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9 Feed Additives Foods are defined by the Federal Food, Drug, and Cos- distinction is made where dietary substances providing one metic Act (Title 21 Code of Federal Regulations (CFR) Â§321 or more defined nutrients that affect body structure or func- (f)) as âarticles used for food or drink for man or other ani- tion are not considered a drug (Hoestenbach, 2004). In con- mals and articles used for components of any other such ar- trast, feed products not containing recognized nutrients and ticle.â Inherently, food and feed (used in reference to ani- claiming health, structure, or performance responses are po- mals) articles provide taste, aroma, nutritive value, or some tentially subject to regulatory scrutiny. Additionally, feed combination. Natural and commercially prepared feeds in- additives used for something other than their intended pur- tended for horses include substances that do not directly pose as defined in the CFR can result in regulatory action by provide essential nutrients, but may influence animal intake, the FDA. health, and performance or feed characteristics. Food addi- The Association of American Feed Control Officials tives, as described within Title 21 CFR (Â§321 (s)), include (AAFCO) writes and revises model bills. A model bill en- any substance intended or reasonably expected to become, compasses food and drug regulations set forth in the CFR either directly or indirectly, a component of food or alters and often is the basis of individual state feed regulations the characteristics of any food and including any substance (AAFCO, 2005). A publication published by AAFCO con- intended for use in the manufacturing, processing, packag- tains a listing of approved animal feed additives and guide- ing, and storing of food. No distinction is made between lines for their intended use and is updated yearly as approved feeds or food additives for food-producing or nonfood- uses of feed additives are subject to change. Other countries producing animals. Concerns about animal safety and po- have similar regulatory bodies that define acceptable uses for tential for residues in human foods derived from animal various nonnutrient feed components. Given the complexity sources have resulted in feed additives being regulated by of regulations, potential for change, and differences across the U.S. Food and Drug Administration (FDA). countries, the scope of this chapter will be limited to current A more conventional description of animal diet feed ad- feed additive regulations within the United States. ditives suggests nonnutritive ingredients that stimulate growth or other types of production, improve the efficiency ADDITIVES AFFECTING FEED CHARACTERISTICS of feed utilization, or benefit the health or metabolism of the animal (Church and Kellems, 1998). The focus here is on As previously defined, feeds provide nutrients required to medications and therapeutic agents in livestock feeds. This sustain normal body structure, metabolism, and productiv- perception of feed additives is consistent with the legal def- ity. Physical characteristics of feed that affect sight, smell, inition of a drug. Besides medicinal agents recognized by taste, and texture impact feed intake (Dulphy et al., 1997; various official pharmacopoeia agencies, the CFR addition- Goodwin et al., 2005a), thereby influencing the animalâs ally defines a drug (21 CFR Â§321 (g)) as any âarticle in- ability to consume sufficient amounts to meet nutrient tended for use in the diagnosis, cure, mitigation, treatment, needs. Additionally, chemical or microbiological alteration or prevention of disease in man or other animals and articles or degradation of the feed and its components during the (other than food) intended to affect the structure or any func- manufacturing and storage process can adversely affect in- tion of the body of man or other animals.â Substances fitting take, animal health, or both (Raymond et al., 2003). Nonnu- the legal definition of a drug must undergo stringent and ex- tritive food additives can provide a number of technologic tensive evaluation to document safety and efficacy before functions to enhance physical characteristics, suitability, and being approved by the FDA for use in medicated feeds. A stability of feed during manufacturing, processing, and stor- 183
184 NUTRIENT REQUIREMENTS OF HORSES age (FDA, 1992; Kantor, 1996; Sumner and Eifert, 2002). sion rate was recommended (FDA, 1997). However, no ad- Technical food additives are used in foods to promote prod- verse effects have been reported with its use in horse feeds. uct consistency, improve or maintain nutritional value, Other synthetic feed-based antioxidants include butylated maintain palatability, retard spoilage, and provide character- hydroxyanisole (BHA; 21 CFR Â§582.3169), butylated hy- istics to influence taste and color (FDA, 1992). droxytoluene (BHT; 21 CFR Â§582.3173), and tertiary butyl Food additives used for technical effects on feeds are all hydroquinone (TBHQ). Both BHA and BHT compounds defined and approved for their intended use within specific are considered GRAS. As of 2005, TBHQ is considered an guidelines for rate of incorporation within Title 21 CFR and acceptable feed ingredient by AAFCO as it is undergoing in- the current AAFCO publication, or by similar regulatory formal review by FDA (AAFCO, 2005). Inclusion of BHT, bodies in other countries. These substances are categorized BHA, and TBHQ is limited to a total preservative content either as generally recognized as safe (GRAS; 21 CFR not more than 0.02 percent (200 mg/kg) of fat or oil (in- Â§582) or permitted (21 CFR Â§573) food additives. An addi- cluding volatile oils) content (AAFCO, 2005). tive with GRAS status (21 CFR Â§570.30) is established by Mixed tocopherols (21 CFR Â§582.3890) are combined either recognizing the substance has been used for many forms of vitamin E isomers with similar antioxidant activ- years with public knowledge of its use and safety or has ity to synthetic compounds, though greater quantities are been scientifically evaluated to be without documented needed compared to synthetic antioxidants (Gross et al., health, residue, or toxicity concerns. Most food additives 1994; Ohshima et al., 1998). Being derived from plants and used prior to 1958 were classified as GRAS as a result of not chemically altered, mixed tocopherols are often mar- their prolonged use without safety concerns under good keted as ânaturalâ antioxidants. The antioxidant properties manufacturing or feeding practices. Most nutrients, except of tocopherols are complex and vary by isomer, concentra- selenium, are considered GRAS. Specific selenium sources tion, and combination interactions (Huang et al., 1994, have been approved as food additives for animals following 1995). Stabilization of tocopherol isomers by esterifica- extensive scientific documentation (21 CFR Â§573.920). It tion to acetate or succinate limits their food preservation should be noted that GRAS substances, although recognized activity. as safe, are not without potential hazard if not used within A number of additional GRAS substances are used as the defined guidelines of good manufacturing or feeding chemical preservatives (21 CFR Â§582 Subpart D) to main- practices. Any nutrient if fed in amounts greatly exceeding a tain feed value and inhibit microbial colonization and defined requirement can induce toxicosis. growth in feeds. Propionic acid (21 CFR Â§582.3081) incor- Following the food additives amendment to the Federal porated at 0.3 and 1 percent (weight/weight) has been shown Food, Drug, and Cosmetic Act in 1958, food additives not to be an effective mold-inhibiting agent for dried grains considered GRAS and all new food additive requests were (Kiessling and Pettersson, 1991). A number of other organic and are required to provide substantial documentation of acids and their combinations are used as chemical preserva- safety and utility before being approved. Though no differ- tives (Kiessling and Pettersson, 1991; AAFCO, 2005). Feed entiation is made in defining food additives for humans or labels must indicate the inclusion of preservative agents by animals, food additives approved for humans are not neces- identifying the compound as âa preservative,â using a state- sarily approved for use in animal feeds. To date, no excep- ment âpreserved with,â âadded to inhibit mold growth,â or tions or qualifications exist for the inclusion of GRAS or similar designation (AAFCO, 2005). permitted food additives in horse feeds. Colors Antioxidants and Preservatives Color additives may be added to feeds to replace, en- Antioxidant preservative compounds are added to dietary hance, or accentuate inherent colors of feed. Allowed sub- ingredients for the purpose of inhibiting oxidation reactions stances used for color in feeds are either certified synthetic to polyunsaturated fats and vitamins. Reactions from expo- compounds (21 CFR Â§74.101 through Â§74.706) or noncerti- sure to oxidizing agents induce formation of highly reactive, fied natural or synthetic sources (21 CFR Â§73.1 through unstable, and self-replicating peroxides and free radicals Â§73.615). Certified colors not only require premarket ap- (unpaired electron species) within fatty acid structures. Fat proval, but each manufactured batch must be certified to en- oxidation results in feed discoloration, deterioration, and fat sure safety. Inclusion of certified color additives must be rancidity and ultimately reduces feed palatability and qual- identified on product labels by color and number (âGreen 3â ity. Feed vitamin activity can be markedly reduced by or âYellow 5â) (21 CFR Â§70.25). Natural color sources in- oxidation. clude certain spices, vegetables, fruits, caramel, and others. Ethoxyquin (21 CFR Â§573.380) is a commonly used syn- Color additives have little to no impact on feed acceptabil- thetic antioxidant approved for use in animal feeds, although ity, but may play an important role in product marketing and some concerns regarding its safety for use in dog foods have consumer appeal. been raised (Dzanis, 1991) and subsequently a lower inclu-
