Fish oil has been used in humans for treatment of rheumatism since at least 1783, when the London Medical Journal reported about it. But it wasn’t until 1914, when August Krogh and his wife visited Greenland Eskimos and studied their dietary habits, when the subject was reopened.
Subsequently, Heinbecker also studied the metabolism of Eskimos and referred to the work of the Kroghs’, indicating that Eskimos eat almost only flesh and that all animals in the North are eaten by Eskimos but they depend mainly on those found in the sea.
Then Danish researchers in the 1970s followed up on these early observations. In a study, it was indicated that the Eskimos are probably the most carnivorous people on earth, with most of them subsisting primarily on meat and fish. The rarity of ischemic heart disease in the Eskimo population was later attributed to the antiatherogenic effect of marine-based oils enriched in Omega-3 fatty acids that were consumed.
Since these early observations, numerous studies and clinical investigations have been conducted on the metabolism of Omega-3 are polyunsaturated fatty acids (PUFAs) in domestic animals and humans as well as in cell cultures. The Omega-3 fatty acids, most notably EPA and DHA, have been found to have important health benefits, including cardioprotective effects, as well as roles in neurologic development and the inflammatory response.
Additional beneficial effects of Omega-3 fatty acids have been observed for hypertension, renal diseases, arthritis, autoimmune disorders, gastrointestinal diseases and cancer. Consequently, recommendations have been made for the general public to increase their dietary intake of fish rich in these compounds, as well as that of domestic animals.
Because of a shift in recent years to diets that contain increased amounts of Omega-6 fatty acids in humans and domestic animals, the importance of increasing the dietary intake of Omega-3 to help balance overall fatty acid effects has become apparent. Therefore, physiologic functions of Omega-3 fatty acids and mechanisms involved in reducing inflammation and influencing gene expression have an impact on companion animal and human health.
Because inflammation provides a basis for many chronic health imbalances, appropriate dietary amounts of Omega-3 fatty acids, such as DHA and EPA, are currently believed to be essential for maintenance of numerous organ and tissue functions. Such functions include health of the skin, kidneys, gastrointestinal tract, neural tissues, cardiovascular system, bones, promotion of cognitive function, immune function and the inflammatory response and alterations in nutrient metabolism that can lead to diabetes mellitus and several cancers.
Using Fish Oils for Clinical Disorders in Dogs
Studies on the use of fatty acids in fish oil for dogs have included those involving dermatologic, cardiovascular, renal, lipid and metabolic disorders as well as osteoarthritis, cognitive function and cancer.
Inflammatory Skin Disorders
Investigators in one examined the effects of fish oil on pruritic skin disease in dogs. Sixteen dogs with idiopathic pruritis, confirmed atopy, or flea allergy were evaluated. A crossover design with a 3-week washout period was used.
Each dog was orally administered an Omega-3 fatty acid capsule containing 180 mg of EPA and 120 mg of DHA / 4.55 kg (180 mg of EPA and 120 mg of DHA / 10 lb) or a control capsule containing 570 mg of linoleic acid and 50 mg of γ-linolenic acid / 4.55 kg (570 mg of linoleic acid and 50 mg of γ-linolenic acid / 10 lb) daily for 6 weeks.
Dogs receiving the DHA and EPA had sig-nificant improvements in pruritis, self-trauma and coat character over time. Compared with the control treatment, the fish oil DHA and EPA capsule significantly improved pruritis, alopecia and coat character. This study indicated the effectiveness of fish oil as an alternative anti-inflammatory for pruritic skin disease in dogs. Before this, dosages at half the amount used in this study had been tried but had yielded variable results.
Dogs with heart failure have low plasma concentrations of EPA, regardless of the underlying disease. Thus, administration of Omega3 fatty acids may help mitigate this condition.
In one study, investigators evaluated 28 dogs with stable chronic heart failure secondary to idiopathic dilated cardiomyopathy. Dogs received fish oil (ethyl ester capsules) or a placebo (corn oil ethyl esters).
Approximately 27 mg of EPA / kg/d (12.3 mg of EPA / lb / d) and 18 mg of DHA / kg / d (8.2 mg of DHA / lb / d) were administered as ethyl esters. Compared with results for the placebo, fish oil treatment resulted in a greater reduction in PGE2, an index of reduced inflammation.
