotective effect: No direct evidence for the complex, but is expected to offer same neuroprotective benefits as sulforaphane alone. Though no studies have been performed in humans or animals testing the in vitro neuroprotective effects of alpha-CD complexed Sulforaphane, neuroprotective antioxidant properties in cell culture were found. (4)
Summary and Highlights of health effects of sulforaphane/alpha-cyclodextrin complex
- Sulforaphane is a Nrf2 activator effective in experimental autoimmune encephalomyelitis.
- Sulforaphane alone is unstable at ambient temperature, needs stabilization.
- SFX-01 is a new, stabilized form of sulforaphane encapsulated in α-cyclodextrin.
- SFX-01 was found to reduce residual disability after experimental autoimmune encephalomyelitis.
- In humans, SFX-01 is well-tolerated. Further work is needed to study the role of
SFX-01 in Multiple Sclerosis.
References:
- WO2021205171A1 – Crystalline complexes – Google Patents, by Evgen Pharma, now called TheraCryf, Plc
- Glen Clack et al A Phase 1 Randomized, Placebo‑Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Enteric‑Coated Stabilized Sulforaphane (SFX‑01) in Male Participants Adv Ther (2025) 42:216–232 https://doi.org/10.1007/s12325-024-03018-1)
- Gold R, et al. “Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis”. (September 2012).The New England Journal of Medicine.367(12):1098–1107.doi:10.1056/NEJMoa1114287.hdl:2078.1/124401.PMID 22992073
- Ian Galea et al SFX-01 reduces residual disability after experimental autoimmune encephalomyelitis, Multiple Sclerosis and Related Disorders Volume 30, May 2019, Pages 257-261
Ps. Based on previous alpha-cyclodextrin -related health benefits, authors of this blog have a question: how about the performance of plain alpha-cyclodextrin alone in similar tests?