Cobalt Deficiency in Ruminants

Robert Bascom Sager • John Maas

Definition and Etiology

A number of syndromes occur in ruminants as a result of a primary cobalt (Co) deficiency in their diet. These include ill thrift or enzootic marasmus and anemia.

Clinical Signs and Differential Diagnosis

Co deficiency in ruminants is associated with the nonspecific signs of decreased growth, weight loss, diarrhea, ill thrift, pica, emaciation, pale mucous membranes (anemia), and lacrimation. Clinical disease is more common in young, growing animals. Sheep are apparently more susceptible to Co deficiency than cattle. Primary differential diagnoses include helminthic parasit­ism; protein-calorie malnutrition; coccidiosis; Johne’s disease; nutritional deficiencies of selenium, copper, or vitamin D; and other chronic diseases that may be associated with weight loss. Co-deficient ruminants are commonly anorexic and fail to thrive on lush pasture or high-quality feeds.

and to the effects of parasitism.⁴ 1 he primary differential diagnosis when considering Co deficiency is invariably internal parasitism.

Clinical Pathology and Diagnosis

Because the role of Co in ruminant nutrition is tied to the formation, absorption, and use of vitamin B₁₂, the most significant biochemical role of Co is correlated with tissue vitamin B₁₂ concentrations. However, the effects of starvation tend to increase vitamin B₁₂ concentrations in the liver and kidneys.⁶ If Co deficiency occurs with other conditions that cause anorexia, the tissue vitamin B₁₂ concentrations may appear falsely elevated (normal). The appropriate analytic methods for serum B₁₂ vary from humans to ruminants, so extrapolation of ruminant serum B₁₂ concentrations analyzed in a human laboratory may not be possible. Serum or plasma vitamin B₁₂ levels exhibit a marked diurnal variation.⁷ In addition, serum vitamin B₁₂ concentration more closely reflects short-term Co intake and can be decreased when adequate liver reserves of vitamin B₁₂ remain. In normal, Co-sufficient ruminants’ serum vitamin B₁₂ values are usually 0.1 to 0.3 ng/mL (parts per billion [ppb]). When serum vitamin B₁₂ values decrease, clinical signs of Co deficiency can become evident.^8,9 Because serum B₁₂ values can give spurious results, the concentration of Co in hepatic tissue is probably the best current standard for determining Co status and making clinical decisions. The liver concentration of B₁₂ for cattle and sheep considered to be adequate is 0.30 to 2.24 μg∕mL (ppm) on a wet weight basis.^10,11 Table 32.25 contains reference ranges for cattle and sheep.

■ TABLE 32.25

Reference Values for Cobalt and Vitamin B₁₂

Pathophysiology

Co deficiency in ruminants induces a deficiency of vitamin B₁₂ (cyanocobalamin). It is the lack of vitamin B₁₂ that is thought to cause the majority of clinical signs and clinicopathologic abnormalities observed. Monogastric species need to ingest vitamin B₁₂ preformed, whereas ruminants can manufacture adequate vitamin B₁₂ if the rumen microorganisms are supplied with adequate Co in the diet. The rumen microorganisms incorporate Co into vitamin B₁₂ and a number of physiologically inactive vitamin B₁₂-like compounds. The production of vitamin B₁₂ from dietary Co was estimated to be approximately 15% in Co-deficient sheep and only approximately 3% in Co­sufficient sheep.¹³ Approximately 50% of the vitamin B₁₂ produced is absorbed in normal animals, but only 3% to 5% of vitamin B₁₂ is estimated to be absorbed by Co-deficient sheep.¹⁴ Although the absorption of vitamin B₁₂ formed in the rumen is not particularly efficient, with normal dietary Co there are usually no clinical problems, and interference by other dietary components does not appear to be clinically important.

Ruminants use the VFAs acetate, propionate, and butyrate as their primary energy sources. Propionate produced in the rumen is the precursor of glucose for ruminant metabolism. The general metabolic steps for conversion of propionate to glucose are shown¹⁵ in Fig. 32.144 use 32-134 from the 5^th edition.

A primary defect in Co-deficient ruminants is the inefficient metabolism of propionate at the point in the pathway at which methylmalonyl-CoA mutase, a vitamin B₁₂-requiring enzyme, catalyzes the conversion of methylmalonyl-CoA to succinyl- CoA.¹⁶ As Co deficiency becomes severe, the rate of propionate clearance from the blood decreases, and the intermediate metabolite methylmalonyl-CoA accumulates. ¹⁷ With severe Co deficiency, the amount of methylmalonic acid excreted in the urine increases. As the half-time for propionate clearance increases, the voluntary feed intake of Co-deficient sheep decreases.¹⁷ These changes correlate with the degree of anorexia and weight loss observed in severely Co-deficient sheep.