FEED ADDITIVES 185 Flavors riander, and echinacea to be selected against (Goodwin et al., 2005b). Apple, banana, carrot, cherry, cumin, fenu- A wide variety of spices, seasonings, flavorings, natural greek, garlic, ginger, oregano, peppermint, rosemary, and oils, and extracts are considered GRAS (21 CFR Â§582.10 turmeric were all universally accepted, but mean consump- through Â§582.50) and could be used to add natural flavors to tion rates varied, with apple, garlic, ginger, and turmeric horse feeds. Additionally, synthetic GRAS compounds (21 having the slower consumption times (Goodwin et al., CFR Â§582.60) mimicking various fruit, mint, and other fla- 2005b). In the same study, using paired flavor-testing com- vors can be added to horse feeds. Beyond the intended pur- parisons, fenugreek and banana flavors were highest pose of providing flavor, a number of herbs and spices have ranked. Consumption time of a mineral pellet was lower been attributed effects often associated with health or dis- (P < 0.01) for banana- and fenugreek-flavored compared to ease mitigation. Inclusion rate for these flavor ingredients unflavored pellets with no difference between flavored pel- using good manufacturing practices are unlikely to have po- lets (Goodwin et al., 2005b). Studies evaluating flavor pref- tential for other beneficial effects. Additionally, any product erences of horses are limited, and feed intake response to claim to this effect is contrary to recognized intended pur- flavor additives is influenced by individual preference, con- pose of the additive and could prompt regulatory action. centration, and feed characteristics. Flavors are often used to improve feed palatability and acceptability directly or indirectly by masking off-taste or Pellet Binders and Anticaking Agents off-odor constituents in feed. Anorectic or sick horses may potentially benefit from flavors if intake is increased, but use Pellet binders are compounds added to feed ingredients in feeds for healthy horses is questionable and potentially is to be compressed through a pellet mold that promote cohe- more for marketing aimed at the horse owner. Randall et al. siveness and inhibit pellet crumbling or breakdown prior to (1978) assessed taste response of weanlings (202 kg body- feeding. Bentonite (21 CFR Â§582.1155) and attapulgite (21 weight [BW]) to salty (sodium chloride), sweet (sucrose), CFR Â§582.1) clays and kaolin (21 CFR Â§582.1) can be sour (acetic acid), and bitter (quinine hydrochloride) tasting added to a maximum of 2 percent of total ration as pelleting solutions using a two-choice preference test procedure aids. Both clays and kaolin have restricted use in medicated (water as the control solution). Foals showed weak to mod- feeds as they potentially interfere in analysis of certain erate preference for sweet solutions between 1.25 and 10 g drugs. Lignin sulfonate (21 CFR Â§573.600) can be incorpo- sucrose per 100 ml (Randall et al., 1978). Sucrose solutions rated up to 4 percent of the finished pellet as a binding aid. were not discriminated against compared to water, which is Ball clay is no longer approved as a feed ingredient in agreement with observed feeding preferences of horses (AAFCO, 2005). for sweetened concentrates (Houpt, 1990). Foals discrimi- Anticaking agents are substances included in finely pow- nated against salty, sour, and bitter solutions compared to dered or crystalline feeds to prevent caking, lumping, or ag- water above 0.63 g NaCl, 0.16 ml acetic acid (3.1 pH), and glomeration. Iron ammonium citrate (21 CFR Â§573.560) 20 mg quinine per 100 ml water (Randall et al., 1978). Other and yellow prussiate of soda (21 CFR Â§573.1020) are used studies have addressed flavor preferences in feeds for horses as anticaking agents in granular salt and are limited to 25 (Burton et al., 1983; Hintz et al., 1989; Pollack and Burton, and 13 ppm in finished product, respectively. Various sili- 1991; Goodwin et al., 2005b). cate compounds are either GRAS (21 CFR Â§582.2122 Peppermint-, carrot-, and wheat syrup-flavored feeds through Â§582.2906) or permitted (calcium silicate, 21 CFR had lower consumption rate compared to apple- or orange- Â§573.260; diatomaceous earth, 21 CFR Â§573.340; pyrophyl- flavored feeds or a control feed containing molasses (Pol- lite, 21 CFR Â§573.900) food additives as anticaking or lack and Burton, 1991). Using flavorings at incorporation pellet-binding aids. Good manufacturing practices limit the rates of 500 or 2,500 g/ton, within-flavor comparisons incorporation of silicate agents to a maximum of 2 percent showed apple and peppermint flavors were preferred at the of the finished product. higher and lower inclusion rates, respectively (Pollack and Hydrated sodium calcium aluminosilicate (HSCAS, 21 Burton, 1991). There also was a reported tendency for pref- CFR Â§582.2729), as well as other aluminosilicate com- erence of the lower inclusion rate for orange flavor com- pounds (zeolites), have been purported as potential myco- pared to the higher incorporation rate (Pollack and Burton, toxin sorbent in animal feeds (CAST, 2003). Bentonite clays 1991). Another study found peppermint flavor, added at the have also been suggested to bind mycotoxins in feeds mak- manufacturerâs recommended level, to have no effect on in- ing them less available for absorption. Philips et al. (1987, take (Hintz et al., 1989). Time to consume 2 kg of a mixed 1988) showed a protective effect of feeding HSCAS to cereal grain sweet feed was increased 45, 57, and 213 per- growing chicks fed a diet containing 7.5 ppm aflatoxin B1. cent when flavored with apple, caramel, and anise, respec- In the CAST (2003) report on mycotoxins, 25 studies were tively (Burton et al., 1983). Paired preference testing with cited as having shown enterosorbent effects of HSCAS or 15 different flavors added to 100 g cereal byproduct meal (1 other bentonite clays in protecting against aflatoxins in a g/100 g) fed to eight mature horses showed nutmeg, co- wide variety of young animals. None of the cited studies had
186 NUTRIENT REQUIREMENTS OF HORSES used horses as an animal model. Although data are support- essential nutrients provided in amounts above those sug- ive of a sorbent effect of clays, primarily HSCAS, evidence gested to prevent a deficiency state. Or they can be other suggests the response is limited to aflatoxins and does not food components known to have vital role(s) in metabolism carry over to other mycotoxins. Inclusion of HSCAS in diets that are not currently recognized as an essential nutrient. did not ameliorate effects of zearalenone (Bursian et al., Other substances may include those for which no function in 1992), deoxynivalenol (DON; Patterson and Young, 1993), metabolism is known, yet their inclusion in the diet is pur- or ergotamine (Chestnut et al., 1992). Additionally, zeolites ported to augment production or facilitate body function. are potential binders of cations and could reduce availability With emphasis on human health, fitness, and good nu- of calcium, magnesium, and zinc if fed in excess of the ap- trition, inclusion of dietary substances for purposes of im- proved rate of 2 percent of total feed (Chung et al., 1990; proving health and performance has spawned an expanding Chestnut et al., 1992). Any product labeling claim relative to market of products and generated new terminology of ânu- mycotoxin binding ability for these compounds is contrary traceutical,â âfunctional foods,â âdesigner foods,â and simi- to the specified purpose of these ingredients as defined in lar descriptors. There are similar interests within horse nu- current regulations and could prompt regulatory action. trition. The term ânutraceuticalâ was coined to encompass perceived dual roles of providing nutritive value (e.g., food) and pharmaceutical activity; however, there is little agree- Other Additives ment on a precise definition (Boothe, 1997). Concerns have A number of other nonnutritive substances are potentially been raised relative to safety and efficacy of such products added to horse feeds to alter form and uniformity. Mineral as well as the role of regulatory oversight (Boothe, 1998). In oil (21 CFR Â§573.680), paraffin, petrolatum (21 CFR 1994 the U.S. Congress passed the Dietary Supplement Â§573.720), and petroleum jelly (21 CFR Â§573.720) can be Health and Education Act (DSHEA), which permitted the included in mineral mixes to reduce dust (AAFCO, 2005). inclusion of such substances in dietary supplements without The inclusion rate of any dust reducer must be less than 3 or prior documentation of safety and utility. Citing safety con- 0.06 percent of the mineral mix or total ration, respectively. cerns for the human food supply, the FDA determined that Talc and mineral oil can be used as die lubricants in the feed DSHEA does not apply to animal feeds (FDA, 1996). This manufacturing process. Emulsifying agents (21 CFR determination was made because a distinction between ani- Â§582.4101 through Â§582.4666) are used to maintain uniform mal feeds intended for food-producing or nonfood species is dispersion of fats and oils in aqueous components of a prod- not considered. Thus, from a regulatory viewpoint, nu- uct. Stabilizers (21 CFR Â§582.7115 through Â§582.7724), traceutical products for use in animal feeds do not exist. Di- primarily gums and alginate substances, maintain final prod- etary supplements included in animal feeds are classified uct uniformity or consistency over various conditions of legally as either drug, food, or both and regulated as either manufacturing, processing, and storage. Sequestrants (21 drug or food according to a written policy matrix (FDA, CFR Â§582.6033 through Â§582.6851) are polyvalent metal 1998). Legal status as a food or drug is determined by the in- ion binders that form soluble metal complexes to minimize tended use of the substance. Under current regulations, man- oxidation from free metal ions and improve final product ufacturers may be restricted in terms of statements regarding stability. substance functions within foods, including some of the functions described below. In feeding horses, as with any species, emphasis should ADDITIVES AFFECTING ANIMAL HEALTH AND be on feeding a complete and balanced diet. Interest in ad- PERFORMANCE ditional dietary supplements to maintain or improve health In addition to substances added to enhance the technical and performance is warranted, but safety to the animal or nonnutritive characteristics of food, a wide variety of nu- should take precedence. The following discussion provides tritive and nonnutritive substances are potentially added to documentation from the scientific literature on the efficacy enhance animal health. Most recognized of these substances of a number of commonly used dietary supplements in are medicinal compounds (e.g., antibiotics, anthelmintics) horses. Discussion of such supplements does not imply es- used to prevent or treat disease conditions. Medicinal com- sentiality, but only serves to provide information on which pounds require extensive premarket study and documenta- to base an informed decision as whether or not to use such tion of safety and efficacy for their intended purpose. Med- substances in diets provided to horses. icinal compound documentation is completed by the manufacturer, at considerable expense, prior to considera- Antioxidants tion for FDA approval as a new animal drug. Beyond me- dicinal compounds, much interest has been focused on the Production of reactive oxygen species (ROS) is a normal potential role of food or food components in promoting consequence of cellular metabolism, leukocyte-induced in- health and well-being, performance, and disease mitigation flammatory response (respiratory burst), and exposure to en- or prevention. These foods or food components may include vironmental oxidizing agents (UV radiation, pollution,
