Nutritional therapies and dietary fads for humans often find their way into veterinary medicine. Sometimes, there is a plausible physiologic rationale or encouraging lab animal research to justify testing specific dietary interventions in dogs and cats, and such interventions may eventually demonstrate meaningful clinical benefits. Dietary interventions for renal disease and urolithiasis, for example, are supported by both pre-clinical and clinical trial data.
Unfortunately, it is common for dietary practices in humans to become popular in veterinary patients even when there is little real evidence to support them or when physiologic differences between humans and companion animals make extrapolations from human nutrition science unreliable. The popularity of grain-free dog foods, for example, is likely explained at least in part by a cultural obsession with the supposed dangers of gluten, despite a lack of evidence to support most of these fears. This now appears to have led to real harm for some dogs who have developed diet-associated cardiomyopathy on these foods.1
One of the many extreme diets for humans that is sometimes promoted as having health benefits for veterinary patient as well is the ketogenic diet. There are groups of activists and veterinarians claiming that ketogenic diets have dramatic benefits for dogs with cancer.2 There is also interest in the potential use of ketogenic diets for epileptic veterinary patients.3–5 In this article, I will briefly review the rationale and evidence for therapeutic use of ketogenic diets.
What is a ketogenic diet?
Ketosis is a physiologic state in which metabolism of carbohydrates is reduced and metabolism of fatty acids is increased, producing elevated levels of ketones, such as acetoacetate and ?-hydroxybutyrate (?OHB). Ketogenic diets are diets which induce a state of ketosis, and they are typically high in fat, low in carbohydrates, and calorie restricted. Ketosis is readily induced in humans by high-fat diets and even short periods of calorie restriction.
Dogs metabolize ketones much more rapidly than humans. It is difficult to induce a state of ketosis with high-fat diets, and much more prolonged periods of caloric restriction are required. However, ketosis can be induced in dogs using dietary fats that are high in certain
medium-chain triglycerides (MCTs).6–8
How does it work?
There are many theories about how ketosis might have beneficial impacts of specific health problems. Ketogenic diets are obviously useful in weight loss because they are calorie restricted, but there is also some evidence that they may suppress appetite more than other kinds of low-calorie diets.9
Ketosis may be neuroprotective due to specific effects of ketones on neurons. There is some evidence that ketone bodies have direct anticonvulsant activity, and the alterations in neuronal metabolism and neurotransmitter function in ketosis may also be beneficial in some conditions. There are even hypotheses that the effect of ketosis on neurons may be mediated by changes in the gut microbiome induced by ketogenic diets. However, there is no clearly proven or widely accepted mechanism for the neuroprotective effects of ketones.10
It has been known since the 1920s than many cancer cells rely preferentially on glycolysis for energy, which has led to speculation that ketosis may be beneficial in slowing cancer growth or metastasis.11
What is the evidence for benefits?
There have been extensive in vitro and animal model studies of ketogenic diets, predominantly intended to evaluate their utility in treating epilepsy and cancer. Such studies have, not surprisingly, shown variable results for different diets, indications, and specific animal models. Overall, however, there is reasonable evidence of this kind to suggest ketogenic diets could be useful in treatment of epilepsy, neurodegenerative disorders, and some cancers.10–12
The clinical trial literature in humans based on this preclinical work has been encouraging for some conditions, though it is rarely clear and conclusive. Systematic reviews of studies evaluating ketogenic diets as a therapy for refractory epilepsy in children do show evidence of efficacy in some patients.13–15 The most recent Cochrane review reports, “promising results for the use of [ketogenic diets] in epilepsy. However, the limited number of studies, small sample sizes and the limited studies in adults, resulted in a low to very low overall quality of evidence.”13 Unfortunately, despite some evidence of benefits in seizure control, long-term compliance with ketogenic dietary therapy is often very poor, due inconsistent efficacy and significant adverse effects.13,16
