The ABC’s of Vitamins A, B, C…
An Explanation of the Vitamin Mineral Pack in Most Pet Foods
by: Mark E. Rogers
for DOGS
Vitamins
General considerations and sources: Vitamins are structurally very diverse organic molecules that serve a multitude of critical biochemical functions necessary for healthy life. Some of their functions are very well understood and their roles clearly defined. Many are still under investigation and are extremely complex. New information is being discovered on nearly a daily basis. Certain vitamins have as few as one or two functions, while others play a role in hundreds or thousands of enzymatic reactions and complex biochemical processes. Many are chemically simple while others, such as vitamin B12, is among the most complex non-protein structures in animal biochemistry. One thing they all have in common is that they are essential.
Sources of vitamins are as diverse as their structures and functions. However, regardless of their source, they have exact chemical structures and, therefore, no matter the source, the function and activity is the same. Synthetic or naturally occurring, thiamin is thiamin, riboflavin is riboflavin, etc. It is far more important that they are consumed in the proper dose then where they came from.
Vitamin A: Vitamin A is a generic term for a large number of related compounds. This discussion will focus on preformed vitamin A (retinol and retinal) and retinoic acid, herein referred to as Pre A and RA respectively.
Five primary functions of vitamin A have been identified: vision, growth, limb and organ development, cellular differentiation, and immunity. All these functions can be maintained by Pre A since retinol and retinal are interconvertable by animals. RA, which can be synthesized from retinal cannot satisfy the functional roles for reproduction and vision. RA is capable of carrying out all other functional roles of vitamin A.
Vision: The role of Pre A in the complex process of vision can be summarized as follows: Pre A binds to the protein opsin in rod cells to form the visual pigment rhodopsin. Absorption of light by the pigment causes a conformational change in the Pre A portion of rhodopsin. This in turn causes release of the conformationally changed Pre A and generation of an electrical signal which travels down the optic nerve to the brain where it is interpreted as vision. The conformationally changed Pre A is converted back to its original form, resetting the cycle.
Growth: The precise action of vitamin A in growth is still under investigation. However, it is known that, in rats, growth can be maintained with low doses of RA. When dosing is withheld, growth ceases due to lack of appetite that occurs 1-2 days after withdrawal of RA. Presumably the failure of growth in vitamin A deficient cats and dogs is due to the same mechanism.
Limb and Organ Development: Both vitamin A excess and deficiency are known to cause birth defects. Pre A and RA are essential for embryonic development. During fetal development RA functions in limb development and formation of the heart, eyes, and ears. Additionally, RA has been found to regulate the expression of the gene for growth hormone.
Cellular Differentiation: RA and related compounds act as a hormone to affect gene expression and thereby influences numerous physiological processes. Through stimulation and inhibition of transcription of specific genes, RA plays a major role in cellular differentiation, the specialization of cells for highly specific physiological roles. Many of the physiological effects attributed to vitamin A appear to result from its role in cellular differentiation.
Immunity: Vitamin A is known as the anti-infective vitamin because it is required for the normal functioning of the immune system. The skin and mucosal cells (cells that line the airways, digestive tract, and urinary tract) function as a barrier and form the first line of defense against infection. Retinoids are required to maintain the integrity and function of these cells. Pre A and RA play a central role in the development and differentiation of white blood cells which play critical roles in the immune response.
Red blood cells, like all blood cells, are derived from precursor cells called stem cells. Stem cells are dependent on retinoids for normal differentiation into red blood cells. Additionally, vitamin A appears to facilitate mobilization of iron from storage sites to the developing red blood cells for incorporation into hemoglobin, the oxygen carrier in red blood cells.
Deficiency: Clinical signs of vitamin A deficiency in dogs are similar to those in other species. Those signs include, anorexia, body weight loss, ataxia, abnormal dryness of the cornea and conjunctiva, conjunctivitis, corneal opacity and ulceration, skin lesions, changes in the lining of the bronchia, and increased susceptibility to infection.
Requirements: The requirements for adult dogs, puppies, pregnant and lactating bitches appears to be identical. The recommended dosage is 200 IU.kg BW-1.d-1.
Thiamin: Thiamin (also spelled thiamine), was the first water soluble vitamin to be isolated. It is commonly known as vitamin B1. It is found in the body as free thiamin or in various forms containing phosphorous groups of several types. It functions as a coenzyme for a small but critically important group of enzymatic transformations. The enzymatic reactions that are vitamin B1 dependent ultimately involve the production of energy from food and/or carbohydrate metabolism.
Although thiamin occurs widely in foods of both animal and plant origin, it is abundant in only a few. Rich sources of thiamin are yeast, wheat germ, kidney, liver, and legume seeds. Thiamin is stable to heat and oxidation at low pH and unstable at higher pH. The pH of dog foods is sufficiently high that the temperatures used in processing dog foods causes significant losses. For this reason, both canned and dry dog foods require thiamin supplementation.
Deficiency: Because of the body’s limited storage of thiamin, clinical signs of deficiency appear more quickly after exposure to a thiamin-deficient diet than for most other vitamins. There are three reported stages to thiamin deficiency in puppies: the first stage of the disease is an initial short duration (18 ± 8 days) induction period in which the dogs appear healthy but grow slowly, intermediate stage of variable duration (59 ± 37 days) of inappetence, failure to grow, body weight loss, and coprophagia (stool eating). This was followed by a terminal period (8 ± 6 days) of neurological involvement or sudden death. The most consistent pathological lesions of thiamin deficiency involve the nervous system and heart. Acute thiamin deficiencies tend to involve the brain and produce severe neurological signs, whereas chronic deficiencies produce pathological changes of the myocardium (muscular tissue of the heart) and peripheral nerves.
