SCIENTIFIC RESEARCH ON THE FOLLOWING INGREDIENTS:

Green-Lipped Mussels

Effect of a diet enriched with green-lipped mussel on pain behavior and functioning in dogs with clinical osteoarthritis ¹

Abstract

This study aimed to establish the effect of a diet enriched with green-lipped mussel (GLM) on pain and functional outcomes in osteoarthritic dogs. Twenty-three client-owned dogs with osteoarthritis (OA) were fed a balanced control diet for 30 d and then a GLM-enriched balanced diet for the next 60 d. We assessed peak vertical force (PVF), which is considered to be the gold standard method, at Day (D)0 (start), D30 (end of control diet), and D90 (end of GLM-enriched diet). The owners completed a client-specific outcome measure (CSOM), which is a pain questionnaire, once a week. Motor activity (MA) was continuously recorded in 7 dogs for 12 wk. Concentrations of plasma omega-3 fatty acids were quantified as indicative of diet change. Statistical analyses were linear-mixed models and multinomial logistic regression for repeated measures. The GLM diet (from D30 to D90) resulted in an increase in concentrations of plasma omega-3 fatty acids (P < 0.016) and improvement of PVF (P = 0.003). From D0 to D30, PVF did not significantly change (P = 0.06), which suggests that the GLM diet had a beneficial effect on gait function. Moreover, PVF (P = 0.0004), CSOM (P = 0.006), and MA (P = 0.02) improved significantly from D0 to D90. In general, the balanced control diet could have contributed to reduced OA symptoms, an effect that was subsequently amplified by the GLM diet.

Source: Pascale Rialland, Sylvain Bichot, 1 Bertrand Lussier, Maxim Moreau, Francis Beaudry, Jérôme RE del Castillo, Dominique Gauvin, and Eric Troncy. “Effect of a diet enriched with green-lipped mussel on pain behavior and functioning in dogs with clinical osteoarthritis.” Canadian Journal of Veterinary Research (2013): 77(1): 66–74.

Clinical efficacy and tolerance of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease ²

Abstract

Aim: To evaluate the efficacy and tolerance of an extract of green-lipped mussel (GLME) in the management of mild-to-moderate degenerative joint disease (DJD) in dogs.

Methods: Eighty-one dogs presumptively diagnosed with DJD were treated orally daily with either GLME or a placebo for 56 days, in a double-blind, placebo-controlled study. In an uncontrolled open-label extension to the study, all dogs were treated with GLME for an additional 56 days (from Days 57-112). Clinical signs were subjectively scored by the owners, and findings of detailed musculoskeletal examinations were scored by one veterinarian. Efficacy was assessed from a qualitative comparison of the proportion of dogs with improved clinical signs, and a quantitative comparison of the scores of the musculoskeletal examinations, between groups. Haematological and biochemical analyses and reports by owners of possible adverse drug reactions were used to screen for evidence of toxicity.

Results: There was close agreement between assessments by the veterinarian and owners. The clinical signs of DJD in both GLME-treated and placebo groups improved significantly over baseline by Day 28; this improvement continued over the entire course of the study. There were no significant differences between groups on Day 28. On Day 56, a higher proportion of dogs in the GLME-treated group had improved clinical signs (p = 0.018), and GLME-treated dogs had marginally better (p = 0.053) musculoskeletal scores than dogs in the placebo group. The differences between the groups were no longer apparent by Day 112, by which time the former placebo group had been receiving GLME for 56 days in the open-label phase of the study. The proportion of dogs in the former placebo group that had improved by Day 112 (29/32; 91%) was significantly greater (p = 0.012) than the proportion improved at Day 56 (15/37; 41%). No signs of toxicity were apparent.

Conclusions and clinical relevance: GLME had a beneficial effect on the clinical signs of dogs presumptively diagnosed with mild-to-moderate DJD. Long-term therapy may be required before improvement is apparent.

Source: B. Pollard, W. G. Guilford, K. L. Ankenbauer-Perkins, and D. Hedderley. “Clinical efficacy and tolerance of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease” New Zealand Veterinary Journal (2006): 54(3):114-8.

Influence of green lipped mussels (Perna canaliculus) in alleviating signs of arthritis in dogs ³

Abstract

This study evaluated the efficacy of green lipped mussel (GLM), added to a complete dry diet, for alleviating clinical signs of arthritis in dogs. A double-blind longitudinal study design was used with 31 mixed-breed dogs exhibiting varying degrees of arthritis. Each dog was evaluated by a veterinarian and joints were individually scored for degree of pain, swelling, crepitus, and reduction in range of movement. Summation of all scores for an individual dog comprised its total arthritis score. At baseline, dogs were randomly allocated to control and test groups. Both groups were fed the same base dry diet, to which 0.3% GLM powder was added for dogs in the test group. The change in total arthritis score by the end of 6 weeks showed there was significant improvement (P < .05) in the test group versus the control group. Significant improvements were also observed in joint pain and swelling scores in the test group. Changes in joint crepitus and range of joint movement were not significantly different between the test and control groups. These findings provide strong evidence that GLM incorporated into a complete dry diet can help alleviate arthritis symptoms in dogs.

Source: L. M. Bui, and R. L. Bierer. “Influence of green lipped mussels (Perna canaliculus) in alleviating signs of arthritis in dogs” Veterinary Therapeutics: Research in Applied Veterinary Medicine. (2001): 2(2): 101-11.

Glucosamine & Chondroitin

Glucosamine and chondroitin use in canines for osteoarthritis: A review ⁴

Abstract

Osteoarthritis is a slowly progressive and debilitating disease that affects canines of all breeds. Pain and decreased mobility resulting from osteoarthritis often have a negative impact on the affected canine’s quality of life, level of comfort, daily functioning, activity, behaviour, and client-pet companionship. Despite limited and conflicting evidence, the natural products glucosamine hydrochloride (HCl) and chondroitin sulfate are commonly recommended by veterinarians for treating osteoarthritis in dogs. There is a paucity of well-designed clinical veterinary studies investigating the true treatment effect of glucosamine and chondroitin. The purposes of this review article are to provide a brief background on glucosamine and chondroitin use in canine osteoarthritis and to critically review the available literature on the role of these products for improving clinical outcomes. Based on critical review, recommendations for practice are suggested and a future study design is proposed.

Source: Angel Bhathal, Meredith Spryszak, Christopher Louizos, and Grace Frankel. “Glucosamine and chondroitin use in canines for osteoarthritis: A review.” Open Veterinary Journal. (2017): 7(1): 36-49.

Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis ⁵

Abstract

Thirty-five dogs were included in a randomised, double-blind, positive controlled, multi-centre trial to assess the efficacy of an orally-administered glucosamine hydrochloride and chondroitin sulfate (Glu/CS) combination for the treatment of confirmed osteoarthritis of hips or elbows. Carprofen was used as a positive control. Dogs were re-examined on days 14, 42 and 70 after initiation of treatment. Medication was then withdrawn and dogs were re-assessed on day 98. Response to treatment was based on subjective evaluation by participating veterinarians who recorded their findings at each visit. Dogs treated with Glu/CS showed statistically significant improvements in scores for pain, weight-bearing and severity of the condition by day 70 (P < 0.001). Onset of significant response was slower for Glu/CS than for carprofen-treated dogs. The results show that Glu/CS has a positive clinical effect in dogs with osteoarthritis.