FEED ADDITIVES 187 chemical agents, tobacco smoke). Generated ROS mole- fluenced by chemical form, dose, dosing frequency, and cules include free radicals (molecules containing an un- dose response, and is extremely variable among individuals paired electron) and various peroxides (e.g., hydrogen per- (Snow and Frigg, 1990). Oral bioavailability of crystalline oxide, lipid hydroperoxides, singlet oxygen). These L-ascorbic acid in the horse is low, using dosages ranging molecules once generated by pro-oxidative reactions are from 5â20 g/d to either single (LÃ¶scher et al., 1984; Snow et self-perpetuating and are capable of damaging DNA, lipids, al., 1987; Snow and Frigg, 1989) or continuous (Snow and proteins, and carbohydrates (Evans and Halliwell, 2001). Frigg, 1990) dosing. Horses supplemented with crystalline Production and continued propagation of ROS is believed ascorbic acid at either 4.5 or 20 g/d had an approximate dou- integral to the pathogenesis of carcinogenesis, aging os- bling of plasma ascorbic acid concentration compared to un- teoarthritis, cardiovascular, and other degenerative diseases supplemented control horses, but the response was not dif- (Clark, 2002). In the horse, oxidative stress from ROS prop- ferent between 4.5- or 20-g dosages (Snow et al., 1987). agation has been associated in the pathogenesis of joint dis- Ascorbyl palmitate, but not ascorbyl stearate, showed ease (Dimock et al., 2000) and recurrent airway obstruction greater bioavailability compared to crystalline ascorbic acid (RAO) (Art et al., 1999; Kirschvink et al., 2002a; Deaton et with a single oral dose (Snow and Frigg, 1989). Deaton et al. al., 2004a). (2003) supplemented ponies with 20 mg/kg BW ascorbic A number of essential nutrients perform all or part of acid equivalent weight from ascorbyl palmitate or calcium their biological role as a metabolic antioxidant protecting ascorbyl monophosphate. Plasma and bronchoalveolar against environmental or metabolic oxidizing agents (Frei, lavage fluid (BALF) ascorbic acid concentrations were 61 1994; Clark, 2002). A number of trace minerals are con- and 68 percent greater with ascorbyl palmitate supplemen- stituents of enzymes having antioxidant activities, namely tation compared to control. Calcium ascorbyl monophos- glutathione peroxidases (selenium), superoxide dismutases phate supplementation increased BALF, but not plasma, (copper, zinc, manganese), and catalases (iron). Other ascorbic acid concentration 39 percent above unsupple- nonenzymatic mineral-dependent antioxidants include ceru- mented controls (Deaton et al., 2003). Snow and Frigg (1990) loplasmin (copper) and ferritin (iron). Additionally, the es- using seven horses in a cross-over study design did not see sential fat-soluble vitamins A and E perform part or all of any significant increases in mean plasma ascorbic acid con- their biologic functions as cellular antioxidants (Frei, 1994). centration with daily crystalline ascorbic acid (20 g/d; 3.2 Â± Antioxidants acting individually or collectively are capable 0.6 mg/l) or ascorbyl palmitate (47 g/d; 4.2 Â± 0.9 mg/l) com- of chemically converting ROS to less reactive or inactive pared to control and unsupplemented periods (2.8 Â± 1.1 mg/l). molecules, thus reducing potential cellular damage. Specific Thoroughbred horses (n = 14) treated intravenously with discussions on biologic activities of these essential trace 5 g ascorbic acid prior to racing had no change in thiobarbi- minerals and vitamins and their requirements are covered in turate reactive substances (TBAR) compared to a 29 percent their respective chapters elsewhere in this report. increase (P < 0.01) in untreated cohorts (n = 30), but treated horses experienced a greater increase (212 vs. 97 percent, P < 0.01) in creatine kinase activity (White et al., 2001). No Other Antioxidants influence on physical performance was determined. Though Other compounds have also been characterized as having plasma ascorbic acid concentrations were greatly increased cellular or extracellular antioxidant properties. These com- with supplementation (75.9 mg/l) and greatly exceeded ob- pounds are currently considered nonessential in the diet of served plasma concentrations with oral ascorbate supple- the horse as they can either be sufficiently synthesized by mentation, there was no effect of racing on plasma concen- the body to meet needs (vitamin C, lipoic acid) or there is tration in treated or untreated horses. insufficient evidence suggesting a dietary requirement Supplementing ascorbic acid may have adverse conse- (Î²-carotene, lutein, lycopene). Beyond being a precursor for quences. Snow and Frigg (1990) observed significant de- vitamin A, Î²-carotene and other carotenoids (lutein, ly- clines in plasma ascorbic acid concentration below that of copene) have been suggested to possess antioxidant proper- unsupplemented controls following periods of supplementa- ties (Frei, 1994). There is a paucity of data supporting any tion (20 g/d ascorbic acid). A decline in endogenous synthe- benefit of adding these compounds (carotenoids and lipoic sis was hypothesized, but a mechanism was not elucidated. acid) as antioxidants to equine diets. Beta-carotene is ad- Tsao and Young (1989) determined that endogenous synthe- dressed in more detail elsewhere in this report (see Chap- sis of ascorbic acid can be down regulated by feeding be- ter 6, Vitamins). tween 0.5 and 5 percent ascorbic acid in the total diet to Vitamin C functions as a water-soluble intra- and extra- mice. Ascorbic acid toxicity was not recognized in horses cellular antioxidant and interacts with vitamin E as a co- administered up to 20 g/d for 1 day (NRC, 1987), but po- antioxidant to restore the antioxidant form of vitamin E tential long-term administration has not been evaluated. (Bowery et al., 1995). However in vivo relevance of this in- Ascorbic acid can act as a pro-oxidant with copper and iron teraction is uncertain (Carr and Frei, 1999). Supplementa- potentially generating lipid radicals and requiring antioxi- tion and availability of dietary ascorbic acid is complex, in- dants to return ascorbic acid to its antioxidant form (Clark,
188 NUTRIENT REQUIREMENTS OF HORSES 2002). Excess ascorbic acid intake could overwhelm the when the horse is vitamin E-deficient has not been tested. bodyâs capacity to recycle ascorbic acid back to its antioxi- Without further studies, supplementation of Î±-lipoic acid as dant state. an antioxidant is not warranted. Reported differences in ascorbic acid in RAO-affected horses with and without inflammation compared to healthy Dietary Application of Antioxidants horses and the implied protective effect of ascorbic acid in RAO pathogenesis is enticing (Kirschvink et al., 2002a; Exercise or other activity increasing oxygen consumption Deaton et al., 2004a); however, data substantiating an inde- will increase the generation of ROS and potentially tip the pendent ascorbic acid effect on disease amelioration are un- balance away from the bodyâs antioxidant defense ability in available. Based on the limited data, variable response to favor of oxidative reactions and resulting cellular damage oral ascorbic acid dosing and clinical trials (White et al., (Hargreaves et al., 2002; Deaton and Marlin, 2003; 2001; Deaton et al., 2002) with equivocal responses to sup- Williams, 2004). Antioxidants have been advocated for di- plementation, recommendations for additional supplementa- etary inclusion in exercising horses to minimize oxidative tion of ascorbic acid to promote antioxidant function cannot stress associated with physical activity, especially for horses be determined. with RAO (Deaton and Marlin, 2003; Williams, 2004). Alpha-lipoic acid has been reported to perform antioxi- Healthy horses supplemented with a commercial dietary an- dant function in humans and laboratory animals (Packer et tioxidant mixture (vitamins E and C, and selenium) or a al., 1995). A similar function was suggested for horses evi- placebo for 4 weeks and subjected to an intermittent, denced by reduced total plasma lipid hydroperoxide con- moderate-intensity exercise test (2 minutes at 70, 80, and 90 centration in Thoroughbred geldings (687 kg BW, n = 10) percent individual oxygen maximum) showed no benefit supplemented once daily with 10 mg/kg BW d,l-Î±-lipoic or detriment of additional antioxidant supplementation acid compared to unsupplemented control horses (Williams (Deaton et al., 2002). A lack of response may be attributed et al., 2002). In this study, supplemented geldings had an un- to exercise intensity not being sufficient to induce oxida- explained greater plasma concentration of total lipid hy- tive stress. However, antioxidant supplementation increased droperoxidases compared to control geldings at initiation of plasma ascorbic acid (P = 0.007) and Î±-tocopherol (P = 0.02) the study. Other than red and white blood cell total glu- concentrations compared to placebo-treated horses (Deaton tathione and glutathione peroxidase, no other antioxidants et al., 2002). Antioxidant effects on pulmonary epithelial that may have impacted overall antioxidant status were lining fluid (ELF) ascorbic acid and Î±-tocopherol concen- measured; thus, the implied role of lipoic acid in observed trations were not significant (Deaton et al., 2002). response may be questioned. No adverse health effects were Recurrent airway obstruction-affected horses in acute cri- observed in lipoic acid-supplemented horses over the dura- sis (exposed to bedding and hay allergens) have indicators tion of the study (14 days), but long-term safety in horses is of oxidative stress evidenced by increased oxidized glu- unknown and must be evaluated before a recommendation tathione concentration and glutathione redox ratio in ELF for use made. (Art et al., 1999; Kirschvink et al., 2002b). Reduced antiox- In a second study using 12 mature Arabian horses (450 idant status was correlated with measures of impaired pul- kg BW), antioxidant supplementation with 10 g/kg BW monary function and increased airway inflammation lipoic acid or 5,000 IU/d Î±-tocopheryl acetate was com- (Kirschvink et al., 2002b). Horses affected with RAO and pared to unsupplemented horses completing a treadmill- having evidence of airway inflammation had lowest ELF based endurance (55 km) exercise (Williams et al., 2004a). ascorbic acid concentration compared to RAO-affected Supplementation with either lipoic acid or Î±-tocopherol im- without airway inflammation and unaffected horses (Deaton proved a number of parameters measured to assess antioxi- et al., 2004a, 2005a). Collectively, these studies suggest dant status. Plasma lipid hydroperoxide concentration was RAO-affected horses have lower airway antioxidant status not different across treatments. However, only white blood and might benefit from antioxidant supplementation. Di- cell apoptosis (programmed cell death) showed significant etary supplementation of an antioxidant mixture (vitamins E interaction between supplementation and stage (time points and C and selenium) for 4 weeks in RAO-affected horses during exercise). White blood cell apoptosis was lower (P = showed improvement in exercise ability and inflammatory 0.05) and tended (P = 0.06) to be lower in vitamin E and score (Kirschvink et al., 2002c) or no effect (Deaton et al., lipoic acid supplemented horses, respectively, compared to 2004b); however, neither study had healthy control horses unsupplemented horses (Williams et al., 2004a). Results for comparison. Nonneutrophilic airway inflammation in- from this study suggest potential antioxidant effects with duced by ozone exposure resulted in oxidation of glu- lipoic acid; however, animal numbers were limited to make tathione, but not ascorbic acid in both RAO-affected and any broad-based interpretation. Vitamin E status of experi- healthy horses (Deaton et al., 2005b). Response to ozone- mental horses was adequate based on initial plasma induced inflammation was not greater in RAO-affected Î±-tocopherol concentrations of control horses (> 4.0 Âµg/ml). horses, in spite of their lower ELF ascorbic acid concentra- Ability for lipoic acid to provide antioxidant protection tion compared to healthy horses.