Requirements: The approximate requirement for dogs is 75 μg thiamin.kg BW-1.d-1. There are no reports of toxicity resulting from oral ingestion of thiamin by dogs.
Riboflavin: Riboflavin is a water soluble B vitamin, also known as vitamin B2. In the body riboflavin is an integral part of two complex coenzymes, FAD (Flavin Adenine Dinucleotide and FMN (Flavin Mononucleotide). Coenzymes derived from riboflavin are creatively referred to as flavocoenzymes, and the enzymes that use them are called, you guessed it, flavoproteins.
One very important class of complex chemical reactions known as redox reactions (oxidation-reduction reactions), are crucial for numerous life sustaining processes. Examples include: obtaining energy from ingested foods (proteins, sugars, and fats), respiration (the utilization of the oxygen an animal breaths), the synthesis of complex molecules (anabolism), the breakdown or metabolism of large molecules into smaller pieces (catabolism), and the capturing and destroying of highly reactive oxygen species. The later activity is commonly referred to as anti-oxidant activity. Redox reactions are most easily defined as the gain or loss of electrons by a chemical species. The movement or transfer of electrons is the real action in chemical reactions. Electrons are the verbs (of sorts) and can be called the movers and shakers in chemistry. We will see that these tiny subatomic particles come up in the description of the activity of vitamins and enzymes quite often.
Several of the B vitamins including riboflavin are critical players in many redox reactions. Flavocoenzymes are important participants in the metabolism of sugars, fats, and proteins. FAD is a part of the electron transport (respiratory) chain, which is central to energy production. In conjunction with liver enzymes flavocoenzymes participate in the metabolism of drugs and toxins.
Flavocoenzymes also play a critical role in protecting organisms from reactive oxygen species (anti-oxidant activity), via numerous enzymatic pathways.
Animal products are an excellent source of riboflavin whereas grains are not. Most foods high in riboflavin are also rich in other vitamins of the B complex.
Deficiency: Riboflavin deficiency has been associated with increased oxidative stress. Because flavoproteins are involved with the metabolism of several other vitamins (vitamin B6, niacin, vitamin K, vitamin D, and folic acid), severe riboflavin deficiency may effect many enzyme systems. Chronic riboflavin deficiency has been associated with anorexia, body weight loss, muscular weakness, flaking dermatitis of the abdomen and the medial surface of the hind legs, and ocular lesions.
Requirements: The approximate recommended daily allowances are 50 and 100 μg .kg BW-1.d-1, for maintenance and growth respectively.
Niacin: Niacin is another water soluble vitamin in the B-complex. It is also known as nicotinic acid or vitamin B3. Nicotinamide is the derivative of niacin used by an animal to form the coenzymes NAD (Nicotine Adenine Dinucleotide) and NADP (Nicotinamide Adenine Dinucleotide Phosphate) which are the forms of niacin that participate in numerous chemical processes required to maintain a healthy living animal. Although the names are similar, none of the forms of nicotinic acid are related to the nicotine (a stimulant and insecticide) found in tobacco.
Living organisms derive most of their energy from redox reactions (oxidation-reduction reactions). As many as 200 enzymes require the niacin coenzymes, NAD and NADP, mainly to accept or donate electrons for redox reactions. NAD functions most often in energy producing reactions involving the degradation (catabolism) of sugars, fats, and proteins, and in the metabolism of alcohol. NADP functions more often in biosynthetic (anabolic) reactions, such as the synthesis of very large molecules, including fatty acids, and steroids such as cholesterol and ultimately testosterone and estrogen. NAD also participates in non-redox reactions which regulate DNA repair, cell signaling (cells talking to one another), cell differentiation, and apoptosis (programed cell death) which is believed to play a role in many cancers. Most of these latter functions are still poorly understood.
Good sources of niacin include yeast, meat, poultry, red fishes (e.g. tuna, salmon), cereals (especially fortified cereals), legumes, and seeds. Milk and green leafy vegetables also provide some niacin. In mature cereal grains such as corn and wheat, niacin is bound to large sugar molecules which greatly reduces its bioavailability.
Deficiency: The most common symptoms of niacin deficiency involve the skin, digestive system, and the nervous system. The symptoms of pellagra, a disease resulting from niacin deficiency (often referred to as “black tongue” in dogs) are commonly referred to as the four D’s: dermatitis, diarrhea, dementia, and death. In dogs niacin deficiency presents as anorexia and body weight loss, reddening of the inside of the upper lip that progresses to ulceration and inflammation of the mucosa of the throat, profuse blood-stained saliva drooling from the mouth, a fetid odor, and diarrhea, among other more severe symptoms.
Requirements: It is suggested that the daily requirement for maintenance of adult dogs is met by 225 ug niacin.kg BW-1, and for growing dogs 450 μg niacin.kg BW-1. It is therefore proposed that 3.4 mg niacin per 1,000 kcal ME (metabolizable energy) be used by all dogs.
Pantothenic Acid: Pantothenic acid, also known as vitamin B5, is essential to all forms of life. Pantothenic acid is found throughout living cells in the form of coenzyme A (CoA), a vital coenzyme in numerous chemical reactions that sustain life. CoA is required for chemical reactions that generate energy from food (fat, carbohydrates, and proteins). The synthesis of essential fatty acids, Vitamin D, cholesterol and other steroid hormones requires CoA, as does the synthesis of the neurotransmitter acetylcholine, and the hormone melatonin. Heme (a large molecule that binds iron), a component of hemoglobin, requires CoA-containing compounds for its synthesis. Metabolism of a number of toxins and drugs by the liver requires CoA.