Source: Grainne McCarthy, James O'Donovan, Boyd Jones, Hester McAllister, Michael Seed, and Carmel Mooney. “Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis” Veterinary Journal (2007): 174(1): 54-61.

Glucosamine, Chondroitin & Hyaluronic Acid

Effect of an Oral Joint Supplement When Compared to Carprofen in the Management of Hip Osteoarthritis in Working Dogs ⁶

Abstract

The goal of this study was to evaluate the effectiveness of an oral joint supplement in working dogs with hip osteoarthritis compared with a positive control group (CG). Fifteen animals were divided in treatment group (TG, n = 10) and CG (n = 5). To TG a commercially available joint supplement, containing glucosamine HCl, chondroitin sulphate, and hyaluronic acid was given for 40 days and a 70-day course of a placebo, to be administered as if it was carprofen. The CG received carprofen for 70 days, and a placebo to be administered as the joint supplement. Response to treatment, measured by the canine brief pain inventory (CBPI) and the Hudson visual analog scale, was evaluated before treatment (T0), after 15 days (T1) and 1 (T2), 2 (T3), 3 (T4), 4 (T5), and 5 (T6) months. With CBPI, no differences were found in pain interference score and pain severity score between TG and CG throughout or when comparing results within groups. Individual results were considered successful in a maximal of three dogs of the TG by T3 (30%) and 1 in CG (25%). With Hudson visual analog scale, improvements where registered with individual results, for 40%-50% of the animals in TG and 60%-80% of cases in CG. The oral joint supplement and carprofen produced some improvements in individual scores but where unable to do so when overall results were considered. Each of these options may not be able, by itself, to fully address the demands of a working dog with joint disease and related pain.

Source: João Carlos Alves, Ana Margarida Santos, and Patrícia Isabel Jorge. “Effect of an Oral Joint Supplement When Compared to Carprofen in the Management of Hip Osteoarthritis in Working Dogs” Topics in Companion Animal Medicine. (2017): 32(4):126-129.

MSM (Methylsulfonylmethane)

Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement ⁷

Abstract

Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption.

Source: Matthew Butawan, Rodney L. Benjamin, and Richard J. Bloomer. “Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement” Nutrients. (2017): 9(3): 290.

Effects of a nutritional supplement in dogs affected by osteoarthritis ⁸

Abstract

Osteoarthritis is a form of chronic joint inflammation caused by the deterioration of the joint cartilage, accompanied by chronic pain, lameness and stiffness, particularly after prolonged activity. Alternative treatments of canine osteoarthritis would be desirable and, recently nutraceuticals, have been proposed for this purpose. Twenty cross breed adult dogs affected by osteoarthritis were enrolled and equally divided into two groups (control vs. experimental). The nutritional supplement (Dynamopet srl, Verone, Italy) was administered for 90 days to the dogs of the experimental group in order to evaluate its metabolic and locomotor effects. All the clinical signs (lameness, pain on manipulation and palpation, range of motion and joint swelling) significantly (p < 0.01) improved during the trial as regards the experimental group. This group showed a significantly lower joint score than the control group (mean value 7.40 vs. 3.80). With regard to haematology, the mean corpuscular volume resulted significantly (p < 0.01) higher in the experimental group, i.e. alkaline phosphatase, cholesterol and triglycerides values decreased and were significantly (p < 0.01) lower than the control one, thus suggesting an improvement in bone remodelling and lipid metabolism. A decrease in the reactive oxygen metabolites and an increase in the biological antioxidant potential demonstrated an improvement in oxidative stress during the trial in the experimental group compare to the control group. Interleukins 6 decreased in the experimental group, while interleukins 10 resulted in the opposite trend. Moreover, the administration of up to 3 months of the studied supplement was well tolerated in the dogs and caused no adverse effects.

Source: Nadia Musco, Giuseppe Vassalotti, Vincenzo Mastellone, Laura Cortese, Giorgia della Rocca, Maria Luce Molinari, Serena Calabrò, Raffaella Tudisco, Monica Isabella Cutrignelli, and Pietro Lombardi. “Effects of a nutritional supplement in dogs affected by osteoarthritis” Veterinary Medicine and Science. (2019): 5(3): 325–335.

Glucosamine & Chondroitin & MSM (Methylsulfonylmethane)

Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial ⁹

Abstract

Background: Glucosamine, chondroitin sulfate are frequently used to prevent further joint degeneration in osteoarthritis (OA). Methylsulfonylmethane (MSM) is a supplement containing organic sulphur and also reported to slow anatomical joint progressivity in the knee OA. The MSM is often combined with glucosamine and chondroitin sulfate. However, there are controversies whether glucosamine-chondroitin sulfate or their combination with methylsulfonylmethane could effectively reduce pain in OA. This study is aimed to compare clinical outcome of glucosamine-chondroitin sulfate (GC), glucosamine-chondroitin sulfate-methylsulfonylmethane (GCM), and placebo in patients with knee osteoarthritis (OA) Kellgren-Lawrence grade I-II.

Methods: a double blind, randomized controlled clinical trial was conducted on 147 patients with knee OA Kellgren-Lawrence grade I-II. Patients were allocated by permuted block randomization into three groups: GC (n=49), GCM (n=50), or placebo (n=48) groups. GC group received 1500 mg of glucosamine + 1200 mg of chondroitin sulfate + 500 mg of saccharum lactis; GCM group received 1500 mg of glucosamine + 1200 mg of chondroitin sulfate + 500 mg of MSM; while placebo group received three matching capsules of saccharum lactis. The drugs were administered once daily for 3 consecutive months VAS and WOMAC scores were measured before treatment, then at 4th, 8th and 12th week after treatment.

Results: on statistical analysis it was found that at the 12th week, there are significant difference between three treatment groups on the WOMAC score (p = 0.03) and on the VAS score (p = 0.004). When analyzed between weeks, GCM treatment group was found statistically significant on WOMAC score (p = 0.01) and VAS score (p < 0.001). Comparing the score difference between weeks, WOMAC score analysis showed significant difference between GC, GCM, and placebo in week 4 (p = 0.049) and week 12 (p = 0.01). In addition, VAS score also showed significant difference between groups in week 8 (p = 0.006) and week 12 (p < 0.001).

Conclusion: combination of glucosamine-chondroitin sulfate-methylsulfonylmethane showed clinical benefit for patients with knee OAK Kellgren-Lawrence grade I-II compared with GC and placebo. GC did not make clinical improvement in overall groups of patients with knee OA Kellgren Lawrence grade I-II.

Source: Andri M T Lubis, Carles Siagian, Erick Wonggokusuma, Aldo F Marsetyo, Bambang Setyohadi. “Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial.” Acta Medica Indonesia (2017): 49(2):105-111.

Glucosamine & Chondroitin & Manganese

Effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate on synovial fluid chondroitin sulfate 3B3 and 7D4 epitope in a canine cruciate ligament transection model of osteoarthritis ¹⁰

Abstract

Objective: To evaluate effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate (CS-G-M) on articular cartilage metabolism in dogs with cranial cruciate ligament (CCL) deficient and reconstructed knees, as reflected by concentrations of synovial fluid 3B3, 7D4 and total sulfated glycosaminoglycan (GAG).

Methods: Sixteen adult dogs that underwent unilateral CCL transection were randomized into four groups. Thereafter, group I (N=3) had a sham CCL reconstruction, group II (N=3) had CS-G-M and sham CCL reconstruction, group III (N=5) had CCL reconstruction, and group IV (N=5) had CS-G-M and CCL reconstruction. Synovial fluid collected at 0, 1, 3 and 5 months was examined by ELISA for 3B3 and 7D4 epitope, and by DMMB assay for total GAG.

