The importance of calcium in nerve function was first identified in the 1800s
( http://www.jstor.org/pss/75500 ). This knowledge is not new. What is new is the link between calcium and horse behaviour.
1. The role of calcium and the other cations in nerve function A very useful reference for this section is The Role of Calcium and Comparable Cations
in Animal Behaviour by RG & PC Wilkins. 2003 Published by The Royal Society of Chemistry. Concentration gradients
There are four biologically active cations. These are sodium (Na+), Potassium (K+), Magnesium (Mg++) and Calcium (Ca++). In nerve cells, electrical potentials
are produced by creating different concentrations of these ions inside and outside the cells. These concentrations (in nM) vary enormously for the different ions and this has implications for the importance
of each ion on nerve function. These are the figures for 'typical mammalian cells':
Ion Intra cellular Extra cellular Approx difference
concentration concentration
Ca++ 10-4
2.5-5.0 37,500 x inside
Na+
5-15 145 14.5 x inside
Mg++
1-3 0.5-2.0 v. little difference
K+
140 5 0.036 x inside
To summarise this, the cells puts a great deal of effort into expelling calcium and sodium from the cell cytoplasm and keeping potassium levels in the cell high. Magnesium levels inside and outside the
cells remain very similar which implies that variations are passive not active. It should be noted that the concentration gradient of calcium is far and away the largest and that the concentration gradient
of magnesium is virtually zero. The calcium, sodium and potassium differentials are maintained by active calcium, sodium and potassium channels in the cell membranes. These are complex, largely protein
structures that actively transport the ions from one side of the cell membranes to another. There are a number of different channel types but that is too complex for this discussion. It is postulated by
Wilkins and Wilkins that the relatively small Mg++
ion is so small that the strains in protein molecules bending around it are considerable. So making protein : ion complexes of calcium is much more attractive than making protein : ion complexes with magnesium. Thus magnesium channels do not appear to exist.
Nerve impulses Maintaining concentration gradients across membranes means that there are electrical 'action potentials' between the sides of the membranes.
In the resting state of a nerve axon the extracellular fluid is low in K+ and high in Na+. The reverse is true of the intracellular fluid. These gradients cause a +ve charge outside the
cell and -ve charge inside. When the nerve impulse passes down the cell membrane. sodium and potassium channels move their ions through the membrane, momentarily reversing the action potential which proceeds
as a pulse down the axon. Ca++
ions are the only ions capable of acting as secondary messengers in a cell. This means that they can take the external message from a hormone, neurotransmitter, odour, light or other primary stimulant and taking that message inside the cell. One way it does this is by affecting the amount that potassium channels open. In the presence of Ca
++ some potassium ions are far more permeable. In this way Ca++
acts as a switch in the nerve cell action potential process. Without calcium the nerve impulse cannot be properly generated. Messages between nerve cells (and between nerve and muscle cells)
Nerve cells talk to each other chemically rather than electrically. The chemicals that pass between them are called neurotransmitters. The release of neurotransmitters (exocytosis) is controlled
by Ca++ ions as is the absorption by the receiving cell (endocytosis). Other chemical messengers such as hormones are also controlled by Ca++ ions in the same way. Magnesium is not
involved in impulse transmission - because there is no concentration gradient across the cell membranes. And it is not directly involved in exocytosis or endocytosis either. However a rise in serum Mg++
levels can block the effect of Ca++ ions and thus cause the inhibition of acetylcholine release from motor nerve terminals (http://www.jstor.org/pss/75500).
In other words magnesium, in excess can act as a sedative. And this appears to be true sometimes in horses getting too much magnesium calmer. Our field experience is that horses vary significantly in their
susceptibility to magnesium levels. Impact of calcium deficiency Of course all this science explains the roles of the various cations in nerve function. It doesn't explain the link
between the biochemistry and nerve mal-function. However personal communication with neuroscientist Professor Bridget Lumb (Head of the Department of Physiology and Pharmacology at The University
of Bristol) tells us that calcium deficient animals suffer, amongst other things, from:
Spontaneous nerve impulse generation Short circuits between adjacent nerve axons.
