The chemical structure of biotin includes a heterocyclic fused ring system with one sulfur atom, two nitrogen atoms and a transverse bond joining the rings (Illus. 11-1). Biotin is a monocarboxylic acid with a carboxybutyl side chain that forms an amide linkage with lysine (called biocytin) in the biotin-requiring enzymes. The nitrogen atom opposite the side chain acts as a transfer point for carboxyl groups in enzymatic carboxylation reactions, which is the primary function of biotin enzymes (Bonjour, 1991). The sulfur atom is present as a thioether bond. Oxidation of the sulfur atom forms either biotin sulfoxide or biotin sulfone, which are metabolically inactive. Biotin, with its rather unique structure, contains three asymmetric (chiral) carbon atoms; therefore, eight different isomers are possible. Of these isomers, only d-(+)-biotin is found in nature and is biologically active (Mock, 1990).
Biotin crystallizes from water as long, white needles. Its melting point is 232° to 233°C (450° to 451°F). Free biotin is soluble in dilute alkaline solutions and hot water and practically insoluble in fats and organic solvents. Biotin is quite stable under ordinary conditions. It is destroyed by nitric acid, other strong acids, strong bases and formaldehyde, and also is inactivated by oxidative rancidity reactions (Scott et al., 1982). Biotin is gradually destroyed by direct exposure to ultraviolet (UV) radiation. Structurally related analogs of biotin vary from zero biological activity, to partial biotin activity, to anti-biotin activity. Mild oxidation converts biotin to the sulfoxide, and strong oxidation converts it to the sulfone. Strong reagents result in sulfur replacement by oxygen, resulting in oxybiotin and desthiobiotin. Oxybiotin has partial biotin activity in chicks (one-third) and rats (one-tenth). Besides these biotin analogs, other compounds exist that can bind biotin to form a stable complex, thus preventing the utilization of the vitamin by animals and/or microorganisms. The microorganism Saccharomyces avidinii produces a biotin-binding protein streptavidin and other compounds that can inactivate free biotin and apparently inhibit biotin synthesis in susceptible microorganisms. A prominent nutrient-drug interaction is that biotin-dependent enzymes are reduced with the epilepsy drug carbamazepine (Rathman et al., 2002). Biotin is present in feedstuffs in both bound and free forms, and much of the bound biotin is apparently unavailable to animal species. For poultry and swine (and presumably for ruminants), often less than half of the microbiologically determined biotin in a feedstuff is biologically available (Scott, 1981; Frigg, 1984, 1987; Saueret al., 1988). Naturally occurring biotin is found partly in the free state (fruit, milk, vegetables) and partly in a form bound to protein in animal tissues, plant seeds and yeast. Naturally occurring biotin is often bound to the amino acid lysine, in a form called biocytin. Biotinidase is a mammalian enzyme that cleaves the biotin-lysine amide bond, freeing biotin for reuse in metabolism. Biotinidase is present in pancreatic secretions and intestinal cells of mammals, as well as systemically. Genetic deficiency of biotinidase causes a biotin deficiency syndrome in humans (Mock, 1990). Studies with animals show that biotin is absorbed intact in the first third to half of the small intestine by active transport and diffusion (Bonjour, 1991; Zempleni and Mock, 1999). In addition, biotin is absorbed from the hind-gut of the pig. Fifty to sixty percent of infused biotin disappeared between the cecum and feces; this was accompanied by more than a four-fold increase of plasma biotin concentration and more than a six-fold increase of urinary biotin excretion (Barth et al., 1986). McCormick and Olson (1984) reported that biotin is transported as a free water-soluble component of plasma. Most studies have found similar results, although biotin may also be partially (10% to 20%) bound to plasma biotinidase (Zempleni and Mock, 1999). The liver, brain, placenta and white blood cells actively accumulate biotin (Zempleni and Mock, 1999). The placenta has a sodium-dependent transporter that transports biotin, pantothenic acid and lipoic acid (Prasad et al., 1997). Prasad et al. (1999) have identified a similar multivitamin transporter for biotin, pantothenate and lipoate in the small intestine.Virtually all living cells contain biotin, due to its role as an enzyme cofactor (Cooper et al., 1997). The highest concentrations are found in the liver and kidney. Intracellular distribution of biotin corresponds to known localization of biotin-dependent enzymes (carboxylases). Biotin is also concentrated in the cell nucleus.
