Introduction

Nutritional and dietary supplements, often called nutraceuticals as an amalgamation of the terms nutritional and pharmaceutical, have continued to develop into a billion dollar industry since the companion animal supplement market emerged in the 1990s. This trend reflects a shift in the mindset of manufacturers, veterinarians and animal owners: rather than relying purely on medicinal products for the prevention and treatment of diseases, nutritional alternatives for both disease management and health promotion are readily available both in conventional pet foods and as individual supplements.

Definitions

The American Veterinary Medical Association (AVMA) defines nutraceuticals as "...micronutrients, macronutrients and other nutritional supplements" used as therapeutic agents. The United States National Research Council (NRC) prefers the term Animal Dietary supplement, defined as: "A substance for oral consumption by horses, dogs, or cats, whether in/on feed or offered separately, intended for specific nutritive, medical, or other benefit to the animal by means other than provision of nutrients recognized as essential or by provision of essential nutrients for intended effect on the animal beyond normal nutritional needs, but not including legally defined drugs." Regardless of the name, regulatory oversight of dietary animal supplements is limited in the US. The EU commission provides more specific regulations to establish safety and efficacy verification. As scientific evidence for dietary supplements emerge, several supplements are readily available and routinely used in companion animal nutrition and veterinary care.

A discussion of all available nutraceuticals is beyond the scope of this presentation; however, common compounds will be highlighted. Information can be found in many places including the Alternative Medicine Foundation (http://www.AMFoundation.org). The top categories of dietary supplements include chondroprotectants, anti-oxidants, fatty acids with anti-inflammatory ability, and "ecotherapy" using prebiotics and probiotics.

Anti-oxidants

Anti-oxidants refer to a heterogeneous group of compounds that prevent free-radical damage to cell membranes, proteins and DNA. They may be beneficial with inflammatory diseases, aging, and certain cancers. While many studies failed to document benefit of a single anti-oxidant, more recent evidence suggests that utilizing a balanced, mixed source of antioxidants may provide benefit with certain diseases. A PubMed search on "antioxidants" and "controlled clinical trial or clinical trial" returned 28 citations. Anti-oxidant treatment improved cardiac functional parameters in dogs with chronic valvular disease, decreased cataract formation when applied topically, increased immune responsiveness to vaccination in young dogs, increased cognition in aged beagles, increased immune-responsiveness in healthy geriatric dogs, decreased oxidative stress of acetaminophen on feline erythrocytes, and improved joint function and pain in dogs with arthritis; however, they failed to ameliorate muscle damage in sled dogs. Antioxidants may be beneficial with certain types of cancer, but controlled studies are lacking in dogs and cats. Common antioxidants used as supplements in food or direct oral intake include vitamin E and C, bioflavonoids, milk thistle, S-adenosyl methionine (SAMe), lipoic acid. While all are available in supplement form, many are included in diets or veterinary specific formulations to treat disease.

Milk Thistle

Milk thistle is a European medicinal plant that contains silimarin (sylmarin, silibinin, sylibin). It is used with hepatobiliary disease because of its anti-oxidant activity, it increases hepatic protein synthesis, stabilizes hepatocellular membranes, chelates iron, and alters cholesterol metabolism. There are no published controlled clinical studies in dogs and cats. One experimental study documented anti-toxic effects of silibinin against deathcap fungus (Amanita) in dogs. Recommended dosages are 50–250 mg/day or 20–50 mg/kg/day.

SAMe

S-adenosyl methionine is a nucleotide-like substance that is a critical intermediate in 3 major metabolic pathways in the liver: transsulfuration, aminopropylation, and transmethylation. Studies demonstrate protective effects in the liver including improved antioxidant status, cell repair and regeneration, reduced fibrosis, and improved cholestasis. Supplementation at 20 mg/kg/day orally in dogs and cats appears safe.

Lipoic Acid

Lipoic acid is a potent mitochondrial antioxidant available as a dietary supplement and is in some pet foods designed to improve or maintain cognition. In dogs doses of 1–5 mg/kg/day appears safe, however toxic signs have been observed in cats at these level.