This later issue is well known in endurance horses that suffer from Thumps (Synchronous Diaphragmatic Flutter). In Thumps, depletion of intra cellular K+
ions (due to prolonged sweating) causes Ca++
ions to leak into the cell to replace them. This causes the axons' surface to short circuit with the adjacent neurons. In horses the nerve to the heart and the diaphragm run together for a while and this error causes the diaphragm to beat at the same rate as the heart. The typical 'first aid' treatment for this is an injectiuon of calcium borogluconate.
Reduction in calcium levels around the cell initially lead to spontaneous firing of the cell but, later, magnesium replaces the missing calcium and inhibits acetylcholine release. http://www.jstor.org/pss/75500 Only the inventors of VCAL
have made the connection between this nerve/brain mal-function and behaviour in horses. But now many horse owners are beginning to reap the benefits of this breakthrough. Summary
It is difficult to overstate the role of calcium in nerve (and muscle) function because it operates and controls the system at so many levels. However calcium only has a positive effect on brain function. It
calms by improving brain function not by sedation. 2. How other calmers work Before returning to calcium it may help to have a brief overview of the
more commonly used nutrients in modern horse calmers:
B Group vitamins are necessary for the formation of some neurotransmitters and, more importantly, they are involved in turning nutritional energy sources (sugars, fats etc) into the cells energy
workhorse - ATP. Because the brain uses vast amounts of energy - not least to maintain the enormous concentration gradient of calcium - any deficiency in the energy process will impact on brain function.
Magnesium is probably the most popular 'calmer' at the moment. Structurally it plays a role in the formation of the myelin sheath of the nerve cell. It also gets involved in the movement of sodium and
potassium ions across the cell membrane which is the mechanism by which nerve impulses work. Magnesium is also involved in the removal of toxic ammonia from the brain. However its most
important role is in the enzymatic regeneration of ATP (from ADP) and many other enzyme activities thus it is vital for the provision of energy for nerve and many other cells in the body. So we can
postulate that many existing calmers work by supporting the brain's significant energy requirements. It makes sense though that such products are going to have very limited effect on horses that are not
in a state of energy deficiency. Since most nervous and spooky horses are like that whatever their energy status this approach seems limited. Tryptophan is another nutrient used in calmers. This
limiting amino acid is a precursor of the neurotransmitter serotonin. Serotonin helps control mood (both positively and negatively) and a shortage may prevent horses from relaxing properly. Serotonin is,
in turn, converted to melatonin which may be reason that a small amount of horses are sedated or sent to sleep by tryptophan. Most of the herbal calmers work by sedating the horse in one way or another.
3. How calcium deficiency affects the behaviour of other species Before discussing calcium and horse behaviour we should consider the link between this important
cation and behaviour in other species. Calcium's biggest problem is that its role in teeth and bones has dominated our thinking about it. As a result the vast amount of research on calcium and its
nutritional performance has been conducted on issues such as rickets and osteoporosis. This is where the RDA's come from on the naive assumption that if the bones are OK there is enough calcium for
everything else. Our experience over many years is that the bones often take calcium at the expense of other organs. The symptoms of calcium deficiency come into three categories. And they show up (if
you are looking for them) in this order:
a) Nerve failure leading to behavioural effects b) Nerve and muscle failure leading to physical symptoms c) Skeletal problems
Unfortunately for humans and animals vets, doctors and nutritionists are so focused on the skeletal function of calcium they often miss the other two. Our primary business is nutrition for cage and
aviary birds and we have over fifteen years experience supplying calcium supplements to these creatures. Calcium deficiency is incredibly common in pet birds. One American research study (conducted by a vet)
suggests that 97% of the pet parrots surveyed were getting less than recommended levels of calcium in their diet (Hess et al 1st Int Symp on Pet Bird Nutrition, Hannover, Germany 1997). Analysis of our
BirdVet Online service shows that about 70% of cases are showing symptoms consistent with calcium deficiency. In pet birds the primary behavioural symptoms of calcium deficiency are:
A typical calcium deficient parrot feather plucks: Bird vets (particularly in the UK) are slowly coming to recognise these issues for
what they are. And equally importantly they are recognising that their traditional blood calcium test (total blood calcium) is very misleading. Most now use 'ionic blood calcium' tests.
