Integrative therapies for improving mobility in senior dogs 

An evidence-based overview of integrative strategies to improve mobility in older canine patients. Addresses oxidative stress, inflammation, diet, exercise, nutraceuticals, and adjunct therapies for osteoarthritis and age-related decline.

As dogs age, declining mobility becomes one of the most common and challenging clinical concerns faced by veterinarians and caregivers alike. Emerging evidence identifies oxidative stress and chronic inflammation as central drivers of musculoskeletal degeneration, osteoarthritis, and reduced quality of life in senior dogs. This article examines an integrative, evidence-informed approach to supporting mobility in aging canine patients, including targeted nutrition and nutraceuticals, to address underlying pathophysiology rather than symptoms alone.

OS and INFLAM are major contributors to age-related disease 

Cellular oxidative stress (OS) and chronic inflammation (INFLAM) are now widely accepted as major underlying risk factors that play key roles in the etiology of a range of human and animal situations and diseases. These include the effects of aging, as well as rheumatoid arthritis, cancer, diabetes, neurodegenerative disorders, cardiovascular and renal diseases, and other chronic disorders. This is supported by tens of thousands of peer-reviewed scientific studies.

OS and chronic INFLAM are influenced by a range of environmental, dietary, and lifestyle factors, and can synergize to exacerbate their effects on human and animal health. Similarly, it is now recognized that specific dietary components, suitable exercise regimens, and certain drugs like NSAIDs, as well as a range of nutraceuticals, can reduce these risk factors significantly. These same principles apply equally to our companion animals, as we share our lives and environments with them.

Factors that impact upon longevity and well-being have been studied for decades, especially as related to comparisons between human beings and the pet animals that share our planet. The great diversity of pet sizes and types, particularly among domestic dog breeds, influences their rates of aging and lifespan. For example, smaller breeds typically live longer than larger and giant breeds.

OS that develops from exposure to reactive oxygen species (ROS) has been documented to affect longevity, although the precise molecular mechanisms are as yet unknown. Molecular biomarkers — including the total antioxidant capacity (TAC) and glutathione peroxidase (GPx) that increase with the body mass of wild but not domestic canines — have been identified to aid in studying longevity and monitoring OS. 

Reactive oxygen species (ROS) 

Sources of ROS include metabolism, aging, disease, exercise, environmental toxins, inflammation and immune activation, poor or imbalanced diet (high fat, sugar).

These factors cause high cell damage, involving malondialdehyde (MAD), isoprostanes, 4-hydroxynonenal (4HNE), protein carbonyls, and DNA cross-linking single strand breaks, modifications, mutations and proteins.

More about oxidative stress 

Gene expression: Up-regulation of antioxidant synthesis occurs to help restore oxidant/antioxidant balance (cell redox).

Adaptive response: Involves changes in gene expression that result in elevated antioxidant defenses. However, inappropriate use of antioxidants may severely blunt the adaptive response.

Cell injury: Physiological reaction draws immune cells and molecules to sites of cell injury. This may be transient or irreversible, leading to cell death by necrosis or apoptosis. Immediate biologic mediators include prostaglandins, leukotrienes, serotonins, histamine, platelet-activating factor, and other enzymes. Chronic or sustained release mediators include tumor necrosis factor-alpha (TNF-α), acute phase proteins, interferons, adhesion molecules and colony-stimulating factors.

Signaling pathways: Moderate amounts of ROS and responsive neurostimulation (RNS) are important regulatory mediators in the cell signaling processes. Mitochondrial cell respiration generates a high rate of ROS during energy production; this creates more OS. The body responds through complex cell signaling pathways to restore the oxidant/antioxidant balance. This physiological mechanism drives vital cellular functions.

Biomarkers of OS

DNA damage: Investigations have been done into measurementsof the products of DNA damage, including 8-hydroxydeoxyguanosine, which is excised from OS-damaged DNA by repair enzymes. Unfortunately, results from various laboratories using the most sophisticated technologies may vary by over an order of magnitude. Hence, such assays are unreliable for clinical use. Only tissue biopsy is confirmatory, but impractical for wellness screening.