Chondroprotectants

Glucosamine and Chondroitin Sulfate

There is evidence of efficacy from experimental studies inducing arthritis and synovitis and from studies utilizing biomarkers of arthritis. In a study by Moreau, et al., evaluating client-owned dogs with arthritis by gait analysis, neither owners nor veterinarians appreciated significant improvement with the nutraceutical compound, but improvement was observed with meloxicam and carprofen. In another study by Gunn-Moore and Slenoy, N-acetyl-glucosamine was not found to be better for cats with idiopathic cystitis when compared with placebo. Many pet foods contain these compounds and are marketed to support joint health; however, dietary levels are substantially lower than recommended therapeutic dosages.

Methylsulfonylmethane (MSM)

Methylsulfonylmethane (MSM, or dimethylsulfone) is an organic sulfur compound belonging to a class of chemicals known as sulfones. It occurs naturally in some primitive plants and is present in small amounts in many foods and beverages. MSM is commonly used (often in combination with glucosamine and/or chondroitin) for helping to treat or prevent osteoarthritis. Retail sales of MSM as a single ingredient in dietary supplements amounted to $115 million in 2003. Yet, no scientific studies demonstrating efficacy in dogs are found in the scientific literature although several studies in people suggest mild to moderate benefit.

Omega-3 Fatty Acids

Omega-3 fatty acids are derived from marine life and possess anti-inflammatory and anti-neoplastic properties. A PubMed search returned 14 citations. Omega 3 fatty acids have been shown to be beneficial in dogs with atopic dermatitis, pruritis, lymphoma, arthritis, and chronic valvular disease. Experimentally, omega 3 fatty acids are associated with decreased proteinuria in dogs with glomerular proteinuria and with sustaining glomerular filtration rate in dogs with induced chronic renal failure. Recently, the National Research Council has recognized omega-3 fatty acids as an essential nutrient for dogs and cats.

Ecotherapy

Prebiotics

Prebiotics refer to resistant starches and fibers that are resistant to digestion by mammalian gut enzymes and select for enteric bacterial that can utilize them as primary fermentation substrates. Various fibers and resistant starches may have deferential effects on the gut microbial population. In other words, not all prebiotics act the same. Fructooligosaccharide (FOS) is the preferred microbial substrate for Lactobacillus spp., Bifidobacter, and Enterococcus spp. Mannan oligosaccharide (MOS) is a yeast wall extract that mimics gut bacterial binding sites. Supplementation with both has been shown to increase organisms beneficial to gut health while reducing fecal pathogens including E.coli and Clostridium sp.and Salmonella. In addition, immunomodulatory function and ammonia trapping have resulted in use in diets promoting immune health and renal disorders.

Probiotics

Probiotics refer to live microbial cultures, typically Lactobacillus spp., Bifidobacter, or Enterococcus spp. They have been recommended for 'normalizing' the gastrointestinal tract in patients with diarrhea, inflammatory bowel disease, and food allergies, but have also been recommended for use with atopic dermatitis, recurrent bacterial urinary tract infections, and chronic antimicrobial administration. Variable results have been found in published studies. Reduction in duration of diarrhea and improvement in canine inflammatory bowel disease scoring when compared with placebo appear to be most consistent. Recently, a probiotic (Azodyl) has become available for companion animals with chronic renal failure and marketed as 'enteric dialysis'. The limited data available demonstrate only a slight reduction in blood urea nitrogen and creatinine. This concept is similar to 'nitrogen trapping' utilizing dietary prebiotics. Other products specific to the veterinary market include Prostora Max from Iams Co. and FortiFlora by Nestle-Purina. Both have extensive safety and limited efficacy data available.

Evaluating Nutraceuticals

Because dietary animal supplements are poorly regulated in many countries, veterinarians must use caution when selecting products. It is important to assess quality, safety and efficacy, although this is often difficult. Recent studies have suggested many products do not contain the active ingredients as stated or contain impurities. Using products from a reputable manufacture that participates in voluntary reporting is a first step. Several websites exist that may help a clinician investigate specific nutraceuticals:

1.  http://www.quackwatch.com

2.  http://www.herbalgram.org

3.  http://nccam.nih.gov

4.  http://www.navigator.tufts.edu/index.html (VIN editor: link not accessible on 11/17/11)

5.  http://www.consumerlab.com

6.  http://www.biovalidity.com

7.  http://www.acvn.org

References

Upon request to: ckirk4@utk.edu