Hormesis, Hay And Horses

(This blog’s header photo is of a modern 6 wheel tractor tedding the hay field before baling.)

In our Facebook group, “The Horse’s Advocate,” a member had a concern about her horse. The “diet” is feeding only pasture and hay, salt and water plus the addition of soybean meal (SBM) to replace the lost amino acids. Here is her post:

My horse just came down with a bad case of grass founder on all four feet for the first time….I have been doing this diet for a year now…got her off of grass and feeding grass hay ( Bermuda & orchard/fescue hay)….she loves the SBM but should i cut it out or maybe decrease?

The following will be a long and scientific answer but in a nutshell, horses need hormesis.  This is the cellular process of resting which helps to clean up cellular debris, remove damaged cells and help the mitochondria switch their fuel source (mitochondrial flexibility). PLEASE read this entirely even though it will sound too far advanced for most of you.  I will summarize along the way in the gold shaded sections and at the end introduce you to a theory of why horses are getting laminitis even though they are off of grain.

The Key Point

The key point of this article is that any animal, (humans, horses, dogs, gerbils) who eat glucose in any form (starch, soft drinks, candy, beet pulp) in excess of their needs on a DAILY basis will become inflamed at the cellular level, develop metabolic syndrome and become ill in one way or another.  Obesity is evidence of inflammation and chronic protein deficiency is secondary to this (sarcopenia in humans or poor top line / hay belly in horses – same thing).

Current research in humans and lab animals have discovered the development of an enzyme called aldose reductase in people and animals who eat abundant glucose every day of their lives.  Many enzymes are developed in animals when certain continuous intake of food require the animal to take action.  An example in humans AND IN HORSES is the development of alcohol dehydrogenase when alcohol intake is daily.  We did this study on ponies in the 1980’s at Cornell because research on liver disease from hepatitis had lots of money.  We fed them 100% (200 proof) alcohol in their meals and measured for alcohol dehydrogenase which was absent at the start of the test. This enzyme is not in children or adults who don’t drink alcohol.  Alcohol is a toxin to the body (sorry folks!) so the body develops this enzyme to turn the alcohol into water.  This is observed as “tolerance.”  When I drink one cup of my wife’s home made, hand whipped egg nog on New Years Eve I become goofy and with 2 cups I’m asleep because I don’t drink alcohol any other time.  

Aldose reductase is a responsive enzyme developed by the body when glucose intake is daily and non-stop year round.  All foods act as signals and the signal of continuous glucose intake is that winter is coming.  Remember all starch is a chain of glucose molecules (https://theequinepractice.com/decomplexicating-equine-nutrition-grazing-not-browsing-part-1/).  Starch is found in growing plants but is gone in dormant plants especially after rain or melting snow.  When food with starch is consumed, the signal to animals (in this case horses) is that winter is coming and the response is, “We need to store more fat!”  The process of making energy within the cell changes and so does the fuel.  Aldose reductase converts glucose into fructose.  These are both sugars but cause a different route in the metabolic pathway within the mitochondria.  This alternate route is inflammatory but is necessary as it is usually temporary.  Winter is followed by spring and food becomes abundant once again.

Glucose is the sugar of starch found in grains and in the nonstructural part of plants.  Fructose is the sugar of fruit but it is now discovered that animals can make fructose when they need to add body fat for winter.

Glucose And Fructose

First let’s describe glucose and fructose.  Both have 6 carbons, 12 hydrogen and 6 oxygen atoms.  Pretend you are joined by 5 other people and you form a ring by holding hands.  This represents the 6 carbon ring structure.  Off of our backs like wings are 1 oxygen with 2 hydrogens.  This represents the glucose molecule C6 H12 O6.  If one person is removed from the ring then it is now a 5 carbon ring.  The displaced person grabs onto someone’s belt behind their back so they are still attached to the molecule but they are no longer part of the ring.  This is fructose, a 5 carbon ring structure with the 6th carbon attached outside this ring.