Protein damage: Measurements of the by-products of protein damage have not been standardized and made sufficiently sensitive to be widely used for assessing human or animal health.

Lipid peroxidation: One of the major outcomes of ROS-mediated injury to tissue is lipid peroxidation. The peroxidation of polyunsaturated fatty acids occurs mostly in membrane phospholipids. Many methods have been developed to measure the levels of oxidized lipids in body fluids. Among the first, and still most widely used, is the measurement of thiobarbituric acid reactive substances (TBARS). The TBARS assay has been widely used to measure lipid oxidation products like MDA in biofluids. However, as typically performed, the TBARS assay suffers from a lack of specificity and from multiple interferences. More recently, methods for quantifying specific oxidized lipids are available, including MDA and prostaglandin PGF2-α in plasma or urine.

Thiobarbituric acid reactive substances (TBARS): This test continues to be the most widely used method for evaluating oxidative injury in clinical studies. Kinetic measurements of TBARS, which quantitate the rate of generation of the TBA complex, provide increased sensitivity.

MDA is a widely recognized biomarker for lipid peroxidation. Although the standard TBARS methodology is subject to multiple interferences, a novel and more accurate assay for the specific quantification of MDA was recently developed.

Interferon and its role in cancer and cardiovascular disease are well established. For humans, several studies support the use of NSAIDs such as aspirin and ibuprofen to reduce risks for both disorders. Many additional biomarkers for various aspects of interferon have been suggested, including the measurement of eicosanoid metabolites and certain cytokines.

Tumor necrosis factor-alpha (TNF-α)is produced primarily by activated macrophages, and is an endogenous pyrogen. It is able to induce fever and apoptotic cell death and is a primary mediator of inflammatory responses.

Nitrous oxide (NO) is produced in mammals by three isoforms of NOS. These isoforms are differentially expressed and regulated and have many physiological and pathophysiological roles, ranging from regulation of vascular tone to inflammation and cancer. During inflammation, the levels of one of the NOS isoforms may increase up to 1,000-fold, giving rise to significant elevations in NO and its by-products, and providing a sensitive barometer for systemic inflammation. NO is highly reactive, with multiple by-products produced in vivo, including peroxynitrate, nitrate and nitrite (collectively NOx).

Note that certain drugs, or by-products from the digestion of foods containing high levels of nitrates, will also contribute to the NOx value obtained by this method.

Urinary protein, when present in large amounts in the urine, is a widely recognized biomarker for kidney damage. A reduced glomerular filtration rate (GFR) along with an increase in urine protein levels occur during inflammation. Recent studies have demonstrated that the decrease in GFR is caused by the action of inflammatory cytokines on the kidney.

Creatinine is the metabolic product of muscle tissue and a normal constituent in urine. However, it is well known that elevated levels of creatinine may be excreted by individuals eating a high protein diet, those undergoing athletic or other physical training, and those suffering from kidney disease. Since meat contains creatine, the precursor of creatinine, a diet rich in meat can lead to a gradual increase in creatinine excretion. Further, cooking meat converts creatine to creatinine, which is quickly excreted and can significantly increase urinary creatinine levels in the hours after ingestion.

Specific gravity (SG) is a measure of a material’s density relative to that of pure water (the SG of water is thus equal to 1.0000). Many publications recommend SG over creatinine for normalization of a wide range of clinical analytes in urine, including steroid hormones, cotinine by-product of nicotine metabolism, heavy metals, and xenobiotic metabolites.

Large molecules such as glucose, albumin, phosphates, sulfates, and heavy metals contribute more to the SG of a urine specimen than low-molecular-weight substances such as sodium, chloride, and urea. Thus, normalization to specific gravity is less ideal for individuals with diabetes and nephrotic syndrome, which causes high concentrations of glucose and protein in urine. Further, starvation and dehydration produce ketones from fat metabolism that erroneously lower SG readings because they are less dense than water.

Antioxidant enzymes and defences 

Vertebrates have multiple and highly regulated antioxidant (AO) systems, so that large changes in healthy individuals would not be anticipated.

In order to minimize damage to essential biomolecules, all organisms that utilize oxygen must have very effective AO systems. These include a range of enzymatic as well as non-enzymatic mechanisms.