FEED ADDITIVES 189 Supplementation of exercising horses with vitamin E tion over 5 days (Weese et al., 2003). An equine-specific or- (Siciliano et al., 1997) or vitamins E and C (Hoffman et al., ganism, Lactobacillus pentosus WE7, was identified as hav- 2001; Williams et al., 2004b), though significantly increas- ing good inhibitory activity against enteric pathogens and ing plasma vitamin E and ascorbic acid concentrations com- colonization ability (Weese et al., 2004). However, it in- pared to unsupplemented horses, failed to show significant duced clinical disease and diarrhea when specifically used reduction in exercise-induced muscle damage as evaluated as a probiotic agent in neonatal foals (Weese and Rousseau, by plasma muscle enzyme activities. Racing Thoroughbreds 2005). provided an antioxidant mixture supplement (containing Administration of Lactobacillus acidophilus to cecally 11.5 g ascorbic acid; 7 g d,l-Î±-tocopheryl acetate; 7 mg cannulated geldings had minimal effects on pH, bacterial selenium; 769 mg zinc; 187 gm copper; and 500 mg populations, and volatile fatty acids with the exception of re- Î²-carotene) over a 3-month period had lower creatine phos- duced butyrate production (Booth et al., 2001). Although phokinase activity at 6, but not 12, weeks, compared to un- fecal lactate concentrations were higher in treated foals, sup- supplemented controls (de Moffarts et al., 2005). The basal plementing a commercial product of mixed lactobacillus hay and oats diet consumed by all horses provided less than bacteria had no effect on foals fed either a starch- or fiber- NRC (1989) recommended daily amounts of vitamin E (120 based diet at weaning (Swanson et al., 2003). In a double- IU), selenium (0.4 mg), zinc (48 mg), and copper (75 mg). blind study using two commercial probiotic products ad- A lack of consistent markers of oxidative stressors or re- ministered for 7 days following colic surgery, no effect was sponses to antioxidants in exercising horses may be attrib- seen on Salmonella shedding, prevalence of diarrhea, dura- uted to differences in level of training, duration, and inten- tion of antibiotic therapy, or length of hospitalization (Par- sity of exercise; ambient conditions; and nutrition (Marlin et raga et al., 1997). In contrast, Ward et al. (2004) found a al., 2002; Williams et al., 2003; de Moffarts et al., 2004). marked reduction in Salmonella shedding in hospitalized Additionally, interpretation of oxidative stress response may horses without gastrointestinal disease administered a probi- be influenced by the analytic marker used (Balogh et al., otic agent compared to a placebo. Concerns about safety and 2001), source of oxidative stress (Deaton et al., 2005a,b), utility and limited number of clinical studies in horses re- and the form of antioxidant. At present, there is a lack of quire further evaluation of probiotic products. data on which to base specific recommendations beyond those for the essential vitamins and minerals that are com- Enzymes ponents of antioxidants. Recent research using antioxidant mixtures is encouraging, but specific recommendations are Enzymes of various sorts have been added to livestock not available. diets to facilitate digestion of ingested feed (Officer, 2000). In ruminant animals, cellulases, hemicellulases, or other cell wall carbohydrate enzymes have been applied to improve di- Direct Fed Microbials (Probiotics) etary fiber digestibility. Similarly, various carbohydrases Direct fed microbials (DFM, also termed âprobioticsâ) (pentosanases and Î²-gluconases) and proteases have been are products intended to be consumed and provide live used in poultry to improve feed energy availability and ani- colonies of lactic acid bacteria, namely Lactobacilli, Bifi- mal performance. In poultry and pigs, phytase has been suc- dobacteria, and entercoli, typically present in the intestinal cessfully used to improve dietary phosphorus availability lumen of healthy animals. Provision of live bacteria is be- from plant sources (NRC, 1998; Augspurger and Baker, lieved to exclude or reduce growth of potential pathogenic 2004). Phytate phosphorus accounts for a significant amount bacteria by competitive inhibition, production of inhibitory of total phosphorus in cereal grains and wheat byproducts substances, promotion of localized immune responses, or al- (Eeckhout and De Paepe, 1994). In horses, potential exists teration of the luminal environment (Weese, 2002a). These for the use of phytase and various cell wall carbohydrate en- bacteria may also provide benefit to the host animal through zymes in improving net availability of dietary phosphorus production of vitamins, enzymes, and volatile fatty acids and fiber, respectively. (VFAs), which may provide nutritional value, aid digestion, Fibrolytic enzymes in horse diets could improve energy and benefit gastrointestinal health. Microbial viability and availability from low-quality grass forages. Cellulase added concentration within commercial human and veterinary to a concentrate (330 g/d) fed with ad libitum timothy hay products has been questioned (Canganella et al., 1997; forage resulted in no improvement in fiber digestibility in Weese, 2002b), as well as the applicability of cultured bac- mature Arabian geldings (OâConnor et al., 2005). Microbial terial organisms to specific host animals (Weese et al., xylanase and cellulase were administered orally at the time 2004). of feeding to eight yearling geldings (341 kg mean BW) re- Attempts to determine colonization capacity of a human ceiving Coastal Bermudagrass (fed at 1.5 percent of BW) strain organism (Lactobacillus rhamnosus strain GG) in and provided sufficient supplements to meet recommended horses found low colonization in adults, even at a very high energy and protein needs (Hainze et al., 2003). Four dietary dose, and consistent colonization in foals with administra- supplements in this study consisted of alfalfa cubes, whole
190 NUTRIENT REQUIREMENTS OF HORSES oats, sweet feed (corn, oats, molasses, soybean meal), or Of greater concern are safety issues for herbs and botan- pelleted concentrate (wheat midds, corn, dehydrated al- icals that might be incorporated into horse feed or supple- falfa). All horses received all four dietary treatments with mented by an owner. Acute and chronic toxicity data for var- and without enzymes. Modest increases (P < 0.1) in dry ious herbal compounds in horses are not well documented matter (DM), neutral detergent fiber (NDF), acid detergent and extrapolation of data from other species may not be fiber (ADF), and hemicellulose digestibility were found in valid in many cases. Garlic is one of the most popular herbs diets supplemented with oats or sweet feed and enzymes. In used for medicinal purposes and perceived to be natural and contrast, DM, NDF, and ADF digestibility slightly declined safe. Garlic is considered GRAS as a flavoring agent in feed, (P < 0.1) for diets supplemented with alfalfa and enzymes. but has potential to cause oxidative damage when consumed Alfalfa contains minimal xylans compared to the other sup- in greater quantities in a variety of species. Horses consum- plements and efficacy of dietary fibrolytic enzymes is de- ing freeze-dried garlic received greater than 0.2 mg/kg BW pendent upon matching feedstuff carbohydrate content to in two daily meals showed oxidative damage to red blood the enzymes supplied (Officer, 2000). Additionally, applica- cells evidenced by increasing Heinz body anemia over time bility of acid insoluble ash methodology as an internal of exposure (Pearson et al., 2005). Horses showed improved marker for estimating cell wall digestibility of alfalfa is hematologic parameters 4â5 weeks following removal of questioned, as it does not contain significant amounts of sil- garlic supplementation. In this study horses voluntarily con- ica compared to grass forages (Van Soest, 1994). sumed a toxic dose (0.25 g/kg BW twice daily) of freeze- Four studies from different laboratories evaluated the ap- dried garlic for 71 days. plication of phytase in equine diets and the impact on di- Additional concerns with phytochemicals in herbs and etary phosphorus availability (Morris-Stoker et al., 2001; botanicals relate to potential interactions with administered Patterson et al., 2002; van Doorn et al., 2004; Hainze et al., pharmacologic agents and positive drug residue violations in 2004). In all studies, true total tract dietary phosphorus di- show and performance horses. Herb compound interactions gestibility was not improved, and only van Doorn et al. with conventional pharmacologic agents may potentially en- (2004) showed increased phytate phosphorus digestibility hance, diminish, or induce a novel response to drug or herb. with added phytase (see discussion in Chapter 5). This is in A number of human dietary supplements containing com- contrast to results observed in pigs and poultry. Although pounds with either sedative or stimulating effects on the phytase source and range of activity was similar across stud- central nervous system could result in residue violations ies, variation in amount of phytate phosphorus supplied or (Short et al., 1998). Though few reports have been published dietary calcium content may account for observed poor re- documenting adverse effects of herbs and botanicals in sponses of dietary phytase. Further research is required to horses, potential risks extrapolated from reports in other adequately assess applicability of enzymes to facilitate nu- species have been reviewed for horses (Poppenga, 2001). trient availability from the equine diet. Joint Supplements Herbs and Botanicals Products containing glucosamine, chondroitin sulfate, or Many herbs are generally recognized as safe (GRAS) a combination, and possibly including manganese ascorbate, and are used in foods as seasoning and flavoring agents. Al- are one of the most common feed additives fed to horses. though in whole form, herbs and other botanicals contain Products may contain various forms of glucosamine (hy- some nutritive value (fiber, vitamins, minerals), their typi- drochloride or sulfate) or substances that may provide a glu- cal inclusion rate does not contribute appreciably to dietary cosamine source. The main impetus for use of these supple- nutrient content. However, a number of herbs and botani- ments is the perception that they are âchondroprotective,â cals contain alkaloids and other phytochemicals that may or supplying âbuilding blocksâ for articular cartilage and po- may not be safe when fed to the horse. Although many tentially effective in delaying, stabilizing, or even repairing herbs and botanicals are used for various health or medici- osteoarthritis lesions (Neil et al., 2005). Any such claim nal effects in humans, dietary use of herbs or botanicals would fit the regulatory definition of a drug, thus requiring with the intention of preventing or treating a disease or al- extensive documentation of safety and efficacy by the FDA. tering body structure, function, or performance defines the At present (2005), no dietary product containing these sub- supplement as a drug, thus requiring regulatory evaluation. stances has received FDA approval for such intended pur- Data supporting such efficacy of use and safety in the horse poses. However, an injectable drug product containing one are not available, and discussion of potential applications form of a glycosaminoglycan is approved for use in horses beyond nutritional value is not within the scope of this re- to treat osteoarthritis (reviewed by McIlwraith, 2004). port. Given the paucity of research data about herbs per- Glucosamine is an amino monosaccharide that can be taining directly to horses and the hazards of extrapolating synthesized in the body from other dietary constituents and, from other species, any claims about the benefits of herbs thereby, not considered an essential nutrient in the diet. Fur- must be viewed cautiously. ther metabolic modification of glucosamine generates inter-