Biotin is an essential coenzyme in carbohydrate, fat and protein metabolism. In particular, biotin is involved in the maintenance of normal blood glucose levels via the gluconeogenic enzymes pyruvate carboxylase and propionyl-CoA-carboxylase (Mock, 1990). Biotin is a cofactor for acetyl-CoA-carboxylase, which is the first and rate-limiting reaction in biosynthesis of long-chain fatty acids. Biotin is also a cofactor in beta-methylcrotonyl-CoA-carboxylase, which catalyzes an essential step in leucine catabolism (Zempleni and Mock, 1999). All four of these biotin-containing enzymes are carboxylases that catalyze the incorporation of a bicarbonate ion into an organic compound, a process sometimes referred to as “carbon dioxide fixation” (Camporeale and Zempleni, 2006). The three primary species of rumen cellulolytic bacteria have an absolute requirement for biotin (Baldwin and Allison, 1983). Biotin is a cofactor in the microbial enzyme methylmalonyl-CoA-carboxytransferase, which catalyzes a step in the synthesis of propionic acid. Omission of biotin from in vitro rumen fermentations reduces propionic acid production (Milligan et al., 1967). Biotin is involved with gluconeogenesis, propionate metabolism, fatty acid synthesis, and amino acid degradation. The nature of the ruminant digestive system imposes a huge dependence on gluconeogenesis because very little glucose is being absorbed (Reynolds, 2007). In ruminants, the rate of gluconeogenesis increases with feed intake, and one of the major substrates for gluconeogenesis is propionate. Metabolic utilization of propionate after its absorption from the gastrointestinal tract is dependent on the transformation of propionate into succinyl-coenzyme A, requiring the successive actions of biotin- and vitamin B12-dependent enzymes. Propionate is first transformed into propionyl-CoA, which is carboxylated to methylmalonyl-CoA carboxylase.Vesely (1982) showed that biotin at physiologic concentrations elevated activity of guanylate cyclase and cGMP concentrations in the liver, kidney, colon, cerebellum and heart. Biotin elevates cGMP concentration and glucokinase activity in liver cells (Spence and Koudelka, 1984) and has been used to ameliorate hyperglycemia and improve glucose tolerance in diabetics (Zhang et al., 1996). Biotin supplementation increased the activity of liver pyruvate carboxylase (Ferreira et al., 2007). Sone et al. (1999) reported that biotin enhances glucose-stimulated insulin release from rat pancreas.The biomechanical properties of hoof horn are determined by its structural characteristics. These characteristics, which include intra- and extra-cellular biochemical composition and arrangement of horn cells, are determined during keratinization and cornification. Any disturbance of this process such as interruption of nutrient supply because of circulatory abnormalities or essential nutrient deficiency may adversely affect horn structure and horn quality (Mülling et al., 1999). Claw horn is a modified derivative of skin and contains significant quantities of the structural protein keratin. Biotin is an essential nutrient in keratin synthesis and lipogenesis, the two major metabolic pathways in keratinization (Sarasin, 1994). It is involved in the differentiation of epidermal cells, and in the production of keratin and intracellular cementing substance (Mülling et al., 1999). The intracellular cementing substance binds together the keratin leaflets of hoof horn.Biotin is required for normal synthesis of long-chain unsaturated fatty acids and essential fatty acid metabolism. Deficiency in rats and chicks inhibited arachidonic acid (20:4) synthesis from linoleic acid (18:2) while increasing linolenic acid (18:3) and its metabolite (22:6) (Kramer et al., 1984; Watkins and Kratzer, 1987a). Biotin deficiency reduced arachidonic acid (20:4) in chicks and thereby reduced plasma prostaglandin E2 (PGE2), because arachidonic acid is a precursor of prostaglandin (20:4) (Watkins and Kratzer, 1987b; Watkins, 1989). The characteristic dermatitis of biotin deficiency may be due in part to aberrations of essential fatty acid metabolism (Zempleni and Mock, 1999). Biotin is also required for normal function of immune cells that actively accumulate biotin (Bonjour, 1991; Zempleni and Mock, 1999). Populations of T- and B-lymphocytes are dependent on biotin supply, and marginal biotin status reduces antibody production (Zempleni and Mock, 1999). More recently, evidence has emerged that biotin also plays unique roles in cell signaling, epigenetic control of gene expression, and chromatin structure (Rodríguez-Meléndez and Zempleni, 2003). Biotin regulates the genetic expression of holocarboxylase synthetase and mitochondrial carboxylases in rats (Rodríguez-Meléndez et al., 2001). Manthey et al. (2002) reports that biotin affects expression of biotin transporters, biotinylations of carboxylases and metabolism of interleukin-2 in Jurat cells.
