23 Nov 2015
Lisa Weeth
Job Title
Figure 2. Supplementation may help prevent age-related cognitive function decline in otherwise healthy geriatric dogs and cats.
Enzymatic and non-enzymatic antioxidants may help cats and dogs, but there is debate about the correct blend of antioxidants and when supplementation should start.
Response varies by species, disease state and compound being used. Studies in older dogs receiving a combination of dietary antioxidants showed better retention of learned behaviours, while dogs and cats with liver disease may have improved antioxidant status when given a single agent to support endogenous antioxidant systems.
Increased intake of a variety of antioxidant compounds has also been proposed as a means of preventing tumorigenesis, though empirical evidence has been contradictory. Overall, evidence shows certain compounds may help maintain health and well-being and manage certain disease states.
Oxidation reactions occur in the mitochondria during normal cellular metabolism.
The transfer of electrons from one chemical species to another can form reactive oxygen species (ROS) in the cell. They have unpaired electrons that are attracted to surrounding lipids, proteins and nucleic acids in an attempt to stabilise their structures.
Antioxidant supplementation, on top of what is provided in the diet, has been suggested as a way to prevent or delay chronic disease progression in dogs and cats.
Enzymatic and non-enzymatic antioxidant systems exist in the cell to stop ROS-induced injury and to slow or prevent cellular damage (Figure 1).
Enzymatic systems include superoxide dismutase (SOD; copper-zinc or manganese), catalase and glutathione peroxidase. Non-enzymatic antioxidants include vitamin C, vitamin E, carotenoids (for example, b-carotene and lycopene), thiol antioxidants (for example, glutathione, lipoic acid and S-adenosylmethionine; SAMe) and flavonoids (polyphenolic compounds).
Both forms of antioxidant work to prevent free radical damage to the cellular structure, but in different ways. Enzymatic antioxidants convert the ROS to less reactive compounds, such as water and oxygen, while non-enzymatic antioxidants donate an electron to “quench” the ROS.
The balance between ROS formation and antioxidant capacity of the cell depends on the antioxidant systems’ demand and the dietary intake of all antioxidant compounds.
Healthy dogs and cats eating complete and balanced diets do not need antioxidant supplementation, though at certain life stages (geriatrics) and with certain conditions (for example, liver disease) the minimum requirements may not meet whole body antioxidant demand.
Total body antioxidant status relies on indirect indicators of oxidative stress (for example, isoprostane and malondialdehyde in urine) and antioxidant levels (for example, a-tocopherol and glutathione peroxidase in lymphocytes).
These diagnostic tests are not routinely available outside academic or industry settings; general practice and non-academic referral veterinary surgeons are often unsure of when to recommend supplementation.
Studies in older dogs receiving a mixed supplementation also showed better retention of learned behaviours compared to age-matched controls5, but there is debate about the “correct” blend of antioxidants to see these effects.
Many formulations of dietary antioxidants are available and are generally considered safe, though safety and efficacy data for most single agent and combination antioxidant blends are lacking.
Supplementation should be used with caution in cats as certain compounds that appear safe for dogs and humans may be toxic or potentiate toxic reactions (for example, lipoic acid6).
The liver is integral in the detoxification of protein metabolites, production of serum albumin and clotting factors, storage of vitamins and minerals, and metabolism of ingested phytochemicals and drugs.
Chronic hepatitis increases ROS production in the liver7 and can perpetuate oxidative damage. Certain compounds are increasingly being used as hepatoprotectants with antioxidant function (Figure 3):
Reactive oxygen species cause cellular damage, have negative inotropic effects and perpetuate inflammatory responses in animals with heart disease.
Dogs with congestive heart failure due to dilated cardiomyopathy or chronic valvular disease have more biomarkers of oxidative stress and damage and low circulating levels of glutathione and vitamin E12,13.
There are no published interventional studies about antioxidant supplementation helping this group of patients.
Excess ROS in the cell (above its antioxidant capacity) can damage membrane lipids, cause single or double-
stranded DNA breaks, modify protein structures and cross-link DNA. It can lead to arrest or induction of transcription, replication errors and genomic instability.
Literature about antioxidant supplementation and cancer incidence in humans shows mixed results. Certain antioxidants lower incidences, but others may increase the risk of specific cancer and have been linked to higher mortality:
l Selenium has been evaluated in dogs as an interventional therapy. Higher intake in older male dogs without a history of prostatic disease showed a drop in DNA damage to prostatic tissue, compared to non-supplemented controls, and higher apoptosis of prostatic cells25.
Companion dogs and cats are increasingly viewed as integral members of the family and their nutritional needs have changed from meeting minimal requirements to optimising intakes for long-term health and well-being.
Good evidence exists for incorporating antioxidants into everyday practice for older animals and those with liver or heart disease. Antioxidants may also help prevent cancer, but once cancer has been diagnosed avoid both enzymatic and non-enzymatic supplements (including flavonoids) to prevent inadvertently protecting cancer cells during radiation or chemotherapy.
Antioxidants may also benefit canine athletes (to balance the increased oxidative stress during periods of strenuous activity) and other chronic inflammatory conditions (such as diabetes mellitus, inflammatory bowel disease or arthritis), though interventional studies are largely lacking.
Antioxidant supplementation may promote health and well-being and help manage certain diseases in companion dogs and cats. Their use should be considered by veterinary surgeons.