There is less evidence to support claims that ketogenic diets have meaningful benefits in human cancer patients. Though there are promising initial results in studies evaluating ketogenic diets for adjunctive treatment of malignant glioma, “because of the paucity of clinical data, the efficacy of [ketogenic diets] for improving survival and quality of life of glioma patients remains to be proven.”17 In terms of other cancers, “evidence supporting the effects of isocaloric ketogenic dietary regimes on tumor development and progression as well as reduction in side effects of cancer therapy is missing…more robust and consistent clinical evidence is necessary before [ketogenic diets] can be recommended for any single cancer diagnosis or as an adjunct therapy.”18
The evidence base is, as always, far more limited in veterinary patients. There are no published clinical studies evaluating therapeutic ketogenic diets in cats. There are a couple of studies evaluating diets high in MCTs in dogs. One study in dogs with epilepsy found that the test diet did induce higher levels of ?OHB than the control diet, however there was no difference in seizure frequency between the groups.4 In both the test and control groups, 30% of the dogs showed a >/= 50% decrease in seizure frequency, which is consistent with the results of other studies for dogs receiving placebo.4,19
In another study, there was a statistically significant difference in the seizure frequency between dogs eating an MCT-rich diet compared with a control diet, though the mean difference was 0.36 seizures per month, which may not be clinically meaningful. Other measures of seizure frequency also differed between the diets, but the effect seemed inconsistent among individuals. While 3 of 21 dogs had complete cessation of seizures and 7 of 21 had a >/= 50% reduction in seizure frequency, 6 of 21 actually had an increase in seizures on the test diet.5
One study has reported improvements in cognitive function testing for aged lab beagles on a ketogenic diet, but there are no studies evaluating impact on function or quality of life in dogs with naturally occurring cognitive dysfunction.20 There are also no published clinical trials evaluating ketogenic diets as treatments for cancer in dogs.
What are the risks?
In humans, long-term compliance with ketogenic diets is often poor due to a combination of lack of efficacy in some individuals, poor palatability, and adverse effects. Gastrointestinal symptoms, pancreatitis, nutritional deficiencies and deficiency diseases, cardiac disease, urolithiasis, and other adverse effects have been reported in humans on therapeutic ketogenic diets.13,16,18,21–24 The safety of these diets in veterinary patients is unclear due to a lack of relevant research evidence.
Bottom Line
Ketogenic diets have been shown to reduce seizures some human patients with epilepsy. There is preliminary evidence such diets may be beneficial in slowing progression of some kinds of cancer, but there are no clear or reliable clinical trial results demonstrating this. There are clear risks to ketogenic diets in humans that limit their use, and long-term compliance is very poor.
There is no compelling research evidence in dogs or cats showing a clinical benefit to ketogenic diets. Despite the dramatic anecdotal claims made by some proponents of these diets, there is currently insufficient evidence to support recommending therapeutic ketogenic diets in companion animals.
References
1. Kaplan JL, Stern JA, Fascetti AJ, et al. Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets. Loor JJ, ed. PLoS One. 2018;13(12):e0209112. doi:10.1371/journal.pone.0209112
2. Nosek J. Could a Change in Diet Cure Your Dog’s Cancer? Mod Dog Mag. May 2019.
3. Larsen JA, Owens TJ, Fascetti AJ. Nutritional management of idiopathic epilepsy in dogs. J Am Vet Med Assoc. 2014;245(5):504-508. doi:10.2460/javma.245.5.504
4. Patterson E, Munana K, Kirk C, et al. Results of ketogenic food trial for dogs with idiopathic epilepsy. [abstract]. J Vet Intern Med. 2005;19:421.
5. Law TH, Davies ESS, Pan Y, Zanghi B, Want E, Volk HA. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy. Br J Nutr. 2015;114(9):1438-1447. doi:10.1017/S000711451500313X
6. Weeth L. Ketogenic diets for dogs: Treend or Truth? In: VMX 2019 Veterinary Meeting and Expo. Orlando, FL; 2019.
7. Pi-Sunyer FX. Starvation-Induced Ketosis: Reduction in Dogs Enriched with Odd-Carbon Fatty Acids. Exp Biol Med. 1974;145(3):786-789. doi:10.3181/00379727-145-37895
8. Crandall LA. A comparison of ketosis in man and the dog. J Biol Chem. 1941;138:123-128. http://www.jbc.org/content/138/1/123.citation. Accessed November 15, 2019.
