Now five years old, KetoPet Sanctuary is a non-profit organization that has tested the feasibility of using a ketogenic diet as an adjunctive therapy in dogs with cancer.

Each year, about six million dogs in the US are diagnosed with cancer. In fact, cancer is the leading cause of death in canines. Yet current therapies tend to be only marginally effective. In this article, we will explore the effects of a ketogenic diet (KD) as part of a protocol for treating cancer.

For nearly a century, the ketogenic diet has been used as a therapy to control seizures in children with drug-resistant epilepsy.^1,2 Moreover, recent research is showing that a KD is a promising therapy for improving human health and performance, weight loss, Alzheimer’s, amyotrophic lateral sclerosis (ALS) type-2 diabetes, traumatic brain injury (TBI), and even cancer in humans.^{3,4,5,6,7,8,9,10,11,12}

Most of the current research involving cancer and the ketogenic diet was inspired by Nobel Prize recipient, Otto Warburg, who identified that almost all cancer cells utilize energy differently than normal cells. These studies showed that cancer cells favor the use of glucose, even in the presence of oxygen, an observation known as the Warburg effect.¹³ Cancer requires somewhere between 20 and 200 times as much sugar as normal healthy cells. Since this hallmark finding, Dr. Thomas Seyfried, Dr. Dominic D’Agostino, Dr. Angela Poff and others have demonstrated that lowering dietary intake of glucose via a KD, thus exploiting the metabolic weakness of cancer, has the potential to slow tumor progression. ^{14,15,16,17,18} Dropping blood glucose levels from 90+ mg/dL down to 60 to 70 mg/dL cuts sugar supply by as much as 50%. Lack of glucose slows cancer growth, and potentially kills some cancers, through metabolic starvation.

This process of starvation, known as Ketosis (see sidebar) also makes cancer cells more susceptible to Hyperbaric Oxygen Therapy (HBOT) and other treatments. In addition to acting as a fuel for the body, ketone bodies act as signaling molecules that down-regulate many cancer pathways, including mTOR, IGF-1 and inflammatory levels. Further, healthy cells are protected by ketone bodies when exposed to chemo-radiation.¹⁹ Ketones have been shown to reduce the effects of radiation on blood and bone marrow by as much as 50%. These studies became the foundation of the work done by the KetoPet Sanctuary, a 501c3 non-profit organization formed in 2014, and the first to systematically test the feasibility and applicability of using a KD adjunctive therapy in canines.

The KetoPet Sanctuary program

KetoPet Sanctuary began aiding dogs with many forms of cancer, who were set to be euthanized, from shelters near Austin, Texas. All dogs undergoing therapy resided exclusively at the Sanctuary. All dogs accepted into the program received formulated nutritional therapy (KD), veterinary and oncology care (surgery, chemotherapy and/or radiation), fluorodeoxyglucose positron emission tomography (FDG-PET) imaging (typically used only in humans), metabolic conditioning, hyperbaric oxygen therapy (HBOT), and of course, lots of love. Through the process, the team ensured seamless control over every aspect of the dogs’ metabolic therapy protocol. To date, most of the dogs have since been adopted. They all receive continued care and support from KetoPet Sanctuary’s veterinarians and scientists.

KetoPet observed that a KD could improve survivorship beyond the initial prognosis of some forms of cancer when used as adjunctive therapy with standard of care. KDs do not guarantee a cure for cancer. Nevertheless, 55% of the dogs who graduated from the KetoPet program are still going for long walks, enjoying play, and experiencing a quality of cancer-free life far beyond their original prognosis. KetoPet is now committed to sharing what they’ve learned about metabolic therapy, HBOT and other cancer therapies with pet parents around the world.

What is a ketogenic diet?

A ketogenic diet (KD) is a nutritional strategy that intentionally manipulates the macronutrient ratio of carbohydrates, fats and proteins to induce a state of ketosis. The average American canine diet (kibble) is greater than 45% carbohydrate. The KD shifts the carbohydrate component to less than 10% and increases fats to 60% to 80% of the total daily calories. Thus, a KD is high in fat, adequate in protein, and low in carbohydrates.