Microbial synthesis of biotin occurs in the intestinal tract of most species, making it difficult to determine minimum requirements for practical diets. Ruminal vitamin synthesis confers an advantage over monogastric species because the contents of the rumen pass through the abomasum and small intestine, which are ideally suited for digestion and absorption of microbial nutrients, including biotin. More important than the minimum requirement is the optimal level of biotin supplementation of livestock diets to prevent marginal deficiency and enhance productivity. Biotin is a required nutrient in the rumen (Baldwin and Allison, 1983). Thus, Bentley et al. (1954) found that biotin stimulated cellulose digestion by washed rumen bacteria. Milligan et al. (1967) reported that omitting biotin from in vitrorumen fermentation significantly reduced production of propionic acid. Biotin is a required cofactor for methylmalonyl-CoA-carboxytransferase, an enzyme that participates directly in bacterial synthesis of propionic acid. Biotin synthesis in the rumen can be affected by diet. For example, feeding urea, a readily available nitrogen source, to cattle increased ruminal biotin content (Briggs et al., 1964). Rumen synthesis of biotin is greatest when dietary biotin is lowest, and as a result, the diet has only a limited effect on overall biotin concentration in ruminal contents (Hayes et al., 1966; Kon and Porter, 1953). Antibiotics appear to have little appreciable effect on biotin levels in rumen contents (Kon and Porter, 1953, 1954; Miller et al., 1986b). Since it had been assumed that the rumen synthesized all of the needed biotin, it was unclear why in recent years, there were benefits from supplementation of the vitamin.A reduction in the forage-to-grain ratio in the diet has been shown to significantly reduce rumen biotin synthesis (Da Costa Gomez et al., 1998) (Figure 11-1). Reducing dietary forage content from 83% to 17% produced a linear decrease in biotin synthesis in rumen continuous culture. Biotin synthesis was reduced by 50% when the forage-to-grain ratio decreased from 83:17 to 50:50 (Abel et al., 2001). From feeding steers a diet of 85.5% grain, Miller et al. (1986) reported little synthesis of biotin occurring in the rumen, but considerable synthesis in the small and large intestine. From a balance study in sheep, the greatest synthesis of biotin in the total tract occurred with concentrate levels of 52% to 77% (Peterson et al., 2004). Nevertheless, serum biotin concentrations were not affected in wethers fed diets ranging from 5% to 91% concentrate (Peterson et al., 2004). In vitro data suggest that low pH (5.5) may decrease utilization instead of synthesis of ruminal biotin due to a decrease in the growth of cellulolytic microbes (Rosendo et al., 2003). Diets having a high concentration of grains can create an acid rumen or change the site of starch fermentation which alters the ruminal and intestinal flora and could, in turn affect synthesis or degradation of microbial biotin. The need for supplemental biotin may be dependent on dietary factors that influence biotin synthesis and destruction.
Miller et al. (1983) reported that grain source affected biotin synthesis in steers fed diets of 85% grain and 15% alfalfa hay. Absolute values of biotin production were small, ranging from 0.1 mg per day with oats to 1.3 mg per day for corn. The ranking of grain sources (low to high) for rumen biotin synthesis was oats, sorghum, barley, wheat and corn. Total rumen biotin synthesis in steers fed high-concentrate rations averaged 1.0 mg per day. Intestinal synthesis exceeded rumen synthesis in these trials (Miller et al., 1986a, b). Zinn et al. (1987), using a diet with 34.5% forage from alfalfa hay, reported apparent rumen synthesis of 2.4 mg per day in steers. Biotin synthesis in the rumen is more fully established after weaning (Kon and Porter, 1954). Biotin deficiency has been produced in calves (Wiese et al., 1947) (Mulling et al. 1999); however, no requirement for young ruminants has been established. Deficiency symptoms were prevented when synthetic milk was supplemented with 10 µg of biotin per kg (4.5 µg per lb) of milk powder and fed at 10% of live weight (1 µg of biotin per kg or 0.45 µg per lb of live weight) (NRC, 1989). The NRC recommends that calf milk-replacer powder be fortified with 0.1 mg/kg (0.45 mg/lb) biotin to ensure adequacy. This rate of addition is similar to that for young pigs (0.08 mg/kg diet). Ewe milk contains approximately 0.75 mg biotin per kg (.34 mg per lb) of solids (NRC, 1985) and cow’s milk approximately 0.35 mg per kg (.16 mg per lb) of solids.