FEED ADDITIVES 191 mediate substrates for chondrocytes and synoviocytes to (9 g) and needed to achieve concentrations within sensitiv- synthesize various glycosaminoglycan (GAG) compounds ity of methods used. Glucosamine concentrations were not including hyaluronan, keratan sulfate, and chondroitin sul- detectable when 9 g were administered orally (Du et al., fate (Neil et al., 2005). Chondroitin sulfate is a GAG con- 2004). In another horse study, after nasogastric administra- sisting of alternating disaccharide subunits of glucuronic tion of 20 mg/kg BW glucosamine HCl, bioavailability was acid and N-acetylgalactosamine. Chondroitin sulfate is a determined to be 5.9 percent (Laverty et al., 2005). Maxi- large polymer and has hydrophilic properties that impart mum serum and synovial fluid glucosamine concentrations compressive resistance to articular cartilage. Glycosamino- were 5.8 Â± 1.7 ÂµM and 0.3â0.7 ÂµM, respectively, with glu- glycan components are structural components of synovial cosamine still detectable in synovial fluid up to 12 hours fluid (hyaluronan) and articular cartilage matrix (chon- after dosing (Laverty et al., 2005). Corresponding peak droitin sulfate) and provide protective and nutritive func- serum and synovial fluid concentrations after intravenous tions to the joints. The premise for the inclusion of glu- administration of the same dose were 288 Â± 53 ÂµM and 250 cosamine, chondroitin sulfate, or their combination in the ÂµM. The glucosamine concentration achieved in synovial diet is to augment endogenous synthesis and reduce cata- fluid after oral administration was markedly lower when bolic joint degradation (reviewed by McIlwraith, 2004; Neil compared to concentrations used in the previously described et al., 2005). in vitro studies. Multiple dosing studies of glucosamine or A number of in vitro studies have examined the effect of chondroitin sulfate in horses have not been reported. glucosamine and chondroitin sulfate, either individually or The number of in vivo studies performed in horses to ex- combined, on the catabolic response of cartilage explants for amine efficacy of glucosamine, chondroitin sulfate, or their a number of species, including the horse. There is some in combination for the treatment of joint disease are limited. vitro evidence that glucosamine and chondroitin sulfate Two clinical studies evaluated utility of oral glucosamine limit GAG degradation and enhance GAG synthesis in car- and chondroitin sulfate supplementation using a population tilage explants incubated with lipopolysaccharide (LPS) or of horses diagnosed with degenerative joint (Hanson et al., preconditioned with interleukin-1, the end result being an 1997) or navicular (Hanson et al., 2001) disease. Both stud- increase in total GAG content when compared to placebo- ies showed improvement in lameness evaluation, but neither treated explants (Fenton et al., 2000; Orth et al., 2002; study included negative controls (nonlame) horses for com- Dechant et al., 2005). Using in vitro bovine articular carti- parison, placebo group (1 study), nor blinding of investiga- lage explants, glucosamine also inhibited the release of ni- tors to treatment (1 study). An experimentally controlled tric oxide and prostaglandin E2 from explants incubated study in healthy horses (n = 12) and healthy horses with with LPS, suggesting it may exert anti-inflammatory effects chemically induced joint disease found no improvement in (Chan et al., 2005). Collectively, the results of these in vitro supplemented horses (White et al., 1994). A second study studies suggest that glucosamine and chondroitin sulfate using healthy horses (n = 15) and healthy horses with chem- could be beneficial to articular cartilage metabolism by pre- ically induced arthritis compared response of oral (2.5 g/d venting GAG degradation, enhancing GAG synthesis, or for 30 d) or intramuscular (600 mg/d for 5 days) chondroitin both. However, these data cannot be taken as proof of effi- sulfate (25 kDa) to nonsupplemented horses (Videla and cacy by oral supplementation in the treatment or prevention Guerrerro, 1998). Orally treated horses showed some im- of osteoarthritis in horses. provements in measured lameness markers compared to un- Quantitative aspects of oral glucosamine and chondroitin treated horses, but not for all parameters. Both of these stud- sulfate administration bioavailability are debated. Of con- ies also had flaws in experimental design (McIlwraith, cern is whether target tissue (synovial fluid or articular car- 2004). Thus, there is a need for appropriately designed clin- tilage) concentrations, consistent with in vitro studies, of ical trials to truly determine utility of oral joint supplements. such compounds can be achieved following oral dosing. Long-term studies also are needed to address the efficacy of Oral bioavailabilities of glucosamine and chondroitin sulfate these agents for the prevention of osteoarthritis, which ap- have been determined in rats, dogs, and humans, but few pears to be the basis for widespread use of oral joint supple- studies have been completed in horses. Mean oral bioavail- ments in horses. ability of low molecular weight chondroitin sulfate (8-kDa Beyond issues of oral availability, variability in product and 16.9-kDa forms, 3 g each) in horses was 32 and 22 per- content and quality, as well as safety, are all potential prob- cent, respectively, and these values were not different (Du et lems with nutritional supplements that need to be consid- al., 2004). However, oral bioavailability of glucosamine HCl ered. Studies of oral chondroprotective products intended (single dose of 125 mg/kg BW) was lower in horses at 2.5 for human or animal use have demonstrated that few consis- percent, much lower than values reported for the dog (Du et tently meet label claims of guaranteed analysis (Adebowale al., 2004). Low bioavailability might be due to poor intes- et al., 2000; Russell et al., 2002). In one study of equine tinal absorption, extensive first pass metabolism, or some products, actual composition in comparison to label claims combination. This single oral dose in horses was 5- to 10- ranged from 63â112 percent for five glucosamine products fold higher than typical recommended levels and 22â155 percent for five chondroitin sulfate products
192 NUTRIENT REQUIREMENTS OF HORSES (Ramey et al., 2002). Most of the published clinical studies chlortetracycline, is approved for use as a growth promotant have used a single product form of glucosamine and chon- in horses. Quarter horse weanlings (n = 8) fed chlortetracy- droitin sulfate, and extrapolation of these results to other cline (27.5 mg/kg total diet) over a 112-day feeding period products containing different chemical forms or concentra- showed greater (P < 0.10) average daily gain (0.97 vs. 0.87 tions of GAGs or chondroitin sulfate cannot be inferred. kg/d) and height gain (11.2 vs. 9.1 cm) compared to non- Short-term safety of glucosamine and chondroitin sulfate supplemented controls (DuBose and Sigler, 1991). Cur- has been evaluated in horses (Kirker-Head and Kirker-Head, rently (2005), no antibiotics and only two anthelmintics (de- 2001). Healthy horses (n = 6) were administered a commer- wormers) are approved for inclusion in horse feeds (21 CFR cial product at 5 times its recommended dose (daily total: 18 Â§558; AAFCO, 2005). Pyrantel tartrate (21 CFR Â§558.485) g glucosamine HCl, 6 g chondroitin sulfate, and 160 mg can be fed continuously as a top dress or mixed grain sup- manganese ascorbate) for 34 days. Although significant dif- plement to horses at 1.2 mg/kg BW for the prevention of in- ferences were found over the course of the study for some testinal helminthes (large and small stronglyes, pinworms, hematologic values, all hematologic, serum chemistry, and and ascarids). Febendazole (21 CFR Â§558.258) can be fed at synovial fluid parameters remained within normal reference either 5 or 10 mg/kg BW for one treatment to control large ranges. Definitive, long-term safety studies have not been and small strongyles and pinworms or ascarids, respectively, reported for horses or other species. with repeat dosing at 6- to 8-week intervals. Neither com- Other compounds characterized to have âchondroprotec- pound can be fed to horses intended for food. Specific feed tiveâ effects include green-lipped mussel (Perna canaliculus) regulations for any given country must be reviewed to as- extract and methylsulfonylmethane (MSM). Extract of green- certain legal status for food additive use. lipped mussel consists of various GAG compounds, omega-3 Of greater concern with horses is the potential for feed- fatty acids, and other substances believed to provide anti-in- based toxicity from a number of antimicrobial agents ap- flammatory activity and may show potential benefit in man- proved for use in other livestock species, but