• Non-enzymatic mechanisms include both hydrophilic (e.g. uric acid, vitamin C, bilirubin, and glutathione), and hydrophobic (most importantly vitamin E) AOs.

• Enzymatic AO mechanisms either directly metabolize ROS (e.g. superoxide dismutase and catalase) or replenish the supply of reduced ROS scavengers (e.g. glutathione reductase).

Many factors influence AO capacity. It is therefore important to be able to quantitatively assess the TAC within biological specimens.

Primary antioxidants: Include catalase, glutathione peroxidase and reductase, and superoxide dismutase (SOD). Under extreme stress, this system can be overwhelmed, and free radicals build up. ROS and RNS, and their by-products, are released into the blood and tissues, leading to tissue and organ destruction and contributing to the development of a variety of diseases.

Secondary antioxidants: Include vitamins C and E, selenium, zinc, CoQ10 (ubiquinone), alpha-lipoic acid, and bioflavonoids (carotenoids, polyphenols). They assist cells in removing free radicals (ROS/ RNS) but need to be replenished by diet and supplements.

Cell injury in impaired renal function

Dogs with impaired renal function of various causes have markedly higher expression of three cytokines and 5-lipoxygenase compared to healthy dogs. The elevated cytokines include interleukins 1-α and 1-β and transforming growth factor-β. These markers are part of the cellular inflammatory response to both acute kidney injury and chronic kidney disease.

Exogenous compounds derived from diet include those listed above plus B-vitamins, CoQ10 (ubiquinone), Omega-3 oils, and polyphenols.

The blood glutathione (GSH) assay and AO 

The transcription of SOD and catalase enzymes is highly regulated by the binding of the transcription nuclear factor-erythroid-2-related factor 2 (Nrf2) to the AO response element. While activated Nrf2 can be evaluated in a research setting, it is not a suitable clinical biomarker. The serum glutathione level, which is dependent on glutathione peroxidase induction, therefore, is a reasonable surrogate biomarker for Nrf2 activity.

Aging and improving mobility

As animals age, they become subject to more OS and cell damage as shown in the reprinted graphic:

• Declining immunity
• Diabetes mellitus
• Periodontal disease
• Cancer
• Cognitive dysfunction
• Cataracts and lens degeneration
• Chronic kidney disease
• Cardiovascular disease
• Osteoarthritis/and musculoskeletal degeneration and reduced mobility.

Diagnostic assessment

Hundreds of methods for measuring biomarkers, developed and employed in biomedical research, support OS and inflammation as major risk factors for multiple diseases. However, with few exceptions, tests for these risk factors have generally been restricted to research laboratories and/or clinical trials and have not been readily available for the routine monitoring of human (or animal) health and wellness.

Furthermore, these biomarkers, especially those for OS and AO, are notoriously unstable, as the ex vivo reaction of air with biofluids during transit, storage and/or processing can cause very large artifactual values. Rapid analysis close to the site of sample collection is essential in order to obtain more reliable results.

The effects of nutraceuticals 

Herbs to reduce inflammation

The following herbals can reduce tissue INFLAM and promote AO activity for all life stages, especially geriatric people and pets:

• Aloe vera
• Andrographis paniculata (King of bitters)
• Arnica
• Basil
• Boswellia
• Gingko biloba
• Green tea
• Hawthorn
• Lavender
• Lemon balm
• Licorice
• Oregano
• Nettle leaf
• Rosemary
• Sage
• Thyme
• Turmeric (curcumin extract)
• Willow bark (a relative of aspirin, but do not combine with NSAIDs)
• Yucca root

Studies have shown that adding oregano essential oil (OEO) to animal feed can significantly improve growth performance and health status and reduce the occurrence of disease. At the same time, pharmacokinetic studies in animals show that the absorption, distribution, metabolism, and excretion processes of OEO in animals have good bioavailability.

For geriatric people and pets, these supplements ease pain and stress, and in doing so enhance an individual’s mobility.