Pantothenic acid is available in a variety of foods. Rich sources of pantothenic acid include liver and kidney, yeast, egg yolk, broccoli, fish, chicken, milk, legumes, mushrooms and sweet potato to name a few. Whole grains are also a good source of pantothenic acid, but refining and processing may result in up to 75% loss, freezing and canning of foods may result in similar losses.
Deficiency: Due to its abundance in a variety of food sources deficiency is virtually unknown. Dogs deprived of pantothenic acid developed low blood glucose, rapid breathing and heart rates, and convulsions. Weanling puppies ceased growth after 3-4 weeks, and adult dogs died if not given pantothenic acid. It is considered non-toxic.
Requirements: The dietary intake generally recommended is equivalent to 200 μg.kg BW-1 d-1.
Vitamin B6: Vitamin B6 is another of the water soluble B complex vitamins. There are three traditionally considered forms of vitamin B6: pyridoxal (PL), pyridoxine (PN), and pyridoxamine (PM). The phosphate ester derivative of pyridoxal (pyridoxal-5/-phosphate, PLP) is the principal coenzyme form and has the most important role in metabolism.
Vitamin B6 (PLP) plays a vital role in the function of approximately 100 enzymes. Because of the multiplicity of enzymatic reactions involving PLP, it follows that PLP plays a vital role in many physiological processes. Some of the more important processes in which PLP plays a vital role are: synthesis of glucose from non-carbohydrate sources (glyconeogenesis), red blood cell formation and function, fat metabolism, neurotransmitter synthesis, nervous system function, hormone modulation, immune response, and gene expression. It is also crucial in the synthesis
of niacin from tryptophan, thus vitamin B6 deficiency can lead to niacin deficiency as well. It is not synthesized in mammals and must therefore be obtained in the diet. It is widely distributed in many food types in bioavailable form. However, in many plant types it is bound to complex sugars which render it much less available. Thus, a strict vegetarian diet would necessitate supplementation.
Deficiency: Acute vitamin B6 deficiency in newly weaned puppies produced anorexia, body weight loss, and death before any marked changes in blood were observed. In older dogs clinical signs also include convulsions, muscle twitching, anemia, congestion of various tissues, and neural degeneration.
Requirements: For growing puppies the requirement is 84 μg .kg BW-1.d-1, and for adult dogs it is 39 μg .kg BW-1.d-1.
Biotin: Biotin is a water soluble vitamin of the B-complex sometimes referred to as vitamin B7. Biotin is required by all organisms but is only synthesized by bacteria, yeasts, molds, algae, and some plants. It is widely distributed in foodstuffs. Additionally, most or all of the requirement may be satisfied by microbial synthesis in the gut. It is a coenzyme in the synthesis of fatty acids, leucine (an amino acid), and in the synthesis of glucose from non-sugar sources, such as amino acids.
Deficiency: Deficiency is rarely seen in dogs unless they are fed a diet high in raw egg whites which contains a protein that binds biotin and reduces its bioavailability.
Requirements: It has been suggested that 2 μg .kg BW-1.d-1 is sufficient for maintenance and 4 ug .kg BW-1.d-1 for growth and reproduction.
Vitamin B12: Vitamin B12 has the largest and most complex chemical structure of all the vitamins. It is unique among vitamins for two reasons. First, it is the only vitamin to contain a metal ion, cobalt. For this reason cobalamin is the term used to refer to all compounds having vitamin B12 activity. Second, wherever cobalamins occur in nature they are the result of synthesis by bacteria or other microorganisms in the rumen, intestine, soil, or sewage. All animals, whether human, dog, or cat, ultimately depend on microbially synthesized cobalamin. While the intestinal flora in dogs intestines can synthesize cobalamins in the presence of cobalt, the site of synthesis is after the site of absorption. Thus, supplementation of the diet with cobalt is not warranted.
In mammals vitamin B12 is a coenzyme for only two enzymes. The first involves the synthesis of the sulfur containing amino acid methionine from homocysteine (another sulfur containing amino acid), with concomitant production of a form of folic acid. Both methionine and folic acid (discussed below) are crucial to a number of unique physiological processes. One very important role of these is the production of all types of blood cells from precursor stem cells. Another biochemical process in which cobalamin plays a vital role is in energy production from the metabolism of fats and proteins.
The major food source of cobalamins are animal products, plant products being essentially devoid of the vitamin. Absorption requires a complex protein, “intrinsic factor” (IF)to which the cobalamin must bind for efficient uptake. In dogs this protein is produced primarily by the pancreas.
Deficiency: Deficiency is rare and all reports appear to stem either from bacterial overgrowth in the intestine that reduces the availability of cobalamin or inherent genetic abnormalities.
Requirements: There is no experimental data to quantify a requirement. However, the NRC recommends a dietary concentration of 0.92 μg .kg BW-1.d-1 for an adult dog at maintenance.
Folic Acid: The terms folic acid and folate are often used interchangeably for this water-soluble B-complex vitamin. Naturally occurring folates exist in many chemical forms. Folic acid, the more stable form, occurs rarely in foods or in mammals but is the form most commonly used in vitamin supplements and fortified foods. The only function of folate coenzymes appears to be in mediating the transfer of one-carbon units. Folate coenzymes act as acceptors and donors of one-carbon units in a variety of chemical reactions critical to the metabolism of nucleotides (one of the primary building blocks of DNA and RNA), and amino acids.