Fish oil treatment also significantly decreased IL-1 concentrations and improved cachexia, compared with results for the placebo. Reductions in IL-1 concentration could be used to predict survival time, which suggested that anticytokine strategies may benefit canine patients with heart failure.
In several studies in other species, Omega-3 fatty acids have also been found to decrease production of the inflammatory cytokines tumor necrosis factor and IL-1, which are often increased in chronic heart failure. Thus, Omega-3 LC fatty acids may also benefit dogs with early chronic valvular diseases.
Additionally, Omega-3 LC fatty acids have been found to reduce vulnerability to atrial fibrillation and to modify atrial structure in dogs with experimentally induced cardiac pacing.
Seven control dogs (no cardiac pacing) and 24 dogs subjected to atrioventricular pacing for 2 weeks were assigned to oral treatment with a placebo or Omega-3 fatty acids (1 g of EPA and DHA / d).
Dogs receiving the fish oil had less inducibility of atrial fibrillation than did the dogs receiving the placebo. Dogs receiving the fish oil also had significantly less local slowing of conduction and conduction heterogeneity and a significantly smaller increase in atrial MMP-9 activity and collagen type I and III messenger RNA expression, compared with results for dogs receiving the placebo.
Additionally, an open-label study (i.e., no control group) in dogs was conducted to assess whether Omega-3 fatty acids prevent vagally induced atrial fibrillation and influence expression of CXs in atrial tissue. Because CX40 and CX43 proteins are primary components of atrial gap junctions, changes in spatial organization of gap junctions or cellular amounts of cardiac CXs are associated with arrhythmogenesis.
Eight dogs were given fish oil daily (1.2 g of EPA and DHA) for 14 days. Eight control dogs had reproducibly induced atrial fibrillation and then were reevaluated after IV administration of fish oil.
That same study also found that oral treatment with fish oils increased atrial Omega-3 fatty acid concentrations, reduced vulnerability to induction of atrial fibrillation and decreased expression of CX40 and CX43 in atrial tissues. These findings support the antiarrhythmic properties of Omega-3 fatty acids.
In addition to helping reduce cardiac arrhythmias, fatty acids in fish oil for dogs reduce cachexia and improve food intake in some dogs with chronic heart failure-induced anorexia.
This latter finding may be important because many dogs with chronic valvular diseases and dilated cardiomyopathy have arrhythmias. There often are no outward signs of cardiac arrhythmias in dogs, however they may result in sudden death. Thus, the use of Omega-3 fatty acids may be beneficial prior to the diagnosis of chronic heart failure.
In dogs with experimentally induced CKD, administration of Omega-3 fatty acids reduced proteinuria, prevented glomerular hypertension and decreased the production of proinflammatory eicosanoids.
Twenty-one dogs were subjected to partial nephrectomy (removal of 15 / 16 of the kidneys) and allocated into 3 groups. The dogs were allowed to recover from the nephrectomy and then fed 1 of 3 diets containing predominantly fish oil, safflower oil or beef tallow as a fat source (16.8% total fat) for 20 months.
The fish oil diet contained 2.28% EPA and 2.1% DHA. This amounted to approximately 760 mg of EPA and DHA / kg of BW0.75, which is more than 2 times the NRC safe upper limit.
Dogs fed the safflower oil diet (i.e., contained high amounts of Omega-6 fatty acids) had increased glomerular enlargement and mean glomerular capillary pressure, compared with results for the other groups.
In the fish oil group, mean clearance of exogenous creatinine was the highest and urine protein-to-creatinine ratio was the lowest. The extent of mesangial matrix expansion, glomerulosclerosis, and renal interstitial cellular infiltrates was similar in the beef tallow and safflower oil groups but was significantly lower in the fish oil group.
Survival rate of the dogs was similar in the fish oil and beef tallow groups, but 4 of 7 dogs in the safflower group had to be euthanized.
An additional study conducted with this method has revealed that administration of Omega-3 fatty acids or antioxidants is renoprotective. Although the recommended dietary amounts of Omega-3 LC fatty acids for dogs with CKD have not been determined, dietary amounts in these studies in dogs ranged from 0.41% to 4.71% DM.
However, with the content of Omega-3 LC PUFAs at 0.41% DM and a total Omega-6-to-total Omega-3 ratio of 5:1, reductions in glomerular hypertension and proinflammatory eicosanoids were evident.