Results: Synovial fluid from CCL transected knees of CS-G-M treated dogs contained significantly elevated concentrations of 3B3 (P = 0.029), 7D4 (P = 0.036) and 7D4/GAG (P = 0.007) in comparison to controls, in a cross-sectional analysis at 3 months. Furthermore, 7D4 and 7D4/GAG concentrations remained significantly elevated (P = 0.012) in CCL transected knees of CS-G-M treated dogs over the 5 month period. However, when epitope concentrations were expressed as a ratio of CCL-transected to contralateral non-operated knee, treatment effect of CS-G-M was no longer significant. Reconstruction of the CCL had no significant effect on synovial fluid epitope.

Conclusions: Administration of CS-G-M was associated with altered concentrations of 3B3 and 7D4 epitope in synovial fluid, suggesting that these compounds may act to modulate articular cartilage matrix metabolism in vivo.

Source: K. A. Johnson, D. A. Hulse, R. C. Hart, D. Kochevar, and Q. Chu. “Effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate on synovial fluid chondroitin sulfate 3B3 and 7D4 epitope in a canine cruciate ligament transection model of osteoarthritis”. Osteoarthritis Cartilage (2001): 9(1): 14-21.

Glucosamine, MSM, Citrus Bioflavonoids & Grape Seed Extract

Pharmacological effects of a C-phycocyanin-based multicomponent nutraceutical in an in-vitro canine chondrocyte model of osteoarthritis ¹⁵

Abstract

Multicomponent nutraceuticals are becoming increasingly popular treatments or adjunctive therapies for osteoarthritis in veterinary medicine despite lack of evidence of efficacy for many products. The objective of this study was to evaluate the anti-inflammatory and antioxidant activities of a commercially available C-phycocyanin-based nutraceutical and select constituent ingredients in an in-vitro model of canine osteoarthritis. Normal canine articular chondrocytes were used in an in-vitro model of osteoarthritis. Inflammatory conditions were induced using interleukin-1β. The nutraceutical preparation as a whole, its individual constituents, as well as carprofen were evaluated at concentrations of 0 to 250 μg/mL for reduction of the following inflammatory mediators and indicators of catabolism of the extracellular matrix: prostaglandin E2 (PGE2), tumor necrosis factor-α (TFN-α), interleukin-6 (IL-6), metalloproteinase-3 (MMP-3), nitric oxide, and sulfated glycosaminoglycans (sGAGs). Validated, commercially available assay kits were used for quantitation of inflammatory mediators. The antioxidant capacities, as well as cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and lipoxygenase (LOX) inhibitory activities of the whole nutraceutical preparation and select constituents, were also assessed using validated commercially available assay kits. The antioxidant capacity of the nutraceutical and constituents was concentration dependent. The nutraceutical and constituents appear to display anti-inflammatory activity primarily through the inhibition of COX-2. The nutraceutical displayed similar strength to carprofen in reducing TNF-α, IL-6, MMP-3, nitric oxide, and sGAGs at select concentration ranges. The C-phycocyanin (CPC)-based nutraceutical and constituents may be able to mediate 3 primary pathogenic mechanisms of osteoarthritis: inflammation, chondral degeneration, and oxidative stress in vitro. The nutraceutical may be clinically useful in veterinary medicine and its efficacy should be further investigated in vivo.

Source: Stephanie E. Martinez, Yufei Chen, Emmanuel A. Ho, Steven A. Martinez, and Neal M. Davies. Canadian Journal of Veterinary Research “Pharmacological effects of a C-phycocyanin-based multicomponent nutraceutical in an in-vitro canine chondrocyte model of osteoarthritis” Canadian Journal of Veterinary Research. (2015): 79(3): 241–249.

Grape Seed Extract

Phytochemical Constituents, Health Benefits, and Industrial Applications of Grape Seeds: A Mini-Review ¹⁶

Abstract

Grapes are one of the most widely grown fruits and have been used for winemaking since the ancient Greek and Roman civilizations. Grape seeds are rich in proanthocyanidins which have been shown to possess potent free radical scavenging activity. Grape seeds are a complex matrix containing 40% fiber, 16% oil, 11% proteins, and 7% complex phenols such as tannins. Grape seeds are rich sources of flavonoids and contain monomers, dimers, trimers, oligomers, and polymers. The monomeric compounds includes (+)-catechins, (−)-epicatechin, and (−)-epicatechin-3-O-gallate. Studies have reported that grape seeds exhibit a broad spectrum of pharmacological properties against oxidative stress. Their potential health benefits include protection against oxidative damage, and anti-diabetic, anti-cholesterol, and anti-platelet functions. Recognition of such health benefits of proanthocyanidins has led to the use of grape seeds as a dietary supplement by the consumers. This paper summarizes the studies of the phytochemical compounds, pharmacological properties, and industrial applications of grape seeds.

Source: Zheng Feei Ma and Hongxia Zhang. “Phytochemical Constituents, Health Benefits, and Industrial Applications of Grape Seeds: A Mini-Review” Antioxidants (Basel). (2017): 6(3): 71.

Pharmacological effects of a C-phycocyanin-based multicomponent nutraceutical in an in-vitro canine chondrocyte model of osteoarthritis ¹⁷

Abstract

Multicomponent nutraceuticals are becoming increasingly popular treatments or adjunctive therapies for osteoarthritis in veterinary medicine despite lack of evidence of efficacy for many products. The objective of this study was to evaluate the anti-inflammatory and antioxidant activities of a commercially available C-phycocyanin-based nutraceutical and select constituent ingredients in an in-vitro model of canine osteoarthritis. Normal canine articular chondrocytes were used in an in-vitro model of osteoarthritis. Inflammatory conditions were induced using interleukin-1β. The nutraceutical preparation as a whole, its individual constituents, as well as carprofen were evaluated at concentrations of 0 to 250 μg/mL for reduction of the following inflammatory mediators and indicators of catabolism of the extracellular matrix: prostaglandin E2 (PGE2), tumor necrosis factor-α (TFN-α), interleukin-6 (IL-6), metalloproteinase-3 (MMP-3), nitric oxide, and sulfated glycosaminoglycans (sGAGs). Validated, commercially available assay kits were used for quantitation of inflammatory mediators. The antioxidant capacities, as well as cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and lipoxygenase (LOX) inhibitory activities of the whole nutraceutical preparation and select constituents, were also assessed using validated commercially available assay kits. The antioxidant capacity of the nutraceutical and constituents was concentration-dependent. The nutraceutical and constituents appear to display anti-inflammatory activity primarily through the inhibition of COX-2. The nutraceutical displayed similar strength to carprofen in reducing TNF-α, IL-6, MMP-3, nitric oxide, and sGAGs at select concentration ranges. The C-phycocyanin (CPC)-based nutraceutical and constituents may be able to mediate 3 primary pathogenic mechanisms of osteoarthritis: inflammation, chondral degeneration, and oxidative stress in vitro. The nutraceutical may be clinically useful in veterinary medicine and its efficacy should be further investigated in vivo.

Source: Stephanie E. Martinez, Yufei Chen, Emmanuel A. Ho, Steven A. Martinez, and Neal M. Davies. “Pharmacological effects of a C-phycocyanin-based multicomponent nutraceutical in an in-vitro canine chondrocyte model of osteoarthritis.” Canadian Journal of Veterinary Research. (2015): 79(3): 241–249.

Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1β activities before and after oral consumption ¹⁸

Abstract

Polyphenols exert a large range of beneficial effects in the prevention of age-related diseases. We sought to determine whether an extract of olive and grape seed standardized according to hydroxytyrosol (HT) and procyanidins (PCy) content, exerts preventive anti-osteoathritic effects. To this aim, we evaluated whether the HT/PCy mix could (i) have in vitro anti-inflammatory and chondroprotective actions, (ii) exert anti-osteoarthritis effects in two post-traumatic animal models and (iii) retain its bioactivity after oral administration. Anti-inflammatory and chondroprotective actions of HT/PCy were tested on primary cultured rabbit chondrocytes stimulated by interleukin-1 beta (IL-1β). The results showed that HT/PCy exerts anti-inflammatory and chondroprotective actions in vitro. The preventive effect of HT/PCy association was assessed in two animal models of post-traumatic OA in mice and rabbits. Diet supplementation with HT/PCy significantly decreased the severity of post-traumatic osteoarthritis in two complementary mice and rabbit models. The bioavailability and bioactivity was evaluated following gavage with HT/PCy in rabbits. Regular metabolites from HT/PCy extract were found in sera from rabbits following oral intake. Finally, sera from rabbits force-fed with HT/PCy conserved anti-IL-1β effect, suggesting the bioactivity of this extract. To conclude, HT/PCy extract may be of clinical significance for the preventive treatment of osteoarthritis.

Source: Elsa Mével, Christophe Merceron, Claire Vinatier, Stéphanie Krisa, Tristan Richard, Martial Masson, Julie Lesoeur, Vincent Hivernaud, Olivier Gauthier, Jérôme Abadie, Geoffroy Nourissat, Xavier Houard, Yohann Wittrant, Nelly Urban, Laurent Beck, and Jérôme Guicheuxa. “Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1β activities before and after oral consumption” Scientific Reports. (2016) 6: 33527

Hyaluronic Acid

Efficacy of an oral hyaluronate and collagen supplement as a preventive treatment of elbow dysplasia ²⁰

Abstract

One hundred and five Labrador dogs were randomly divided into two groups to determine the number of animals that develop elbow dysplasia when treated with an oral supplement compared to untreated ones. Efficacy of the oral treatment was also evaluated once illness was diagnosed. The supplement (Hyaloral) contained hyaluronic acid, hydrolysed collagen, glucosamine, chondroitin sulphate, and gamma oryzanol. Clinical evaluation of the elbow joints was completed at months 3, 6, 12, and 20 by orthopaedic evaluations, radiography, serologic and blood analysis, and veterinarian evaluation of dysplasia symptoms. All side effects were recorded. In the control group, 33.3% of the dogs developed radiographic evidence of elbow dysplasia compared to 18.5% in the treated group. Symptoms of dysplasia at 12 months differed between the treated (12.5%) and control (61.5%) animals and were significantly different at 20 months (p < 0.05). Differences in lameness along with movement and swelling of the elbows between groups were observed after 12 months. The treated group had improved significantly by the last visit (p < 0.05). No adverse side effects were reported. In conclusion, oral treatment with Hyaloral may have a potential cumulative action that provides protection against dysplasia and significantly improves symptoms of elbow dysplasia.

Source: Simón Martí-Angulo, Núria García-López, and Ana Díaz-Ramos. “Efficacy of an oral hyaluronate and collagen supplement as a preventive treatment of elbow dysplasia” Journal of Veterinary Science. (2014): 15(4): 569–574.

The role of hyaluronic acid in joint stability--a hypothesis for hip dysplasia and allied disorders ²¹

Abstract

The concentration of hyaluronic acid (HA) and proteins in synovial fluids of hip and shoulder joints of a variety of canine breeds has been investigated. In the Australian Kelpie, a working dog with a low incidence of hip dysplasia, shoulder synovial fluid viscosity and HA concentration were higher than in similar joints of Alsatians in which hip dysplasia is relatively common. Moreover, the HA levels and viscosity in shoulder fluids of animals with clinically defined hip dysplasia were substantially lower than in all other breeds studied. On the basis of these findings, we propose that hip dysplasia and other joint abnormalities may arise as a consequence of a deficiency in the levels of HA in synovial fluids.

Source: D. Cullis-Hill and P. Ghosh. “The role of hyaluronic acid in joint stability--a hypothesis for hip dysplasia and allied disorders” Medical Hypotheses. (1987): 23(2):171-85.

Hyaluronic acid concentrations in synovial fluid of dogs with different stages of osteoarthritis ²²

Abstract

To compare hyaluronic acid (HA) concentrations measured in synovial fluid (SF) of joints with different stages of canine secondary osteoarthritis (OA), clinical-orthopedic, radiographic, macroscopic intra-operative and SF findings of 49 joints were assessed. The sum of single findings was correlated to HA concentrations measured by a commercially available ELISA. Joints were categorized into three OA-groups: non-osteoarthritic, mildly osteoarthritic, and severely osteoarthritic. A significant negative correlation was found between severity of OA and HA concentrations (r = -0.696; P < 0.001). Median values of HA concentrations decreased with increasing severity of the disease. Statistically significant differences in HA concentrations were observed between the OA-groups (P < 0.001). Due to overlapping values between groups, it was concluded that synovial HA concentrations may only indicate a trend of osteoarthritic disease activity but is not suitable for staging the disease.

Source: H. D. Plickert, A. Bondzio, R. Einspanier, A. Tichy, and L. Brunnberg “Hyaluronic acid concentrations in synovial fluid of dogs with different stages of Osteoarthritis” Research in Veterinary Science. (2013): 94(3):728-34.

Vitamin B1 (Thiamine)

The Role of Thiamine and Effects of Deficiency in Dogs and Cats ²³

Abstract

Recent pet food recalls for insufficient dietary thiamine have highlighted the importance of adequate thiamine intake in dogs and cats, as thiamine is an essential dietary nutrient with a critical role in energy metabolism. Prolonged thiamine deficiency leads to clinical signs that can span several organ systems, and deficiency can be fatal if not reversed. In this review, the current knowledge of thiamine metabolism will be summarized. Dietary recommendations for dogs and cats will be discussed, and the risk factors and clinical signs associated with thiamine deficiency will be examined.

Source: Georgia Kritikos, Jacqueline M. Parr, and Adronie Verbrugghe. “The Role of Thiamine and Effects of Deficiency in Dogs and Cats.” Veterinary Sciences (2017): 4(4): 59.

Vitamin B9 (Folic Acid)

Folic acid in physiology and pathology ²⁴

Abstract

This paper presents current knowledge of the biological functions of folic acid, the effects of its deficiency in the organism, as well as the possibilities of its therapeutic use. Folic acid (folate, B9) is a vitamin of special importance in normal cellular functions. Tetrahydrofolate (TH4-folate) is the biologically active form of folic acid. The main role of folic acid in biochemistry is the single-carbon transfer reaction (e.g. transfer of a methyl, methylene, or formyl group). Folic acid is involved in the transformation of certain amino acids as well as in the synthesis of purines and dTMP (2'-deoxythymidine-5'-phosphate) needed for the synthesis of nucleic acid (DNA), required by all rapidly growing cells. In humans, folate deficiency results in serious pathologies, the most important of which are neural tube defects, megablastic anemia, acceleration of the arteriosclerotic process, changes in the central nervous system, and the development of certain types of cancer. To increase the intake of folic acid, preventive actions include dietary education, the main objectives of which are to increase the intake of natural folate in the daily diet, add folic acid to selected dietary products (e.g. fl our, pasta, rice), and encourage supplementation with folic acid-containing pharmaceuticals.

