Transcript Cancer - Oxford Labs

Cellular Oxidative Stress &
Chronic Inflammation, Part 2
W. Jean Dodds, DVM
AHVMA 2016
Columbus, OH
Cellular Oxidative Stress & Cell
Homeostasis
 Cells are in homeostatic equilibrium when in oxidative balance
 Occurs when the antioxidants (reducing agents) are balanced with
the oxidants (oxidizing agents)
 When oxidant levels exceed antioxidants (termed cell redox) , the
cell undergoes oxidative stress
 Basic mechanism of all sickness and chronic disease
(Mandelker, JAHVMA 41: 22-24, Winter, 2016)
Cellular Optimal Health
 Even with chronic health conditions, cells still have a
remarkable ability to repair, regenerate and renew
 Creating optimum health at the cellular level involves two key
nutritional steps:
• feeding a diet rich in functional foods that tells the epigenome to
initiate healthy gene expression; and
• reducing or removing foods sending harmful messages to the
epigenome, and causing unhealthy gene expression
 Ideal diet contains Three Keys --
variety, nutrient-dense, whole foods
Nutritional Ecology
 Study of animal nutrition based on ecology and
evolution
 Science that spans many fields including ecology,
nutrition, behavior, morphology, physiology, life history,
and evolutionary biology
 Focuses not specifically on the organism or its
environment, but rather on the dynamic interface
between organism and environment
(Raubenhemer & Simpson Ann Rev Nutr 36:603-626, 2016)
Nutritional Geometry
 Framework for examining how mixtures of nutrients (and
other dietary components) influence biological outcomes
such as health and disease
 Differs from studying a particular nutrient in isolation
 Focus on mixtures allows for modeling how nutrients
interact to determine the nutritional properties of foods
and how foods in turn combine into meals, diets, and
dietary patterns that influence health
(Raubenhemer & Simpson Ann Rev Nutr 36:603-626, 2016)
Overweight = Increased Health Risk
 Cardiorespiratory diseases: airway obstruction in brachycephalic
breeds, and laryngeal paralysis
 Endocrine disorders: hyperadrenocorticism (Cushing’s disease) and
hypothyroidism
 Functional alterations, like decreased respiratory capacity, exercise
intolerance, heat intolerance/stroke and decreased immune functions
 Metabolic abnormalities, like hyperlipidemia and dyslipidemia
 Neoplasia, including transitional cell carcinoma (TCC)of the bladder
 Orthopedic disorders, like osteoarthritis, anterior cruciate ligament
rupture and intervertebral disk disease
 Urogenital system conditions, including TCC of bladder
Obesity Regulates Gene Expression
 Poor diet leads to health problems by creating fat, but also
changes the expression of obesity-related genes
 Foods that suppress genomic expression for obesity may not only
result in weight loss, but also reduced risk of obesity-related diseases
 More fat cells create more cytokine secretion ( pro-inflammatory
cell messengers) leading to more chronic, systemic inflammation
 Fat regulating hormones = adiponectin that modulates metabolic
processes like glucose regulation and fatty acid oxidation, and
leptin, that acts on the brain to regulate food intake and body
weight, and signals satiety
 Green tea enhances adiponectin.
Oxidative Stress & Chronic Inflammation =
CANCERS
Background

Cancer responsible for about half the canine and feline deaths in the USA.

Leading cause of death in dogs older than two years.

No definitive conclusion why some individuals get cancer.

Estimated 5 -10% of all cancer cases originate purely from genetic
predisposition, but 90-95% are the result of lifestyle & environmental factors.