When glucose enters the metabolic pathway (the Kreb’s cycle) it causes ATP (adenosine triphosphate) to lose one of its 3 P (phosphorous) atoms to become ADP (adenosine diphosphate or 2 P).  It then does it again to become AMP (adenosine monophosphate or 1 P).  This process is conservatively limited by the enzyme phosphofructokinase so that only about 10% of the total ATP is used.  Beyond this point mitochondrial exhaustion begins (glucose metabolism is turned off and glycolysis is started) and the mitochondrial metabolic pathway pathway is limited.  An enzyme called AMP kinase is triggered which adds back the P atoms so that the AMP becomes ATP again and ready for the next use.  A side note here.  The drug metformin enhances this AMP kinase and is used to increase intracellular ATP thus countering mitochondrial exhaustion.

When glucose is the fuel, energy is created by the engine inside the cell (the mitochondria).  A recycling program then takes over well before it is needed to restore the chemicals needed to make more energy so the cell is always ready.

But what happens when fructose is used as the fuel?  After the ATP is converted into AMP with the loss of the 2 P’s and the creation of energy, the path goes in a different direction:  

1) The enzyme used to digest fructose (fructokinase) causes up to 50% ATP depletion (greater mitochondrial exhaustion).  

2) The loss of ATP causes hunger and thirst and increases body fat (energy storage) and glycogen (glucose storage) because glucose is no longer metabolized by the mitochondria but rather through glycolysis which does not use oxygen.  This is a survival mechanism in all all animals facing starvation with the end result of increased body fat and the start of metabolic syndrome.  The excess glucose from starch has to go somewhere as it is not being used and the best storage for it is body fat and liver fat (leading to non-alcoholic fatty liver disease in humans).

3) The satiety hormone leptin (note – not lectin) is blocked by increased glucose intake further increasing hunger and food intake.  The point here is that as the energy factories are shutting down, the continual intake of sugar needs to be stored because when the food stops (winter), the animal will need to get the energy from somewhere.

4) The last point here is that instead of ATP kinase putting the P atoms back onto the AMP molecule, the enzyme AMP deaminase is used turning AMP into uric acid (UA).  This is significant in humans and in lab animals studied because UA is the cause of inflammation in the kidneys and the islet cells of the pancreas.  What does this do to their health?  A lot!

When fructose is the fuel, energy is still created inside the cell but the reserves of supplies are greatly reduced AND the recycling program shuts down.  In addition another chemical is produced (uric acid) that is not normally found. This is OK in a short term situation such as a season but when it continues, it definitely effects the health of humans and lab animals and, I presume, horses too (but nobody is researching this in horses).

The islet cells of the pancreas make insulin.  When inflamed by uric acid, the islet cells make less insulin with subsequent insulin resistance and type 2 diabetes in humans (from the paper “The association between elevated serum uric acid levels and islet β-cell function indexes in newly diagnosed type 2 diabetes mellitus: a cross-sectional study”  –  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846453/  –  The conclusion is quoted here:  “In our study, insulin resistance and insulin secretion increased with rising serum UA levels in both men and women.”)

UA also inflames the kidney which is the regulator of blood pressure (hypertension).  There is a direct correlation between high blood UA levels and hypertension in humans and in lab animals studied.  What this means in humans and in all animals tested is that a continuous intake of glucose throughout the year causes higher fructose in the diet.  This causes high blood uric acid levels which leads to insulin resistance, high blood triglycerides, fatty liver, obesity, metabolic syndrome and heart disease associated with hypertension.  To drive home this point, when animals are given a medicine that blocks the enzyme that creates fructose from glucose OR when they are placed on a very low glucose and zero fructose diet, the hypertension and all the signs of metabolic syndrome are reversed and normalized!  Calorie restriction is what this is called in humans and is the leading theory behind increased longevity and more importantly, an increased health span.

Reducing the availability of starch and restricting it to only what the horse needs to survive the work load and the seasonal elements will lead to the elimination of inflammation which is at the heart of almost every problem we see in our horses.

Now The Hard Part For Horse Owners

Hay is last summer’s grass.  In the 1950’s in the industrialized nations very few people owned tractors.  Grass was cut with mowers pulled by draft horses, picked up by pitch fork, pulled into barn hay mows with a claw on a rope using pulley systems and finally distributed in the loft by hand and fork (search on YouTube for “making hay with horses”).  In the 1960’s the US started the Eisenhower Interstate system of roads (https://www.fhwa.dot.gov/interstate/history.cfm).  By 1970 hay was being made into bales and distributed by trucks along high speed roads to small distribution centers we called farm stores.  The concept of horses eating hay then is only about 60 years old.  Originally hay was used to feed livestock during the hard times of winter to help them survive.  Now horse owners believe that hay is a staple and must be fed ad lib during every hour of every day.  While I have been one of the biggest proponent of feeding horses continuously as suggested by all horses lacking a gall bladder (very few animals are born without this), I believe I was wrong.