For canines, a KD can range from 69% to 90% fat, 9% to 30% protein, and 1% carbohydrates, depending on the dog and purpose. KDs with a higher percentage of fats (87%+) are favored for seizure control in dogs with epilepsy; however, these higher percentages are not needed to induce ketones, nor do they appear to significantly increase ketone levels in the blood.

KetoPet observed that canines routinely entered ketosis using an 82% fat/17% protein/1% carbohydrate formulation. After a period of time (120 days minimum), dogs may be able to maintain ketosis on a lower formulation (69% fat/30% protein/1% carbohydrates), allowing for more protein intake, although each dog is different. Optimization of carbohydrate and protein intake must be validated through dietary monitoring and modification, along with ketone and glucose testing, to determine what works best for each dog. Additionally, optimal blood ketone levels for cancer therapy are not yet known.

As compared to other low-carb diets such as Atkins, the KD requires only adequate protein. As with carbohydrates, the body can convert excess protein into sugar, thus disabling ketogenesis. Commercially-packaged dog foods can contain up to 80% of calories from carbohydrates. Therefore, all processed kibble diets are too high in carbohydrates to induce ketosis.

Nutritional fact panels on pet foods do not list carbohydrates, which makes it difficult to determine how much digestible carbohydrate a product contains without sending it to a lab for detailed analysis. Even products that claim to be grain-free and raw can still contain high amounts of carbs in the form of fruit, sweet potatoes, carrots and other ingredients.

Implementing a ketogenic diet in canines

Some commercially-available raw food products, or a meticulous homemade diet, can allow pet owners to implement a ketogenic diet at home. However, the math required to calculate the meal plan can be daunting. KetoPet has created a free online calculator that helps pet parents formulate ketogenic meal plans for their dogs (ketopetsanctuary.com/calculator).

Despite the KD’s clear therapeutic potential, the success experienced at KetoPet is largely attributed to the strict protocols that were followed. The KD can also contribute to success at home when strict protocols and adjunctive therapies are consistently implemented. These include:

• Rigorous macronutrient control and elimination of glucose sources
• Repeated blood glucose and ketone testing
• Dietary adjustments based on glucose/ketone results and canine body composition
• 20 to 30 minutes of metabolic conditioning twice daily. Daily exercise increases heart rate, burns calories and stimulates mitochondria. These benefits also keep insulin low, thus helping to battle cancer
• Use of HBOT
• Use of standard of care when deemed appropriate by veterinary oncologists
• Regular FDG-PET diagnostic testing and evaluation.

9 common ketogenic Diet myths

1. “The diet is unpalatable.”

Fats contain more calories per gram of food. Therefore, less volume is consumed to attain satiety. This decreased need for volume is often perceived as appetite loss or disdain for the diet.

2. “High fat causes pancreatitis.”

Oxidized phospholipids (oxPLs) accumulate at sites of inflammation and are involved in a wide range of inflammatory diseases. Combined with high insulin, anti-nutrients and heat, lipid compounds can generate a massive neutrophil infiltration within necrotic areas of peripancreatic adipose tissue, thus aggravating pancreatic conditions. Processed kibble diets are heated, high in glucose, and high in anti-nutrients, meeting all the parameters of pancreatic stress. Adding fat from fresh food sources may then push an already struggling pancreas over the edge. Despite the thought that high-fat diets in dogs often lead to pancreatitis, this is rarely, if ever, the case with a raw uncooked KD. Natural, raw unprocessed fats are easily digestible in a normal healthy canine intestinal tract. Cooked fats create highly inflammatory volatile fatty acids, causing the only instances of pancreatitis KetoPet vets have seen.

3. “High fat causes diarrhea and vomiting.”

Dietary transitions commonly cause digestive detox, particularly when transitioning from processed to fresh foods. Digestive upset regurgitation, and occasional loose stool or diarrhea can occur as a result of positive changes in the gut microbiome and intestinal bacterial population when starting a different macronutrient profile diet. A quality probiotic, fiber source, or digestive enzyme supplement can assist the transition.

4. “It causes excessive weight loss.”

KDs cause a purging of excessive water stores, a loss of white fat and gain in brown fat, thus altering body composition. Loss of retained water (sometimes as much as 10% to 15% of body weight) is sometimes perceived as excessive weight loss. Rigorous weight monitoring and dietary adjustments prevent this weight loss.

