Performance Enhancing or Performance Restoring

I read the line "performance enhancing or performance restoring" as part of a quote from a regulatory veterinarian from a discussion regarding drug use in the equine industry.  I like the line, because it helps to create potential criteria that determines a drug or herb's potential use and implications.

In recent news, a well known and respected TB trainer was in the spotlight due to having a high incidence of acute deaths in horses under his care.  The exact cause is unknown, however, early reports from veterinary autopsies have indicated possible cardiac failure as well as diffuse hemorrhage internally.  I am hopeful that further conclusions can be made regarding the final diagnosis in order to help curb the issue in the future, but my concern is that the deaths are closely linked to medication abuse.

When reading many of the articles regarding these events, one becomes engulfed by the large number of corresponding comments being made, usually from other trainers in the industry.  Overall, the biggest concern and implications being made are regarding abuse of various 'performance enhancing' medications.  It would be one thing if it was the public (non-horse owners) making these statements, but in this case, the majority of them are coming from trainers themselves, calling for action and calling for change in the industry.

I brought up a discussion regarding banned substances several weeks back, but it continues to weigh on my mind as a veterinarian as well as horse lover.  This issue crosses disciplines, from the TB industry to barrel racing.  Drugs are being abused and used for the wrong purposes.  Using the title of this blog as a guide, let's look at a short list of commonly used medications, their original intended uses as well as what they are being used for,  by their generic names:

• Furosemide:  a commonly used diuretic intended to reduce fluid accumulation in the body associated with heart failure.  Currently being used to aid in the management of EIPH by inducing a low level of dehydration, leading to a reduced pulmonary (lung) blood pressure and hopefully reduced bleeding.  Side effects include dehydration and electrolyte abnormalities.
• Clenbuterol:  a bronchodilator (opens the airways) used to help alleviate the clinical signs associated with COPD and certain airway conditions.  Currently being used to open the airways to enhance air movement as well as for its purported stimulatory effects.  Side effects include cardiac stimulation, possible arrythmias, death and excitement.
• Dexamethasone:  a corticosteroid used most commonly to reduce the clinical signs of allergic type reactions in the horse.  Currently being used to reduce inflammation and pain associated with a variety of conditions.  Side effects include possible induction of hyperadrenocorticism, increased water consumption/urination, water retention and gastric ulcers.
• Methylprednisone:  see above description for dexamethasone. Commonly injected into joints to reduce inflammation and pain.
• Phenylbutazone/Flunixin Meglumine:  both are non-steroidal anti-inflammatory medications designed to reduce pain by blocking COX enzymes and prostaglandin formation.  Side effects include gastric ulceration as well as potential kidney/liver complications.

There are many other medications, but overall we need to ask ourselves if they are performance enhancing or performance restoring and whether if we are inflicting more harm upon these animals than good? In the view of the equine industry, most medications are viewed as performance enhancing, but one really has to look at how they accomplish this feat.  In most instances, the medications are covering up a medical condition that is holding the athlete back in terms of performance.  Maybe the condition is an arthritic joint, or a tight back or a respiratory condition such as EIPH.  Performance is restored indirectly by reducing the inhibiting condition.  The problem that comes with this approach is that in many instances there are secondary complications produced such as bone fractures due to blocking pain response or overall worsening of the condition due to masking of clinical signs.  This can lead to a need to increase the medication dose, use of multiple medications to achieve more pronounced results or euthanasia of the animal due to catastrophic injury.

In many cases, herbs can be used to achieve "performance restoring" effects which are different than the effects of many medications.  Most medications are simply covering up clinical signs without addressing the underlying problems.  Herbs can have similar effects, but tend to also address the bottom line problem whether if it is a nutrient deficiency, poor circulation or impaired cellular health.  Herbs can reduce inflammation naturally as well as pain,similar to various medications, but they do it differently and more completely by returning inflammatory protein levels to normal levels and without side effects.  Performance is restored in many cases through the use of herbs not only due to the reduction of inflammation and pain, but cellular health is restored which means improved energy production and tissues are stronger.

Users of our Cur-OST products not only report improvement in pain and inflammation levels, but healing of wounds are noted, energy levels are increased and likewise performance is restored.  In many cases, the damage to the body is done whether if it is in the joint or the lungs and is unlikely to be reversed.  That being said, it is possible to slow progression of the condition and minimize clinical signs through the restoration of health.  In many instances, this is accomplished through restoring healthy cellular function, which impacts every tissue in the body.

The bottom line is that we can "cover up" clinical problems through the use of various medications or we can take a deeper look at what is causing those problems to manifest.  When we look deeper, we find opportunities to improve cellular function and restore health.  This then reduces the need for those medications but more importantly creates a healthier and stronger athlete...naturally!  Considering that herbs are plant material and essentially food, it then drives the point home that nutrition is the key to overall health.

Just my thoughts.

Tom Schell, D.V.M.