It has been demonstrated by the observations of Dr Katherine Houpt, VMD (Cornell professor emeritus) that horses chew between 10,000 and 40,000 chews per day.  With the assumption that 1 chew equals 1 second, this means 10,000 to 40,000 seconds per day are used to intake food.  There are 86,400 seconds in a day.  Using math, a horse is then only eating between ⅛ and ½ of the day.  While this makes logic for me I decided to dig deeper.  There is science behind what happens when we do not eat.  However we first need to assume that every cell in body (all animals) requires energy every moment of life – like a car needs fuel converted into energy to run or it just stops.  We must also assume that all animals don’t take in the raw materials constantly but they go through a process of taking in a meal then when they are not eating, having these raw materials go through the process of digestion into fuels, transport and distribution of these fuels, consumption of the fuels and storage of any unused fuel.

The creation of energy by the cells happens during every moment of life.  Taking in the materials (food) needed to make fuel for this process is intermittent both during a 24 hour period AND during a 365 day year.  To buffer this inconsistent intake of food the body stores fuel as body fat.  The more food taken in beyond daily needs the more body fat that develops.  When this occurs every day and year round, the bad side of things occurs such as disease.

For this part of the discussion we will call the mitochondria of the cell “the factory.”  Fuel goes in and energy comes out along with waste.  The better the fuel the less waste and the less work the cell must do to clean up.  But with more waste the clean up crew starts to complain.  With more complaining, management restricts the tools needed to clean up.  Why? Because management is too busy worrying that winter is coming.  They have too much glucose so they start to change how energy is created as they look for ways to store the excess.  They even start to convert the amino acids into more glucose because the danger signs of a very long winter (an ice age) is coming.  Survival is the highest priority while clean up, maintenance and repair are low priorities.  The means justify the ends.  We will die trying to save the ship.  Etc…

Normally during winter when the availability of glucose diminishes to near zero the cell starts using the more efficient fuel of fat (https://theequinepractice.com/decomplexicating-equine-nutrition-part-7-the-high-fat-diet/).  The horse takes fat stored as body fat and converts it to ketone bodies which are 20 to 28 times more efficient in producing energy with a lot less waste.  The clean up crew goes to work with vigor.  After all, if there is no end in site to cleaning up horse poop with no time left to ride then what is the incentive to keep working?  But with less poop the cleaning becomes fun, right?  With less worry, management has time to bring you coffee and food for your morning break!  Keep dreaming….

Now that there is extra time and energy within the cell, maintenance and repair become a priority.  This is called hormesis.  The cell uses many techniques to repair things and one of those is called autophagy.  “Auto” means self and “phagy” means eat.  The cells literally eat all the waste material and remove it from the cells.  Another process is called apoptosis which is the scheduled death of a cell – like euthanasia of a very old horse unable to get up off the ground.  There are many more processes used every moment to repair damaged proteins (heat shock proteins) and DNA and RNA (sirtuins).  But let me stay with the simple explanation of hormesis and horses.

In winter, horses are supposed to lose their body fat while maintaining their muscle.  When we see this fat loss we need to say, “My horse is repairing and maintaining and will remain healthy and sound because I am seeing hormesis at work.”  If winter becomes harsh with very low temperatures and unbearable wind and snow then add the hay.  That is what it is for.  Otherwise being a good horseman requires us all to acquire a fine eye for when to add food beyond what they are finding in the pasture.  As good stewards of our horses we need to recognize the importance of hormesis and know they need this metabolic rest period seasonally.

I can hear all of you say that you have no pasture.  I see that.  Adding hay then is a requirement but don’t feed it 24 hours a day.  Limit it to what the horse needs to maintain their body weight.  For all who are competing, use your eye.  As the work load increases then add more energy.  About 100 years ago the work required of horses to plow and harvest for all the people moving to the cities was life threatening to the horses.  They lost too much condition so farmers started to add grain to compensate.  Does your horse work that hard?  Then adding grain in the form of whole grains probably won’t bother them as they are consuming the excess glucose and NOT triggering the production of fructose.  But if your work load is less, the need to feed glucose 24 hours a day and 7 days a week is not only unnecessary, it is also harming them at the cellular level.