Brain-boosting foods and supplements

• Blueberries – improve memory, reduce risk of cognitive decline, lower systolic blood pressure
• Dark leafy greens (e.g. spinach, kale) — slow down age-related cognitive decline
• Beans and other legumes — lower cognitive decline, high in fiber
• Nuts – only those safe for pets (pistachios, hazelnuts, walnuts, peanuts, but not Macadamia nuts)
• Fruit – bananas, apples, pears, watermelon, cranberries, pomegranates, pineapple
• Herbs — sage, spearmint, and lemon balm; help with sleep, anxiety and working memory
• Bacopa monnieri and Gingko biloba – for mental alertness, but conflicting research
• CoQ10 — neuroprotective, like n-acetylcysteine (NAC)
• Sulphoraphane from cruciferous vegetables – can cross blood-brain barrier
• Lion’s Mane mushroom — has brain-protective properties

Nutraceuticals for aging pets

A current article by Dr. Vanessa Aberman describes nutraceuticals that can benefit common ailments in aging pets, including cognitive dysfunction, muscle atrophy, and heart health. Specifically, she summarized the use of melatonin, valerian root, homotaurine, apoaequorin, and carnitine/α-lipoic acid combination products for dogs with cognitive dysfunction, and CoQ10 for heart disease. Supplementation of resveratrol, α-tocopherol acetate, and ursolic acid may benefit dogs with sarcopenia and decreased muscle mass, although more definitive data are still needed.

The primary cause of joint pain is stated to be processed sugars in foods and beverages. These can be high in saturated and trans fats, and refined carbohydrates. Many nutraceuticals are documented to be beneficial, as listed in the below review by Colletti and Cicero:

Nutraceuticals to relieve osteoarthritic pain and improve mobility 

• Avocado/soybean unsaponifiables — vegetable extracts made from fruits and seeds of avocado and soybean oil [1:2];daily intakereduces pain from inflammatory interleukins 1,6,8 and prostaglandins.

• Boswellia serrata — rich in boswellic acids; decreases pain, increases knee and hip flexion, increases walking distance, reduces TNF-α and interleukin1.

• Capsaicin — from chili pepper, creates heat that reduces pain and stiffness.

• Collagen –– contained in foods like fish and meat; biologically active amino acids are proline and hydroxyproline; modulate humoral and cellular immune response, stimulate chondrocyte glycosaminoglycan synthesis.

• Curcumin/turmeric (Curcuma longa) — has chondroprotective, AO and anti-INFLAM effects, decreases interleukins 1β and 6, and type II collagen degradation.

• Devil’s claw (South African herb) — anti-INFLAM, pain relieving; has AO and appetite suppressant effects.

• Gingerols (ginger) –– reduces inflammatory markers, decreases joint pain while standing and walking, modulates gut microbiome.

• Ginko biloba — AO, may benefit cognitive function, mood, and circulation by boosting blood flow to the brain.

• Glucosamine/chondroitin –– reduces ROS by lowering interleukins 1 and 6, and TNF-α; maintains plasma NO, improves tissue regeneration.

• Green tea — reducesROS, prostaglandins, cyclooxygenase, interleukins 1β, TNF-α, NO and NF-kB.

• Hyaluronic acid –– mucopolysaccharide that provides chondroprotection; offers mechanical effect by lubricating joint capsule to decrease friction and reduce nociceptors that activate pain.

• L-carnitine –– may help support weight loss, brain function, and disease prevention.

• Methylsulfonylmethane (MSM) – inhibits NF-kB and phosphorylation; reduces interleukins 1, 1β, TNF-α, cyclooxygenase, and NO; activates Nrf2.

• Omega-3 fatty acids (EPA and DHA from fish oils, flax, some other plants).

• Pycnogenol — similar to polyphenols.

• Polyphenols (pomegranate juice, pine bark, green tea) – anthocyanins thathave anti-AO and anti-INFLAM effects.

• S-Adenosylmethionine (SAMe) – protects liver cells and liver function.

• Soy isoflavones — potent AO and activator of Nrf2 pathways.

• Systemic multi-enzyme therapy (Wolf’s Solution to reduce body’s fibrin buildup from inflammation) – anti-INFLAM.

• Vitamin C –– ascorbic acid; highly effective AO reduced ROS and NO; important for synthesis of collagen, carnitine and neurotransmitters. Note that while dogs and cats can synthesize their own vitamin C in the liver, the amounts are often insufficient.

