The Lack of Standardization and Pharmacological Effect Limits the Potential Clinical Usefulness of Phytosterols in Benign Prostatic Hyperplasia

Abstract

The prevalence of benign prostatic hyperplasia (BPH) markedly increases with age. Phytotherapeutic approaches have been developed over time owing to the adverse side effects of conventional medications such as 5-reductase inhibitors and α1-adrenergic receptor antagonists. Therefore, dietary supplements (DS) containing active compounds that benefit BPH are widely available. Phytosterols (PSs) are well recognized for their role in maintaining blood cholesterol levels; however, their potential in BPH treatment remains unexplored. This review aims to provide a general overview of the available data regarding the clinical evidence and a good understanding of the detailed pharmacological roles of PSs-induced activities at a molecular level in BPH. Furthermore, we will explore the authenticity of PSs content in DS used by patients with BPH compared to the current legislation and appropriate analytical methods for tracking DS containing PSs. The results showed that PSs might be a useful pharmacological treatment option for men with mild to moderate BPH, but the lack of standardized extracts linked with the regulation of DS containing PSs and experimental evidence to elucidate the mechanisms of action limit the use of PSs in BPH. Moreover, the results suggest multiple research directions in this field.

Keywords: benign prostatic hyperplasia; campesterol; dietary supplement; phytosterol; sitosterol.

Figure 1

Cholesterol with carbon numbering according to IUPAC.

Figure 2

The structures of the most common phytosterols found in dietary supplements (free-form FPS and conjugated CPS); green radical—fatty acid residue.

Figure 3

Schematic representation of mechanism involved in BPH. Anti-androgenic, anti-inflammatory, antioxidant, and pro-apoptotic mechanisms of PSs. PS: phytosterols, ES: estrogen, T: testosterone, DHT: dihydrotestosterone, Bcl-2: B-cell lymphoma 2, Bax: Bcl-2- associated X protein, ERK: extracellular signal-regulated protein kinase, JNK: Jun N-terminal Kinase, EGF: epidermal growth factor, TGF-β: transforming growth factor β, PP2A: phosphatase A, 5-αR: 5α-reductase, COX-2: cyclooxygenase-2, iNOS: inducible nitric oxide synthase, RTK: receptor tyrosine kinase, TGFBR: TGF-β receptor, ROS: reactive oxygen species; PG: prostaglandins; Akt: protein kinase B; SPh: sphingomyelin; Sph-synthase: sphingomyelin synthase.

Figure 4

Main steps in the determination of total phytosterols. IS (internal standard) TMS (Trimethylsilyl ether); HPLC (high liquid chromatography); GC (gas chromatography); NP (normal phase); RP (reverse phase).