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When our dog, Gus, was diagnosed with osteosarcoma, he had surgery and chemotherapy. But I knew the clock was ticking. Is there any way to stop metastasis? I changed his diet, lowering sugar and carbohydrates, the preferred fuel for cancer cells.
Gus lived about 13 months after diagnosis, and honestly, I have no idea whether his dietary change had any impact.
Around that time, I remember talking to a researcher here in Seattle at Fred Hutch Cancer Research Center. He’s an oncologist who specializes in treating sarcoma patients. I asked if he had recommended any dietary modification to his patients. His answer was no; there was just insufficient evidence that it would help.
That was 7-8 years ago.
Talking to the same researcher recently, I found him very optimistic about what’s now called metabolic therapy.
There has been a significant shift in thinking in recent years, thanks to new studies and clinical trials.
1. Metabolic therapy exploits the unique metabolism of cancer cells that relies on glucose. Two examples are the ketogenic diet and the fasting-mimicking diet.
Metabolic therapy for cancer focuses on altering the metabolism of cancer cells to inhibit their growth and promote their death. Cancer cells often have a unique metabolism that relies heavily on glucose (a phenomenon known as the Warburg effect), making them more sensitive to changes in nutrient availability and metabolic pathways. Metabolic therapy aims to exploit these differences by targeting the metabolic vulnerabilities of cancer cells.
A ketogenic diet and fasting-mimicking diet are two examples of metabolic therapy.
The ketogenic diet reduces glucose availability by promoting ketosis, forcing cells to use ketones for energy. Cancer cells are less efficient at using ketones compared to normal cells, which may slow tumor growth. The classical ketogenic diet uses a high fat, low carbohydrate, low protein diet at a ratio of 4 to 1 or 3 to 1 (fat : carbohydrate+protein)
So it's not just reducing carbs, but reducing proteins as well and increasing fat intake.
In contrast, a fasting mimicking diet (FMD) relies on cyclic caloric restriction.
Some of the published human patient studies describe the repetition of five days of restricted caloric intake, followed by normal eating.
FMD reduces insulin, reduces blood glucose, and increases ketones. The fuel source for cells becomes stored glycogen and fat instead of glucose. This change can help create a favorable environment for the survival of healthy cells and killing cancer cells.
2. Metabolic therapy is being evaluated to treat many different conditions in human patients.
The ketogenic diet was originally formulated to treat epilepsy patients over 100 years ago. However, it is now being used to help patients with various conditions, including diabetes and neurological conditions such as bipolar disorder and Alzheimer’s.
It doesn't produce remission for everybody, but there have been enough case studies and individual reports to know that it can be very effective for a subset of patients.
3. In one case report, a patient with aggressive cancer used the ketogenic diet to achieve very long remission (10+ years).
A patient named Pablo Kelly, who lives in the United Kingdom, was diagnosed with terminal glioblastoma. Typically, glioblastoma patients only survive six to nine months. This patient rejected conventional treatments, including chemo and radiation therapy, and instead opted for a ketogenic diet. He was initially diagnosed in 2014 but is, ten years later, still alive today.
Youtube video: https://www.youtube.com/watch?v=BxFzPWr7qq8
He achieved long remission and is still alive (2024).
4. In mouse studies, the Ketogenic diet produced excellent results - but only when combined with conventional therapy.
We talked in-depth to one of the researchers active in metabolic therapy studies, Professor Adrienne Scheck. She investigated in the study whether a ketogenic diet could more effectively help fight brain cancer in mouse models.
She found that mice on a ketogenic diet survived slightly longer than those on the standard diet.
So, the Kaplan-Meier survival curve is slightly shifted to the right. It was a modest difference. The median survival times of standard vs ketogenic diet mice were 23 days versus 28 days.
But, a dramatic difference was observed when she compared the survival times for animals treated with radiation therapy.
Cancer progression was no longer observed for the majority of the mice on the ketogenic diet treated with radiation therapy (blue line), and those mice survived significantly longer.
The ketogenic diet made cancer cells much more sensitive to radiation treatment, and other mouse studies have observed similar results with different types of cancer and therapies, including chemotherapy.
5. A Ketogenic diet helps a dog with mast cell tumor.
How about canine patients?