Source: Hanna Czeczot. “Folic acid in physiology and pathology” “Folic acid in physiology and pathology.” Postepy Higieny i Medycny Doswiadczalnej (Online) (2008): 62:405-19.

Vitamin B2 (Riboflavin)

Emerging roles for riboflavin in functional rescue of mitochondrial β-oxidation flavoenzymes ²⁵

Abstract

Riboflavin, commonly known as vitamin B2, is the precursor of flavin cofactors. It is present in our typical diet, and inside the cells it is metabolized to FMN and FAD. As a result of their rather unique and flexible chemical properties these flavins are among the most important redox cofactors present in a large series of different enzymes. A problem in riboflavin metabolism or a low intake of this vitamin will have consequences on the level of FAD and FMN in the cell, resulting in disorders associated with riboflavin deficiency. In a few number of cases, riboflavin deficiency is associated with impaired oxidative folding, cell damage and impaired heme biosynthesis. More relevant are several studies referring reduced activity of enzymes such as dehydrogenases involved in oxidative reactions, respiratory complexes and enzymes from the fatty acid β-oxidation pathway. The role of this vitamin in mitochondrial metabolism, and in particular in fatty acid oxidation, will be discussed in this review. The basic aspects concerning riboflavin and flavin metabolism and deficiency will be addressed, as well as an overview of the role of the different flavoenzymes and flavin chemistry in fatty acid β-oxidation, merging clinical, cellular and biochemical perspectives. A number of recent studies shedding new light on the cellular processes and biological effects of riboflavin supplementation in metabolic disease will also be overviewed. Overall, a deeper understanding of these emerging roles of riboflavin intake is essential to design better therapies.

Source: Bárbara J. Henriques, Rikke K. Olsen, Peter Bross, and Cláudio M Gomes. “Emerging roles for riboflavin in functional rescue of mitochondrial β-oxidation flavoenzymes.” Current Medicinal Chemistry. (2010): 17(32): 3842-54.

Vitamin B7 (Biotin)

Clinical study on the effect of biotin on skin conditions in dogs ²⁶

Abstract

In a collaborative study with small-animal veterinary surgeons, dogs with fur and skin conditions were treated with biotin (approximately 5 mg biotin/10 kg body weight/day) for 3 to 5 weeks. In total 119 cases could be treated which were reported to show symptoms such as dull coat, brittle hair, loss of hair, scaly skin, pruritus or dermatitis. Cases requiring other treatments with e.g., glucocorticoids, were excluded from the study. In 60% of the cases all symptoms were reported to be cured after the biotin treatment and in a further 31% an improvement was noted; in only 9% no effect was recorded. All breeds responded but to a variable extent: e.g., in Poodles the response was lower (no response in 6 out of 11 cases) than in Alsatians where all improved and 14 out of 29 were completely cured. The results confirm the favourable effect of biotin for treatment of fur and skin conditions in dogs.

Source: M. Frigg, J. Schulze, and L. Völker. “Clinical study on the effect of biotin on skin conditions in dogs.” Schweizer Archive for Tierheilkdunde. (1989): 131(10): 621-5.

Vitamin B12 (Cobalamin)

Cobalamin deficiency in dogs and cats ²⁷

Abstract

Cobalamin is a member of the B-group of vitamins and a cofactor for metabolic processes like nucleic acid synthesis, amino acid synthesis, and the citric acid cycle. Mammals are unable to synthesize cobalamin and therefore rely on adequate food intake. Cobalamin absorption is a complex process in the stomach, duodenum, and ileum, requiring a functional exocrine pancreas. Thus, a great number of gastrointestinal diseases like chronic enteropathies, intestinal lymphoma, or exocrine pancreatic insufficiency can lead to hypocobalaminemia. Furthermore, some dog breeds (Giant Schnauzer, Border Collie, Australian Sheperd Dog, and Beagle) can have a primary, hereditary cobalamin deficiency (Imerslund-Gräsbeck syndrome). Clinical signs of cobalamin deficiency comprise anorexia, vomiting, diarrhoea, failure to thrive, and neuropathies. Laboratory findings like non-regenerative anemia, leukopenia, hypoglycemia, and hyperammonaemia have also been described. When hypocobalaminemia is suspected usually in dogs and cats, the cobalamin concentration is usually measured by immunoassay. Because the concentrations of cobalamin in blood and cells can differ the sole measurement of the vitamin concentration is of limited informative value. Treatment depends on the underlying disease aiming at eliminating the cause of hypocobalaminemia. However, successful therapy of gastrointestinal diseases often requires an additional oral or parenteral cobalamin supplementation. In patients with Imerslund-Gräsbeck syndrome, a regular and lifelong cobalamin supplementation is essential.

Source: Franziska Hanisch, Linda Toresson, and Thomas Spillmann. “Cobalamin deficiency in dogs and cats” Tierarztliche Praxis Ausgabe K, Kleintiere/Heimtiere (2018): 46(5): 309-314.

Glucosamine, Chondroitin, CoQ10, Manganese, B vitamins: Thiamine (B1), Riboflavin (B2), Niacin (B3), Pantothenate (B5), Pyridoxine (B6), Folic Acid (B9), & Cyanocobalamin (B12)

Functional foods in pet nutrition: Focus on dogs and cats ³⁰

Highlights:

• Functional foods provide health benefits when integrated in the diet.
• This review shows evidence of use of functional foods in pets.
• Functional food can reduce the risk of disease and/or support the body.
• Pets are a valuable model to study the role and mechanism of functional foods.

Abstract

Functional foods provide health benefits if they are consumed on a regular basis as part of a varied diet. In this review, we discuss the availability and role of functional foods in pet nutrition with a focus on dogs and cats. Indeed, functional foods modify gastrointestinal physiology, promote changes in biochemical parameters, improve brain functions and may reduce or minimize the risk of developing specific pathologies. This evidence derives largely from clinical studies while only limited evidence is available from studies in dogs and cats. Therefore, functional food consumption should be further investigated in pet nutrition to understand how dietary interventions can be used for disease prevention and treatment.

1. Background
Novel foods and food components have been identified as “functional” because they provide health benefits beyond the provision of essential nutrients, such as vitamins, minerals, water, proteins, carbohydrates and fats (Hasler, 2000). The role of functional foods has been investigated in dogs (Canis familiaris) and cats (Felis catus) in order to better understand their metabolism, thus optimising companion animal nutritional and health status (Swanson et al., 2003). After a long history of coexistence, the most common pets in modern societies are dogs and cats. Dogs and cats present significant differences in digestive-related processes but, while cats are carnivorous, dogs appear to be omnivorous like human beings (Bosch et al., 2015). Dogs share some carnivorous traits with cats as both lack salivary amylase, have a short gastrointestinal tract and are unable to synthesize vitamin D (National Research Council, 2006). In contrast, there are 3 genes, AMY2B, MGAM and SGLT1 that have evolved only in dogs during domestication and are involved in starch digestion and glucose uptake (Axelsson et al., 2013). Another characteristic of the dogs digestive system is that they can synthesise several essential nutrients such as niacin, taurine and arginine (Bosch et al., 2015). As far as cats are concerned, they can catabolise and use amino acids as a source of energy for gluconeogenesis (Morris, 2002). Cats have a diet consisting of 52% protein, 36% fat and 12% carbohydrate (Plantinga et al., 2011). Therefore, we have to study pet nutrition considering dogs and cats separately. A human-pet parallel exists as pet owners provide their dogs and cats with alternative foods, such as commercially available “natural”, raw food and vegetarian diets as they are considered family members (Michel, 2006). The parallel between humans and animals is further strengthened by the evidence that, similarly to human babies who copy adults' redundant actions (Brugger et al., 2007, Cook et al., 2014, Lyons et al., 2007, Topal et al., 2008), companion animals acquire the wrong eating habits from their owners (Marshall-Pescini et al., 2012). This evidence suggests that understanding pet nutrition is also important to study human nutrition; however, this is not object of this article and has been reviewed elsewhere (Di Cerbo et al., 2014).