“Basically, cancer is often a fatal disease caused by mutations in the genes
of certain susceptible cells. These genetic mutations, usually caused by
inflammation or excessive oxidation, convert normal cells into cancer cells
that divide rapidly and grow uncontrollably, pushing their way into the
surrounding tissues composed of otherwise normal cells”.
Dr. Shawn Messonnier, 2006.
Cancer & Immune Surveillance
 Cancer cells are created in the body every day
 Healthy immune system distinguishes these mutated cells from
normal cells and kills them
 Compromised immune system allows these cells to live and divide
until they create cancerous tumors
 Cancer cells exist in a ‘wound healing’ environment, which they
help create, and are energy hungry
 Cancer cells preferentially use protein for energy and prefer certain
amino acids, like arginine, at the expense of the host
 Cancer diets often contain arginine to replenish and repair
depleted sources
More Behavior of Cancer Cells
 Cancer cells preferentially metabolize glucose for energy
 Different pathway than normal cells; form lactate causing local
acid environment
 Body must expend energy to convert lactate back to glucose
 Cancer diets should thus be low in carbohydrates
 But, end-stage cancer diets need carbohydrates to replace
depleted energy stores
 Most cancer cells cannot oxidize fats, so cancer diets need high
quality, high fat content, especially omega-3 fatty acids
 But, these high fat diets are unsuitable for pets prone to
pancreatitis or liver disease.
 Provide bioavailable vitamins & minerals
Cancer Cell
T-Lymphocytes Attacking Cancer Cell
Breast Cancer Cell SEM
Lymphoma Cell
Leukemic Cells in Blood
Melanoma Cell
Predisposing Factors & Cancer
 Obesity
 Foods with high Glycemic Index (GI)
 Glutens (release zonulin from bowel)
 Fluoride (accumulates in bones; osteosarcoma risk)
 Environmental toxins
 PBDE (polybrominated diphenyl ethers) (flame
retardants; especially toxic for cats)
 Secondhand smoke
 Topical flea/tick preventives
 Adverse vaccine reactions
Obesity & Cancer
 Obesity alters metabolism of hormones that maintain and
control balance of cell proliferation, differentiation, and
apoptosis
 Pro-inflammatory cytokines produced by fat cells activate
transcription factor (NK-fB) that promotes carcinogenesis and
other inflammatory diseases
 NK-fB activated by hyperglycemia of obesity
 Link between gene expression
in fat and insulin resistance =
high risk for type 2 diabetes and cancer
 15 types of cancer in people are linked to long term obesity,
especially bowel cancer that occurs later in life
High Glycemic Index Carbs & Cancer
 Promote carcinogenesis and hyperinsulinemia
 High risk for type 2 diabetes and colon-rectal cancer
 Avoid refined sugars and flours
Glutens & Cancer
 Releases zonulin from bowel which causes “leaky gut”
 Immune attack of inflammatory invader proteins
triggers diseases (IBD) and cancers
 Avoid glutens in animal cancer diets
Fluoride & Cancer
 Fluoride accumulates in bones, results in high risk for
osteosarcoma
 Dogs 10 times more likely to have osteosarcoma than people
 High fluoride levels in food and fluoridated water
 Dry dog foods have 1.6-2.5 times EPA‘s safe fluoride level
 Pet foods contain bone meal, meat meal and meat byproduct meal
 Promotes mitosis and rapid growth of osteoblasts
 Dogs with cancer should avoid bone meal and animal
byproducts, and drink fluoride-free water
Environmental Toxins & Cancer
Common environmental toxins include:
 Lawn and garden pesticides, herbicides, fertilizers, swimming
pool products
 Household cleaning, carpet and laundry products
 Construction materials
 Automotive products including antifreeze
 Batteries and battery acids
 Personal care and hygiene products
Pet care and grooming products
PBDEs (polybrominated diphenyl ethers)
& Cancer
 Flame-retardant chemicals used in clothing, furniture and
electronics for 40 years
 Leak into environment; known disruptors of endocrine function,
especially thyroid gland
 Linked to developmental problems, and even cancer, in animals
 Residues found in serum, foods and house dust of cats and dogs
PBDE levels in cats were 20 -100 times those in humans, while levels
in dogs were 5-10 times higher-- -- as dogs metabolize them faster
than cats, and have an enzyme that helps detox them
See Environmental Working Group (www.ewg.org)
Secondhand Smoke & Cancer
 Research studies found that dogs exposed to large amounts
of second-hand smoke eventually have substantial changes
to their lung tissue
 Changes range from fibrosis to pre-cancerous and even
cancerous lesions
Topical Flea/Tick Preventives & Cancer
Products used to eradicate, like monthly spot treatments
squeezed between the shoulder blades, contain toxic
chemicals that pose both immediate and chronic health
risks to dogs—including death
Topical Flea/Tick Preventives & Cancer
(cont’d)
 In 1989, Purdue University Veterinary School found that dogs
receiving 1-2 topical pesticides per year had 60% increased risk of
bladder cancer. Dogs given more than 2 applications per year were
3.5 times more likely to develop bladder cancer. The risk was
increased even more in overweight or obese dogs
