Khat (Catha edulis), a plant that has been cultivated for centuries in East Africa and the Arabian peninsula, could one day be used in a food supplement to help improve a couple's chances of conception, said researchers from the Centre for Reproduction, Endocrinology and Diabetes at King's College London.
Traditionally, chewing khat leaves has been thought to improve a man's sex drive and ability to maintain an erection, but there is a question mark over whether prolonged use might adversely affect the male reproductive system, possibly causing abnormalities in sperm.
The plant is also illegal in many regions outside of the UK, including the rest of the European Union and the US. The plant contains the stimulant cathinone, which is not very stable and is broken down into cathine (pseudonorephedrine) and norephedrine. These belong to a group of chemicals called phenylpropanolamines (PPAs), which are structurally similar to amphetamines and adrenaline. Both cathinone and cathine are classified as controlled substances in the US.
However the King's researchers studied the effects of PPAs on mouse and human sperm and found the first evidence that they stimulate the final stage of sperm maturation (capacitation), when sperm develop the ability to fertilize an egg. They then maintain the sperm in a potentially fertilizing state for longer, allowing them more time to reach an egg.
Lynn Fraser, professor of reproductive biology at King's College London, suggested the findings might lead to over-the-counter products to boost fertility during attempts at natural conception, as well as providing another way to help infertile couples during IVF treatment.
"A number of PPAs related to the compounds we have studied are currently used in prescription and over-the-counter products, such as herbal dietary supplements used for weight loss and treatment of asthma," said Fraser.
"We envisage the development of products that could be taken by individuals, either couples who might be having trouble conceiving or even those who have just decided to try to conceive, and who have no obvious problems. PPAs could also be used in IVF clinics as additives to sperm prepared for IVF or artificial insemination."
One in six couples experience difficulty in conveiving at some point in their lives, according to the UK-based National Infertility Awareness Campaign. A recent survey by the group has also found that government funding for infertility treatment remains patchy or even non-existent in some areas of Britain. It is more readily funded elsewhere in Europe, such as France, but the average IVF live birth success rate is only 14 per cent per cycle, according to UK figures.
Fraser and colleague Dr Susan Adeoya-Osiguwa tested the effect of cathine on mouse and human sperm. They found that cathine and norephedrine significantly stimulated capacitation in mouse sperm. It also prevented the acrosome reaction, the final phase of capacitation when the cap (acrosome) present in the sperm head ruptures and releases enzymes that enable the sperm to enter the egg.
Cathine had a similar effect on human sperm and also stimulated the production of cAMP (cyclic adenosine monophosphate - a chemical messenger within cells) in uncapacitated sperm whilst inhibiting it in capacitated sperm.
"We know that cAMP stimulates sperm motility and that it plays an important role in the phosphorylation of many proteins, some of which allow sperm to 'switch on' and acquire fertilizing potential," said Fraser.
She said the study provides the first evidence that cathine can regulate the availability of cAMP, first stimulating and then inhibiting its production; and that inhibition of cAMP in capacitated cells appears to be the molecular basis for preventing the acrosome reaction.
"This study has shown for the first time that PPAs have a direct effect on sperm, initially stimulating the final maturing process and then preventing spontaneous acrosome reactions in mature sperm, thus maintaining them in a potentially fertilizing state," concluded the researcher.
When mouse sperm treated with cathine were mixed with unfertilised eggs, they were able to fertilise much more quickly than untreated control sperm; this indicates that PPAs do not interfere with the acrosome reaction induced in the fertilising sperm by the egg, added Fraser.
More research has to be carried out in animals to evaluate the effects on the ovaries, the testes and the sperm, before this work can be translated into treatments for people.
But the preliminary data suggest that PPAs, at appropriate doses, might provide a new approach for enhancing natural fertility.
"The fact that other PPAs have already been approved for use in preparations taken by humans should make the development of any product easier than if one had to start from scratch; toxicity testing will have been carried out already for the related compounds," noted Fraser.