Several studies have focused on investigating health benefits of ingredients found in commercially available functional foods in humans; these ingredients may also exert their beneficial effects on dogs and cats but, at least in some cases, have not been investigated yet. The interest in the adequacy of commercially available pet foods has been growing worldwide (Zicker, 2008). Functional foods, strongly appreciated for their health benefits, include fruit and vegetables (Slavin and Lloyd, 2012), botanicals (Guidetti et al., 2016), whole grains (Borneo and Leon, 2012), dietary supplements including pycnogenol, collagen, low-molecular-weight hyaluronic acid, chondroitin sulfate and glucosamine sulfate (Di Cerbo et al., 2015a), beverages (Corbo et al., 2014, Shiby and Mishra, 2013), prebiotics and probiotics (Di Cerbo et al., 2012, Di Cerbo and Palmieri, 2015, Di Cerbo et al., 2013, Iannitti and Palmieri, 2010, Ricciardi et al., 2014, Romano et al., 2014, Blaiotta et al., 2016) [probiotics efficacy in canine and feline welfare has been reviewed elsewhere (Grzeskowiak et al., 2015)]. Most of these functional foods can improve satiety (Delzenne and Kok, 2001, Reimer et al., 2012) and reduce postprandial glucose and insulin concentrations (Delzenne and Kok, 2001), thus reducing diabetes-related comorbities. Inulin and oligofructose, two functional foods, can modify the intestinal microflora in dogs, cats (Hussein et al., 1999) and humans (Van Loo et al., 1999). Dietary fibers, which are commonly found in pet foods (de Godoy et al., 2009), can modify the intestinal microflora by promoting commensal bacteria growth (Tungland, 2003). Decrease in gastric emptying, blood cholesterol concentrations (Brennan and Cleary, 2005), gastric transit time, dilution in diet calorie density as well as increase in satiety (Rebello et al., 2013), glucose uptake rate (Jenkins et al., 2008) and fecal excretion (Wenk, 2001) can also be ascribed to dietary fibers.

Whole grains, whose main sources are wheat, corn, oats, barley and rye (Slavin et al., 2001), are rich in dietary fibers, trace minerals, vitamin B and E (Fardet, 2010), bioactive compounds, e.g. tocotrienols, lignans and polyphenols, lipotropes and methyl donors, such as choline, methionine, betaine, inositol and folate and antinutrients; these are defined as compounds that interfere with the absorption of nutrients such as phytic acid, tannins and saponins endowed with antioxidant and anti-carcinogenic effects (Fardet, 2010, Jones and Engleson, 2010, Jonnalagadda et al., 2011, Slavin et al., 2001). Cereal grain is mainly used (~ 90%) in animal feeding and its nutritional composition ranges from 21% to 27% of total dietary fiber, 12%–16% of crude protein and 18%–22% of crude fat (Kahlon, 2009). Corn is another valuable fiber source since it possesses no detrimental effects on palatability and nutrient digestibility, also lowering the glycemic response in adult dogs (de Godoy et al., 2009). Although corn fiber contains phenolic compounds with known antioxidant, anti-mutagenic and cholesterol-lowering effects (Wilson et al., 2000) that can reduce the incidence of colon cancer in humans (Lamy et al., 2014), these effects have not been investigated in dogs and cats. Therefore, further studies are warranted. Rice bran is an excellent source of essential amino acids since it is particularly rich in sulfur-containing amino acids, micronutrients such as magnesium, manganese and B vitamins (Ryan, 2011), bioactive molecules such as tocopherols, tocotrienols, polyphenols like ferulic acid and α-lipoic acid, phytoesterols, γ-oryzanol and carotenoids such as carotene, lycopene, lutein and zeaxanthin, all of which have strong antioxidant, anti-inflammatory and chemopreventive properties in management and prevention of chronic diseases such as cardiovascular disease, type-2 diabetes, and obesity (Ryan, 2011). In addition, rice bran oil contains a good fatty acid profile including mostly mono- and poly-unsaturated fatty acids [oleic acid (38.4%), linoleic acid (34.4%) and α-linolenic acid (2.2%)] and about 1.5% γ-oryzanol, all of which have a strong antioxidant capacity, as observed in rodents, rabbits, non-human primates and humans (Cicero and Derosa, 2005). During pet food heat processing, the Maillard reaction, i.e. a non-enzymatic browning and flavoring reaction (van Rooijen et al., 2013), reduces the bioavailability of essential amino acids such as lysine (Friedman, 1996). Therefore, pet food can supply less lysine than the animal may require thus needing the addition of a dietary supplement to integrate such deficiency. Understanding the nutritional benefits of functional foods currently available is of key importance to provide dogs and cats with the correct diet to keep them healthy. For this reason, softwares are available online to allow the consumer to choose the appropriate pet food based on the desired ingredients and diet (BlueBuffalo, n.d, Purinaone, n.d, Forza10usa, n.d.).

2. Aim and searching criteria
The aim of this review is to discuss the availability and use of functional foods in dogs and cats. We searched Pubmed/Medline using the keywords “dogs”, “cats”, “functional”, “food”, “nutraceutical” and “diet” alone or combined. Selected papers from 1941 to 2017 were chosen based on their content.

