Sildenafil and analogous phosphodiesterase type 5 (PDE-5) inhibitors in herbal food supplements sampled on the Dutch market

Abstract

Herbal food supplements, claiming to enhance sexual potency, may contain deliberately added active pharmacological ingredients (APIs) that can be used for the treatment of erectile dysfunction (ED). The aim of this study was to determine whether herbal food supplements on the Dutch market indeed contain APIs that inhibit phosphodiesterase type 5 (PDE-5) inhibitors, such as sildenafil and analogous PDE-5 inhibitors. Herbal food supplements intended to enhance sexual potency (n = 71), and two soft drinks, were sampled from 2003 up to and including 2012. In 23 herbal supplements, nine different PDE-5 inhibitors were identified; in a few cases (n = 3), more than one inhibitor was indentified. The presence of these APIs was however not stated on the label. The concentrations of PDE-5 inhibitors per dose unit were analysed. Furthermore, the potential pharmacologically active properties of the detected PDE-5 inhibitors were estimated by using data from the scientific and patent literature regarding (1) in vitro PDE-5 activity, (2) reported effective doses of registered drugs with PDE-5 inhibitor activity and (3) similarity to other structural analogues. It was concluded that 18 of the 23 herbal food supplements, when used as recommended, would have significant pharmacological effects due to added APIs. Adequate use of existing regulation and control measures seems necessary to protect consumers against the adverse effects of these products.

Risk characterisation of constituents present in jamu to promote its safe use

“…Ching et al (2012) and Holt and Johnston (2019) Lactic acidosis and heart failure be of use to ensure consumer safety. This may hold especially for adulteration of jamu with so-called phosphodiesterase-5 (PDE-5) inhibitors for the treatment of erectile dysfunction, given that this type of adulteration is frequently encountered also in other types of botanical preparations, for which not only adulteration with sildenafil but also with many illegal drug analogues has been reported (Reeuwijk et al 2013;Ahmed et al 2015;Nissan et al 2016;Saberi et al 2018). In case of overdosing, or use of illegal sildenafil analogues with higher potential than the approved drug, there is a risk for especially people using antihypertensives such as nitrates (e.g.…”

O Uso De Citrato De Sildenafil Como Estimulante Sexual E Os Efeitos Adversos / The Use Of Sildenafil Citrate As A Sexual Stimulator And The Adverse Effects

“…Como muitos outros medicamentos, o sildenafil pode ser facilmente adquirido sem receita médica e usado por pessoas sem qualquer consideração das doses terapêuticas, resultando em toxicidade grave (REEUWIJK, et al, 2013). Hepatotoxicidade induzida por sildenafil foi relatada por alguns estudos quando administrados na forma de medicamento ou em suplemento de ervas contendo sildenafil (NISSAN et al, 2016).…”

Scientific and Regulatory Perspectives in Herbal and Dietary Supplement Associated Hepatotoxicity in the United States

“…An important category of liver injury caused by exposure to both herbal and non-herbal preparations is hepatotoxicity caused by an adulterant(s) [ 72 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 ]. Adulterants that should not be present in dietary supplements may be introduced intentionally or unintentionally into the supply chain at any step between the planting phase and production and packaging phase of the marketed formulation.…”

“…Other adulterants that have been identified in the weight-loss products include diethylpropione, 1,3-dimethylamine (DMAA), fenproporex, furosemide, rimonabant, and cetilstat [ 119 ]. In the case of sexual performance enhancing supplements, high rates of product adulteration with phosphodiesterase-5 inhibitors, including sildenafil, tadalfil and vardenafil have been observed [ 119 , 120 , 121 , 122 ].…”