Deficiency: Dogs fed a folate deficient diet exhibit signs of body weight loss, a decline in hemoglobin (the oxygen carrier in red blood cells), a decrease in red cell volume, and loss of appetite. These symptoms are all relieved by one or more injections of folic acid.
Requirements: It is suggested that the folate requirement is satisfied by 54 μg per 1,000 kcal ME (metabolizable energy) for all physiological stages.
Vitamin C: In dogs, unlike humans there is no requirement for vitamin C supplementation due to their ability to meet their dietary requirements by synthesis from glucose. However, under conditions of high activity, stress, injury, or illness, supplementation is likely to be beneficial.
Choline: Choline is not by strict definition a vitamin, it is an essential nutrient. Although it can be synthesized in small amounts by most animals there is still a nutritional requirement. It is often classified as a vitamin of the B-complex. It has five major biological functions: structural integrity of cells, cell signaling, nerve impulse transmission, lipid (fat) transport and metabolism, and as a major source of single-carbon units (methyl groups) in numerous biosynthetic pathways.
Cell structure: Choline is used in the synthesis of phospholipids (phosphorous containing fats, e.g. lecithin) that comprise one of the main structural elements of cell membranes.
Cell signaling: Several choline containing phospholipids are precursors in the synthesis of intracellular (within a cell) messenger molecules whose importance and complexity is just beginning to be investigated and understood. One metabolite of choline is platelet activating factor (PAF) which is a signaling molecule in the highly complex blood clotting cascade process.
Nerve impulse transmission: Choline is a precursor to the important neurotransmitter actetylcholine, which is involved in muscle control, memory, and numerous other functions.
Lipid transport: Fat and cholesterol consumed in the diet are transported to the liver by specialized proteins. In the liver fats and cholesterol are packaged into lipoproteins (a combination of proteins and fats) called very low density lipoproteins (VLDL) for transport through the blood to tissues that require them. Choline is a required component of VLDL particles. Without adequate choline levels, fat and cholesterol accumulate in the liver.
Methyl group donor: Similar to folate derivatives, choline can act as a single-carbon donor in many important biochemical processes. Whereas folate can donate only one single-carbon unit, choline can actually donate three equivalents.
Deficiency: Choline deficiency in dogs was associated with a loss of body weight, vomiting, an increase in fat content of the liver, and death.
Requirements: The NRC recommendation for all physiological stages is 345 mg per 1,000 kcal ME (metabolizable energy) or ~ 45 mg.kg BW-1.d-1 for a dog at maintenance.
Vitamin D: Vitamin D is a generic descriptor for a group of related compounds. The active form of the vitamin which is often referred to as a hormone as a result of some of its biological functions is called 1,25-dihydroxy-vitamin D {1,25-(OH)2D}. Its biosynthesis is extremely complicated, requiring synthetic steps in the skin, liver, and kidneys depending on the precursor molecule. One step in its synthesis can occur from one of the biosynthetic precursors to cholesterol on exposure of this compound to UV-B radiation. Humans can efficiently carry out this process but it appears that dogs and cats are much less efficient in this pathway. In dogs and cats supplementation with vitamin D3, another precursor to the final, active form of the vitamin is most effective but there are several other naturally occurring precursors. We will refer to the active form of vitamin D simply as “D”.
D has a wide range of biologically important functions many of which have only recently come to light and which are still under active investigation. One very important role of D is to maintain a narrow serum concentration level of calcium ions. Calcium ions play a critical role in the functioning of the nervous system, and are vital to proper muscle contraction. Calcium is also a vital component of bone, and D plays a role in transport of calcium both in and out of bone tissue. D also plays a crucial role in modulation of the immune response. It has been found to be important in blood pressure regulation and insulin secretion.
Deficiency: Since calcium, phosphorous, and vitamin D nutrition interact in the maintenance of normal mineral balance, there are gross clinical similarities in signs resulting from deficiencies of any one of these nutrients. Defective mineralization of the skeleton and lameness are clinical signs of vitamin D and calcium deficiency.
Rickets, a common disorder resulting from vitamin D deficiency is more pronounced in rapidly growing puppies then in mature dogs. The most obvious signs are lethargy and decreased muscle tone. Other clinical signs include profound muscle weakness, bending of long bones (to the extent of weight bearing), and listlessness, as well as many others.
Requirements: There have been no definitive studies to define the minimal vitamin D requirements of puppies. Growing animals, because of high demand for calcification of the skeleton, are most sensitive to a dietary deficiency of vitamin D whereas mature dogs are relatively resistant. The dietary recommendations for all dogs including lactating and pregnant bitches is 2.75 μg per 1,000 kcal ME (metabolizable energy).
Vitamin E: Vitamin E is the generic name for a family of eight related fat soluble compounds. The most biologically significant is called α-tocopherol. Due to its fat solubility, the primary site for vitamin E activity is in the lipid portion of cell membranes where it functions as an anti-oxidant. In this role it protects polyunsaturated fatty acids (PUFAs) from oxidative damage by highly reactive oxygen species and free radicals.
A free radical is a highly reactive electron deficient chemical species that can cause severe and irreparable damage to tissues. Often, but not exclusively, these are an electron deficient oxygen containing species. This is where the term anti-oxidant arises from. An anti-oxidant prevents damage by these highly reactive oxygen species and other free radicals. However, a more accurate description is that an anti-oxidant prevents damage from any electron deficient chemical species. Electron deficient species do not wish to remain this way so they remove an electron from any nearby molecule available. Removal of an electron is called oxidation, and leads to the notion of oxidative damage. An anti-oxidant (vitamin E, vitamin C, etc.) is a molecule that reacts rapidly and preferentially with a free radical in a manner that does not cause permanent damage to itself. This prevents the free radical from destroying other molecules for instance the PUFAs, skin, or DNA, that can lead to biological malfunctions, degradation, and diseases such as cancer. Due to its anti-oxidant activity, vitamin E is used as a natural preservative of fats in foods.