5. “The KD causes constipation.”

Loss of excessive water stores causes losses in electrolytes. A lack of appropriate electrolyte supplementation can potentially lead to side effects.

6. “Raw foods are full of salmonella & pathogens.”

All forms of food may contain pathogens. Since 2006, according to FDA and CDC publications, dry kibble is the only category of pet food validated to have caused illness in humans, sickening 190 people.²⁰ FDA references also indicate that 27.6% of dogs shed salmonella in their feces, regardless of diet; 56% of dogs fed salmonella do not shed it in feces; and only 0.6% of dogs fed salmonella exhibit any symptoms. Healthy dogs tolerate moderate levels of pathogens well. Dogs with suppressed immune systems are statistically less likely to be exposed to pathogens when fed commercially-available raw foods rather than kibble. Grocery store meats are more likely to harbor pathogens, as they are intended to be cooked for human consumption. Therefore, care must be taken to attain clean sourcing and nutritional adequacy when creating homemade diets.

7. “The KD can cause fatty liver disease.”

Deterioration of hepatic function can result in abnormal bile flow and accumulation of toxins in the bloodstream. High fat consumption does not cause hepatic deterioration. However, a KD may exacerbate previously diagnosed fatty liver conditions.

8. “The KD causes ketoacidosis.”

When insulin is not present, or there is resistance to it, glucose levels rocket above 300 mg/dL. Alternatively, ketosis or fasting results in glucose levels averaging 50 to 100mg/dL. Additionally, ketoacidosis causes the body to uncontrollably produce ketones, with levels reaching 15 to 25 mM versus the maximum of 7 mM induced by ketosis.

9. “Fats increase cholesterol, triglyceride and atherosclerosis risk.”

The majority of recent studies have suggested that the KD can lead to significant benefits in biomarkers of metabolic health, including blood lipid profiles. In these studies, the KD positively altered blood lipids, decreasing total triglycerides and cholesterol while increasing the ratio of HDL to LDL.

Pet owners must understand that even a small quantity of carbohydrates or excess protein, or overfeeding, can rapidly inhibit ketosis. Furthermore, enhanced ketone production and utilization can take up to several weeks (keto-adaptation). Patients may experience mild hypoglycemic symptoms during this transitional period. In some cases, canines may also require a reduction in the quantity of vegetables consumed in order to produce higher levels of ketones. In severe health conditions, such as cancer, it is optimal to maintain a KD for a minimum of 120 days.

Note: Certain conditions are either less affected or exacerbated by implementing ketogenic diets. Working under the direct supervision of a veterinary clinician experienced in ketogenic diets is imperative to achieving the desired outcome.

Blood ketone and glucose validation

One of the many benefits of a KD is that the pet parent can validate the diet at home by measuring blood glucose and blood ketones (specifically BHB) with a simple blood meter. This is the same method used by diabetics to measure their blood glucose levels, except it uses an interchangeable ketone blood strip instead of a glucose strip. Only specific commercial blood meters offer a dual operating mode. If the dog’s blood glucose levels are at or below 75 mg/dL and his blood ketone levels at or above 0.3 mM, then he is in a state of ketosis.

Although KetoPet uses 0.3mM as their guideline, your clients may find that their dogs’ ketone levels will be much lower when compared to a human’s, especially if the dogs are active. Thus, a dog may have an average blood ketone reading of 0.2 mM. If the blood glucose is within range, this may be that particular dog’s average level of ketosis. KetoPet hypothesizes that dogs may use ketones for fuel more efficiently than humans do, meaning there is less circulating in the blood. However, this theory has yet to be proven. At the beginning of the program, KetoPet tested blood glucose and blood ketone levels often (as frequently as every day, depending on the dog) to optimize their meal plan. Once the numbers were seen consistently, testing was reduced to once or twice a week.

It’s important to note that urine ketone strips are not a reliable indicator for dogs, since small amounts of ketones can be found in normal dog urine. Even in humans, ketone urine test strips are only effective for the first few days of a ketogenic diet, if at all. In the early stages of a KD, the body will produce a small number of ketones, and they may not be detectable in the urine. It takes time/adaptation for the body to efficiently use ketones for fuel. As a result, they are temporarily passed in the urine. Once keto-adapted, ketones will no longer be present in urine because the body will use them as fuel. Although not an individual diagnostic test for ketosis, blood glucose measures may be lower than average because of the decreased need for glucose as the primary energy source, making it essential to measure both glucose and ketones.

