Laminitis: 90% Metabolism?

By Dr Carol Michael

Introduction
Equine Metabolic Syndrome (EMS) is a condition that starts with raised blood glucose levels. Recent research has shown that oral antidiabetic drug, Metformin, is largely ineffective at normalising glucose levels in horses. Is it possible, therefore, to add a beneficial functional food to the diet (in a similar way to adding plant sterols to lower cholesterol) using an extract from an indigenous plant that is freely available to grazing horses, to prevent the onset of insulin resistance and life threatening bouts of laminitis. Research has shown that the plant compound in question is able to prevent and diminish adipose tissue and at the same time, is able to exert an antidiabetic effect.
The problem
EMS was first recognised by veterinarians in 2002 and is recognised as a number of clinical symptoms including obesity, insulin resistance and laminitis. It is similar to metabolic syndrome, the human version, and is considered to be a disease of our time and is a body condition that precedes other serious life threatening conditions such as diabetes and heart disease. Veterinarians may prescribe Metformin, a synthetic anti-diabetic drug; when prescribed to people, its effect was to lower blood glucose by up to 40 % more than in people given dietary advice and asked to count calories.
Metformin is usually given to people with type 2 diabetes, classed as people with high blood glucose and low levels of circulating insulin and is thought to increase tissue sensitivity to circulating insulin. However, in a recent study on the effect of oral administration of metformin, on insulin sensitivity in insulin resistant ponies, published in The Veterinary Journal, researchers found that Metformin had little positive effect and a question was raised about the bioavailability of this synthetic drug.
In the light of this study, and with no anti-diabetic drugs available for horses; still the most important goal for vets and equine practitioners is to halt the progress of EMS from raised blood glucose levels into insulin resistance thus potentially avoiding the further and more life threatening effects of laminitis.
One of the most important risk factors and components of EMS is the presence of adipose fat deposits on the neck, at the top of the tail and around the sheath. The fat deposits or BMI can be measured using a weight tape and a score of greater than 3 for the neck area can be considered an indication that the animal has EMS. The description for a score of 3 is ‘crest enlarged or thickened so that fat is deposited in the middle of the neck rather than towards the poll or withers giving it a mounded appearance, crest fills cupped hand and starts to lose its side to side flexibility’. Some horses and ponies can have a fairly lean overall appearance and still have the cresty necks and fat pads above the tail.
Currently the best advice to owners of horses with a body index greater than 3 is a calorie counting diet with limited starch content and an increased exercise programme. For animals with adipose deposits of greater than 3, energy metabolism may be significantly compromised and the important metabolic pathways for lipid and glucose metabolism and uptake into the muscle and liver may be affected by the release of hormones or signalling proteins called adipokines from these stores.
White adipose tissue is no longer considered as just fat designed to store energy, but it is in fact more of a hormone and it plays a part in regulating physiologic and pathologic processes, including immunity and inflammation.
Furthermore, cross-talk between lymphocytes and adipocytes can lead to altered immune regulation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines leptin, adiponectin, resistin, and visfatin, as well as cytokines and chemokines, such as TNF-alpha, IL-6, monocyte chemoattractant protein 1, and others.
Some animals that have EMS and suffer from laminitis are confined to limited exercise or no exercise at all because of the instability of the laminae. Many owners find calorie counting and dietary restrictions onerous and difficult to manage and are unable to increase the amount of exercise to level needed to effect a change and the EMS pony is liable to deteriorate.
A solution
It would be clearly advantageous if certain beneficial and inexpensive ingredients could be added to the daily diet of affected or at risk animals that were able to assist in the regulation of glucose, thus improving health and avoiding the full blown onset of insulin resistance and laminitis.
With this in mind, over the past four years a combined EU funded research project with the analytical chemistry department at Bangor University in North Wales has been under way to examine the plants that ponies prefer if left to their own devices. These indigenous plants are then analysed with especial interest to any anti-diabetic/anti-fat deposit properties that the plant may possess.
A herd of eight, purebred Welsh Mountain Section A ponies grazed unhindered over 11 acres of a mixture of heathland, grass, marsh, ancient woodland and rocky outcrop. The land is laid out in a natural ‘Paradise Paddock’-like formation as endorsed by hoof care professional, Jamie Jackson of the AANHCP. It has a track around the outside with a wide selection of grasses and a large 2-acre rocky outcrop in the middle, and its varying terrain and lay out encourages a certain amount of wandering as a herd. Two of the ponies were from families that were known to suffer from recurrent laminitis, all of the ponies were from families that had been bred in mid or north wales over the past 50 years.
The ponies had a surprisingly predictable and regular rota of plants to eat depending on the season. It appears that at certain times of the year, some plants were far more attractive than at other times. In particular, young silver birch twigs and young holly leaves in late winter early spring each containing a mass of medicinal anti-oxidants. One particular plant ingredient with a long history of research and several patents for its medicinal properties is an active plant compound called ecdysterone. Phytoecdysteroids are components of 5 % of all wild plants and of particularly and significant interest for its use as a functional food additive for horses suffering from EMS is a plant from the Chenopodium family. Spinach and quinoa are members of this group, with spinach named by the World Health Organization as a superfood. Chenopodium alba is the indigenous plant available to grazing horses; it is a commonly seen and available plant sometimes invasively so in Europe and North America, and is grown as a crop in India and Africa as it has a similar taste to spinach, though is less bitter and more palatable.
Phytoecdysteroids are triterpenes that have been shown to reduce fat body mass and have a beneficial effect on glucose levels in the body with an effect similar if not greater than that of Metformin. A triterpene is a precursor to a steroid and research has shown that ecdysteroids have anabolic but not androgenic activity and bind to IGF-1 binding sites in an advantageous manner. The ecdysteroids are able to exert a lowering effect on glucose and lipid levels in the blood, thus lessening the damaging effect and the development of insulin resistance. As EMS in its early stages is in fact a body condition of raised blood glucose levels in obese ponies it is possible that a more beneficial health state may be attained by the regular addition of ecdysterones to the diet. The added benefit is the reduction in the size of the lipids in the adipose tissue and a decrease in the amount of fat laid down on the neck and at the top of the tail.
In a pilot study of over 100 horses with a body score of greater than 3 for adipose deposits, within two weeks of receiving the additive in the daily feed ration the adipose deposit scores had fallen to a score of 2 or less.
Chenopodium alba is already grown as a crop in the UK and plans are now under way for an extraction plant in a partnership biomass development project to ensure that the industry is British based.
In light of these findings, Superfix, a Welsh based company has developed a feed additive containing the critical dose dependant quantity of the ecdysteroid compound to inhibit and diminish high blood glucose levels and reduce adipose tissue deposits. Further research is now under way to find the release mechanism of insulin in IR animals.

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