Currently, dietary inclusion of Omega-3 fatty acids ranging from 0.4% to 2.5% DM has been recommended for dogs with CKD.
Osteoarthritis and Joint Health
Inflammatory pathways play a critical role in chondrocyte response to injury and subsequent repair or the development of arthritis. One possibility for providing relief for osteoarthritis is via reducing PGE2 production subsequent to providing dietary Omega-3 fatty acids, which compete with arachidonic acid as substrates for COX and LOX enzymes.
Reduction of thromboxane A2 and LTB4 production is also possible by use of dietary Omega-3 fatty acids, which may also suppress proinflammatory mediators IL-1, IL-2 and tumor necrosis factor in cartilage.
In a study in dogs, investigators evaluated the HJC status by use of synovial tissue and subchondral bone from the femoral head of 12 clinically normal dogs and 18 dogs undergoing total hip replacement because of osteoarthritis of the hip joint. Significantly more COX-2 protein was detected in the HJC of osteoarthritic hip joints than in clinically normal hip joints.
There was no significant difference in concentrations of COX-1 or LOX protein, although the amount of LOX protein was slightly but not significantly increased. The PGE2 concentrations in clinically normal and osteoarthritic HJCs were similar, but the LTB4 concentration in osteoarthritic HJCs was significantly greater than in the clinically normal HJCs.
Also, significantly more COX-1, COX-2 and 5-LOX protein was detected in femoral head tissue of the osteoarthritic joints, compared with concentrations in femoral head tissue of the clinically normal joints. There were no differences in PGE2 or LTB4 concentrations in clinically normal and osteoarthritic femoral head tissue.
Analysis of these data suggests that COX-2 and 5-LOX are appropriate targets for the management of signs of pain associated with naturally occurring osteoarthritis in dogs and that the Omega-3 fatty acids may modify the activities of these enzymes.
Primary hyperlipidemias of dogs are initially treated by use of a low fat diet with reevaluation after 6 to 8 weeks. Low fat diets may not result in complete resolution of the problem, especially when there is a high concentration of endogenous triacylglycerol (i.e., very low density lipoprotein).
In such cases, fish oil capsules at a dosage of 1,000 mg / 4.54 kg (1,000 mg / 10 lb) daily can be used to supplement the diet. On a metabolic BW basis, this dosage equates to approximately 120 mg of EPA and DHA / kg of BW0.75 for a 10-kg dog.
Anecdotally, one dog which had idiopathic hyperlipidemia with multiple lipomas reportedly had resolution of the conditions, including the lipomas, after treatment for 6 weeks with a low fat diet plus fish oil at this dosage. Use of fish oil at 75% of the dosage controlled the problem for more than one year.
Emerging Areas for Omega-3 Fatty Acid Treatments in Dogs
A beneficial role for Omega-3 fatty acids in colon, breast, prostate and other types of cancer has been described. Although colon cancers are infrequent in dogs, mammary gland tumors are seen as well as prostate cancer, but these conditions develop more frequently in dogs which have not been spayed or neutered, which is common in some European countries.
It is noteworthy that canine prostate tissue has an extremely low content of Omega-3 fatty acids and this finding appears similar to that for human prostate cancer tissue. Lymphomas and osteosarcomas are more frequently seen in canine populations and lymphomas and osteosarcomas of dogs have several similarities with these tumors in humans.
Genome-wide comparative analysis of transcriptional changes in mammary gland tumors of dogs and humans has been investigated, including the expression of approximately 10,000 orthologous genes in dogs and humans. There was a substantial overlap of genes downregulated in the mammary gland tumor samples, compared with results for their normal counterparts.
Pathway analysis of the gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, and the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the dogs with mammary gland tumors, which suggest a close interspecies similarity in the network of cancer-signaling circuitries.
Increased lipid peroxidation is believed to kill cancer cells because cancer cells are less able than normal cells to inactivate oxygen radicals that form as a consequence of peroxidation and less able to survive this altered cell response.
The combination of incorporating highly peroxidizable lipid (i.e., DHA) into tumor cell membranes in combination with pro-oxidants can reduce tumor burden and decrease growth rates in mouse-implanted human breast carcinomas with minimal adverse effects. Such an approach in combination with chemotherapy after surgical excision may reduce tumor recurrence.