Stem Cells and Potential For Therapy

Stem cells are essentially specialized cells that possess the ability to transform or differentiate into one of many different types of cells present within the body.  That includes the potential ability to differentiate into cardiac, nerve, muscle, tendon, bone and many other types of cells.  Stem cells are classified into two broad groups, dependent on their origin: embryonic or adult.  Embryonic stem cells are the cause of much of the controversy surrounding stem cells, due to be derived from the blastocyst, which is an early stage embryo.  Adult stem cells are derived from the patient themselves and usually extracted from the blood, bone marrow or adipose (fatty) tissue.  

Stem cells have gained tremendous popularity in veterinary medicine and seem as if they have been the talk of the medical industry for the past couple of decades.  For several years, there was much controversy regarding stem cells, especially regarding morals and ethics amongst many religious communities.  So, what is all the hype about stem cells and what is their potential? 


In order to be classified as a stem cell, the cell line must demonstrate potency as well as the ability to self renew, which means that that particular stem cell can divide and produce more stem cells.  Potency is by definition the ability to differentiate into specialized cells or any adult cell type.  The terms generally assigned to potency in true stem cell lines are Omnipotent and Pluripotent.  Omnipotent stem cells are produced as a result of the joining of an egg and sperm cell.  Essentially, omnipotent stem cells yield embryonic cells and could, if allowed, produce a complete living organism.  Pluripotent cells are the next step down and are a result of the further division of Omnipotent stem cells, which creates the blastocyst.  Embryonic stem cells usually demonstrate Omnipotent or Pluripotent capabilities.  Adult stem cells are generally classified as having multipotent capabilities, which means they can differentiate into many different cell types but usually only of closely similar cell types from which they were extracted.

Embryonic stem cells have demonstrated the highest level of capabilities and potential, mainly due to their assigned potency, however, due to their source or origin, much debate has been raised.  Given their controversy, there are no approved medical therapies at this time in regards to embryonic stem cells and some research has actually been halted.  The other major drawback to using embryonic stem cells is the risk for rejection as they are transplanted from one source to the next.

Adult stem (somatic) cells are present in all individuals as a means of repair and regeneration.  The actual number of adult stem cells drops with age, but the hope is that with extraction, self renewal can take place in culture and increase their numbers for clinical use.  The positive side to using adult stem cells is that risk of rejection is very low and in fact non-existent due to using cells derived from the patient themself.  Adult stem cell therapies have been used for many years and a prime example is in patients receiving bone marrow transplants for treatment of various leukemias.  There are many other potentials for adult stem cell therapies including cardiovascular disease, liver and kidney disease, bone disorders including fractures and tendon conditions.  In the veterinary community, the biggest focus is on tendon therapy as well as some bone related conditions such as arthritis and OCD lesions. 

Adult stem cells are most commonly obtained either through the bone marrow or fatty tissue.  In my experience, the number one source, due to ease of extraction, is the fatty or adipose tissue.  As mentioned, one drawback is that with age, cell numbers appear to decrease, which may yield low numbers upon extraction.  The other concern regarding adult stem cells is their level of potency and ability to differentiate into the particular cell type needed.  It appears, based on research, that adult stem cells are most likely to differentiate into cell types similar to that which they were extracted.  Dependent on their origin, they appear to be already locked in, per se, on forming that particular cell type.  Essentially, it may prove to be difficult to get a stem cell programmed for muscle or tendon repair to differentiate into a cardiac or nerve cell.  This process of differentiation is rather complex and involves many signaler chemicals.  Given this process of differentiation, the concern has been raised that it is possible that injection of stem cells could produce the formation of various tumors, mainly due to the process of differentiation being hard to control.



In the end, stem cells offer much hope and potential for aiding in the management of many diseases affecting humans and animals.  There is much research and discovery still to be made regarding their extraction and overall usage, but right now, we are just in the infancy stages.  The results thus far are promising, but overall response rate statistics are hard to find and are variable, which may reflect patient to patient variability in terms of cell line potency. The process of harvesting, culturing and re-injecting stem cells is an expensive process and one that is not covered by many insurance carriers due to their research nature, but may be a worthwhile consideration for medical conditions that are unresponsive to traditional therapies.

Tom Schell, D.V.M.
www.curost.com

(Images borrowed from Wikipedia)

IRAP Therapy In Horses

Joint disease in the horse is the number one cause of ongoing lameness and a result of many factors including excessive or ongoing trauma, genetics, diet and lifestyle influences.  Degeneration within the joint leads to cartilage erosion, remodeling of the joint, ongoing pain and reduced range of motion in more severe cases.  It is a condition that is best prevented and managed in the early stages versus in the advanced stages.

Therapies for joint disease in the horse now includes joint injections with corticosteroids, hyaluronic acid, polysulfated glycosaminoglycans and over the past several years, there is a new kid on the block termed IRAP or Interleukin-1 Receptor Antagonist Protein. IRAP therapy is supposed to help manage the inflammation and joint deterioration more effectively through the use of the body's own natural resources.