The decreased growth, weight loss, unthrifty appearance, and anorexia are closely correlated to the observed abnormalities of carbohydrate metabolism. The diarrhea commonly observed with Co deficiency is not well explained; however, an increase in susceptibility to parasitism⁴ might explain a portion of this clinical observation.

The anemia that is associated with Co deficiency occurs late in the development of the syndrome and is characterized as normocytic normochromic.¹⁸ Co deficiency results in the depression of the vitamin B₁₂-containing enzyme 5-methyltetrahydrofolate homocysteine methyltransferase.¹⁹ This interference with the recycling of methionine has a marked influence on folate metabolism. In addition to potentially

FIG. 32.144 Pathway for conversion of proprionyl coenzyme A (CoA) from proprionate to succinyl CoA.

resulting in anemia through inefficient folate metabolism, the decreased activity of this methyltransferase could lead to a deficiency of methionine; this is a possible reason for nitrogen retention and the decreased body growth and wool growth observed.

■ Epidemiology and Cobalt Requirements Co deficiency in ruminants occurs in selected regions throughout the world and in association with a variety of soil types. Clini­cally recognizable Co deficiency is reported in New Zealand, Australia, Brazil, United Kingdom, Ireland, Scandinavia, and North America. In the United States, Co deficiency is most commonly seen in Florida, in the Northeast, along the eastern seaboard, in the upper Midwest, and around the Great Lakes.²⁰ Although various soil types are associated with Co deficiency, heavy fertilization with limestone reduces the Co available to plants and animals.²¹ The dietary requirement of Co by ruminants is generally recommended to be 0.1 mg/kg of dry matter (DM) of the complete ration.^22-24 The Co requirement of young, rapidly growing lambs is thought to be 0.2 mg/kg (ppm) of DM of the diet.²⁵ When pasture Co concentrations are less than 0.07 mg/kg of DM or 0.04 mg/kg of DM for sheep and cattle, respectively, signs of deficiency can be expected to develop. On a practical basis, diets with 0.1 mg/kg of DM are considered to be adequate. Legumes have relatively high Co concentrations. Rapidly growing grasses have much lower Co concentrations, and cereal grains are poor sources of Co.²² Oilseed meals are generally good sources of Co. Co supple­mented at levels above NRC recommendations (0.2 mg/kg versus 0.1 mg/kg) has been associated with increases in the immune response to one antigen in cattle.⁵

■ Treatment and Control Treatment is best accomplished in the short term with vitamin B₁₂ injections. Ruminants poorly absorb oral vitamin B₁₂; thus injections are the most efficient.

Rations with 0.1 to 0.2 mg/kg (ppm) of DM Co would be expected to prevent Co deficiency in ruminants. Salt-mineral mixes containing 0.1% Co also provide adequate supplementa­tion. 0.1% Co in salt can be made by mixing Co carbonate (which is 46% Co) at the rate of 4.35 pounds/ton of salt, or 1 g of Co carbonate per pound of salt. A pound equals 453.59 grams.

Co sulfate as a top dressing for pastures (1.5 kg/hectare every 3 to 4 years or 0.3 kg/hectare every 1 to 2 years) has been used to increase Co concentration of pasture forage. Heavily limed pastures²¹ and soils high in manganese oxide²⁷ decrease Co availability, and Co top dressing of the pastures or Co (B₁₂) supplementation to the animals should be considered.

A variety of rumen pellets containing Co are used to supple­ment grazing ruminants. These pellets have been successful in maintaining normal Co status in animals.^25-29 The pellets are not commercially available in the United States at this time.

The perennial grass, Phalaris tuberosa, can cause a syndrome in ruminants that is referred to as “phalaris staggers.” Co supplementation can aid in prevention of this syndrome because it inactivates or decreases absorption of the neurotoxin contained in P. tuberosa, Phalaris minor (canary grass), or Phalaris hybrids (ronpha).²⁹ The increased level of Co in the rumen is the important factor in preventing this condition; administration of oral or parenteral vitamin B₁₂ is not effective.²⁶ Treatment of clinical phalaris staggers with Co is not effective, however.

Because Co is poorly absorbed, toxicity is an uncommon problem, and diets in excess of 30 mg/kg of DM are necessary for toxicosis to occur in most cases.^22-24

A recommendation by the National Research Council of increased levels for Co (mg/kg DM) for beef cattle has been made since 2016. This increase has recommended increased Co levels of 20 mg / kg DM from the previous 10 mg/ kg DM. Research has reflected increased NRC Co levels improved performance (ADG) in Simmental bulls (Stangl, et al.). Increased NRC Co levels in feedlot steers showed increased antibody titers of M. haemolytica leukotoxin (P postsurgical complications.