Effects of the Gut microbiota on Amygdalin and its use as an anti-cancer therapy: Substantial review on the key components involved in altering dose efficacy and toxicity

Abstract

Conventional and Alternative Medicine (CAM) is popularly used due to side-effects and failure of approved methods, for diseases like Epilepsy and Cancer. Amygdalin, a cyanogenic diglycoside is commonly administered for cancer with other CAM therapies like vitamins and seeds of fruits like apricots and bitter almonds, due to its ability to hydrolyse to hydrogen cyanide (HCN), benzaldehyde and glucose. Over the years, several cases of cyanide toxicity on ingestion have been documented. In-vitro and in-vivo studies using various doses and modes of administration, like IV administration studies that showed no HCN formation, point to the role played by the gut microbiota for the commonly seen poisoning on consumption. The anaerobic Bacteriodetes phylum found in the gut has a high β-glucosidase activity needed for amygdalin hydrolysis to HCN. However, there are certain conditions under which these HCN levels rise to cause toxicity. Case studies have shown toxicity on ingestion of variable doses of amygdalin and no HCN side-effects on consumption of high doses. This review shows how factors like probiotic and prebiotic consumption, other CAM therapies, obesity, diet, age and the like, that alter gut consortium, are responsible for the varying conditions under which toxicity occurs and can be further studied to set-up conditions for safe oral doses. It also indicates ways to delay or quickly treat cyanide toxicity due to oral administration and, reviews conflicts on amygdalin's anti-cancer abilities, dose levels, mode of administration and pharmacokinetics that have hindered its official acceptance at a therapeutic level.

Recent updates and future perspectives about amygdalin as a potential anticancer agent: A review

“…This result indicated that the toxicity of amygdalin was likely to depend on the microorganisms in the intestine. And then Jaswal et al found that the amount of hydrogen cyanide (HCN) produced by different intestinal microbes hydrolyzing amygdalin was different. Probiotic consumption, obesity, diet, age, etc all can change the distribution of intestinal microecology, which affects the production of HCN in human body.…”

Gut microbiota: a new angle for traditional herbal medicine research

“…In addition, gut microbiota can increase the toxicity of several THM, such as amygdalin, hydrolyze this to HCN under the anaerobic Bacteroidetes phylum in the gut and cause toxicity. 193 In summary, both historic and modern science validate the efficacy of THM, however research and development in this eld has staggered due to the complexity of ingredients and the unknown mechanism of action. Thus, in recent years, research on gut microbiota has brought a new perspective into the study of THM.…”

Reduction of cyanide content of bitter almond and its oil using different treatments

“…In addition, the cyanide content in bitter almond decreased with increasing temperature at the same boiling time. The result was explained as follows: the glycosidase activity was activated with increasing temperature over a range of temperatures, which facilitated the conversion of the amygdalin into HCN (Yu et al, 2005;Jaswal et al, 2018). The formed HCN was rapidly volatilised due to its low boiling point (25.7-26.5°C) (Khare et al, 1994).…”