• Vitamin D — important for bone health; immunoregulates inflammation by influencing macrophages, dendritic cells and T and B lymphocytes; reduces TNF-α and interleukin 1 inflammatory pathways that deteriorate cartilage. Found in mushrooms, fatty fish, egg yolks, and vitamin D and D3 fortified products.

An integrative approach to improving mobility in senior dogs addresses the underlying causes of age-related decline, such as oxidative stress and chronic inflammation. By combining dietary adjustments, nutraceuticals, and adjunct therapies, we can significantly enhance the quality of life for aging canine patients. This evidence-based strategy not only helps alleviate symptoms of conditions like osteoarthritis but also supports long-term health by targeting the root causes of musculoskeletal degeneration. As research continues to evolve, these therapies hold promise for advancing the care of senior dogs, providing them with more comfort and improved mobility in their later years.

Author’s published OS and ROS diet study

Three groups of 20 healthy adult greyhounds each had blood samples drawn before, and two and four weeks after, being fed one of three different diets:

• Group 1: Regular grain-free commercial maintenance diet (14% fat)

• Group 2: Prepared balanced diet with beans, canned pheasant, and vegetables for dogs with food sensitivities (9% fat)

• Group 3: Grain-free light commercial diet with lower fat content (7%) for dogs with high triglyceride levels.

Each dog had standard markers of OS (GSH, TAC, and MDA) measured from the blood samples drawn at the three time periods. Glutathione was measured in whole blood; TAC and MDA were measured on separated serum. Additional assays included microRNA (miRNA), and TNF-α.

Results showed some subtle but not striking differences between the oxidative markers of the three diets during the three time points of the four-week study:

• GSH levels, which should reflect Nrf2 activation, showed levels in decreasing order of Light diet > Regular diet > Beans diet. Thus, GSH levels decreased appreciably for the high protein diet (Group 2) and increased for the low carbohydrate diet (Group 3).

• TAC showed no significant difference at the four-week time period, but levels declined over the same period for all three diets. TAC represents the sum of all scavengers of low molecular weight ROS (primarily uric acid and vitamins E and C).

• MDA showed no significant differences.

The Beans (Group 2) and Light (Group 3) diets, which provide high protein versus low carbohydrate content respectively, while they differ in basic nutrients, are not known to vary in antioxidants or Nrf2 inducers (like glutathione).

Flavonoids play a key role in combating OS

Flavonoids, the large family of polyphenolic compounds synthesized by plants, play a pivotal role in the Nrf2 regulatory pathway of OS stress. Dietary flavonoids provide multiple health benefits and work mainly by acting as antioxidants and activators of Nrf2 pathways and the body’s defensive systems.

Flavonoids comprise the following subclasses: anthocyanidins (pigmented vegetables and berries), flavanols (quercetin, green and other teas, kale, broccoli, berries, and apples), flavanones (citrus fruits, parsley, thyme, and celery), and isoflavones (genistein; soybeans, legumes).

Compounded vs human medical products in animal practice 

While recent research identified 1,564 new medications licensed for various animal species, this number is far below the over 35,000 new medications registered for humans, as reported by the U.S. Food and Drug Administration.

Nevertheless, the field of veterinary pharmacology is rapidly expanding, and the use of compounded medications has become increasingly important in clinical veterinary therapy. These products can be compounded with tasty flavors that make it easier to medicate fussy pets, especially cats. However, veterinarians still have to resort to prescribing human medications when veterinary products are unavailable or more costly,

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AUTHOR PROFILE

W. Jean Dodds, DVM

Dr. Jean Dodds received her veterinary degree in 1964 from the Ontario Veterinary College. In 1986, she established Hemopet, the first non-profit national blood bank program for animals. Today, Hemopet also runs Hemolife, an international veterinary specialty diagnostics service. Dr. Dodds has been a member of many committees on hematology, animal models of human disease and veterinary medicine. She received the Holistic Veterinarian of the Year Award from the AHVMA in 1994, has served two terms on the AHVMA’s Board of Directors, chairs their Communications Committee, and currently serves on the Board of the AHVMF, as well as its Research Grant and Editorial Committees.