Several other roles for vitamin E have been proposed that do not involve its anti-oxidant activity. Some of these include modulation of prostaglandin (biomolecules involved in inflammation) synthesis, protein modification reactions, and the synthesis of anti-oxidant enzymes.
Deficiency: A wide range of clinical signs of vitamin E deficiency have been reported in dogs. These include degeneration of the skeletal muscles associated with muscle weakness and reproductive failure in both males (degenerative changes of the testicles leading to a lack of semen) and females (birth of weak and dead puppies). Others include subcutaneous edema, anorexia, depression, and eventual coma.
Requirements: The NRC recommendation is for 22 IUs of vitamin E .kg-1 for all physiological stages.
It is hoped that this brief introduction to vitamins and minerals has helped in your understanding of the critical role they play in the maintenance of good health. Hopefully, this description of these highly complex molecules, and minerals has also given you a greater appreciation for the fascinating complexity and elegance of biological functions and the amazing degree of interdependence of various systems in a living organism.
Minerals
General considerations and sources: Minerals are just metal ions. Minerals can be defined as metal salts where the metal ion is positively charged and the counter ion is negatively charged. Metals play many critical roles in the biochemistry of living organisms. The metal ions must be supplied in a form that makes the metal biologically available. Metal oxides, e.g., copper oxide, are essentially useless as a source of the metal ion. The metal oxides have very low bioavailability. Many other metal salts also have low bioavailability. Several decades ago it was discovered that the bioavailability of metals could be dramatically increased by using metal chelates. Metal chelates are metals that are bonded non-covalently to an organic molecule. Quality pet foods supply most metals as the metal proteinate. These are metals weakly bonded to an amino acid or small protein fragment. Metal proteinates, e.g., manganese proteinate, dramatically increase the bioavailability of the metal ion.
Chloride: Chloride ion (denoted Cl-) is the term used to describe the form of the element chlorine as it is found in living organisms, and strictly speaking is not a mineral. The role of Cl- is perhaps the most complex of all the nutritive “minerals”. Its overall function is to maintain the electrical balance of the vast majority of chemical transformations in the body. This includes but is not limited to: all muscle contractions, nerve impulses, the movement across cellular membranes, and therefore the concentration inside and outside of cells, of virtually all other ions such as sodium (Na), potassium (K), calcium (Ca), etc.
Chloride is found in limited concentrations in most foodstuffs, requiring that many animal diets be supplemented with Cl- containing salts. Some commonly used sources are sodium chloride (table salt), calcium chloride, and potassium chloride.
Deficiency and Requirements: There is very limited information on deficiency of Cl- in the diet of dogs. The recommended daily requirement is 300 mg Cl- per 1,000 kcal ME (metabolizable energy).
Zinc: Zinc is a metal denoted by the symbol Zn. It is found throughout the body, mainly as an intracellular (within cells) constituent, but is present in most tissues in low concentrations. Zinc has many essential functions in the body. It acts as a cofactor in approximately 200 Zn-containing enzymes that are involved in cell replication, protein and sugar metabolism, skin function, and wound healing. Zinc is also thought to play a crucial role in the structure and function of biological membranes as well as in the stabilization of DNA and RNA.
The sources of Zn in pet foods are quite varied. Animal sources, particularly beef products, and other red meats as well as whole grains are good sources of zinc, as are legumes. Nonetheless, most petfoods are supplemented with Zn in many different forms, including zinc sulfate, zinc carbonate, and zinc proteinate (zinc bound to amino acids, also referred to as a chelate).
The absorption of dietary Zn is largely a function of other substances in the diet that alter its bioavailability. Most animal products and seafood are a good source of Zn and the amino acids that make up their proteins may aid in absorption. Vegetable products are more likely to contain compounds that interfere with zinc bioavailability. The most notable of these is phytate (also know as xylitol, a carbohydrate or sugar), which is present in many cereal grains such as corn and wheat, and in oils from soy, peanut, and sesame.
Deficiency: Zinc deficiency is rare in most dogs but some breeds appear to have a genetic predisposition for this syndrome. It is most common in northern breeds, (e.g. Alaskan Huskies or Malamutes) and requires lifelong supplementation. The most common clinical signs of Zn deficiency appear in growing puppies and include very poor growth rates and skin lesions, most notably in areas of contact or wear such as foot pads.
Requirements: A diet containing 15 mg Zn per 1,000 kcal ME (metabolizable energy) should provide adequate Zn intake for a 15-kg adult dog consuming 1,000 kcal ME d-1.
Iron: Iron is another important metal (denoted by the symbol Fe), that is a dietary requirement in dogs. Its primary function in the animal is in the synthesis of hemoglobin and myoglobin (oxygen carries in red blood cells and muscle tissue respectively). It is also important in maintaining hematocrit values (the ratio of red blood cell volume to total blood volume) and in several enzyme systems that are important in obtaining energy through metabolism of various food stuffs.
Milk is a poor source of iron but meat meals, bone meal, and cereal grains are all good sources of dietary iron. It is present in dog foods in both inorganic forms such as ferrous sulfate and organic forms such as hemoglobin in red meats. Its absorption and thus its bioavailability is complex and highly variable.