3. Functional foods and dog nutrition
Several studies focused on the role of functional foods in dog nutrition (Adolphe et al., 2012, Cortese et al., 2015, Destefanis et al., 2016, Di Cerbo et al., 2016, Di Cerbo et al., 2014, Di Cerbo et al., 2015b, Di Cerbo et al., 2017, Fahnestock et al., 2012, Pasquini et al., 2013, Ponzio et al., 2013, Sechi et al., 2015, Sechi et al., 2017, Spears et al., 2004, Swanson et al., 2002, Tidu et al., 2013) are summarized in Table 1. For instance, in adult male beagles, oligofructose-enriched diet decreased fecal ammonia and Clostridium perfringens concentrations, while total aerobesincreased, thus ameliorating the overall dog health (Flickinger et al., 2003). Fructooligosaccharides (FOS), were used alone or in combination with mannan-oligosaccharide in dogs fed on a meat-based diet (Swanson et al., 2002). Dogs showed greater ileal immunoglobulin A concentration, whereas they displayed lower fecal total indole and phenol concentrations, if compared with untreated controls. A further study tested a 6-month maintenance diet (FOS as well as corn, fish meal, processed proteins of chicken, poultry fat, beet pulp, yeast, fish oil, minerals, dried yeast (Bio mannan-oligosaccharides), Yucca schidigera, Vitamin A, D3 and E, choline chloride, copper chelate of amino acids hydrate, DL-methionine, taurine, L-carnitine and tocopherols, Grifola frondosa, Curcuma longa, Carica papaya, Punica granatum, Aloe vera, Polygonum L., Haematococcus pluvialis, Solanum licopersicum, and Vitis vinifera) on oxidative stress markers in 12 adult dogs (Pasquini et al., 2013). These dogs presented oxidative imbalance in the form of increased derivatives of reactive oxygen metabolites (d-ROMs) and reduced biological antioxidant potential (BAP; a spectrophotometric test that evaluates blood plasma antioxidant potential by measuring its ferric reducing ability) and retinol. At 6 months, a significant reduction in d-ROMs, primarily hydroperoxides and platelets, as well as an increase in both retinol and BAP was observed, suggesting a restored oxidative balance. This evidence supports the idea that an adequate diet may be crucial to achieve a good oxidative balance in dogs. Conversely, oxidative imbalance may occur after consuming a high glycemic index meal (Adolphe et al., 2012). In order to test this hypothesis, the authors compared postprandial responses of 4 complex carbohydrate sources (barley, corn, peas and rice) vs. a simple carbohydrate (glucose) in 6 dogs reporting that peas had the lowest glycemic index value (29%) compared to barley and rice (51 and 55%, respectively) and could be considered as part of a balanced diet. A further study by Ponzio et al. (2013) evaluated the effects of a specific diet (hydrolyzed fish protein, hydrolyzed potato protein, dried yeast, FOS, vitamin E, ascorbic acid, vitamin B12, niacin, vitamin A, calcium pantothenate, riboflavin, pyridoxine hydrochloride, thiamine mononitrate, folic acid, choline chloride, DL-methionine, l-carnitine, Yucca schidigera extract, beta-carotene, Lepidium meyenii, and Tribulus terrestris) on reproduction in 14 fertile male dogs, divided in 4 age groups (1–2 years, 3–4 years, 5–7 years, and 8–10 years), over a 4-month period, which was preceded by a 3 months pre-treatment period with their usual diet (Ponzio et al., 2013). A constant improvement in metabolic activity (free thyroxine and testosterone) was observed within 45 days since the beginning of the diet enriched with antioxidants with a consequent positive effect on fertility and thyroid activity. Qualitative analysis of semen showed a significant increase in motility and vitality in dogs aged between 2 and 7. These results suggest that a diet enriched with antioxidants can be used to achieve a better reproductive performance. The canine model has been used to investigate the relationship among cognitive impairment in aging, brain-derived neurotrophic factor (BDNF) and diet, but also among behavioral disturbances, neuroendocrine parameters modification and diet (Behavioral, SANYpet S.p.A., Padua, Italy) (Di Cerbo et al., 2017, Fahnestock et al., 2012, Sechi et al., 2015, Sechi et al., 2017). These studies showed that dogs receiving two different antioxidant- and botanical-enriched diets (rice, fish meal, vegetable fats and oils, fish oil, beet pulp, minerals, dehydrated yeast, FOS, Yucca schidigera, Grifola frondosa, Curcuma longa, Carica papaya, Punica granatum, Aloe vera, Polygonum cuspidatum, Haematococcus pluvialis, Solanum lycopersicum, Vitis vinifera, and Rosmarinus officinalis) presented significantly higher BDNF (Sechi et al., 2015), lower d-ROMs and normalized neuroendocrine parameter levels as well as an overall improvement in behavioral disturbances and their related clinical signs (rice flour, fish protein hydrolysate, potato protein hydrolysate, minerals, Punica granatum, Valeriana officinalis, Rosmarinus officinalis, Tilia spp., Crataegus oxyacantha L. tea extract, and L-tryptophan), if compared to animal fed on a control diet (Di Cerbo et al., 2017, Sechi et al., 2017). This evidence suggests that dietary intervention might be a valuable alternative for treatment of cognitive deficits and behavioral disturbances in dogs.

Table 1. Studies of functional foods and functional food-containing diets in dogs.

BAP, biological antioxidant potential; BDNF, brain-derived neurotrophic factor; d-ROMs, derivatives of reactive oxygen metabolites; FOS, fructooligosaccharides; MOS, mannan-oligosaccharides.

Halitosis is a condition affecting both dogs and humans impacting their relationships (Di Cerbo et al., 2015b). A randomized placebo-controlled cross-over clinical evaluation assessed the effectiveness of a dedicated diet (Forza10 OralActive, SANYpet S.p.A., Padua, Italy) in improving chronic halitosis in 16 dogs of different breeds and ages (Di Cerbo et al., 2015b). Briefly, it was possible to evaluate the efficacy of the diet (rice, fish meal, vegetable fats and oils, fish oil, beet pulp, minerals, dehydrated yeast, FOS, Yucca schidigera, propolis, Salvia officinalis, lysozyme, bioflavonoids, Thymus vulgaris, and Ribes nigrum) on oral volatile sulfur compounds, e.g. methyl mercaptan, hydrogen sulfide and dimethyl sulfide, using gas chromatography, which evaluated the concentration of the aforementioned compounds over 30 days. A significant decrease in halitosis-related sulfur compounds was observed. Moreover, such improvement was still evident at 20 days post interruption of the diet supporting the long-lasting efficacy of the compound. Di Cerbo and coworkers observed a pivotal role of a functional diet (hydrolyzed proteins of fish and vegetable origin, minerals, used as glidants, Melaleuca alternifolia, Tilia platyphyllos scapoli et cordata, Allium sativum L., Rosa canina L., and zinc) in relieving chronic otitis externa-associated symptoms limiting the need of pharmacological therapy to treat this condition (Di Cerbo et al., 2016). In this study, 15 adult dogs of different breeds and ages, affected by chronic otitis externa, received a functional diet along with pharmacological therapy (OTOMAX, 8 drops a day for 7 days). The nutraceuticaldiet, endowed with anti-inflammatory and antioxidant activities, significantly decreased the mean score intensity of all symptoms (occlusion of ear canal, erythema, discharge quantity, and odor) after 90 days of intervention. In this evaluation, dogs received the pharmacological treatment for the first 8 days of diet supplementation, while they received diet alone for the remaining 82 days. This result is of significant relevance in light of the growing of antimicrobial resistance to pharmacological therapy and represents a starting point for developing functional foods endowed with antibacterial activity. A further study investigated the effect of an immune-modulating diet (IMMD) or standard diet (SD) combined with anti-Leishmania pharmacological therapy (meglumine antimoniate and allopurinol), in 2 groups of 20 dogs (IMMD and SD groups) of different breeds and ages, affected by canine Leishmaniasis (CL), at 0, 3, 6 and 12 months (Cortese et al., 2015). The IMMD restored the levels of regulatory T cells that are reduced during CL, if compared to dogs receiving the SD, at 3, 6 and 12 months. At 6 and 12 months, dogs fed on the IMMD also showed a decrease in T helper cells comparable to the levels observed in healthy dogs. This evidence suggests that a specific diet can regulate the immune response in dogs affected by CL during pharmacological treatment. The same immune-modulating diet resulted particularly effective in reducing the overall mean intensity of tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge which are the most common symptoms of canine keratoconjunctivitis sicca (Destefanis et al., 2016).