The content and bioavailability of biotin in feedstuffs is highly variable (Table 11-1). For example, 59 samples of corn analyzed for biotin varied between 56 and 115 µg per kg (26 and 52 µg per lb) (Frigg, 1987).
Less than one-half of the biotin in feedstuffs, as determined by microbiological assay, is biologically available (Frigg, 1976, 1984, 1987). Sorghum had an availability of 10% to 20%, while the bioavailability of corn ranged from 75% to 100% (Buenrostro and Kratzer, 1984). For alfalfa meal, corn, cottonseed meal and soybean meal, bioavailability of biotin is estimated at 100%. However, biotin availability is variable for other feedstuffs, for example, 20 to 50% in barley, 62% in corn gluten meal, 30% in fish meal, 20% to 60% in sorghum, 32% in oats and 0 to 62% in wheat (McDowell, 2004). Sauer et al. (1988) determined the apparent ileal digestibility of biotin from several common feedstuffs fed to pigs. Biotin digestibility was 55.4% in soybean meal, 2.7% in meat and bone meal and 3.9% in canola (rapeseed) meal. Likewise, the ileal digestibility of biotin was 21.6% for wheat, 4.8% for barley and 4.0% for corn. In contrast, supplemental biotin fed in the same experiment had an ileal digestibility of 93.5%.
Information is lacking on the biotin availability of feedstuffs in ruminants. Experiments with the rumen simulation technique (RUSITEC) indicated that rumen availability of biotin from barley/hay rations of varying forage to grain ratio ranged from 65% to 77% with a mean of 70% (Da Costa Gomez et al., 1998). The primary source of biotin for ruminants is that synthesized by microorganisms in the rumen. Although biotin synthesis occurs across a wide range of diets (Hayes et al., 1966), increasing the proportion of grain in the ration reduces net synthesis by over 50% (Da Costa Gomez et al., 1998). Miller et al, (1986a) found that rumen biotin synthesis varied with the cereal grain source fed. Frigg et al., (1994) estimated from bio-kinetic data that net ruminal biotin synthesis of mature Holstein cattle was negligible. Available data suggest that 1 to 5 mg of biotin are synthesized per day in the rumen of cattle and 1 to 3 mg per day are absorbed.
Milk of ruminants is an excellent source of biotin. Cow’s colostrum contained from 1.0 to 2.7 µg biotin per 100 ml (Foley and Otterby, 1978). Recent studies report milk biotin levels of 8 to 9 µg per 100 ml (Midla et al., 1998; Fitzgerald et al., 2000). In these same studies, feeding 20 mg per day of supplemental biotin increased milk biotin levels to 16.2 to 22.6 µg per 100 ml. The milk of a ewe is reported to contain over twice as much biotin as that of a cow (NRC, 1985).
Supplemental d-biotin was reported to have a net bioavailability in mature Holstein cattle of 50% to 60% with a half–life in the body of 6 to 18 hours (Frigg et al., 1993, 1994). Steinburg et al. (1994) reported an apparent bioavailability of 40% in lactating dairy cows. Kluenter and Steinburg (1993) and Steinburg et al. (1996) fed graded oral doses of d-biotin in a stabilized, spray-dried form and studied the effects on plasma and milk biotin levels in lactating dairy cows. Biotin was supplemented between 0 and 80 mg per day. Plasma biotin was significantly higher in dry cows than in lactating cows. Significant diurnal variation occurred in plasma biotin, which increased within one hour of feeding supplemental biotin and continued to increase until four hours after the second daily feeding (Kluenter and Steinburg, 1993). In both studies, a highly significant linear regression was found between oral biotin intake and both plasma output in milk (r2=.96) (Figure 11-2). Therefore it is clear that orally supplemented biotin is absorbed in proportion to dose up to 80 mg per day. The short systemic half-life of biotin concentrations and with biotin output in milk (r2=.96) (Figure 11-2). Therefore, like most water-soluable vitamins, it is clear that orally supplemented biotin, requires daily supplementation if plasma and tissue levels are to be consistently increased in ruminants.
