Equine metabolic syndrome management: Can they ever eat grass? (Proceedings)

Management of Equine Metabolic Syndrome (EMS), the most accepted term for a syndrome of middle-aged obesity accompanied insulin resistance (IR) and insidious-onset laminitis, can be challenging as it primarily involves client education and acceptance to comply with dietary recommendations to effect weight loss. In addition, an understanding of the differences in nonstructural carbohydrate content of various forages is important for appropriate dietary recommendations to be made. Next, implementation of an exercise program for both at risk and affected horses (those with laminitis) is strongly recommended but can be difficult to implement in equids suffering from laminitis. Although medications (thyroid hormone and metformin) and dietary supplements (magnesium, chromium, vanadium, cinnamon, etc.) have been advocated to both assist with laminitis recovery and enhance weight loss, data supporting use of these agents is limited.

Endocrinopathic laminitis

Unfortunately for horses, syndromes of IR and cortisol excess (EMS [cortisol excess at the tissue level] and pituitary pars intermedia dysfunction [systemic cortisol excess]) appear to be accompanied by alterations in the integrity of the basement membrane between the epidermis and dermis of the laminar bed. Over time, weakening and degradation of the basement membrane can lead to separation of the epidermal-dermal junction and development of laminitis. The most recently advanced term for this type of laminitis is endocrinopathic laminitis. The mechanisms behind development of laminitis appear to be complex and remain incompletely understood. Nevertheless, research over the past decade has provided new insights into some of these mechanisms and may lay the groundwork for novel approaches to treatment of this devastating problem in horses.

Anatomy and physiology of the equine foot

The equine hoof is a complex epidermal-dermal structure evolved to support the large body mass of the horse. Although not typically thought of as skin, the hoof is actually comprised of the same basic epidermal-dermal layers as skin. However, the area of epidermal-dermal attachment has changed from a nearly straight junction to an interdigitating junction of primary and secondary lamellae. This "laminar bed" markedly increases the surface area for attachment of the epidermis (hoof capsule) to the underlying dermis, thereby, increasing the strength of attachment and capacity to support weight. The primary lamellae (600-800 within each hoof) are long finger-like projections and interdigitation of the epidermal lamellae and the dermal lamellae holds the hoof capsule onto the underlying dermis. However, the real strength of attachment is provided by the secondary lamellae that consist of numerous short projections off each primary lamella. Secondary lamellae can be thought of as velcro-like projections that provide incredible strength of attachment to the primary lamellae. At the junction of the epidermis and dermis lies the basement membrane. The basement membrane consists of a lamina lucida, a lamina densa, and extracellular matrix. Within these layers are several proteins including laminin, type IV collagen, type VII collagen, integrins, anchoring filaments, and others. In addition to forming the supporting extracellular matrix of the basement membrane, these proteins, along with others, also anchor or attach the secondary epidermal lamellae to the basal cells of the secondary dermal lamellae.

Mechanisms involved in basement membrane damage in laminitis

Epidermal tissues have somewhat different metabolic requirements and machinery than other organs. Specifically, the epidermis has an absolute requirement for glucose as an energy substrate. Pollitt and coworkers have nicely demonstrated this glucose requirement using an in vitro hoof explant model system. When cubes of hoof material were incubated in various media, integrity of the basement membrane was lost after 48 hours of incubation in media without glucose. In contrast, integrity of the basement membrane was maintained when glucose was present in the media. Another piece of evidence, albeit indirect, is the efflux of lactate from epidermal and hoof tissue. This has been demonstrated by the finding of higher lactate concentrations in digital venous plasma than jugular venous plasma.

With an acute insult to the laminar tissue, as in spontaneous diseases or with the carbohydrate overload model for induction of laminitis, another mechanism for damage to the laminar bed is induction of matrix metalloprotease (MMP) activity. Specifically, increased amounts of the active forms of the basement membrane degrading enzymes, Eq-MMP-2 and Eq-MMP-9, have been found in laminar tissues affected by laminitis 48 hours after carbohydrate overload. Of interest, the damage to the basement membrane caused by glucose deprivation and activation of MMPs differs. With glucose deprivation, the anchoring filaments detach from the basal cells of the secondary dermal lamellae. In contrast, with activation of MMPs, the anchoring filaments and other proteins of the extracellular matrix are destroyed.

Role of cortisol in development of laminitis

Although development of laminitis with use of exogenous glucocorticoids is clinically recognized in horses, the mechanism(s) for this adverse drug effect of glucocorticoids has not been well established. One likely contributing factor is alteration in glucose uptake by tissues due to decreased tissue sensitivity to insulin under the influence of glucocorticoids. If glucocorticoid action leads to decreased glucose uptake and utilization, and glucose is absolutely required for maintenance of the integrity of the lamellar basement membrane, then glucocorticoids could lead to slow, insidious degradation of the basement membrane and eventual separation of the lamina.

