Virtually any nutrient you can name has an effect on function of the immune system, but one of the most important is protein.
Diets low in protein tend to be low quality in terms of other deficiencies, as well. Because of interaction between all nutrients in the diet, it can be difficult to isolate the effects of protein malnutrition but multiple studies point to a specific role for protein.
Protein is needed to manufacture and complement the enzymes used in the complement pathways, to generate antibodies and cytokines, and to support rapid division of immune system cells. Deficiency impacts every cell type and every function.
Extensive information is now available on the effects of specific amino acids. Arginine is a conditionally essential amino acid in humans, meaning it can be both synthesized and obtained from the diet but diet and/or synthesis may not always be enough to support normal development or disease states. Very little is known about arginine requirements in horses, but it is interesting to note that mare's milk is high in arginine and increases in the later stages of lactation, suggesting dietary arginine from grasses is likely not enough for horses under 1 year old.
Arginine in hay averages in the neighborhood of 4.5% of the crude protein, so a horse eating a 10% protein hay would be getting 0.4% arginine in the diet overall. Grains and grain products contain 0.5 to 1% arginine.
As far as we know, there are no overt arginine deficiency symptoms shown in horses, and it's unrealistic to think that all horses are on arginine deficient diets - at least not at maintenance levels. However, it's not a far stretch to think that baseline dietary arginine intake may not be sufficient to support stressful states, and that arginine supplementation is reasonable to assist with fighting infections (and tissue healing).
In the immune system, a key role of arginine is in the generation of large amounts of nitric oxide. This uses up the local arginine, depriving the cells lining the blood vessels and causing blood vessels in the area of injuries or infections to contract. With circulating organisms (e.g. bacteremia, bacteria in blood or toxemia, toxins in blood – aka “blood poisoning”), the reaction is bodywide and severe blood flow restriction occurs which can cause shock or laminitis.
Glutamine is another nonessential amino acid that becomes helpful in larger amounts during times of tissue injury or infection. Glutamine can improve the intestinal barrier, reduce inflammatory reaction, and promote immunity recovery
In brief, glutamine functions include:
l Regulate T cell proliferation, cytokine production and sensitivity to cytokines
l Regulate B cell antibody production and secretion
l Influence the number of activated killer cells
l Support for Macrophage activity
l Serves as an important energy source for immune system cells because of its easy conversion back to Krebs cycle intermediates.
l Support levels of antioxidant glutathione
An Example of More is Not Better
As above, arginine is used by the immune system to produce large amounts of nitric oxide during nonspecific inflammatory responses. This is the sledge hammer approach to driving a picture nail, but is necessary to protect the body from invaders on a right here and right now basis, until antibodies and the cell-mediated immune system can kick in. This part of the inflammatory response is normally self-limiting and will begin to tame down in 3 days after arginine levels drop, but until then you definitely don't want to supplement arginine. Arginine supplementation to a horse battling a serious bodywide infection like purpura from Strangles can actually be harmful, if not fatal.
Arginine in the face of some viral infections is also a bad idea. Viruses like Herpes have high requirements for arginine and you will be feeding the infection if you give it. In fact, lysine competes with arginine for cellular uptake and is used as a therapy with Herpes infections.
Finally, cancers also have a very high requirement for arginine. A horse with a malignancy should never receive supplemental arginine. It will only fuel the tumor. Arginine depleting diets have been used as a therapy in cancer.
As more details emerge about specific effects of individual amino acids, we will eventually be able to fine tune supplements to get very specific effects. For now, glutamine combined with a high biological quality protein is excellent immunity support. The protein source of choice is whey.
Help for Your Horse's Immune Health, Part 2
The horse's immune system is on guard 24/7 all year, but winter poses some special challenges. Extremes of weather trigger hormonal reactions that influence the immune system. Breathing cold, dry air has been linked to higher rates of respiratory infections which may be because the barrier function of the mucosa lining the respiratory tract is compromised. Horses kept in closed up barns have high exposure to respiratory irritants (dust, molds, ammonia) and are exposed to high concentrations of airborne infectious organisms.
The foundation for supporting a strong immune system is a solid diet with adequate calories, protein, vitamins and balanced minerals. You can also build on that base with targeted supplements.
Allergic reactions, tissue responses to parasites, inflammatory responses and many of the white blood cell reactions that destroy organisms or damaged cells generate large amounts of free radicals. This friendly fire has to be controlled or damage to the immune system cells and other tissues will result. A well nourished body has several built in antioxidant defenses but there are also plant based antioxidants that can help.
Plant polyphenols is a large class of natural compounds with strong antioxidant capacity. Grape seeds and skin have been extensively studied, in part because of the “French paradox” which is the observation that the French have very low levels of heart disease despite eating a diet that would be expected to cause it. The polyphenol content of red wine is believed to be the explanation.
The skin and seeds of grapes, particularly red grapes, are rich in polyphenols of the anthocyanidin and proanthocyanidin class. The most well known of these is resveratrol. Another well studied class is the bioflavonoids, particularly bioflavonoids from citrus fruits which includes hesperidin, quercetin and rutin. All of these compounds are potent antioxidants.
Grape polyphenols also have direct effects on the immune system. They stimulate a population of T lymphocytes called gamma delta T cells. These cells can contribute to both nonspecific immediate and delayed targeted immune responses to organisms and damaged cells. They also have the capacity to rein in inflammatory reactions. These cells are concentrated in the mucosal linings of the respiratory tract, gut and urinary/reproductive tract – the portals to the body.
There is less detailed information available for the citrus bioflavonoids. Control of inflammatory reactions via their antioxidant activity has been clearly shown. There is also some evidence that they can improve responses of T and B lymphocytes.
Vitamin C is definitely an important antioxidant in the immune system. Whether it has direct effects on immune system cells remains to be seen. Horses can synthesize their own vitamin C so it is difficult to identify effects from suboptimal levels of vitamin C. However, it has been clearly shown that vitamin C levels in lung fluid from horses with chronic lung disease are low.
A complicating factor with vitamin C is that it will worsen oxidative stress in horse that are iron overloaded, which may apply to many horses. To avoid making matters worse by supplementing vitamin C, levels should be kept low, e.g. 1000 mg/day.
The B vitamins are required to support active division of immune system cells and some have specific immune system functions. Riboflavin is involved with both the destruction of organisms by primitive immune cells and in cellular immunity. Thiamine is also essential to normal functioning of T cells in the cellular immune system. Folic acid deficiency has been clearly linked to increased infection risk. While the chance of severe deficiency is low for most horses, supplementation is reasonable during stressful periods and in no way harmful.