The availability of food for horses living in nature ebbs and flows.  The body needs the abundance of food to prepare for the time when food is scarce.  They build reserves with the excess food knowing that tough times are ahead so they are willing to pay the cost of doing this (inflammation).  When food is scarce (winter), the cells clean up and repair.  This needed repair period is missing in horses kept in the flow state of abundant food availability – and our horses are becoming ill from it.


Carbohydrate dependency (https://theequinepractice.com/decomplexicating-equine-nutrition-part-6-carbohydrate-dependency/) is the root cause of ills and unsoundness in horses today with the secondary development of chronic protein deficiency (https://theequinepractice.com/decomplexicating-equine-nutrition-08-**the-importance-of-protein/) that I talk so much about.  It is very important to understand that if glucose is fed continuously, the amino acid deficiency will be more difficult to restore.  In laminitis, feeding soybean meal will help to restore the connections between the hoof and coffin bone.  But I think it is more important to eliminate any inflammation first and foremost.  From current research in humans and based on what I have said above, I have a hypothesis.  There is so little known about uric acid in horses but what we do know is that the hooves are a vascular bed of fine capillaries.  If UA causes inflammation of kidneys with secondary effects on blood pressure then would it make sense that UA also causes inflammation with the capillary bed of the hooves?  The same thought of inflammation of the islet cells and the increase in insulin resistance (IR) may also be associated with this very fine mesh of blood vessels.  I am sure that the chronic protein deficiency leads to decreased cystine disulfide bonds in the hooves making their structure and attachments weak.  Therefore it is very important to replace this lost amino acid through the addition of methionine (which converts to cystine and makes up 26% of the hoof).  However, in every case of laminitis there is usually insulin resistance. I believe that IR is secondary to the increase of blood uric acid  (this may be a new idea in the horse world).  High blood UA is directly related to the activation of AMP deaminase that converts AMP into more UA.  The increase of AMP deaminase is directly related to the increase in fructose which is made from the conversion from glucose by the enzyme fructokinase which is developed in animals on a high glucose diet.

Feeding glucose (starch) every day of the year leads to insulin resistance, metabolic syndrome and hypertension in humans and in other mammals tested.  This is probably all due to the new discovery that glucose is converted into fructose with the production of high uric acid in the blood.  This inflames the kidneys and pancreas with subsequent illness.  Testing in horses has not been done but I propose the possibly that this same process leads to the inflammation of the laminae of the hooves.

Excess glucose > conversion into fructose > increased blood uric acid > IR, diabetes, hypertension, fatty liver, obesity and other signs of metabolic syndrome.

I hope this lengthy discussion will help you understand why your horse foundered on grass.  There is so little known about these enzymes and UA in horses and the role in laminitis.  I think this will help you look at it from a fresh perspective. It has for me as these are relatively new findings over the last 10 years of research and NOT in my text books in the 1980’s.  We all know there is an epidemic of obesity, diabetes, metabolic syndrome, non-alcoholic fatty liver, dementia and heart disease in humans.  We also are seeing obesity and metabolic syndrome in our horses in levels I did not see 50 or even 30 years ago.  And it is getting worse.

 Read these and blogs from others.  Avoid agenda driven information where they are trying to sell you something.  What you will find is that simplicity works in most cases – that pulling teeth is a last resort.

I truly hope your horse fully recovers but you must decrease active inflammation and then remove all causes of future inflammation.  This will require you to rethink how you are feeding your horse and throwing out all you were taught as it is not working with this horse.  Other horses may be OK with feeding hay every day or even grain but more and more horses are being pushed to the edge.  I hope this long winded discussion will let you know that at least in humans, the answers to metabolic syndrome seem imminent.  Pfizer is working on a drug to block aldose reductase which will soon be released.  I can see it being used in horses.  Allopurinol will block the production of UA from AMP and metformin will encourage the phosphorylation of AMP back into ATP.  Some vets have tried these medicines but there are not a lot of qualified studies using them in horses.  Be sure top ask your vet about them as you proceed.  Thanks for being a part of this group and searching for answers.  Doc T