In one clinical trial, investigators evaluated the effects of Omega-3 fatty acids in 32 dogs with lymphoma. Treatment dogs received a diet supplemented with men- haden fish oil and arginine, whereas control dogs received an identical diet supplemented with soybean oil.
The diets, fed before and after remission, were provided over a period in which the dogs also received up to five doses of doxorubicin. The amount of EPA in the fish oil diet (on a DM basis) was 29 g / kg of diet (13.2 g lb of diet) and that of DHA was 24 g / kg of diet (10.9 g / lb of diet).
Dogs fed the fish oil diet had significantly higher mean serum concentrations of DHA and EPA, compared with concentrations in the control dogs. The fish oil group also had lower plasma lactic acid responses to IV administration of glucose and diet tolerance testing.
Most notable was the fact that increasing the serum DHA content in the dogs was associated with longer disease-free intervals and survival times in the dogs with stage III lymphoma fed the fish oil diet.
Cognitive Function, Neurologic Health and Aggression
A randomized, double-blinded, controlled clinical trial was conducted to evaluate effects of dietary enrichment with antioxidants, mitochondrial cofactors, and 0.01% DHA in dogs with age-related behavioral changes.
Pet dogs more than 7 years old that were consistently recognized by their owners as having at least 2 behavioral characteristics of age-related cognitive decline were evaluated. Dogs were assigned to receive an enriched diet or control diet.
Clinical features of age-related behavioral changes were measured by use of a standardized informant-based questionnaire completed by the owners. Of the 142 dogs enrolled, 125 (61 fed the enriched diet and 64 fed the control diet) completed a 60-day feeding period.
Significant improvements were found for 14 of 16 behavioral attributes for the enriched-diet group versus only 4 of 16 for the control group. In addition, significant advantages at day 60 were seen in agility, recognition of family members and recognition of other animals.
Dogs consuming the enriched diet also had a significant improvement with regard to excessive licking and patterned pacing behaviors. However, it should be mentioned that although the enriched diet contained 0.01% DHA, it was also enriched with a complex mixture of antioxidant components and mitochondrial cofactors. Thus, the extent to which DHA played a role in the improvements remains to be established.
Fish oil in combination with phenobarbital was used to control idiopathic epilepsy in a dog. In that case report, a 2-year-old female Great Dane with a history of recurrent seizures was evaluated. Phenobarbital failed to adequately control the seizures and it was decided to use fish oil (2 g / d) rather than potassium bromide as an adjunct to the phenobarbital.
The frequency of epileptic seizures markedly decreased after the fish oil diet was fed for 50 days. During the subsequent 18-month period, seizure frequency decreased to 1 seizure / 3 months, a reduction of approximately 85%, compared with the frequency for phenobarbital alone.
These same authors have reported that long-term treatment with Omega-3 fatty acids promotes neuroprotection and increases the number of parvalbumin-positive neu- rons in the hippocampus of rats with epilepsy. Results for the dog in the case report are consistent with this finding, which suggests that intake of Omega-3 fatty acids may be an option for the treatment of epilepsy in dogs.
Finally, aggressive behavior is a common problem reported by dog owners. In humans, plasma concentrations of Omega-3 fatty acids have been linked to behavioral alterations, including aggression.
In one study, investigators evaluated 18 adult male German Shepherd Dogs with no clinical signs other than aggression. Eighteen healthy male dogs with no history of behavioral and neurologic disorders served as control animals.
Compared with concentrations in the healthy control dogs, aggressive dogs had lower DHA concentrations and a higher total Omega-6-to-total Omega-3 ratio. No differences were observed in plasma arachidonic acid or EPA content. In addition, cholesterol and bilirubin concentrations were also decreased in the aggressive dogs.
These findings suggest that low plasma concentrations of Omega-3 fatty acids may adversely impact behavior in dogs, which may result in increased aggressive behavior.
The use of dietary Omega-3 fatty acids as adjunctive treatments for several clinical disorders has been evaluated to a great extent in dogs. Evidence has accumulated regarding beneficial responses with dietary inclusion of Omega-3 fatty acids or their provision for inflammatory conditions such as atopy and some renal disorders as well as cardiovascular problems, hyperlipidemias and osteoarthritis.
Emerging areas of investigation include their role in IBD, cancer, cognitive function and behavior. As further studies are conducted and published, refinements in the recommendations for the use of Omega-3 fatty acids will likely be added to the diverse clinical veterinary applications for these metabolically functional dietary fats.
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