Melatonin for Dogs

Melatonin is a naturally occurring hormone produced at night that has promising lines of evidence for its ability to help fight cancer.

What Is Melatonin?

Melatonin is a hormone that is primarily produced at night by the pineal gland located towards the back of your dog’s brain.1 Physiological levels of melatonin in healthy dogs depend on their daily and seasonal circadian cycle.2 For example, melatonin production is at its highest during autumn and winter nights when your dog’s sleep is at its deepest, typically in the very early morning hours between midnight to 2:00AM.3

Melatonin is produced naturally, but you can give your dog’s melatonin production a boost. Methods include providing sleeping spaces that are dark and fully enclosed, covering windows with blackout curtains or shades in the room your dog rests in, removing all sources of “blue light” that may emit from TV, phone, computer, or tablet screens, unplugging nightlights, and charging devices distantly from where your dog sleeps to avoid the omittance of any potentially interfering electrical fields.2 You can also supplement your dog’s diet with foods that contain melatonin, such as eggs and fish4, or give a melatonin supplement.

There are many commercial over-the-counter supplements containing melatonin, as well as prescription prolonged release formulas and an implant. Adding a melatonin supplement to your dog’s regimen can incur many benefits, particularly in helping support their fight against cancer.

Evidence for Efficacy

Research suggests that melatonin acts on a number of pathways that reduce the viability and proliferation of cancer cells. It has also been shown to have antioxidant and anti-inflammatory activity5. This has been most widely shown in cells studied in the laboratory harvested from abnormal mammary tumor growths.

While studies on dogs are lacking, some studies have been able to show a link between cancer and melatonin in humans. For example, patients with colorectal carcinoma had significantly lower levels of melatonin production at night when compared to healthy cancer-free individuals.6

Other results with different cancer types have been mixed. One review study examining the circadian rhythm of melatonin secretion in breast cancer patients found that while some research reported high levels of melatonin at night and low levels during the day in breast cancer patients, others reported a reduced peak in melatonin produced at night and an overall lower range of melatonin levels recorded throughout the patient’s daily circadian cycle.7

Clinical trials involving human subjects have provided a striking amount of evidence in the overall anticancer benefits of melatonin when used as an adjuvant therapy with conventional treatments such as chemotherapy. Data reflective of higher survival rates, reduced reports of negative side effects, faster tumor regression, and other metrics related to therapeutic efficacy suggest that melatonin can be beneficial for a wide range of cancers that are being treated.5 One study investigating the effects of melatonin on patients receiving chemotherapy for lung cancer found that 20 mg of melatonin per day increased both tumor regression rates and 5-year survival rates.8

Mammary Cancer

An observation that the oral consumption of melatonin appeared to stop the spread of mammary cancer in female dogs led the researchers of one study to investigate the interaction of melatonin with estrogen receptors.3 The study found that while melatonin decreased cancer cell viability and proliferation in both tumors with estrogen and those without, the result was greater for female dogs whose tumors did have estrogen, showing a potential link of efficacy between the two.

Another study investigated a special subset of canine mammary carcinoma cells that are “unanchored”.4 These cells are particularly difficult to treat due to their resistance to conventional cancer therapies and their ability to migrate, often making them responsible for tumor reoccurrence. Remarkably, the study’s authors found a significant decrease in cell viability and movement when they were treated with melatonin, suggesting that the hormone may be a valuable asset to the treatment of mammary cancer in dogs.

Another study observed that the development and spread of mammary cancer in dogs often involves the movement of asymmetrical epithelial cells that have lost the ability to adhere to other cells.9 This is called the Epithelial-Mesenchymal Transition, and it’s activated by Transforming Growth Factor beta (TGF-β). TGF-β is a small protein that plays big and wide-ranging roles in cell signaling, and tells cells when and where to divide. Previous work suggests that melatonin as a hormone appears to participate in and influence the TGF-β pathway. To investigate this further, researchers treated a canine mammary cell line with melatonin and examined cell migration. Results confirmed that melatonin acts on the TGF-β pathway and can reduce the spread of mammary cancer cells.