errantly fed to aging osteoarthritis, though clinical responses have been horses (Hall, 2001). Colitis and diarrhea have been reported equivocal (Cobb and Ernst, 2005). Methylsulfonylmethane is in horses fed feeds contaminated with lincomycin (Raisbeck intended as a source of bioavailable sulfur. Sulfur is a com- and Osweiler, 1981) and tetracycline (Keir et al., 1999), as ponent of many compounds associated with joint structure well as others (Hall, 2001; Larsen, 1997). Although the and function. Studies evaluating a potential chondroprotec- mechanism is unknown, antibiotics are believed to impart tive effect of MSM in horses have not been reported. their toxic effect on horses by altering cecal and colonic mi- crobial populations allowing proliferation of pathogenic bacteria (Larsen, 1997; Hall, 2001). Medicinal Compounds Ionophores are a special class of feed-based antibiotic Antimicrobial agents, primarily antibacterial (antibiotic) agents commonly used in poultry and ruminant diets to con- compounds, can be naturally or synthetically derived. An- trol coccidia parasites and promote feed efficiency and tibiotics have been included in livestock feeds for three main growth (Russell and Strobel, 1989). Currently approved purposes: disease treatment, disease prevention, or perfor- ionophore compounds for some livestock species (primarily mance enhancers (CAST, 1981; NRC, 1999). In some ruminants) include lasalocid, maduramycin, monensin species, low-level incorporation (subtherapeutic) has been sodium, narasin, salinomycin, and virginiamycin (21 CFR shown to promote growth rate, improve feed utilization, re- Â§558; AAFCO, 2005). Potential for ionophore agents to in- duce morbidity and mortality, and improve reproductive duce toxicosis varies by compound and target species, with function. Higher antimicrobial levels (therapeutic) are ad- horses being more sensitive compared to other livestock ministered to prevent or treat infectious disease conditions species. Ionophore toxicity cases in horses have been re- (NRC, 1999). ported for monensin (Matsuoka, 1976; Bila et al., 2001; Regulatory control of medicinal compounds is main- Peek et al., 2004), lasalocid (Hanson et al., 1981), and sali- tained by the FDA to address concerns about animal safety, nomycin (Rollinson et al., 1987; Nel et al., 1988; Nicpon et drug residues in foods, and microbial drug resistance. Ex- al., 1997). tensive scientific evaluation and controlled studies must be In contrast to other ionophore agents, virginiamycin has completed to show safety (animal and residue concerns) and been administered at subtherapeutic levels to manipulate efficacy before a therapeutic drug can be included into feed. hindgut microbial populations in horses fed high-grain diets If approved, strict guidelines are defined for target species, (Rowe et al., 1994; Johnson et al., 1998). Standardbred drug incorporation rate into feed, and specific time periods horses (496 kg BW) fed high-grain diets (8 kg/d) supple- for the drug to be removed from the feed before animals can mented with 0, 4, or 8 g/kg grain of virginiamycin showed enter the human food chain. lower blood d-lactate concentration, higher (P < 0.05) fecal Horses can respond to feed-based antimicrobials similar pH, and lower (P < 0.001) lameness incidence when con- to other livestock species. It must be emphasized that for suming either dose of virginiamycin (Rowe et al., 1994). In most world jurisdictions, no antibiotic agent, including an in vitro model using equine cecal contents, virginiamycin
FEED ADDITIVES 193 inhibited overgrowth of lactic acid-producing gram positive E. coli population was reduced in the 8-g treatment, with no bacteria and production of vasoactive amine compounds as- difference between 0- and 24-g treatment groups. Other bac- sociated with grain overload and altered colonic fermenta- teria were not different across treatment groups. Foals tion (Bailey et al., 2002). Although some positive effects drenched with 10-g arabinogalatan, another fermentable might be realized, use of virginiamycin or any other iono- oligosaccharide complex, for the first 14 days of life had less phore agent in horses is not recommended because of their days with high fecal scores (diarrhea) and therapeutic treat- potential toxicity in horses. Virginiamycin is not available in ments compared to placebo-drenched foals (Werner et al., most countries as a feed additive due to its antibiotic prop- 2001). No differences were seen between foal groups on erties. In the limited jurisdictions where legally permitted, serum immunoglobulin concentrations or hematology pa- virginiamycin may only be fed when under the direct super- rameters over a 30-day period from birth. vision of a veterinarian. Pregnant Thoroughbred and Quarter horse mares (n = 6 per group) were fed 0 or 10 g mannose oligosaccharide sup- plement from 56 days prior to foaling through 84 days of Oligosaccharides lactation (Ott, 2002). Supplementation had no effect on Oligosaccharides are a diverse group of complex poly- mare BW, body condition, or immunologic parameters saccharides containing various sugar moieties resistant to measured. Foal blood immunoglobulin A, G, and M, con- hydrolysis by mammalian digestive enzymes, but are read- centrations were not influenced by supplementation, though ily fermentable by enteric bacteria. Dietary supplementation foals from supplemented mares had higher blood im- of oligosaccharides in various species has been suggested to munoglobulin M concentration on the day of birth. Although promote nonpathogenic colonic bacterial growth and main- unexplained, foals from supplemented mares had lower tain colonic health (Roberfroid, 1997; Flickinger et al., birth weights and maintained lower body weight throughout 2003). Since the intended purpose of dietary oligosaccha- the duration of the study. Foals from unsupplemented mares ride supplementation is to stimulate bacterial growth, it had experienced more cases of diarrhea requiring treatment (5/6 previously been characterized as âprebioticâ (Roberfroid, control vs. 0/5 supplemented, P = 0.02). Diarrhea cases were 1997). Specific mode of activity in promoting colonic health defined as only those severe enough to justify therapy, sug- is dependent upon the constituent sugar moiety of the gesting normal foal heat diarrhea was not confounding study oligosaccharide. Fructooligosaccharides (FOS) are naturally results. It could not be ascertained whether the observed occurring short to medium chains of fructose residues linked protective effect against foal diarrhea was a result of indirect with Î² 2-1 glycosides bonds. Bacterial species such as Bifi- (mare) or direct (foal) consumption of the supplement. Be- dobacteria are capable of hydrolyzing these Î²-glycosidic nage et al. (2005) did not find any effect of mannan bonds, using FOS as a potential energy source to support oligosaccharide on immunity, measured as white blood cell bacterial growth (Campbell et al., 1997). Fermentation pro- counts or antibody titers, in young, mature, or aged horses. duction of VFAs is believed to decrease intestinal pH ad- Based on these limited number, mostly preliminary studies, versely altering the environment for pathogenic bacteria. evidence is not supportive of a perceived role of immune Alternatively, FOS-stimulated bacterial growth may lead to system stimulation from feeding oligosaccharides; however, competitive exclusion of pathogenic bacteria. Fructooligo- their role in reducing risk of intestinal disease in the horse saccharide (T60.105) has tentative status as a feed ingredi- should be further explored. ent (AAFCO, 2005). Oligosaccharides of mannose are also believed to reduce Omega-3 Fatty Acids adverse affects of pathogenic bacteria by inhibiting their ad- herence to enterocytes by mannose-specific lectins, as Linoleic acid (C18:2, n-6) and Î±-linolenic acid (C18:3, shown in human cell culture (Ofek and Beachey, 1978) and n-3) are considered essential fatty acids for most species. A poultry models (Oyofo et al., 1989a,b). Saturating the gut minimum requirement for linoleic acid in horses was defined environment with dietary mannose supplementation can re- as 0.5 percent of DM (see Chapter 3); however, no specific duce the probability of bacterial attachment to epithelial cell requirement has been defined for Î±-linolenic acid. Potential membrane mannose moieties. Glucomannans may also play health effects of supplementing omega-3 fatty acids are re- a protective role in preventing absorption of mycotoxins in lated to antagonistic biologic responses to eicosanoid media- horses (Raymond et al., 2003, 2005). tors derived from cyclooxygenase or lipooxygenase from Limited studies have addressed potential benefits of membrane-derived omega-3 fatty acids compared to similar oligosaccharide supplements for horses. Yearling Quarter metabolites from omega-6 fatty acids (Miles and Calder, horses (n = 9; 401 kg mean BW) supplemented with FOS at 1998; Calder, 2001). In general, omega-3 derived eicosanoid three levels (0, 8, 24 g/d) in a 3 Ã 3 Latin square study de- mediators have antagonistic properties to omega-6 derived sign showed a linear dose effect of lower fecal pH and in- mediators. Collectively, data from studies where omega-3 creased short-chain VFA concentrations, consistent with in- fatty acid-enriched diets were fed to horses (see Chapter 3, creased bacterial fermentation (Berg et al., 2005). Fecal Health Effects of Dietary (n-3) vs. (n-6) Fatty Acids) show