There is a published report of a 7-year-old dog with a mast cell tumor on his face. His parents decided not to seek surgery or other conventional treatment.
The pet parents tried switching his diet, for example, lowering carbohydrate content and trying a raw vegetable and fish diet. But the tumor kept on growing.
The dog was finally put on a ketogenic diet in July 2013, and that’s when his tumor began to shrink.
His mast cell tumor completely disappeared without any surgery or other conventional therapy. There was no recurrence of the tumor. He survived until June 2019, when he was euthanized for a different cause.
The published study reports that this dog was given raw chicken leg with bone, raw chicken egg, and some fats. The fat to protein+carb ratio was approximately 1.3: 1.
Are there other reports of dogs whose survival was enhanced with the help of a ketogenic diet?
6. Ketopet Sanctuary Team shared what happened when dogs with cancer were given diet therapy together with standard-of-care and other complementary therapies.
About 10 years ago, a team interested in the benefits of the ketogenic diet started something called Keto Pet Sanctuary in Texas. They adopted from shelters dogs with terminal cancer and treated them with standard-of-care cancer treatments, including a combination of chemotherapy, radiation therapy, and surgery.
But in addition to that, they were fed a raw ketogenic diet optimized calorically for each dog’s needs. Typically it consisted of raw 70/30 ground beef and/or ground chicken breasts, fat source (such as MCT powder, coconut milk, butter, heavy cream), and vegetables (cabbage, green beans, broccoli, brussels sprouts). The diet was balanced with prebiotics, probiotics, essential oils, and vitamins and minerals. Blood ketone and blood glucose levels were measured multiple times a week.
Each dog was also given hyperbaric oxygen therapy. They're monitored and cared for, taken for a walk, and played with, and they really took good care of all these dogs.
Here is a summary of cancer survival for 22 dogs shared in a publication.
Survival statistics were not shared since there was a variety of cancer types, including mast cell tumors, hemangiosarcoma, and lymphoma.
Many of the dogs lived longer than anticipated with conventional treatments alone.
For example, one dog, Callie, diagnosed with hemangiosarcoma, which is always deadly, lived for multiple years.
Another dog, a 6-year-old German Shepherd, had lymphoma and was treated with combination CHOP chemotherapy. He was also put on the keto diet and got hyperbaric oxygen therapy, mistletoe extract, and other supporting therapies. This dog lived in remission for 27 months, which is significantly longer than typical lymphoma remission times.
Have there been any clinical trials showing survival statistics with canine patients? The answer is no, so far. However, there have been studies looking at the side effects of chemotherapy.
7. Clinical studies show fasting dramatically reduces chemotherapy side effects for canine patients.
Two studies led by veterinarians at UC Davis and another team led by Prof Shay Bracka at Oregon State University looked at the side effects of fasting on chemotherapy. The results were published in 2014 and 2021.
Both studies showed that short-term fasting can significantly reduce the gastrointestinal side effects of chemotherapy.
Short-term fasting before chemotherapy treatment slows down the normal healthy cells while cancer cells continue to divide. So, the normal cells are protected, while cancer cells are sensitized to cytotoxic chemotherapy killing.
8. A new study (supported by Canine Cancer Alliance) is investigating immune response after short-term fasting.
Professor Shay Bracka, now at Ohio State University, is leading a new study investigating the impact of fasting on immune response. The study is enrolling patients with melanoma and osteosarcoma and is examining tumor samples before and after surgery for anti-cancer immune activity.
Conventional treatments like chemotherapy and radiation therapy try to directly kill cancer cells. However, a more effective approach is to recruit the immune system to fight cancer and create a tumor microenvironment (TME) that is inhospitable to tumor cells.
The study will find out if short-term fasting can create an anti-cancer immune environment, attracting cancer-killing T-cells and other cells and immune-stimulating molecules into TME.
9. A recent clinical study involving human patients reported enhanced antitumor immunity with a fasting-mimicking diet (FMD)
A study published in 2022 described blood and tumor sample analysis results for cancer patients on a fasting-mimicking diet (FMD).
In this very exciting clinical trial (the NCT03340935 trial), they enrolled 101 advanced cancer patients, many with incurable metastatic cancer. These patients received regular cancer therapies such as chemotherapy, targeted therapy, or immunotherapy and were all on cyclic 5-day FMD, followed by roughly 25 days of regular eating.