Pet food palatability has also been object of study since this feature is of key importance in terms of suitability and safety. Spears et al. (2004) examined palatability of a dry canine diet and its effect on digestion of stabilized rice branby determining fecal characteristics, food intake, selected immune mediators and blood lipid characteristics (Spears et al., 2004). In the first experiment, the authors compared the palatability of 4 diets containing poultry fat (Test diet 1) or soybean oil (Test diet 2) combined with either 12% stabilized (Test diet 3) or defatted rice bran (Test diet 4) which were fed on 20 dogs for 4 days. Food intake improved in dogs fed on Test diet 1 combined with 12% stabilized rice bran. In the second experiment, 36 beagles received 6 diets containing 12% stabilized or defatted rice bran diet combined with poultry fat, beef tallow, or poultry fat:soybean oil (50:50). Dogs on a defatted rice bran diet showed significantly lower plasma phospholipidtotal monounsaturated fatty acids with respect to those on a stabilized rice bran diet. They observed that stabilized rice bran was well tolerated in dogs with no detrimental effect on nutrient digestibility and fecal characteristics and without promoting changes in inflammatory and immune responses. Moreover, stabilized rice bran diet presented better palatability compared to the defatted rice bran diet.

4. Functional foods and cat nutrition
Compared to dogs, cats are carnivorous animals with different nutritional needs (Legrand-Defretin, 1994). Thus, specific functional foods have been investigated in cat nutrition, as summarized in Table 2. In a randomized, double-blind, controlled clinical trial involving 55 cats with chronic diarrhea, the efficacy of either a high (10%) or low fat (23%) highly digestible diet (soy flakes, soy protein isolate, turkey and turkey by-product meal, corn starch, oat meal, oat fiber, beef tallow, vitamins and minerals) was evaluated by assessing the fecal score (FSa). All cats responded to the diets tested with an increase in FSa within the first week, achieving a maximum response to diet supplementation within 3 weeks. Furthermore, one third of the cats developed normal stools. No significant differences were observed in response to both diets, indicating that dietary fat amount is not a key factor in dietary management of cats with diarrhea (Laflamme et al., 2011).

Table 2. Studies of functional foods and functional food-containing diets in cats.

In a further study, inclusion of 26% full-fat rice bran in a purified cat diet led to a significantly lower mean whole blood taurine concentration, if compared with controls fed on a purified diet containing 26% corn starch (Stratton-Phelps et al., 2002). The lower taurine concentration observed in cats fed on the rice bran diet was due to increased fecal excretion of conjugated bile acids in addition to changes in hindgut microbiota due to the indigestible protein fraction of rice bran able to degrade taurine (this amino acid is not degraded under physiological conditions). Based on this outcome, a higher concentration of dietary taurine (> 0.05%) should be included in feline diets that contain rice bran. Cats can self regulate food selection and intake to balance macronutrient intake regardless of differences in moisture content and textural properties of commercial cat diets (Hewson-Hughes et al., 2013).

Even under artificial selection (domestication), where humans largely determine the diet of the animal, evidence suggests that, when provided with a choice of foods with different nutritional profiles, cats consume different quantities of different foods to balance their nutrient intake. This was shown by Hewson-Hughes and co-authors (Hewson-Hughes et al., 2013) by feeding 45 cats on 2 different commercial diets (wet diet: Sheba® chunks in jelly, Turkey and Chicken variety, Wd; dry diets: (Whiskas® TOP, Chicken variety, Dd) in different combinations (1 wet + 3 dry; 1 dry + 3 wet; 3 wet + 3 dry). Diets were offered simultaneously and separated by a phase in which diets were offered sequentially in 3-day cycles. This study shows a convergence upon the same dietary macronutrient composition within each experiment as well as over the course of the 3-day cycles. Moreover, despite differences in dietary options, the macronutrient composition of the diets was remarkably similar across all experiments. Besides composition, acceptance and digestibility of nutrients are other key factors that need to be taken into account in cat nutrition. Since apple pomace has a low digestibility (Fekete et al., 2001), it was mixed with a meat-based diet at an inclusion level of 10, 20, and 40% and fed to 9 adult neutered European shorthaired obese cats (Fekete et al., 2001). Inclusion of apple pomace (10 or 20% of the diet) did not decrease food palatability, reduced the energy density, slightly changed the digestibility of fat, and considerably decreased the digestibility of crude protein. Energy density decreased proportionally to the percentage of apple pomace added to the diet. Unfortunately, at a 40% inclusion rate, a lower food intake was observed. Therefore, inclusion of palatable fibrous components at a restricted inclusion rate in the diet of obese cats represents a good way to reduce food energy content and maintain a physiological level of food intake.

5. The pet food market
Adequacy and safety of food supply are of great interest to consumers (Buchanan et al., 2011). Generally, pet owners do not refuse to provide foods that can support health and wellness of their animals, but at the same time, doubt their safety. For instance, incorporation of corn and wheat that have documented antioxidant and anticancer activity (Wood et al., 1994) into pet foods has been perceived as negative by a subgroup of pet owners who believe that they are of lower quality or of poor nutritional value for dogs and cats, despite them matching the Association of American Feed Control Officials (AAFCO) standards (Carter et al., 2014). Pet owners have shown increased interest in holistic, natural diets containing wholesome ingredients, such as oats (Avena sativa) and barley (Hordeum vulgare), which can reduce the risk of obesity (Jones and Engleson, 2010) and prevent diabetes mellitus (the greater the intake of whole grains is, the lower the fasting insulin levels are likely to be) (Pereira et al., 2002). Besides food nutrition-related benefits, safety issues should also be taken into account. In recent years, pet food safety has represented a substantial challenge because of the direct impact of food contaminations on both animals and humans (FDA, 2005). Such contaminations could also lead to nutritional deficiencies despite a correct diet formulation. However, the effect of contaminations (caused, for instance, by microorganisms) of pet foods on animal health has not been extensively investigated due to the multitude of possible sources of contamination (LeJeune and Hancock, 2001). Moreover, most commonly used pet foods in the UK employ products of unknown animal origin including bovine, porcine and chicken DNA in various proportions and combinations often not explicitly indicated on the product labels (Maine et al., 2015). Therefore, the pet food industry still has various challenges to overcome in order to provide better nutriments to dogs and cats.

6. Conclusions
Due to a reduction in the number of family components in industrialized countries, the role of pets such as dogs and cats as ‘family members’ has gained increasing importance (Shepherd, 2008), and their health and well-being have become a prominent challenge for their owners (Buchanan et al., 2011). As a matter of fact, companion animals, most commonly dogs and cats, provide a positive impact on humans' emotional (Allen et al., 1991, Serpell, 1991) and physical health (Friedmann and Thomas, 1995, Headey, 1999). Due to the difficulty understanding pet food labels, consumers' education becomes a key issue for the marketing of functional foods. In addition, research on pet food is still scarce. Accurate claims on food labels help consumers select products that satisfy their desire to promote animal care and improve their pets' health. Food scientists and healthcare professionals should therefore work together to improve consumers' education by accurately characterizing new scientific developments or achievements in nutrition. The ultimate success of functional pet foods will depend on delivering bioactive components in a predictable, safe and functional manner to effectively reduce the risk of disease and support the domestic animal's body. Future basic and applied nutritional research should further explore the role and mechanism of functional foods in dogs and cats.

Source: AlessandroDi Cerbo, Julio Cesar Morales, Medina BeniaminoPalmieri, Federica Pezzuto, Raffaella Cocco, and Gonzalo Flores TommasoIannitti. “Functional foods in pet nutrition: Focus on dogs and cats.” Research in Veterinary Science. (2017): Volume 112: 161-166

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