194 NUTRIENT REQUIREMENTS OF HORSES promotion of anti-inflammatory mediators for various in- tion. Metal ion availability from these inorganic sources is flammatory cell types similar to what is observed in other variable. Generally, oxide and sulfate forms have the lowest species (Henry et al., 1991; Morris et al., 1991; Hansen et al., and highest availability, respectively (Ammerman et al., 2002; Hall et al., 2004a,b). Based on their anti-inflammatory 1995). Concerns about availability have prompted interest in properties, several potential health benefits from supple- use of organic trace mineral sources. On a relative availabil- menting omega-3 fats to horses have been proposed (Mc- ity scale, organic mineral forms are equal to or modestly Cann and Carrick, 1998). Practical application suggests in- greater in mineral bioavailability compared to inorganic sul- flammatory mediated disease processes, such as recurrent fate sources across most species (Ammerman et al., 1995). airway obstruction (heaves) or fly-bite hypersensitivity, Reviews of organic mineral supplementation studies in cat- might possibly be mitigated with omega-3 fatty acid supple- tle (Spears, 1996) and swine (Jondreville and Revy, 2002) mentation; however, few clinical trials have been completed note the mechanism accounting for improved bioavailability to support this contention. of organic minerals is unknown and tremendous variability Two studies using a similar double-blinded, cross-over exists among sources. experimental design tested potential mediation of allergic Jondreville and Revy (2002) suggested a lack of clear ev- skin reactions to Culicoides spp. with omega-3 fat supple- idence in swine feeding studies supporting greater mineral mentation in hypersensitive horses (Friberg and Logas, availability from organic sources compared to inorganic 1999; OâNeill et al., 2002). Calculated daily intake of forms. In contrast, Spears (1996) noted improved animal Î±-linolenic acid in the two studies was between 108 and performance in a number of ruminant studies, but whether 110 g Î±-linolenic acid from linseed. This intake was consis- the response was truly due to organic mineral source or ad- tent with a suggested dose extrapolated from human studies, ditional dietary mineral intake was undetermined. Prevailing but not substantiated for the horse (McCann and Carrick, perceptions suggest greater metal absorptive efficiency via 1998). Friberg and Logas (1999) found no quantifiable ef- cotransportation across the intestinal mucosa, but evidence fect of oil source (linseed [n-3] vs. corn [n-6]) on improve- is lacking. A preponderance of data using rat intestinal loop ment in dermatologic lesion size (quantified by digital im- models suggest no difference in absorptive efficiency be- aging) or pruritic behavior (timed observations) exhibited by tween metals from inorganic or organic forms (Hill et al., the horses. Interestingly, these findings are in contrast to 1987; Hempe and Cousins, 1989; Beutler et al., 1998). Or- participating horse ownersâ perceptions (study was double ganic mineral forms may protect the metal ion from micro- blind) where 12 of 16 owners believed supplementation with bial alteration in the rumen environment thus accounting for linseed oil reduced pruritis in their horse compared to 1 of the differential response to organic mineral supplementation 16 with corn oil supplementation. observed in swine and ruminant studies. In a separate study, mean skin reaction area (mm2) to an Organic mineral sources are not equivalent and encom- intradermal injection of Culicoides spp. extract was smaller pass a wide spectrum of metal-ligand structures. Potential (P = 0.02) in horses supplemented with 0.45 kg flaxseed ligands include one or more amino acids, proteins of vary- compared to 0.45 kg wheat bran after 42 days of supplemen- ing size, polysaccharides, or propionate. Feed ingredient tation (OâNeill et al., 2002). However, fatty acid profiles definitions for various organic mineral products have been from skin biopsy samples did not show expected changes in designated, as shown in Table 9-1 (AAFCO, 2005). Mineral omega-3 or omega-6 fatty acids reflective of supplementa- availability from an organic source is dependent upon the tion. Neither of these studies included negative control type of bonding (ionic or covalent) between metal and lig- horses (nonsensitized to Culicoides spp.) for comparison. and, ligand size, and how each are influenced by pH (Hynes Also, both studies used shorter supplementation periods (6 and Kelly, 1995). Weaker metal-ligand bonds (ionic) and weeks) compared to other horse studies (8â12 weeks) moni- small ligand size result in a less stable molecule, whereas toring fatty acid composition and inflammatory cell re- strong bonds (covalent) and large ligand size result in sponses to different fat sources (Henry et al., 1991; Morris et greater stability, but also create availability concerns (Hynes al., 1991; Hansen et al., 2002; Hall et al., 2004a,b). Although and Kelly, 1995). measured changes in biochemical mediators of inflammation Eight studies from five laboratories have compared or- in response to dietary fatty sources (n-3 vs. n-6) are persua- ganic and inorganic mineral sources supplemented to sive, further research is needed to determine if such changes horses. Study designs varied in organic mineral source (pro- have potential in mediating inflammatory disease processes teinates, n = 5 vs. amino acid chelates, n = 3); partial (45â80 in horses and an appropriate therapeutic dose. percent, n = 4) or complete (n = 4) replacement of inorganic mineral sources; animal age (weanlings, n = 1; yearlings, n = 3; adult, n = 4); and evaluation criteria. With the excep- Organic Trace Minerals tion of the Ott and Asquith (1994) study, where mineral sup- Inorganic trace mineral sources, principally oxide, sul- plementation was at or slightly below (copper only) NRC fate, chloride, and carbonate forms of a specific mineral ion, (1989) recommendations, all other studies supplemented have been primary sources of dietary mineral supplementa- trace minerals in excess of NRC (1989) recommendations,
FEED ADDITIVES 195 TABLE 9-1 AAFCO Feed Ingredient Definitions for Organic Mineral Products Feed Ingredient Product Number Description Metal amino acid complex 57.150 Product resulting from complexing of a soluble metal salt with amino acid(s). Declared as a specific metal amino acid complex (âZinc, amino acid complexâ) Metal (specific amino acid) complex 57.151 Product resulting from complexing a soluble metal salt with a specific amino acid. Declared as a specific metal, specific amino acid complex (âZinc lysine complexâ) Metal amino acid chelate 57.142 Product resulting from the reaction of a metal ion from a stable metal salt with amino acids with a mole ratio of one metal to one to three moles of amino acids to form coordinate covalent bonds and heterocyclic ring(s). Declared as a specific metal amino acid chelate (âManganese amino acid chelateâ) Metal polysaccharide complex 57.29 Product resulting from complexing of a soluble salt with a polysaccharide solution. Declared as spe- cific metal complex (âCopper polysaccharide complexâ) Metal proteinate 57.23 Product resulting from chelation of a soluble salt (mineral) with amino acids and/or partially hy- drolyzed protein. Declared as specific metal proteinate (âCopper proteinateâ) Metal propionate 57.160 Product resulting from a reaction of a metal salt with propionic acid. Declared as a specific metal propionate (âZinc propionateâ) Selenium yeast T57.163 Dried nonviable yeast cultivated in a selenium-supplemented fermentation allowing selenium to be incorporated into cellular organic material ranging from 30 to 80 percent increase to nearly four times Studies were completed with mature and miniature horses the recommendations. Most studies stated the higher rate of fed either proteinate or specific amino acid chelate organic supplementation was consistent with current industry feed- trace mineral sources. Organic sources were fed at either ing standards. 45â50 or 100 percent of the inorganic supplementation rate Using weanlings (n = 12) and 100 percent replacement of and dietary mineral content ranged from slightly below to inorganic mineral sources with amino acid chelate sources, four times NRC (1989) recommendations. No effects of trace no effects of organic compared to inorganic minerals were mineral source were found in hoof growth characteristics (Si- found on hoof growth, hardness, or tensile strength (Sici- ciliano et al., 2001a), liver mineral content (Siciliano et al., liano et al., 2003a). However, improved (P < 0.01) immuno- 2001b), or trace mineral digestibility and retention (Wagner logic response, measured as higher total immunoglobulin et al., 2005; Baker et al., 2005). Pregnant mares fed either and mean IgM concentrations, to porcine red blood cell in- proteinated (50â80 percent replacement) or inorganic trace jection was observed in organic mineral supplemented mineral sources at or slightly below NRC (1989) recommen- weanlings (Siciliano et al., 2003b). In yearlings (n = 15), dations showed no effects of mineral source on mare trace hoof growth, but not strength, was increased (P = 0.02) and mineral status, weight gain, or subsequent reproductive effi- hip height gain was greater (P = 0.02) when fed proteinated ciency (Ott and Asquith, 1994). Growth rate and bone min- minerals compared to similar concentrations from inor- eral content were not different between foals born to organic ganic mineral sources (Ott and Johnson, 2001). No effects of or inorganic mineral-supplemented mares. trace mineral source (inorganic vs. proteinated) on bone Collectively, all studies comparing organic to inorganic density or mineral content were observed (Ott and Johnson, sources of trace minerals suggested minimal to no difference 2001; Baker et al., 2003). Improved copper digestibility and in biologic utilization or animal performance, consistent with availability and greater average daily copper and zinc bal- results from swine studies. In fact, some studies reported im- ance were reported in yearlings fed proteinated mineral proved responses to inorganic compared to organic mineral sources (45 percent replacement of inorganic amounts) sources (Siciliano et al., 2003a; Baker et al., 2005). However, compared to inorganic sources (Miller et al., 2003). These age and rate of supplementation effects on trace mineral me- data are difficult to interpret as they are confounded by al- tabolism need to be further evaluated. Results from studies tered trace mineral regulation as a result of experimental an- using weanling and yearling horses tended to show more pos- imals experiencing an infectious disease during the study. itive responses from organic mineral sources (Ott and John- Yearlings fed specific amino acid chelates (100 percent re- son, 2001; Siciliano et al., 2003b; Miller et al., 2003). Further placement) or inorganic trace mineral sources at similar lev- study is needed to find a proper balance between sufficient di- els (4 Ã NRC recommendations) showed no difference in etary mineral supplementation in support of productive ani- growth or trace mineral digestibility and balance (Naile et mals and minimizing manure mineral content and environ- al., 2005). mental load all within an economically viable system.