In humans, calcium deficiency can lead to ADD/ADHD symptoms as this quote from http://intelegen.com/nutrients/add.htm suggests:
Calcium
A calcium deficiency can also induce ADD/ADHD behaviour. A child deficient in calcium exhibits irritability, sleep disturbances, anger, and
inattentiveness. The first signs of a calcium deficiency include nervous stomach, cramps, tingling in the arms and legs, and painful joints. A
calcium deficiency can also lead to ADD/ADHD behaviour. Children sensitive to dairy products must receive daily calcium supplementation in
capsule, chewable, or liquid form. Children up to 10 years of age need 1000 mg of calcium daily; adolescents need 1,200 to 1,500 mg daily. For
those involved in sports activities, calcium supplementation is a must.
Many years ago school children in Britain all got 1/3rd pint of milk a day and ADHD was virtually non-existent. But now, on chips and burgers, it is
increasingly common and Jamie Oliver has highlighted the impact of diet of behaviour and learning. This is precisely the effect we are claiming for calcium in
horses. It is not unreasonable to describe many horses as having an attention deficit problem. 4. Our trial results for VCAL supplementation in horses
In 2008 we conducted a trial in the UK on a number of 'difficult horses'. They were all initially given a calcium only supplement. The supplements were either a
chelate (citrate, metalosate or gluconate) or the inorganic calcium carbonate. This was followed up by chelate or inorganic magnesium.
90% of the horses getting a calcium chelate showed a significant improvement in behaviour. On a scale of 1-5 (1 = no change, 5 = brilliant)
the average rating of the improvement in these horse (as given by their owners) was 3.6 Of the horses given calcium carbonate only 50% showed a very small
improvement (2 on the scale of 1-5). It is proposed that this effect has more to do with stomach acidity issues than calcium supplementation.
These horses were given double or quadruple the calcium dose of those on the chelate trial. Of horses given chelated magnesium 30% showed an improvement (4 on
the 1-5 scale). But 43% deteriorated (-2.3) and 27% showed no change.
Our conclusion is that a very large number of horses that show difficult behaviour or poor concentration levels are struggling enough for calcium that their brain function is impaired.
Because of the focus on skeletal calcium and the dominance of research on inorganic, insoluble calcium sources in feeds and supplements, it is our view that
the recommended levels of calcium (and magnesium for that matter) are no longer appropriate. Increasing levels of calcium and magnesium using inorganic ingredients (Ca
carbonate, phosphate or Mg oxide) seems to have relatively little effect. However using smaller quantities of calcium and magnesium from chelated
sources (much closer to the normal sources of these minerals in natural, wild diets) considerable benefits can be achieved.The popularity of magnesium supplements (for other energy related conditions
such as laminitis as well as behavioural problems) supports the assertion that the RDAs developed in the 1970s are inappropriate. We are confident that this
realisation will become equally true of calcium over the next few years.
5. Market feedback on VCAL in horses At the time of writing VCAL has been in the UK market for nine months (in EquiFeast products). Feedback from customers is excellent. 76% of customers
report strong positive effects (score of 4.0 on a scale of 1-5). 24% report no change (or did not repurchase and could not be contacted for comment). No reports of negative effects have been received. Clearly existing calming supplement technologies do not have nearly as high a success rate as this. |