Biotin is commercially synthesized and available in various forms. Pure crystalline biotin is normally too concentrated for use in feed manufacturing, because only small quantities are required in the diet. Biotin is commonly available as a 2% product, which is produced either by blending crystalline biotin with a carrier (triturate) or by the more sophisticated process of spray drying. Spray-dried biotin has more-uniform biotin activity and higher numbers of particles per gram than the triturates. These properties enhance the mixing and distribution of biotin in feeds and supplements.
Because it is a required cofactor in four key metabolic enzymes, biotin deficiency adversely affects many tissues, especially those with high rates of metabolic activity or cell division. Biotin is required for normal function of the thyroid and adrenal glands, reproductive and nervous systems. Its effect on the cutaneous system is most dramatic. The classic sign of biotin deficiency in animals and humans is a characteristic red, scaly dermatitis, especially around the eyes, nose and mouth. Metabolic changes include lactic acidosis, aciduria and increase in urinary excretion of 3-hydroxyisovaleric acid, a metabolite of leucine (Zempleni and Mock, 1999). The blockage in propionic acid metabolism results in accumulation of 3-hydroxypropionic acid in urine (Zempleni and Mock, 1999). Production of essential fatty acids is abnormal in biotin deficiency (Watkins, 1989), which may be the mechanism by which skin lesions are produced (Mock, 1991). Immune function is compromised by biotin deficiency, with reductions in plasma immunoglobulins and both T- and B-lymphocytes (Zempleni and Mock, 1999). Biotin deficiency in calves is characterized by paralysis of the hind legs, generalized weakness and reduced urinary excretion of biotin (Wiese et al., 1946). The condition was corrected by parenteral administration of biotin. Flipse et al. (1948) reported a potassium-biotin interrelationship in calves, in which calves fed purified diets low in potassium and biotin developed progressive paralysis of the hind legs that spread to the forelegs, neck and respiratory system. Death resulted within 12 to 24 hours of the first symptoms. The condition could be cured by parenteral administration of either potassium salts or biotin. A more recent study (Mulling et al., 1999) produced biotin deficiency in a calf for the purpose of studying its effects on hoof growth and keratinization. The calf displayed the classic biotin deficiency symptoms of dermatitis around the muzzle and eyes. The hoof epidermis displayed several specific abnormalities including a marked decrease in keratin production, a reduction in intracellular cementing substance, a very thin germinative cell layer and thin hoof sole with a brittle and crumbly consistency. The normal border of cornification between live and dead horn layers had completely disappeared in the biotin-deficient calf. The authors concluded, based on their observations, that biotin is clearly essential for normal keratinization and hoof horn quality (Illus. 11-2).
Source: Schmid, 1994
A study of biotin deficiency in Angora and Cashmere goats (Mengal et al., 1998) reported that biotin deficiency significantly reduced hoof growth and concentration of cysteine and lysine in hoof horn, which are involved in the cross-linking of protein. No major breed-by-treatment interactions were reported. The consistent reduction in hoof disorders observed experimentally in response to supplemental biotin in dairy and beef cattle and improvement in milk production (discussed in Fortification Considerations section) suggest that marginal biotin deficiency occurs for these animals under intensive management with high production levels (Illus. 11-3). Similar responses in poultry, horses and swine have been interpreted as marginal biotin deficiency (McDowell, 2000).