 Use veterinary prescribed products rather than OTC or pet store
supplies, as should be safer
 Organophosphates, carbamates and pyrethrins/pyrethroids pose
severe health risks; clearly not for dogs with cancer
 Use common sense preventives measures instead (bathing dog and
bedding, combing, keeping grass short, natural repellants)
Adverse Vaccine Reactions & Cancer
 Both MLV and inactivated, killed vaccines can produce serious
adverse reactions including death in susceptible animals
 Injection-site sarcomas can occur at sites of vaccination in both
dogs and cats
 Removal of the tumor can still result in recurrence – which has
promoted worldwide policies to vaccinate pets in certain preferred
locations on the body and to record where vaccines were given
 Most commonly associated with rabies, feline leukemia, but can
occur after any vaccination
 Affected pets should not be revaccinated; for rabies, need to
receive written exemption/ waivers instead
Toxic Exposures & Cancer
Example: Bispenol-A (BPA), chemical used to make plastics
and resins harden but stay flexible
 Despite known hazards, used in plastic water bottles, food containers,
and to line inner surface of canned goods
 95% of population has BPA exposure
 Leaches into food & beverages it contacts
 Has estrogenic properties
 Affects many body tissues and functions: prostate, testes, mammary
glands, brain; body size, and behavior
 Only use canned goods labelled BPA-free. But related compounds
are being used like Bisphenol-F and -S
Diet & Cancer
 Dietary changes can prevent 30-40% of all cancers
 Remove harmful foods that block effects of functional food
 Promote DNA methylation (turmeric = curcumin, folate, cruciferous
vegetables, SAMe, vitamin B-12)
 Green leafy & yellow orange vegetables
 Herbs & Ginger
 Milk thistle (Silybum marianum); has active flavonoids
 Berries (blueberries, cranberries, aronia); Pomegranates
 Medicinal Mushrooms
 Prebiotics (Spirulina) & Probiotics
 Vitamin D
 Omega-3 fatty acids
Supplements & Cancer
 Anti-oxidants (reduce free radical damage)
• Vitamins A, C, E and Co-Enzyme Q10
 Pro-oxidants (increase free radicals; enhance cancer cell death)
• High dose curcumin (turmeric)
 Anti-angiogenic (reduce cancer’s blood supply)
• Fractionated pectin and shark cartilage
 Immune modulators (increase or decrease immune system needs)
• Mushrooms like Coriolus versicolor and Cordyceps sinensis
 Specific gene expression/ chemical pathway modulators
• Quercetin down-regulates mutant p53 gene and functions in
tumor suppression; but also promotes cell division and cancer.
Quercetin suppresses expression of the RAS gene which can
cause cancer
Phytochemical Nutrients &
Cancer
 Phytochemicals [plant chemicals that help prevent disease],
including carotenoids (e.g. beta-carotene, lutein, zeaxanthin),
flavonoids (e.g. quercetin, resveratrol, rutin), and phytosterols
 Green leafy vegetables like spinach, broccoli, kale, lettuce, Italian
parsley, Swiss chard, collards, bok choy or turnip greens
 Yellow orange vegetables like squashes, carrots, pumpkin, yellow
beets, yams, and sweet potatoes
 Both the green leafy and yellow orange vegetables when given 3
times a week or more decrease canine TCC bladder cancer risk by
92%
Anti-Angiogenic Foods
Beneficial in mast cell tumors
 Apples
 Artichokes
 Berries (blackberries, blueberries, raspberries)
 Bok choy
 Cherries
 Curcumin (turmeric)
 Ginseng
 Kale
 Lavender
 Maitake mushrooms
 Olive oil
 Parsley
♣ Pumpkin
Herbs & Cancer
Herbs that enhance immune function (Fougère, 2012)
 Cordyceps sinensis
 Echinacea
 Astragalus
 Withania
 Siberian ginseng
 Essiac
 Cats claw
 Pau d’Arco
 Shitake and Reishi mushrooms
Supplements for Balancing
the Immune System
 Immune function requires zinc, selenium and vitamin E,
vitamin B6 , and linoleic acid; and carotenoids, especially
lutein and beta-carotene
 Sterols + Sterolins in combination = immune balancing and
stress modulating fats from fruits, vegetables and medicinal
plants (e.g. ModuCare by Thorne)
 Natural antioxidants and preservatives (e.g. vitamins E and
C, citric acid, rosemary, turmeric, oregano, blueberries,
cranberries, pomegranates)
Dietary Supplements
 Novel or restricted protein source diet, pre-biotics
(spirulina), probiotics (FOS, MOS) , antioxidants
 Carotenoids, kelp, garlic, high fiber foods, nutritional herbs
 Medicinal herbs, vitamins E and C, apple cider vinegar
 Essential oils, flower essences, unpasteurized yogurt
 Taurine and DMG for epileptics, milk thistle or denosyl
methionine as liver cleanse, herbal pain remedies
Herbs / Nutrients to Use with Caution
 Rosemary, Oregano, Fennel and Sage– added today as pet
food preservative and antioxidant. NOT to be given to
epileptics. (Peppermint Oil can help protect epileptics)
 Grapes and Raisins – toxic to dogs; acute renal failure
 Corn, Corn Starch, Fructose from Corn – associated with food
sensitivity, intolerance
 Wheat and Wheat gluten -- associated with food sensitivity,
intolerance
 Onions – cause Heinz body hemolytic anemia; Garlic , safe in
moderation
 Vasoactive Amines – tuna, mackerel, skipjack, bonito
“Let food be thy medicine and
medicine be thy food.”
Hippocrates