The Hidden Truth of 'Phellemine' in Red Yeast Rice Supplements and the Toxicity Controversy

The recent detection of febrifugin, a research substance for malaria treatment, in a red yeast rice health supplement from the Japanese pharmaceutical company Kobayashi Pharmaceutical has caused a major stir. While febrifugin itself has little to no connection with the red yeast rice supplement, the controversy surrounding its toxicity is heating up.

Febrifugin is a natural yellow powder compound that is a metabolic product of Penicillium citrinum (FKI-4410), a type of green mold. Although first reported in 1932, it began gaining attention as a potential new antimalarial drug due to its strong insecticidal effect against chloroquine-resistant malaria parasites.

However, febrifugin itself presented a fatal problem. Mouse experiments revealed that a subcutaneous injection of 5mg/kg of febrifugin twice resulted in the death of 4 out of 5 mice within 3 days, demonstrating its strong toxicity. Consequently, drug development for febrifugin itself was halted, and research shifted towards developing derivatives, including 'tropone', 'tropolone', 'hinokitiol', and '7-hydroxytropolone', by modifying its chemical structure.

So, why was febrifugin detected in Kobayashi Pharmaceutical's red yeast rice health supplement? Experts believe that the red yeast rice production process was contaminated with the febrifugin-producing mold. Red yeast rice undergoes a two-stage fermentation process called 'Jongkuk' and 'Jeguk', requiring strict temperature and humidity control. It is suspected that external mold contamination occurred at one of these stages.

Meanwhile, there is debate about whether febrifugin itself causes nephrotoxicity. Shinjiro Inoue, Professor Emeritus at Tokyo Institute of Technology, pointed out that "based solely on the content of the paper on febrifugin toxicity, it's difficult to conclude that it is highly toxic." He explained that the paper describes an experiment where febrifugin was administered to malaria-infected mice, and while 4 mice died, it cannot be definitively concluded that the deaths were solely due to febrifugin.

Furthermore, Professor Inoue argued that the toxicity resulting from the interaction between febrifugin and other components of red yeast rice, such as 'monacolin', should also be considered. The fact that adverse events have only been observed in red yeast rice products with high monacolin content suggests that attributing the issue solely to febrifugin may be an oversimplification.

Ultimately, as the health supplement issue becomes more complex, the controversy surrounding febrifugin intensifies. Further experiments are expected to continue clarifying whether febrifugin is toxic and the mechanism by which it might induce nephrotoxicity. Kobayashi Pharmaceutical must address public concerns by promptly identifying the cause and disclosing information.