Part 2 of this article will be published in the next issue of IVC Journal, and will present case studies from KetoPet Sanctuary.

For more information, the KetoPet eBook, resources and publications, visit KetoPetSanctuary.com.

¹Thiele, Elizabeth. “Assessing the Efficacy of Antiepileptic Treatments: The Ketogenic Diet.” Epilepsia 44 Suppl 7  (2003): 26-29.

²Wilder, RM. “The Effect of Ketonemia on the Course of Epilepsy.” Mayo Clin Bulletin 2  (1921): 307-08.

³Boden, Guenther, et al. “Effect of a Low-Carbohydrate Diet on Appetite, Blood Glucose Levels, and Insulin Resistance in Obese Patients with Type 2 Diabetes.” Annals of internal medicine 142 6 (2005): 403-11.

⁴Broom, Gina M., Ian C. Shaw, and Julia J. Rucklidge. “The Ketogenic Diet as a Potential Treatment and Prevention Strategy for Alzheimer’s Disease.” Nutrition (Burbank, Los Angeles County, Calif.) 60  (2018): 118-21.

⁵Kossoff, E. H. , and A. L Hartman. “Ketogenic Diets: New Advances for Metabolism-Based Therapies.” Current Opinion in Neurology 25  (2012): 173-8.

⁶Mancinelli, Kristen. The Ketogenic Diet: A Scientifically Proven Approach to Fast, Healthy Weight Loss. The Ketogenic Diet: A Scientifically Proven Approach to Fast, Healthy Weight Loss: Ulysses Press, 2015.

⁷McDonald, Tanya J. W. J. W., and Mackenzie C. Cervenka. “Ketogenic Diets for Adult Neurological Disorders.” Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 15 4 (2018): 1018-31.

⁸Paoli, A., et al. “Beyond Weight Loss: A Review of the Therapeutic Uses of Very-Low-Carbohydrate (Ketogenic) Diets.” European journal of clinical nutrition 67 8 (2013): 789-96.

⁹Prins, Mayumi. “Cerebral Metabolic Adaptation and Ketone Metabolism after Brain Injury.” Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 28 1 (2008): 1-16.

¹⁰White, Hayden, and Balasubramanian Venkatesh. “Clinical Review: Ketones and Brain Injury.” Critical care (London, England) 16 2 (2011): 219.

¹¹Yancy, William, et al. “A Low-Carbohydrate, Ketogenic Diet to Treat Type 2 Diabetes.” Nutrition & metabolism 2  (2005): 34.

¹²Zhao, Zhong, et al. “A Ketogenic Diet as a Potential Novel Therapeutic Intervention in Amyotrophic Lateral Sclerosis.” BMC neuroscience7  (2006): 29.

¹³Warburg, O. “On the Origin of Cancer Cells.” Science (New York, N.Y.) 123 3191 (1956): 309-14.

¹⁴Poff, A. M., et al. “Ketone Supplementation Decreases Tumor Cell Viability and Prolongs Survival of Mice with Metastatic Cancer.” International journal of cancer. Journal international du cancer 135  (2014): 1711-20.

¹⁵Poff, A. M., et al. “Non-Toxic Metabolic Management of Metastatic Cancer in Vm Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy.” PloS one 10 6 (2015).

¹⁶Poff, Angela, et al. “The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer.” PloS one 8 6 (2013): e65522.

¹⁷Seyfried, Thomas, et al. “Cancer as a Metabolic Disease: Implications for Novel Therapeutics.” Carcinogenesis 35  (2014): 515-27.

¹⁸Seyfried, Thomas, and Laura Shelton. “Cancer as a Metabolic Disease.” Nutrition & metabolism 7: 7.

¹⁹Woolf, Eric C., et al. “The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model.” PloS one 10 6 (2015).

²⁰Kent, Chelsea, “Risk statistics regarding categories of pet foods.” AAFCO Feed Bin. (2018).