9. Castellana M, Conte E, Cignarelli A, et al. Efficacy and safety of very low calorie ketogenic diet (VLCKD) in patients with overweight and obesity: A systematic review and meta-analysis. Rev Endocr Metab Disord. November 2019. doi:10.1007/s11154-019-09514-y
10. D’Andrea Meira I, Romão TT, Pires do Prado HJ, Krüger LT, Pires MEP, da Conceição PO. Ketogenic Diet and Epilepsy: What We Know So Far. Front Neurosci. 2019;13:5. doi:10.3389/fnins.2019.00005
11. Weber DD, Aminazdeh-Gohari S, Kofler B. Ketogenic diet in cancer therapy. Aging (Albany NY). 2018;10(2):164-165. doi:10.18632/aging.101382
12. Khodadadi S, Sobhani N, Mirshekar S, et al. Tumor cells growth and survival time with the ketogenic diet in animal models: A systematic review. Int J Prev Med. 2017;8(1):35. doi:10.4103/2008-7802.207035
13. Martin-McGill KJ, Jackson CF, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database Syst Rev. 2018;11:CD001903. doi:10.1002/14651858.CD001903.pub4
14. Martin K, Jackson CF, Levy RG, Cooper PN. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev. 2016;2:CD001903. doi:10.1002/14651858.CD001903.pub3
15. Araya-Quintanilla F, Celis-Rosati A, Rodriguez-Leiva C, Silva-Navarro C, Silva-Pinto Y, Toro-Jeria B. [Effectiveness of a ketogenic diet in children with refractory epilepsy: a systematic review]. Rev Neurol. 2016;62(10):439-448. http://www.ncbi.nlm.nih.gov/pubmed/27149186. Accessed November 15, 2019.
16. Cai Q-Y, Zhou Z-J, Luo R, et al. Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. World J Pediatr. 2017;13(6):528-536. doi:10.1007/s12519-017-0053-2
17. Noorlag L, De Vos FY, Kok A, et al. Treatment of malignant gliomas with ketogenic or caloric restricted diets: A systematic review of preclinical and early clinical studies. Clin Nutr. 2019;38(5):1986-1994. doi:10.1016/j.clnu.2018.10.024
18. Erickson N, Boscheri A, Linke B, Huebner J. Systematic review: isocaloric ketogenic dietary regimes for cancer patients. Med Oncol. 2017;34(5):72. doi:10.1007/s12032-017-0930-5
19. Munana KR, Zhang D, Patterson EE. Placebo Effect in Canine Epilepsy Trials. J Vet Intern Med. 2010;24(1):166-170. doi:10.1111/j.1939-1676.2009.0407.x
20. Pan Y, Larson B, Araujo JA, et al. Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs. Br J Nutr. 2010;103(12):1746-1754. doi:10.1017/S0007114510000097
21. Bergqvist AC, Schall JI, Stallings VA, Zemel BS. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. Am J Clin Nutr. 2008;88(6):1678-1684. doi:10.3945/ajcn.2008.26099
22. Choi JN, Song JE, Shin J Il, Kim HD, Kim MJ, Lee JS. Renal stone associated with the ketogenic diet in a 5-year old girl with intractable epilepsy. Yonsei Med J. 2010;51(3):457-459. doi:10.3349/ymj.2010.51.3.457
23. Willmott NS, Bryan RAE. Case report: scurvy in an epileptic child on a ketogenic diet with oral complications. Eur Arch Paediatr Dent. 2008;9(3):148-152. doi:10.1007/bf03262627
24. Bank IM, Shemie SD, Rosenblatt B, Bernard C, Mackie AS. Sudden cardiac death in association with the ketogenic diet. Pediatr Neurol. 2008;39(6):429-431. doi:10.1016/j.pediatrneurol.2008.08.013
My thoughts exactly. It’s also very important to realize when feeding a diet that is so high in fat, the portions need to be drastically reduced and for smaller dogs that can mean that they get almost no food at all. I’ve also heard very strange practices regarding the keto diet such as feeding butter and heavy whipping cream..?? Very strange to say the least.
I agree that the evidence for ketogenic diets in epilepsy is underwhelming and the problems may outweigh the risks. What do you think about supplementation of diet with MCT oils without trying to induce ketosis? Is the potential benefit worthwhile because of limited risks of providing only around 6.5% of the calorie intake from the supplement?
There is some evidence for MCT-supplemented diets (e.g. Purina neurocare),though anecdotally they do not seem to make a huge difference. Low risk and potential worth trying.
Thanks for the reply. My (English) Cocker Spaniel started having seizures about 5 weeks ago at the age of 6. My vet has started him on phenobarbitone 30mg twice per day. I am supplementing this with 4ml of MCT oil twice per day.
It will be impossible to tell what treatment does what especially with an essentially variable condition like seizures but I will continue and hope for a good outcome and QoL.