Deficiency: Clinical signs of Fe deficiency in dogs include suboptimal hemoglobin levels and hematocrit values. Other signs include poor growth rates, pale coloring of mucosal membranes, lethargy, weakness, and diarrhea. There is no known toxicity from dietary sources of Fe.
Requirements: The dietary requirements for Fe are highly variable and are dependent on a great many factors. General requirements for puppies can be estimated to be 22 mg Fe per 1,000 kcal ME (metabolizable energy). For adult dogs the requirement is 0.5 mg Fe·kg BW-1·d-1.
Copper: The bodies of dogs contain a very small amount of copper (a metal denoted by the symbol Cu). The majority of Cu in the body is found in the liver bound to a protein rich in sulfur groups called metallothionein. The primary role of copper in the body is as a cofactor for enzymes that catalyze oxidation reactions. These enzymes play a role in the formation of connective tissue, the synthesis of melanin (a pigment that helps maintain hair color) from tyrosine, and the synthesis of myelin (a conductive coating around nervous tissues that maintains nervous system function). It is also an important cofactor for the proper functioning of a number of enzymes that provide a defense against oxidative damage.
Copper is not found in high concentrations in many of the ingredients used in the manufacture of pet foods. The bran and germ portions of grains and animal liver are reasonable sources of Cu. Most pet foods are supplemented with various forms of Cu.
Deficiencies and Toxicity: There are very few reports on the adverse effects of Cu deficiencies in puppies or adult dogs. However, there is considerable evidence for Cu toxicosis in several breeds of dogs with suspected or proven hereditary defect resulting in the excessive accumulation of Cu in the liver, including Bedlington terriers, West Highland white terriers, and Skye terriers. This can result in permanent or fatal liver and brain damage. The disease has been studied predominantly in Bedlington terriers. Liver accumulation of Cu may reach greater then ten times the level in unaffected dogs. There are treatments that involve feeding either diets low in Cu concentration, or the use of drug therapy to sequester the excess copper and aid in its excretion.
Requirements: It is suggested that the dietary RA (recommended allowance) for a growing puppy is 2.7 mg Cu per 1,000 kcal ME. Little data is available for adult dogs but extrapolation from the data on puppies and lactating bitches suggests a diet containing 1.5 mg Cu per 1,000 kcal ME would provide a sufficient supply for a 15 kg adult dog consuming 1,000 kcal ME·d-1. During gestation a daily allowance of 0.16 mg Cu·kg BW-1·d-1 is suggested, and during lactation, 0.70 mg Cu·kg BW-1·d-1, assuming 30% bioavailability in both cases.
Manganese: Manganese, denoted Mn, is present in animal tissues in very low concentrations. It functions mainly as a structural component of metalloenzymes (enzymes that rely on metals as a cofactor), or more frequently as an activator of other metal cofactors in a variety of enzymes. Mn is also known to be important for normal bone development and neurologic function.
Pet food ingredients that contain reasonable quantities of Mn include cereal grains, animal, poultry, and seafood products. Nonetheless, supplementary Mn is frequently added to petfoods, mainly in the form of inorganic salts, and as proteinates.
Deficiencies: There are no clinical or experimental studies on Mn deficiency in dogs. However, from studies in other mammals, it appears that Mn deficiency is manifested in newborn or growing animals by retarded bone growth and shortening and bowing of the forelegs, and in adult animals by lameness, and or enlarged joints, poor locomotor function, and ataxia (loss of full control of bodily movements) of all of which appear to be the result of inhibition of new bone cell growth.
Requirements: It is suggested that for safety purposes, a daily intake of 35 µg Mn·kg BW-1·d-1 be maintained for growing puppies.
Losses
In contrast to the relatively minor effect of processing on the bioavailability of proteins, carbohydrates, fats, and minerals, processing can have a major effect on the vitamins present in the final diet. This is especially evident for those vitamins that have been added to the diet in pure form or as a concentrate. Although it is not our intention to discuss the formulation and manufacture of commercial petfoods, the potential losses of vitamins that occur during manufacture and storage should be appreciated.
Depending on the vitamin, different approaches have been used to reduce the losses from processing and storage. Changing the chemical form of the vitamin to a more stable compound has been used with some vitamins. One example, is using a salt, as in the case of thiamine mononitrate instead of the the free form, thiamin. Incorporation of the vitamin in a beadlet is another approach to greater stability and enhances the dispersion of the vitamin in the feed mixture. Typically the vitamin is emulsified with gelatin, starch and glycerin and sprayed to form beadlets that are subsequently coated with starch. Further treatment of the beadlet, for example by heat to form a hardened bead (often referred to as a cross-linked beadlet) gives enhanced protection of the vitamin during processing. The majority of the vitamin A used by pet food manufacturers in the United States is in the form of cross-linked beadlets. For many of the vitamins of the B complex, spray drying is used to enhance the stability and form a free-flowing powder.
The inactivation of almost all vitamins that occurs in the preparation of extruded foods and canned foods is directly related to the temperature and duration of the processes and the presence of free metals. Losses on drying and enrobing (adding fat or digest to the exterior of the dried extruded product) are similarly time and temperature dependent. During storage the moisture content, temperature, pH, and reactive metal ions effect the rate of vitamin loss. Having metals in less reactive form such as chelates or as salts can decrease the loss of many vitamins. Protection of fats in the diet from oxidation is an important factoring in reducing the formation of free radicals which can destroy many vitamins. Some foods contain synthetic preservatives, BHT (butylated hydroxytoluene) for example, which have been used to scavenge free radicals. Recently this practice has been supplanted by use of natural preservatives such as mixed tocopherols (vitamin E) and/or rosemary extract, which also effectively scavenge free radicals.