Next, regulation of cortisol activity at the tissue level is largely mediated by the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11-β-HSD1). In the horse's foot elevated 11-β-HSD1 oxo-reductase activity may enhance the action of cortisol on the metabolism of extracellular matrix of lamellar connective tissue and the regular turnover of anchoring filaments connecting basal cells to the lamellar basement membrane. In short, local cortisol activity may downregulate the natural turnover of the anchoring filaments in the basement membrane. In contrast to more acute insults such as grain overload in which activation of MMPs leads to rapid degradation of the basement membrane, the effects of cortisol excess are more chronic and insidious in onset. As a consequence, endocrinopathic laminitis is often a long-standing subclinical problem before overt lameness becomes apparent.

Recently, investigators at the University of Missouri demonstrated increased 11-β-HSD1 oxo-reductase activity in both skin and laminar tissue collected from horses with both acute (carbohydrate overload model) and naturally occurring chronic laminitis. This novel finding is an attractive explanation for the long recognized syndromes of obesity-associated laminitis in horses as well as laminitis associated with pituitary pars intermedia dysfunction. However, it is also important to recognize that the pathogenesis of laminitis in both of these syndromes of endogenous glucocorticoid excess remains incompletely understood.

Carbohydrate content of forage

It is well recognized that "sweet feeds" and other concentrates high in soluble carbohydrate (with a high glycemic index) are best avoided in obese, IR, laminitic horses. Despite proliferation of "low starch" feeds, it is also important to recognize and to recommend to clients that overweight horses do not need any concentrate feeds at all. In fact, all essential nutrients and energy can often be found in good quality forage, although many practitioners and nutritionists continue to recommend addition of a vitamin and mineral supplement to a forage only diet. Such supplementation may not always be necessary but would certainly be prudent in areas of the country where specific nutrients (i.e., selenium) may be low.

Lush grass pasture and some hays can also be a rich source of soluble carbohydrate. In fact, grazing lush spring pasture can be similar in dietary intake of soluble carbohydrate to feeding a high concentrate ration. Soluble carbohydrates are those that can be absorbed in the small intestine and lead to increases in glucose and insulin concentrations. In contrast, insoluble carbohydrates are contained in plant cell walls and require bacterial fermentation in the cecum and large colon for digestion. The end products of fermentation are volatile fatty acids that are absorbed in the large intestine and provide more than 50% of an equids daily energy needs.

Studies in which soluble carbohydrate content of pasture grass has been measured at various times of the year have shown a spring rise, peaking in April through June depending on latitude. In addition, there is a diurnal pattern to pasture soluble carbohydrate content. Specifically, during daylight hours fructan content ( one of the soluble carbohydrates in forage) increases. During the night, plant cells utilize fructan as an energy source in the absence of photosynthesis much as liver glycogen is utilized in mammals in the hours preceding meal ingestion.

Not surprisingly, serum insulin concentrations in equids grazing pasture at these various times of the year have shown substantially greater increases when pasture soluble carbohydrate content is high (spring and to a lesser extent in fall). Further, in ponies with historical pasture-associated laminitis, a more dramatic increase in insulin concentration is observed after grazing, in comparison to ponies that have never had laminitis.

Whether or not it is "safe" to allow overweight equids to graze pasture as a forage source remains controversial. Pasture, especially lush spring and early summer pasture, should be considered similar to feeding concentrates high in soluble carbohydrates and should be avoided. Further, if pasture is to be utilized it may be preferable to turn equids out in the early morning hours while plant fructan content is relatively low. On the flip side, being turned out to pasture has the benefit of some exercise, as compared to being in a stall or small dirt lot. Grazing muzzles can be a good compromise for turning overweight horses out on pasture.

Hay is usually cut once the forage plants have neared maturity; thus, hays typically have less soluble carbohydrate content than pasture with grasses having less than legumes (alfalfa and clover). However, various batches of hay cut from nearby fields may appear similar but can have variation in soluble carbohydrate content depending on maturity, time of day that hay was cut (often in the late afternoon to allow the dew to dry off – when fructan content may be highest), or whether or not there may have been frost damage (fructan is not utilized when the plants are frozen). Unfortunately, the only true way to assess forage soluble carbohydrate content is to have the forage analyzed. This is not really important for horses that are in good weight and in a regular exercise program but it is warranted when trying to identify a hay source for an overweight, IR, and possibly laminitic horse. In the absence of forage analysis, hay can also be soaked for 30-60 minutes prior to feeding in an effort to leech out some of the soluble carbohydrate.

Dietary management of overweight horses

It is clearly difficult to have owners comply with dietary recommendations that eliminate all concentrate feeds and pasture turn out for their overweight horses. Thus, I recommend that a horse owner approach the problem of an obese horse in much the same way that they may have to approach a family member with a substance abuse problem. An intervention is needed and for the horse the drug is too much feed. If an owner accepts this approach and follows strict dietary recommendations for 60-90 days, improvement (specifically weight loss) can usually be seen providing positive reinforcement for further owner compliance.

