There have been some interesting developments over the last couple of years with reference to doping. Some of the owners of horses that have failed tests vehemently deny giving their horses a drug of any kind and seemed genuinely confused as to why this might have occurred.  There may well be an answer as many feeds and supplements contain plant chemicals which are molecularly almost identical to the synthetic drugs which cause the failed test (the FEI web site clearly states that any compound which is of a similar molecular make up to a banned substance is also banned).  As more plants are made into medicines the WHO predict a significant increase in medicines made from plants (70% by 2020) because of the decline in the petrochemical industry, more horses are likely to fail a test through the lack of information available on herbal/plant remedies and formulas. Significant funding is available for the research of plants to treat chronic diseases such as cancer, diabesity and inflammation which will lead to the development of synthetic chemicals from a plant chemical platform resulting in a significantly higher chance of failed dope tests from herbal remedies. The burden must lie more with the governing bodies in relation to threshold levels of normally ingested food materials and the difference between these and the performance enhancing compounds such as sedatives and stimulants and those that are able to relieve pain. Many chemicals from plants have a medicinal use and as horses eat a lot of plants there is bound to be a crossover point! Human sports dope testing has a list called the monitored (licit) substances in which tests are developed to distinguish between those banned substances found in food and those which originate from drug abuse or doping.     

 How does a seemingly innocent food suddenly become a banned substance, let’s look at an example.

 Coumarin is on the FEI prohibited substances list and its activity is described as an anti-coagulant. The medical dictionary defines coumarin as a ‘toxic white crystalline lactone C9H6O2 with an odour of new-mown hay found in plants or made synthetically and used especially in perfumery and as the parent compound in various anticoagulant agents (warfarin ).  

The synthetic drug Warfarin is also on the FEI prohibitive list, was originally developed over 50 years ago from a spoiled clover crop which contained a bacterial metabolite of coumarin. Clover is grown as a hay crop in North America and many meadow hays of the UK contain clover. Therefore, figuratively speaking, what quantity of hay might give rise to a positive dope test?

More than 1,000 coumarins have been identified from natural sources, especially green plants and many spices such as cinnamon, vanilla and turmeric. The pharmacological and biochemical properties and therapeutic applications of simple coumarins depend upon how the core molecular compound is manipulated. More complex related compounds include warfarin anticoagulants, aflatoxins and the psoralens (photosensitizing agents) but they all have a core coumarin nucleus which will give a positive on a dope test.  Coumarin itself has long-established efficacy in slow-onset long-term reduction of lymphoedema. Coumadins are also prohibited, these are coumarin type chemicals manipulated to give slightly different mechanisms of action but again the core molecule is coumarin. 

 Pharmacognosy (Tease and Evans;) the most respected and accurate source of information about the use of medicinal plants report that the highest content of coumarin is found in alfalfa and clover.  The coumarin content increases when the plant is cut as a crop (including hay, alfalfa, red clover, sweet clover) a chemical called trans-glucosyloxycinnamic acid is converted to coumarin, conversion also takes place if the plant is damaged (as in the case of hawthorn and horse chestnut during the cutting of a hedge) the aroma of the new-mown crop, which intensifies as drying increases is an indication that coumarin (benzo-alpha pyrone) is being formed. The highest content of coumarin is contained in sweet clover which is grown extensively in America and Canada as a hay and forage crop and red clover which is found in UK swards and is sold as a seed mix suitable for equine pasture. Some plants such as sunflowers and soya are actually manipulated or engineered to produce more coumarins as this increases the plants ability to resist disease. Alfalfa, hay, clover, sunflowers and soya are popular and common additions to the horse’s diet, so how do horse owners know they won’t fail an FEI dope test?   

Whilst coumarins are on the prohibited list, salycilic acid, described in the FEI list as a non- steroidal anti-inflammatory drug is on the controlled substance list. The medical dictionary describes salicylic acid as a phenolic acid that is used in making pharmaceuticals and dyes, as an antiseptic and disinfectant, especially in the treatment of skin.

Aspirin is made from Acetyl-salycilic acid and was developed in 1853 from willow bark and meadow sweet which contain a natural ingredient called salicin a similar chemical compound with similar attributes to Aspirin but possibly without the detrimental gastric side effects. Both salicin (willow and meadow sweet)  and acetylsalycilic acid (aspirin)break down in the body to form salycilic acid and this metabolite is found in the urine, so at this point there are no differences between the synthetic and the natural chemicals as they leave the body in the urine they are the same chemical compound.

  • Is it acceptable to state on the packaging of formulas containing salicins (meadow sweet, willow, yarrow)   that they are approved (or will not fail a dope test) by the FEI, BHA and any other governing body, or should the label explain that the urine metabolite is on the controlled medication list?    

  • Do the supplements and feeds that include willow and meadow sweet add a standardized extract with a quantifiable amount of salicin or if using the complete herb do they undertake separate batch tests using chromatography to determine levels of actives so that they are able to advise people who are involved in top level competition about the likely levels of salycilic acid in their horses urine?

  •     Meadow sweet is also an anti-coagulant well known for its inter-reaction with warfarin. The flowers of Filipendula ulmaria (Meadow sweet) contain heparin which is an effective anti coagulant though it is not on the prohibited list, should meadow sweet be included on the prohibited list along with coumarin because it has a known anti-coagulant activity and the wording on the FEI site is that any other biological substance with a similar action or mechanism is also banned?

Another slightly more sinister example of a banned plant chemical is ephedrine which is described as a high level stimulant and related to norepinephrine, it is also molecularly similar to octopomine which is found in many shell fish including green lipped muscle and other commonly used compounds which make up joint supplements (glucosamines).

Most chemicals are sold as 90% pure but what makes up the other 10% (tests have found traces of octopomine in glucosamine), the only way round the problem is to buy 100% pure,  some cheaper products will contain only 65% pure glucosamines, this leaves a massive margin for error and inaccuracies.  Where does all this leave the end user of a feed or supplement? It is a grey area with many pitfalls for the unwary, supplements containing the words ‘contains no banned substances’ is a very brave statement to make with a multi-chemical /ingredient formula especially if a company lack the forensic equipment needed to make the analysis.

Another equine supplement additive that is has become very popular is the last few years is ripe/bitter orange peel. Though bitter orange peel from the fruit citrus aurantium contains synephrine and octopomine which are both on the prohibited list, synephrine is found in all types of orange peel and is also found in orange juice. The only part of an orange free from these alkaloids is the oil used in fragrance and flavouring. Synephrine is a recognised vasoconstrictor and weight loss aid. In human sports Synephrine has a (currently licit) status of a monitored compound rather than a prohibited drug, due to the fact that humans eat and drink orange juice/marmalade/peel. Scientists are currently working on an adequate urinary threshold limit for human sports which will allow the differentiation of synephrine originating from the diet or caused by the intake of the drug.

Synephrine in equine sports is a banned substance according to the FEI list of prohibited substances.

This raises a few more questions in relation to its use in horses, as the FEI web site states that synephrine is currently a banned substance rather than a monitored substance does this reflect the fact that horses don’t normally eat orange peel therefore it shouldn’t be found in their diet?

The FEI web site also adds that the compound originates in citrus aurantium does this mean that synephrine is not banned if it comes from any other type of orange peel/fruit as all contain high levels of this alkaloid?

On the web site it clearly states that synephrine is a banned substance, does this mean that if a horse is tested and has been given a supplement containing orange peel it will fail a dope test? Would it be fairer for competitors, for the FEI to put orange peel on a monitored substance list to perhaps alert them to the fact that a natural compound might contribute to a failed dope test if given in excess?