Typical, as well as low and high recoveries, of vitamins incurred in the extrusion and drying processes of expanded foods have been summarized in Table 1. The recoveries of vitamins in these processes vary widely; for some vitamins such as nicotinic acid, recoveries are generally good, whereas for others such as vitamin A they are most consistently lower. Table 1 illustrates that the general trend is lower recovery rates for fat soluble vitamins (vitamin A, D3, etc.) than for B vitamins.
See Table 1 at the end of this discussion for information on vitamin loss and recovery.
Supplement to The ABC’s of Vitamins A, B, C…
An Explanation of the Vitamin Mineral Pack in Most Pet Foods
FOR CATS
by: Mark E. Rogers
The overall biochemical activity and actions of vitamins and minerals are no different for cats then for dogs. The main differences are in the symptoms and effects of deficiencies and their requirements.
Vitamin A: Cats, unlike dogs and humans, cannot convert carotenoids into usable forms of vitamin A. Therefore, carotenoid sources of vitamin A precursors from plants are of no value to cats. Cats require retinol or retinal. As with dogs, retinoic acid cannot carry out the functional roles for reproduction and vision, but are functional for all other vitamin A activity.
Deficiency: Clinical signs of deficiency include conjunctivitis, xerosis with keratitis (drying and inflammation of the cornea) and vascularization of the cornea, negative response to light, slow pupillary response to changes in light, and cataract formation. Signs of deficiency can be similar to taurine deficiency.
Requirements: The NRC recommendation for growing kittens is 1 mg retinol·kg-1 diet. This is equivalent to 200 µg retinol/1,000 kcal ME (metabolizable energy) and is also recommended as the AI (adequate intake) for growth in kittens and maintenance in cats. For lactating and pregnant queens, 400 µg retinol/1,000 kcal ME is proposed as an AI.
Toxicity: Naturally occurring cases of hypervitaminosis are almost exclusively the result of overfeeding diets high in, or exclusively composed of, liver, especially fish liver. Excessive supplementation of vitamin A is unnecessary and dangerous. Because vitamin A is a fat soluble vitamin, excess retinol and its derivatives are cleared slowly from the animal.
Thiamin: Three stages of thiamin (B1) deficiency have been described. Stage 1 is characterized by anorexia. Stage 2, by the appearance of neurological signs including those involving posture and short tonic convulsive seizures; and the third or terminal stage by progressive weakness, prostration, and death. The first stage occurs in 1-2 weeks of consumption of a deficient diet and may be accompanied by emesis. Remission is rapid on feeding a diet containing sufficient thiamin.
Requirements: Thiamin concentrations of 5 mg·kg-1 diet for all life stages and conditions including pregnancy and lactation. Since thiamin requirements are linked to energy consumption, this requirement may increase when diets containing a low amount of fat as a proportion of total energy contribution are fed. There are no reports of hypervitaminosis from oral thiamin intake.
Riboflavin: In acute riboflavin (B2) deficiency, cats exhibit anorexia, loss of body weight, and periauricular alopecia with epidermal atrophy (hair loss between eyes and base of ears with skin degradation). Chronic deficiency results in cataracts, fatty livers, and testicular atrophy.
Requirements: Requirements are met with 4 mg·kg-1 diet, or 800 µg/1,000 kcal diet for all life stages and conditions. No toxicity has been reported for oral dosing of riboflavin.
Niacin: (B3) Signs of deficiency include anorexia, elevated body temperature, and fiery red tongue with ulceration. Young cats fed niacin deficient diets ceased growing after 10-15 days, lost weight and died in 15-50 days.
Requirements: Cats are unable to convert tryptophan to nicotinic acid and therefore must derive their entire requirement for niacin from their diet. The NRC proposes a minimum requirement of 40 mg nicotinic acid·kg-1 diet, or 8 mg/1,000 kcal ME. Niacin contribution from cereals should be considered to have a bioavailability of 30% or less or should be disregarded entirely. There are no reports of toxicity for excessive intake of niacin in cats.
Pantothenic Acid: (B5) The primary sign of deficiency is failure to grow.
Requirements: A dietary requirement of 1.25 mg/1,000 kcal ME is sufficient for an adult cat at maintenance and growing kittens. There are no reports of toxicity from pantothenic acid in cats.
Vitamin B6: Signs of deficiency include growth depression, microcytic hypochromic anemia (abnormally small red blood cells containing low concentrations of hemoglobin), convulsive seizures, and kidney lesions in cats fed B6 deficient diets. The lesions are from calcium oxalate crystal build up in the kidneys.
Requirements: A minimal pyridoxine requirement of 2 mg·kg-1 diet or 500 µg/1,000 kcal ME is proposed for cats in all life stages and conditions. There is no known toxicity to B6.
Cobalamin (vitamin B12): Weaned kittens given a B12 deficient diet grew normally for 3-4 months after which time there was a cessation of growth followed by body weight loss at an accelerating rate until supplementation was started. Supplementation resulted in immediate, steady weight gain. Deficient cats also exhibit hair coat that appears to be wet.
Requirements: A concentration of 20 µg·kg-1 diet or 4.5 µg/1,000 kcal ME is sufficient for all life stages and conditions. There is no known B12 toxicity.
Folic Acid: Long term folate deficiency in cats is associated with a decrease in growth and an increase in plasma iron concentration. A concentration of 0.6 mg folic acid·kg-1 diet is sufficient for all life stages and conditions. Extremely high concentrations of folate do not result in toxic effects.