196 NUTRIENT REQUIREMENTS OF HORSES In 2004, the FDA permitted use of selenium (Se) yeast in viewed results from 71 published scientific reports on the horse feed at a rate not to exceed 0.3 ppm of added selenium use of yeast additives in ruminant diets. Modest changes in the total diet (21 CFR Â§573.920(h); FDA, 2004). Sele- were reported for measures of rumen fermentation, dry mat- nium yeast (T57.163) contains selenomethione and seleno- ter intake, growth, and feed efficiency with live yeast cul- cysteine, organic forms of selenium quite different from tures. Most pronounced was the observed increase in rumen those previously described. In contrast to organic chelates bacterial numbers, both cellulolytic (20 percent) and non- and complexes where the metal ion is bound to one or more cellulolytic (95 percent) bacteria. Across yeast products (ac- ligands, selenium in seleno-amino acids has replaced the tive and nonfermentative culture), modest improvement sulfur atom within methionine and cysteine amino acids. (1â3 percent) in dry matter intake and milk production were Seleno-amino acid absorption is believed to occur via amino observed. Consistency across studies on observed effects acid transporters (Weiss, 2003), thus improving bioavail- suggests the greatest impact of yeast products are through ability over inorganic forms (selenite, selenate) as evidenced promotion of bacterial growth and independent of live yeast in ruminants by improved muscle, milk, and liver selenium in the fermentation system (Robinson, 2002). content compared to inorganic sources (Ullrey et al., 1977; Similar to published ruminant studies with yeast addi- Ammerman et al., 1980; Pehrson et al., 1999; Gunter et al., tives, live yeast cultures were most studied in horses. A ma- 2003). Direct incorporation of seleno-amino acids into body jority of these studies evaluated the potential of enhanced and milk proteins accounts for these observations and may fermentation and fiber or nutrient digestibility in the horse. also account for a lesser response in selenium-dependent Unlike observed effects in ruminant studies, supplementa- glutathione peroxidase activity in comparing inorganic sele- tion of yeast in horse diets tended to show some beneficial nium and selenium yeast sources (Weiss, 2003). effects on fermentation, but results were equivocal across Few studies have addressed selenium yeast supplementa- studies. Using an in vitro fermentation system with cecally tion in the horse. Pagan et al. (1999) reported improved di- fistulated inocula, time to reach 50 percent gas production gestibility and retention comparing selenium yeast (2.75 was shortened with the addition of 10 mg live yeast culture mg/d Se) to sodium selenite (2.9 mg/d Se) sources. How- added to hay, beet pulp, or 50:50 mix of hay and beet pulp ever, no differences in serum or whole blood selenium con- as substrate, suggesting augmentation of fermentation centrations were observed. Similar to observations in cattle, (McLean et al., 1997). Yeast supplementation induced min- late pregnant mares supplemented with selenium yeast (3 imal (Moore et al., 1994) to no increase (Medina et al., mg/d Se) compared to inorganic sources (selenite at 1 or 3 2002; Lattimer et al., 2005) in cecal or colonic bacterial mg/d Se) had greater colostrum and milk selenium concen- colonies. Similarly, yeast supplementation effects on fer- tration and gave birth to foals with improved selenium sta- mentation products were minimal to none (McDaniel et al., tus (Janicki, 2001). Further study is needed to determine the 1993; Krusic et al., 2001), though when feeding low-forage potential physiologic effects improved selenium status might or high-starch diets, yeast supplementation altered fermen- have on animal health and performance. tation to increase (9â14 percent) acetate (Medina et al., 2002; Lattimer et al., 2005) and lower (36 percent, high- starch diet) lactate (Medina et al., 2002). Studies measuring Yeast Culture or Extract cecal and colonic pH found minimal effect of supplemental A number of yeast products are defined as feed ingredi- yeast (McDaniel et al., 1993; Krusic et al., 2001; Lattimer et ents by AAFCO (2005), including dried yeast (active or al., 2005). In contrast, more alkaline cecal pH with yeast nonfermentative), yeast culture, and yeast extract (tentative supplementation was observed when feeding higher con- ingredient designation). Most yeast products are derived centrate diets (Moore and Newman, 1993). Yeast supple- from Saccharomyces spp. cultures, primarily S. cerevisiae, mentation attenuated the decline in cecal pH at 4 hours or Aspergillus oryzae. Active dry yeast must contain a min- post-feeding when low-forage (43 percent: Hall and Miller- imum of 15 billion live yeast cells per gram. Yeast culture is Auwerda, 2005) or high-starch (3.4 g/kg BW: Medina et al., a dried product containing viable yeast cells and the culture 2002) diets were fed to horses. media on which the yeast was grown. Yeast extract is a dried No improvement in nutrient apparent digestibility was re- or concentrated product of cell contents from mechanically ported for mature horses (Webb et al., 1985; Hall et al., ruptured Saccharomyces cerevisiae cells. Dried yeast must 1990), but others have reported improved digestibility for contain a minimum of 40 percent crude protein, whereas one or more nutrients when horses were fed yeast cultures. yeast extract contains a minimum of 9 percent crude protein. Improvement in DM, NDF, and ADF digestibility with yeast Various yeast products are used in ruminant diets. Yeast supplementation was reported for mature (Pagan, 1990; additives are believed to either directly facilitate fiber diges- Glade, 1991a) and yearling (Glade and Sist, 1988) horses, tion and dry matter intake (active cultures) or contain whereas another study using yearlings found only hemicel- metabolites or compounds having stimulatory properties on lulose digestibility improved with yeast supplementation bacterial growth to facilitate fermentation and animal per- (Glade and Biesik, 1986). Improved nitrogen digestibility formance (active or nonfermentative). Robinson (2002) re- (5.1â8.8 percent) and retention with yeast supplementation
FEED ADDITIVES 197 was the most consistently reported response to yeast supple- Augspurger, N. R., and D. H. Baker. 2004. High dietary phytase levels max- mentation (Godbee, 1983; Glade and Biesik, 1986; Glade imize phytate phosphorus utilization but do not affect protein utilization in chicks fed phosphorus- or amino acid-deficient diets. J. Anim. Sci. and Sist, 1988; Glade, 1991a,c; Switzer et al., 2003). Two 82:1100â1107. studies reported improved digestibility with one or more Bailey, S. R., A. Rycroft, and J. Elliott. 2002. Production of amines in minerals. Improved magnesium digestibility was reported equine cecal contents in an in vitro model of carbohydrate overload. J. by Pagan (1990) and Switzer et al. (2003) with yeast sup- Anim. Sci. 80:2656â2662. plementation. Phosphorus digestibility, independent of Baker, L. A., T. Kearney-Moss, J. L. Pipkin, R. C. Bachman, J. T. Halibur- ton, and G. O. Vneklasen. 2003. The effect of supplemental inorganic source, was increased 22.3 percent across two different and organic sources of copper and zinc on bone metabolism in exer- whole collection trials feeding forage (66 percent) and sweet cised yearling geldings. Pp. 100â105 in Proc. 18th Equine Nutr. Phys- feed (Pagan, 1990). iol. Soc. Symp., East Lansing, MI. Studies evaluating the role of yeast on horse performance Baker, L. A., M. R. Wrigley, J. L. Pipkin, J. T. Haliburton, and R. C. Bach- are limited. Improved weight gain, height, and feed effi- man. 2005. Digestibility and retention of inorganic and organic sources of copper and zinc in mature horses. Pp. 162â167 in Proc. 19th Equine ciency were observed in weanling horses supplemented with Sci. Soc., Tucson, AZ. live yeast culture (Mason, 1983; Glade and Sist, 1990). No Balogh, N., T. Gaal, P. S. Ribiczeyne, and A. Petri. 2001. Biochemical and growth advantage was observed with yearlings (Bennett et antioxidant changes in plasma and erythrocytes of pentathlon horses be- al., 1991). Pregnant mares fed 20 g live yeast 4 weeks prior fore and after exercise. Vet. Clin. Path. 30:214â218. to foaling had improved digestibility of dietary energy, pro- Benage, M. C., L. A. Baker, G. H. Loneragan, J. L. Pipkin, and J. C. Hal- iburton. 2005. The effect of mannan oligosaccharide on horse herd tein, and fiber resulting in greater milk production and im- health. Pp. 17â22 in Proc. 19th Equine Sci. Soc., Tucson, AZ. proved foal growth (Glade, 1991a,b,c). Administration of Bennett, K., J. C. Loch, E. M. Lattimer, and E. M. Green. 1991. Effect of 10 Ã 109 live Saccharomyces boulardii every 12 hours for 14 yeast culture supplementation on weight gains, skeletal growth and days resulted in reduced severity and duration of clinical bone density of third metacarpal in yearling Quarter horses. J. Anim. signs associated with enterocolitis compared to placebo- Sci. 69(Suppl. 1):324 (Abstr.). Berg, E. L., C. J. Fu, J. H. Porter, and M. S. Kerley. 2005. Fructooligosac- treated horses (Desrochers et al., 2005). In this study, sup- charide supplementation in the yearling horse: effects on fecal pH, mi- plemented yeast could be found in feces during supplemen- crobial content, and volatile fatty acid concentrations. J. Anim. Sci. tation, but there was no ability to determine colonization 83:1549â1553. potential of the colon. Beutler, K. T., O. Pankewycz, and D. L. Brautigan. 1998. Equivalent uptake Variation in observed responses between studies may be of organic and inorganic zinc by monkey kidney fibroblasts, human in- testinal epithelial cells, or perfused mouse intestine. Biol. Trace Elem. attributed to differences in the amount of yeast supplement Res. 61:19â31. being fed, composition and treatment diet interaction, and Bila, C. G., C. L. Perreira, and E. Gruys. 2001. Accidental monensin toxi- diet adaptation time. Results across the studies would sug- cosis in horses in Mozambique. J. S. Afr. Vet Assoc. 72:163â164. gest some potential benefits to feeding yeast when high- Booth, J. A., P. A. Miller-Auwerda, and M. A. Rasmussen. 2001. The effect starch or low-fiber diets are being fed (Medina et al., 2002; of a microbial supplement (Horse-Bac) containing Lactobacillus aci- dophilus on the microbial and chemical composition of the cecum in the Hall and Miller-Auwerda, 2005). Improvements in nutrient sedentary horse. Pp. 183â185 in Proc. 17th Equine Nutr. Physiol. Soc. digestibility, especially nitrogen, are suggested, but the Symp., Lexington, KY. exact mechanism for this response is not evident. Constant Boothe, D. M. 1997. Nutraceuticals in veterinary medicine. Part I. Defini- feeding of yeast may have greater potential for mediating an tions and regulations. Comp. Cont. Educ. Pract. 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