It is commonly recommended that an adult horse receive 2% of its body mass in weight of daily forage intake for maintenance. However, horses with EMS are "easy keepers", likely due to presence of thrifty genes and they may need only 1.5-1.7% of their body mass in daily forage. In the 6th revision of the Nutrient Requirements of Horses (2007) prepared by the Committee on Nutrient Requirements for Horses of the National Research Council Board on Agriculture and Natural Resources, the average recommended daily energy intake for a sedentary adult horse (1000 pounds) was 16.7 Mcal/day with a minimum value of 15.2 Mcal/day. The latter amount digestible energy can easily be provided by 15 pounds of good quality hay daily. To put energy intake into perspective, if an owner feels they must add a pound of concentrate feed twice daily to the ration, this would increase daily energy intake by 3 Mcal/day (to about 18 Mcal/day). After a year, an additional 1000 Mcal would have been fed and would have produced a 100 pound increase in body mass!

Thus, in order to produce weight loss, even less than 15 pounds of hay needs to be fed daily. However, this feed restriction could result in an unhappy horse that may start chewing on wood or other parts of its surroundings. A compromise can be achieved by finding a lower quality of hay (generally an over mature hay) that could be fed in a similar amount. If an adequate hay source cannot be identified, soaking the hay would be another option to decrease energy content. The diet is started at 1.5% of the horse's body mass but it is important to realize that current body weight is greater than ideal body weight. As a consequence, forage intake is slowly decreased over 4 weeks to 1.5% of the target body weight. The only way that such a diet can be appropriately fed is to weigh the daily hay ration. This can be accomplished by placing the daily ration in a hay net or plastic bag and holding it while the owner steps on their bathroom scale (that they have brought to the barn).

A weight loss of approximately 50 pounds is required to produce a numerical reduction in body condition score. This can be loosely equated to an energy deficit of about 350 Mcal for the average adult horse. The goal should be to accomplish this 50 pound weight loss within 60-90 days after the diet has been started. If that target is not reached, a further reduction (10-15%) in hay intake will be required or hay soaking will need to be started if not yet implemented. Once ideal body weight has been achieved, it is important to continue to limit feed intake and provide minimal pasture access in order to maintain ideal weight.

Further management of overweight horses

Another important management tool is implementation of an exercise program. A caloric deficit can be accomplished both by limiting feed intake as well as by increasing caloric expenditure through exercise. It is well recognized that overweight human patients accomplish and maintain weight loss more effectively if diet is combined with an exercise program and the same is likely true for horses. Unfortunately, the major complication of EMS is chronic laminitis and a painful gait may limit the ability to exercise. However, as soon as the horse is deemed comfortable enough to walk, regular hand walking for 20-30 minutes three to five times a week can be useful. In addition to burning calories, exercise also improves tissue sensitivity to insulin and may further limit ongoing lamellar damage.

Appropriate hoof care is also essential in horses with obesity-associated laminitis. Dietary restriction and exercise may lead to desired weight loss but substantial lameness may persist if the angle of the distal phalanx within the hoof capsule remains uncorrected by proper trimming and possibly shoeing. Judicious use of non-steroidal anti-inflammatory drugs is also often required to alleviate the pain of chronic laminitis.

Medications and supplements from managing EMS

Although there is a great desire for pharmacological intervention in both human and equine metabolic syndromes, there will likely never be a "magic pill" for either weight loss or to markedly improve tissue insulin sensitivity. Supplementation with thyroid hormone has been demonstrated to produce further weight loss, as compared to diet alone, when overweight horses were administered twice the daily recommended dose for a year. Next, a recent study by Durham and coworkers reported potential benefits of metformin (15 mg/kg, PO, q 12 hours) in 18 insulin resistant horses and ponies with laminitis. Results of insulin sensitivity testing showed improvement within 1-2 weeks of starting the medication but the improvement did not persist with long-term treatment and four patients continued to suffer recurrent bouts of laminitis. However, no adverse effects of metformin were observed and the relatively low cost of this drug makes it a likely candidate for further study. Thiazolidinedione drugs also increase insulin sensitivity in humans and cats, but their use in EMS is only speculative at present.

It has been suggested that anti-oxidants might also be beneficial. Vitamin E can safely be administered to horses at high levels (10,000 units, PO/day) but supportive data for improvement in EMS are lacking. Currently, data that show therapeutic value for chromium, magnesium, vanadium, or cinnamon supplementation for insulin insensitive horses are also lacking.

At present, prevention of obesity, especially in those breeds at greater risk for EMS, is the best advice that is available and equine veterinarians should strongly consider assessing body weight and fat stores (by using a weight tape or other measures to estimate weight and assigning a body condition score) as part of their annual preventive care practices.