Source: Schmid, 1994
Next to fertility problems and mastitis, lameness is considered the most expensive health problem in dairy herds. The cost of treating an affected cow was estimated to be US $240 (Kossaibati and Esslement, 1995). Loss of income also occurs because cow productivity declines well before the onset of clinical signs and continues after a lame cow has been diagnosed and treated (Green et al., 2002). Green et al. (2002) reported a reduction in milk yield from up to 4 months before to 5 months after an episode of lameness was diagnosed and treated, with lame cows produced approximately 360 kg (792 lb) less milk, a further net cost of approximately US $48 per affected cow, assuming a net income of US $0.14 per kg ($0.06 per lb) milk. The need for biotin supplementation for feed and hoof integrity and other production parameters are well established for poultry, swine and horses (McDowell, 2000). Research toward the end of the last century revealed the benefits of supplemental biotin on health and production of dairy and beef cattle. Biotin is an important factor for the development of strong hoof horn. It is involved in the differentiation of epidermal cells, and in the production of keratin and intracellular cementing substance (Mülling et al., 1999). In adult ruminants, biotin supplementation leads to improved hoof health. A series of controlled studies with dairy and beef cattle have demonstrated that the incidence of several common hoof lesions is significantly reduced by supplemental biotin (Seymour, 2001). Significant beneficial effects of biotin were indicated for interdigital dermatitis and sole bruising, interdigital dermatitis and sole hemorrhage, vertical fissures and coronary band lesions in beef cows, white line separation, sole hemorrhage and hoof wall grooving, healing of sole ulcers, and generalized lameness in pastured dairy cows. Lameness is an important cause of poor health, welfare and production in cattle. Research studies have reported improved hoof health of dairy cows fed 20 mg per day of supplemental biotin (Hochstetter, 1998; Midla et al., 1998; Bergsten et al., 1998; Fitzgerald et al., 2000; Hedges et al., 2001; Higuchi and Nagahata, 2001; Pötzsch et al., 2003). A controlled field study with 180 dairy cows, Hagemeister and Steinberg, (1996) reported that cows fed 10 mg per day supplemental biotin exhibited a significant reduction in the incidence of sole ulcer and heel horn erosion over a two-year period. Days open were reduced in the biotin group during the second year. Response time of similar hoof disorders was more rapid (six to 10 months) when 20 mg per day of biotin was fed continuously. Hochstetter (1998) reported that feeding 20 mg per day of supplemental biotin significantly reduced the overall incidence and severity of sole ulcer, sole hemorrhage and heel horn erosion in lactating dairy cows in a 12-month clinical experiment.
Reporting from Canada, Hedges et al. (2001) recorded incidence of hoof disorders in 900 cows from 5 farms. Overall incidence of lameness was 68.9% with a range of 31.6% to 100% per farm. The incidence rate of one the four most frequently reported causes of lameness was 13.8% for heal horn erosion. There was a significant decrease in lameness in cows supplemented with biotin.
A controlled clinical study was conducted using 100 first-lactation heifers on a large, commercial dairy herd in Ohio (Midla et al., 1998). Heifers were fed either 0 or 20 mg per day of supplemental biotin from calving through the first lactation. Biotin supplementation resulted in a significant reduction in white line separation by 100 days in lactation (Figure 11-3) and a significant increase in 305-day milk production (693 lb, or 314 kg). From 5 farms representing 900 cows, overall lameness was 68.9%, with 12.7% of cows having white line separation (Hedges et al., 2001). With all farms polled, the risk of lameness caused by white line separation in cattle supplemented with biotin was approximately halved.
Pötzsch et al. (2003) reported from the United Kingdom that supplementation with biotin reduced white line disease (WLD) lameness by 45% in multiparous cows down to 8.5 cases per 100 cows, whereas the effect of biotin supplementation in primiparous cows was not significant. Although numerical reductions in WLD lameness were observed for shorter periods of supplementation, a supplementation length of at least 6 months was required to significantly reduce the risk of WLD lameness in multiparous cows.
A controlled, clinical trial with 56 dairy cows over 11 months found that 20 mg per day supplemental biotin resulted in a significant reduction in the incidence of digital dermatitis and sole bruising (Distl and Schmid, 1994) (Figure 11-5, 11-6). Similar results were found in a randomized clinical field trial with 40 dairy cows where 20 mg per day of biotin resulted in a reduction in the incidence of digital and interdigital dermatitis over an eight- to 12-month period (Hochstetter, 1998) (Figure 11-7).
A clinical field study of 236 claw lesions with exposed corium in 160 cows in 82 dairy herds found that cows fed 20 mg per day of biotin experienced significantly better healing of the lesions (Lischer et al., 1996) (Figure 11-8). A regression analysis of the data found a highly significant linear relationship between serum biotin concentration and the rate of new horn formation over the lesions. Biotin supplementation also increased the quality of new horn. Hochstetter (1998) reported that supplemental biotin resulted in increased keratinization and cementing of hoof horn and an increase in biotin concentration in the live epidermis (horn-forming) tissue layer of the hoof.