The published results described how FMD increased anti-tumor immune cell activation in breast cancer patients. They were able to measure increasing markers of cytotoxic T-cell activation as well as T-memory cells. They measured a reduction in T-cell exhaustion markers as well as a reduction in T regulatory cells that suppress the immune response.
They were also able to measure the increased presence of other anti-cancer immune cells, such as dendritic cells and natural killer cells (see the figure below).
A cyclic fasting-mimicking diet also reduced immuno-suppressive immune cells such as neutrophils, macrophages, and myeloid-derived suppressor cells (MDSCs). (See our previous webinar for the importance of modulating tumor microenvironment in the fight against cancer)
The study concluded that a fasting-mimicking diet is safe for patients, it results in consistent blood glucose decrease, and it enhances anticancer immunity.
10. A subset of patients with advanced cancer enjoyed long-term remission
A related paper from the same team in Italy also shared what was happening to some of the patients in their NCT03340935 trial.
Published in 2022, they identified at least five patients with what they described as exceptional tumor response. These are patients with very advanced cancer, such as metastatic lung cancer, metastatic pancreatic cancer, and triple-negative metastatic breast cancer. Today’s standard-of-care therapies alone do not help these patients.
However, with the addition of FMD, five patients enjoyed long-term remission lasting more than 40 months.
This is an extremely exciting result from a human clinical trial. Hopefully, some of these findings can be applied to help canine patients in the future.
11. Advanced breast cancer patients lived longer with a fasting-mimicking diet added, compared to chemotherapy alone.
In a recent paper, the same Italian team analyzed a subset of their data for advanced breast cancer patients.
They compared the overall survival (OS) of 14 triple-negative breast cancer (TNBC) patients receiving chemotherapy (first-line carboplatin-gemcitabine) plus cyclic FMD in the context of the NCT03340935 trial with the overall survival of 76 TNBC patients treated with carboplatin-based chemotherapy alone.
Patients undergoing cyclic FMD in combination with chemotherapy had better overall survival when compared to patients receiving chemotherapy alone (median OS 30.3 months vs 17.2 months).
The Kaplan Meier survival curve above shows a significant difference between patients treated with chemotherapy (red) versus patients treated with chemotherapy while on a fasting-mimicking diet (blue).
Could FMD or metabolic therapy also enhance immunotherapy treatments?
Could it make canine cancer immunotherapy treatments - for example, EGFR/HER2 Yale vaccine, Gilvetmab, Torigen vaccine, Ardent vaccine, or Immunocidin treatment be more efficacious?
This year, a group published a mouse study where they combined a ketogenic diet with immunotherapy treatment.
12. A new mouse study shows that immunotherapy resistance can be broken with ketogenic diet and/or ketone supplementation.
The University of Notre Dame research team carried out studies with mice using a form of immunotherapy: a PD1 checkpoint inhibitor drug. For many cancer types, including prostate cancer, this type of immunotherapy is ineffective.
However, when these immunotherapy-resistant mice were put on a ketogenic diet or given supplements, immunotherapy became effective for a subset of the mice.
This study may pave the way for future research exploring how the ketogenic diet may enhance cancer immunotherapy treatment and also examine the possibility that ketone supplementation might be able to replace the diet.
So, in summary, there has been a growing number of metabolic therapy studies in recent years. These exciting studies have shown that metabolic therapy may induce an anti-cancer tumor microenvironment and immune response, and could synergize with different cancer treatments.
There is, however, variability in response both for animals and humans. More research is needed to investigate how dietary intervention can best be added to enhance the efficacy of anti-cancer therapies for dogs.
Ask your vet if ketogenic diet is appropriate for your pet. Here's a keto diet calculator.
Check out other articles and videos
Questions? Email us at info@ccralliance, and we'll get back to you as soon as we can!
Canine Cancer Alliance is a non-profit organization supporting research for canine cancer cures.
All information the Canine Cancer Alliance website provides is for informational purposes only. It is not intended to be a substitute for professional veterinary advice.
Always seek guidance from your veterinarian with any questions regarding your pet’s health and medical condition.
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