Biotin: Clinical signs of biotin deficiency in cats include accumulation of nasal, salivary, and eye secretions, progressive alopecia, dermatitis, and weight loss. Unless a diet very high in raw egg white is fed, supplementation should be unnecessary. A concentration of 60 µg biotin·kg -1 diet should be sufficient for animals in all life stages and conditions. Toxicity is not reported even at very high dosing.
Choline: At suboptimal concentrations of dietary choline body weight gain in kittens is depressed. A concentration of 2.4 g choline·kg-1 diet is sufficient for growing kittens, and is recommended for cats in all life stages and conditions. Toxicity is not an issue.
Vitamin C: In cats & dogs, unlike humans, there is no requirement for vitamin C supplementation due to their ability to meet their dietary requirements by synthesis from glucose. However, under conditions of high activity, stress, injury, or illness, supplementation is likely to be beneficial.
Vitamin D: Early signs of deficiency include reluctance to move, reduction in grooming, reduction in food intake, body weight loss, and eventually severe rickets. Early indications can also include the appearance of a short stilted gait and progress to broad based gait and paralysis in severe cases.
Requirements: The recommended dose for growing kittens and during lactation and pregnancy is 6.25 µg cholecalciferol (D3)·kg-1 diet which is equivalent to 1.4 µg cholecalciferol/1,000 kcal ME. This dosing is sufficient for adult cats at maintenance. Overdosing is uncommon and usually results from consumption of rat poison, or overfeeding liver, especially tuna liver.
Vitamin E: Signs of deficiency include depression, anorexia, and hypersensitivity to pressure on the underside of the abdomen on physical examination. Internal examination also reveals an orange coloration of adipose (fat storage) tissues.
Requirements: Due to the higher fat concentration in cat diets, they are more susceptible to vitamin E deficiency then dogs. Because of the relationship between quantity of consumed PUFAs (polyunsaturated fatty acids) and vitamin E requirements, it is not possible to give a single vitamin E requirement for all diets. Diets higher fat content especially PUFAs require more vitamin E. The NRC suggested 30 mg of α-tocopherol (vitamin E)·kg-1 diet for diets low in fat (< 10% of the dry weight) assuming adequate selenium content (0.12 mg Selenium·kg-1 diet). For diets higher in PUFAs especially those rich in fish oils, the recommendation is 120 mg α-tocopherol·kg-1 diet. A ratio of 0.6 mg α-tocopherol/gram of PUFA should be maintained. Vitamin E is considered the least toxic of the fat soluble vitamins and and no SUL (safe upper limit) has been established.
Minerals
Despite the simple structures of minerals compared to vitamins, mineral requirements, deficiencies, and toxicities are often more difficult to asses and define.
Copper (Cu): Copper has an interesting activity in cats that appears to be quite different than for dogs. There appears to be a direct relationship between sufficient systemic copper concentrations and the conception time in queens exposed to toms. This review does not allow for elaboration on the subject but the interested reader is encouraged to pursue their interest in peer reviewed scientific literature on the relationship between copper and conception time in cats.
Deficiency: The only outward sign of copper deficiency is decreased weight gain. Sampling of liver tissue will also reveal low Cu concentrations. Copper deficiency in queens can also lead to an increase in the time of conception after exposure to a tom.
Requirements: The RA (recommended allowance) for growing kittens is 2.1 mg Cu/1,000kcal ME. This provides a daily intake of 0.47 mg Cu·kg BW-1d-1. For adult cats (especially queens of breeding age) The AI (adequate intake) of Cu is 1.2 mg Cu/1,000 kcal ME, or 0.075 mgCu·kg BW-1d-1. The AI for gestating or lactating queens is 2.2 mg Cu/1,000 kcal ME. Since there are no data on copper toxicity in cats and the above values are reasonable close, a diet providing 2.2 - 2.5 mg Cu/1,000 kcal ME should be considered safe and sufficient for cats in all life stages and conditions.
Zinc (Zn): There is little or no data on Zn deficiency in cats and kittens. One report indicates skin lesions in kittens fed a Zn deficient diet. Based on the importance of Zn in mammalian biochemistry, it is safe to assume that adequate intake of Zn is critical to the health of cats. The NRC recommends a diet containing 15 mg Zn/1,000 kcal ME for gestating and lactating queens. This provides 2 mg Zn·kg BW-1d-1 which should be adequate for cats in all life stages and conditions. One report suggests that a diet containing 600 mg Zn·kg BW-1d-1 showed no adverse effects so this can be assumed to be a SUL for cats.
Iron (Fe): Signs of deficiency are similar to dogs-pale mucus membranes, lethargy, weakness, weight loss or lack of weight gain.
Requirements: For kittens 20 mg Fe/1,000 kcal ME, and adults 1.25 mg Fe·kgBW-1d-1.
Manganese (Mn): There is little information on Mn requirements in cats and kittens. However, the NRC’s best estimate is a diet containing 2mg Mn/1,000 kcal ME should provide sufficient concentrations of this important metal for cats in all life stages and conditions, assuming the Mn source is as a proteinate or other highly bioavailable source.
References:
1. Linus Pauling Institute, Oregon State University
2. Nutrient Requirements of Dogs and Cats, National Research Council, The National Academic Press 2006.
3. Small Animal Clinical Nutrition, Hand, M.S., Thatcher, C.D., Remillard, R.L., Roudebush, P., Novotny, B.J., Eds., Mark Morris Institute, 5th Edition, 2010.