One of the larger and more recent trials (Fitzgerald et al., 2000) took place with pastured dairy cows in the Atherton region of northern Australia. Lameness is a problem in this region due to seasonal calving during the wet season, a diet of high quality pasture with supplemental grain, and the long walking distances to and from milking by way of partially paved, partly mud cow lanes. A total of 20 farms (10 control and 10 biotin-supplemented) with a total of 2,700 cows participated in the study. Both the farmers and the evaluators were blind to the treatments to prevent bias. After four months of supplementation, the cows fed 20 mg per day of biotin had a significant reduction in overall lameness, antibiotic treatments, and application of hoof shoes (Figures 11-10, 11-11). The participating farmers kept track of lameness during the trial. The economics of biotin were favorable with a milk price of approximately $9.30/cwt. Besides demonstrating a beneficial effect of biotin on hoof health, the results showed that hoof disorders of dairy cattle are not limited to confinement housing systems. Hoof disorders are more related to the overall level of “hoof stress” in a herd. Increased hoof stress increases the need to rebuild hoof horn and therefore the need for essential nutrients.
Schmid (1995) conducted a longitudinal study of five dairy cows both before and during biotin supplementation (20 mg per day). After four months of biotin supplementation, heel horn tensile strength increased significantly (12% to 30%), and clinical appearance of the hoof improved compared to scores prior to supplementation. Coronary (wall) horn tensile strength increased after 15 months of supplementation, which is consistent with its rate of growth. Hoof hardness was not affected by biotin supplementation. Coronary (hoof wall) horn was much harder than sole horn (76 versus 48 Shore D degrees).
Biotin has been studied primarily as a benefit to hoof integrity in cattle, however, a number of recent studies have shown that feeding supplemental biotin at the rate of 20 mg/cow/day increased milk production significantly (Bonomi et al., 1996; Midla et al., 1998; Bergsten et al., 1999; 2003; Seymour, 2001; Zimmerly and Weiss, 2001; Majee et al., 2003; Pötzsch et al., 2003; Girard and Matte, 2006; Ferreira et al., 2007; Enjalbert et al., 2008; Chen and Liu, 2010; Girard and Desrochers, 2010; Chen et al., 2001). In these positive studies, supplemental biotin increased milk production, from approximately 1 to 2.8 kg (2.2 to 6.2 lb) per cow per day. Dry matter intake and milk yield were 0.7 kg (1.54 lb) and 1.7 kg (3.74 lb) per day respectively, higher for cows supplemented with 20 mg biotin per day compared to control cows (Majee et al., 2003; Chen et al., 2001). Some studies have shown biotin to have no effect on milk yield (Fitzgerald et al., 2000; Rosendo et al., 2004). Biotin was reported to increase milk yield and milk components in high producing cows but had no effect in low producing cows (Ferrira et al., 2007; Chen and Liv, 2010). In one study, biotin and vitamin B12 given together increased milk production and milk protein yields compared with the control diet (Girard and Desrochers, 2010). Rosendo et al. (2004) also found milk from biotin-supplemented cows tended to have a greater concentration of protein (2.80% versus 2.73%). Biotin supplementation had an influence on hepatic lipidosis (fatty liver) in dairy cows around calving (Rosendo et al., 2004). Low energy intake before and after partuition causes the dairy cow to mobilize fat from its adipose tissue, which can result in fatty liver infiltration (Grummer, 1993). During that period and especially during development of fatty liver, control of gluconeogenesis by the hepatic rate-limiting enzymes seems to be altered (Rukkwamsuk et al., 1999). Rosendo et al. (2004) provided 20 mg of biotin per day an average of 16 days prepartum and 30 mg daily from calving through day 70 postpartum. Although milk production was not improved in the study, (Rosendo et al., 2004) cows supplemented with biotin demonstrated improved metabolic status. Specifically, blood glucose concentrations were higher and blood nonesterified fatty acid (NEFA) concentrations were lower in the early weeks post calving. Lower NEFA concentrations indicate that the cows supplemented with biotin were mobilizing less body fat to support their milk production and relying more on dietary energy. Biotin supplementation also decreased liver fat in postpartum cows at a faster rate than control cows. A liver with less fat is better able to synthesize glucose for milk production and to detoxify ammonia from excess intake of protein. Biotin has previously been shown to reduce the incidence of fatty liver and kidney syndrome in rapidly growing broiler chickens (McDowell, 2000). A number of periparturient diseases such as ketosis, retained placenta, metritis, milk fever, mastitis, and laminitis are associated with fatty liver (Breukink and Wensing, 1998). If supplemental biotin improves milk production through either an increased ruminal fiber digestion or hepatic gluconeogenesis in dairy cows (Weiss and Zimmerly, 2000), an additional benefit of improved energy status in dry and periparturient cows may mean a reduction in the occurrence of metabolic disorders such as fatty liver and ketosis.