As we have discussed in prior blogs and emails, inflammation is a complex subject and involves the ongoing release of several cytokines responsible for cellular changes and deterioration.  Interleukin-1 is one of many cytokines, which act at many levels and are thought to be directly involved with cartilage loss.  As a result of ongoing inflammation, IL-1 is released by various types of cells and binds to receptors at other cellular locations to inflict action.  IRAP therapy works on the principle of blocking the receptor at which IL-1 binds within the joint, thereby reducing inflammation and pain.  Blood is withdrawn from the horse, incubated in a special syringe that helps to stimulate the IL-1 receptor blocker and then injected into the joint.  In most cases, it is recommended to complete a three injections series, one week apart.  Cost can vary between clinics, but is reported to be between $1000 and $2500 for the complete series.  Effectiveness is variable and at the time of this writing, I am unable to find published research dictating response rates, but it has been reported that if there is going to be a response, it will be seen by the second or third injection.  Length of response rate is again variable, with most horses benefiting from results lasting 6-12 months, but then requiring either a booster injection or potentially a restart to the injection series.  It has been noted that horses requiring further injections tend to show a reduced response rate.

Considerations:
IRAP therapy blocks the receptor in which IL-1 binds to within the joint, thereby in theory reducing inflammation, pain and further joint deterioration.  As we have discussed in the past, inflammation involves several cytokines being produced and IL-1 is not the only one responsible for cartilage deterioration and pain production.  For instance, there are other Interleukins that play a part in the cycle of inflammation and there are other cytokines such as MMP's (matrix metaloproteinases) that are responsible directly for cartilage erosion.  Even though we may be able to block the receptors at which IL-1 attaches within the joint, we are doing very little to impact the production of the other destructive cytokines.  By using IRAP therapy, we are also doing little to impact the production of IL-1 overall and systemically, IL-1 levels will likely be on the rise even though they may be blocked from exerting their action within that specific joint.  Overall, the effects of IRAP are localized and impact only a small portion of the inflammatory cycle.

The other consideration of course is cost and potential side effects from therapy.  It is reported that side effects to the IRAP are very low due to using blood from the patient as part of the therapy, which is good, however, we are still sticking a needle into the joint on weekly intervals.  With each repeated injection comes the risk of bacterial infection and the act of sticking a needle into the joint actually spurs on the process of inflammation.

Inflammation is Systemic:
Inflammation is an ongoing process and involves many cytokines, each with their own specific action.  IRAP therapy is a new tool in the medicine chest for equine veterinarians, but from my perspective may have some major limitations.  Considering the large number of cytokines being produced as a result of the inflammatory cascade, why not potentially target them at their source, instead of just trying to block their action?  After all, inflammation is a systemic problem and in most instances, if there is one joint affected, there is another close by or potentially higher up in the leg or even the back that is taking extra pressure due to favoring or shifting of weight.  We need to look at the problem from a systemic point of view, because that is where the problem lies.

Blocking Cytokines At Their Source:
Is it possible to reduce the production of these cytokines at their source or at a cellular level?  The answer is yes, but it is somewhat complicated.  The process of inflammation involves the production of cytokines but also involves the release of free radicals with resultant oxidative stress, which actually can be a viscous circle of events, all playing a role in joint deterioration.  Wouldn't it possibly be better to reduce the production of IL-1 systemically, versus just blocking where it binds?

Curcumin, as a case example, has been shown in research trials to block the NF-kB transcription factor, which is directly responsible for the production of several cytokines, including IL-1.  Curcumin has been shown to downregulate the production of many types of Interleukins, Prostaglandins, TNF and MMP's.  The effects are seen systemically instead of just locally, so the patient is benefiting overall from the health effects of mitigating the inflammatory response.  Curcumin has also been shown to upregulate NRF2, which is directly responsible for production of naturally occurring antioxidants within the body, which help to reduce oxidative stress damage.

It sounds like Curcumin is the 'end all be all' of inflammation therapy, but it too has its limits.  One of the limitations is dosing, which can vary dependent on the severity of the condition. There are many herbs that impact the process of inflammation and considering some limitations of curcumin, I have found it best to herbs together to get the best effect overall.  Boswellia, for instance, counteracts inflammation at a different level than curcumin, which is mainly through lipoxygenase inhibition.  When combined with curcumin, along with other anti-inflammatory herbs, the results can be incredible.  This was demonstrated in our published paper in 2006 evaluating synovial cytokines pre and post curcumin administration in which 80% of horses responded with reduced synovial cytokine levels and a reduced lameness score.  

Again, there are always going to be limitations.  IRAP is generally listed for use in mild to moderate cases of osteoarthritis.  Usage of herbal formulas, like our Cur-OST formulas, are also best for early or mid stage cases, but can still have profound effects in later cases.  Joint deterioration is not reversible and generally involves more than one joint.  The progression of joint disease can be potentially mitigated by reducing cytokine production, but it is best when done at a systemic level. 

In my experience, it may be a more sound decision to try to reduce systemic cytokine levels first before performing a more invasive and targeted therapy.  The results may actually be seen sooner and affecting the patient systemically, not to mention at a much reduced cost.

Just my opinion.

Tom Schell, D.V.M.