In the study by Midla et al. (1998) using only first-lactation heifers, 305-day milk production was increased significantly (+314 kg, or 693 lb) in response to feeding 20 mg per day of supplemental biotin daily. This response was measured over the entire lactation and accompanied a significant reduction in the incidence of white line fissures.
Bonomi et al. (1996) reported a consistent 1-kg increase in daily milk production in Italian Holstein cows fed 10 mg per day of supplemental biotin (Figure 11-12). These authors also reported that supplemental biotin increased blood glucose concentration and milk component yields. The milk increase was observed during the first month of supplementation, which began at calving.
Bergsten et al. (1999) analyzed 305-day milk yield in 98 dairy cows fed either 0 or 20 mg per day of supplemental biotin via computer feeder. Data were adjusted for parity, days in milk and previous lactation milk yield. Cows fed supplemental biotin produced 878 kg (1,932 lb) more milk over 305 days (Figure 11-13). There was a significant reduction in sole hemorrhage and hoof wall ridging in the biotin-supplemented cows, although hoof health was generally good at the outset of the study.
In a controlled 100-day experiment milk production linearly increased with biotin supplementation (36.9, 37.8, and 39.7 kg (81.2, 83.2 and 87.3 lb) per day for 0, 10, and 20 mg per day of supplemental biotin, respectively (Zimmerly and Weiss, 2001). (Figure 11-14). These results indicate that biotin status of cows was marginal with respect to metabolic processes (i.e. enzyme activities) involved in milk production. The direct involvement of biotin in the enzymatic pathways of rumen propionic acid synthesis and hepatic gluconeogenesis from propionic acid, as well as in fat and protein metabolism, provides a logical basis for such an interpretation.
Biotin supplementation of calf milk replacer is warranted based on the biotin content of milk, studies of biotin deficiency in calves and unknown aspects of the development of rumen synthesis of biotin. For dairy cattle, the National Research Council (NRC, 1989) recommends that milk replacer for calves should contain 0.1 mg per kg (0.45 mg per lb) biotin. In acute cases of biotin deficiency in calves, single biotin injections of 100 µg subcutaneously or 1 mg intravenously reversed the deficiency (Wiese et al., 1946).
A reproductive effect of supplemental biotin was found for dairy heifers (Bergsten et al., 2003). First lactation heifers fed supplemental biotin had significantly fewer days from calving to conception and required fewer inseminations per pregnancy than controls of the same parity. Biotin supplementation reduced days from calving to conception in some previous studies, although cow numbers were limited (Bonomi et al., 1996; Fitzgerald et al., 2000; Voigt et al., 2000). In relation to reproduction in other species, a marginal biotin deficiency is found to be common in normal human pregnancy and is highly teratogenic (fetal malformations) in mice (Mock, 2009). Biotin is one of the more chemically stable vitamins, but losses during storage can occur. Biotin is readily destroyed by fat rancidity (Pavcek and Shull, 1942). Preparing fresh feeds, limiting storage time and storing feed in a dry, well-ventilated area will minimize rancidity and other stability problems. Diets high in pro-oxidants such as poor quality, unsaturated fats or oils should be avoided. Biotin is relatively stable in multivitamin premixes and is fairly stable during processing. However, significant losses can occur in premixes that contain choline and trace minerals. In a high quality premix containing only vitamins, biotin will retain 90% to 100% of initial activity over three months of storage. However in the presence of choline and trace minerals retention is reduced to 70% to 90% of original activity (Gadient, 1986). Spray-dried biotin is stable for 18 months or more in the original, unopened container.
Studies with poultry and swine indicate that those species can safely tolerate dietary levels four to 10 times their nutritional requirements of biotin (NRC, 1987). Birds are very tolerant of high levels of biotin, and because the vitamin is excreted intact, toxicity is very rare (Leeson and Summer, 2001). In view of the rapid metabolic turnover of biotin, toxicity is unlikely to occur in livestock. Studies in humans and laboratory animals have shown a high tolerance level for oral biotin and few if any toxicity symptoms (Bonjour, 1991). Relatively high levels of supplementation have been used in humans to combat weak fingernails, dermatitis and hair loss and as a therapy for diabetes without noticeable adverse reactions (Bonjour, 1991).
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