Mast Cell Tumors

The impacts of melatonin have also been studied in mast cell tumors. One study was able to do this with eight live dogs diagnosed with mastocytoma that had not spread to other parts of their bodies.10 The researchers combined melatonin with another supplement called delta tocotrienol, which is commonly used to disrupt the cell cycle of parasites.

The dogs were treated with 4 mg of melatonin and 150 mg of delta tocotrienol two times a day, five days a week, for a total of three months. Seven of the eight dogs had their tumors surgically removed prior to this treatment, and only one had a cancer relapse. In addition, the tumor nodules that could not be removed due to their location either disappeared or significantly reduced in size.

Common Uses

The benefits of melatonin have been well observed in canines, and it’s become a widely accepted treatment in integrative veterinary medicine. Much of the literature surrounding the potential efficacy of melatonin in dogs focuses on canine mammary carcinoma.9, 10, 11 However, this doesn’t mean that melatonin can’t be helpful with other cancer types, including mast cell tumors.10

Like most cancer related research, the majority of studies involve human patients. However, many of these can be applied to canines and human studies are nonetheless often relevant and helpful indicators of use and efficacy.

In humans, melatonin has been shown to help with oral cancer, which is marked by inconspicuous, but rapid, tumor development with high levels of resistance to radiochemotherapy.12 Though studies are lacking overall in comparison to other cancer types, those that are in the literature indicate that melatonin has oncostatic effects against oral cancer. It increases radiochemotherapy toxicity, decreases drug resistance, and causes changes in epigenetics (the way in which cells control how genes act in the body) that promote tumor suppression.12

Skin cancer is another area in which the use of melatonin is receiving increased attention. Melanoma is a type of skin cancer that is aggressive and complex, but studies are slowly illuminating how melatonin functions as a protective agent for every organ in the body, including the skin, helping to minimize the risk of and dangers associated with melanoma.13

This has even been extended to uveal melanoma, a highly rare and deadly form of cancer that often starts as a series of small undetectable dormant tumors but eventually macrometastasizes.14 In a review study that examined 147 publications related to the topic, melatonin was found to suppress cancer cell growth, slow down its spread, improve immune system function, and act as an anti-inflammatory. As observed in previous types of cancer, its benefits in improving the effectiveness of radiotherapy and chemotherapy were also noted, similar to that seen with other cancer types.14

In addition to the above, melatonin has exhibited helpful benefits to human patients across several different types of cancer, including ovarian, cervical, endometrial, liver, renal, gastric, pancreatic, prostate, and colorectal cancer.5

Consistently, regardless of cancer type, the benefits of melatonin as an adjuvant therapy are resounding. Not only has melatonin been shown to protect against the toxicity of chemotherapy and radiotherapy, decrease drug resistance, induce apoptosis, and improve overall quality of life while receiving treatment 5,13,15, studies have also shown that it helps counteract the adverse effects of chemotherapy on cognitive function and performance, improved quality of sleep, and mitigated symptoms associated with depression.16

Melatonin may also help dogs who are nearing the end of their lives and experiencing negative side effects associated with later stage cancer, such as weight loss.17 Broadly, it can be beneficial for promoting better sleep in any dog, regardless of their cancer status or risk. It’s also used to treat alopecia,18 or hair loss not caused by allergies, and symptoms associated with canine cognitive disorder, such as anxiety.19

Safety and Side Effects

It is safe to give human-grade melatonin supplements to your dog. These products are typically held to stricter manufacturing standards than pet-grade supplements, and therefore may be safer. However, always be sure to check the inactive ingredients for xylitol or birch sugar – this sweetener is sometimes added to flavored or chewable human products (including gummies) but is extremely toxic to dogs.2,21

Overall melatonin is extremely well-tolerated.10 As with any oral supplement, your dog may experience digestive upset that could lead to vomiting or diarrhea. Allergic reactions may also occur and can vary in severity.18 You will likely observe sleepiness soon after administration.18

Melatonin will stay in your dog’s system for approximately 24 hours18, so short time side effects will likely not last more than a day. Longer term effects may include weight gain or changes in fertility.18 Changes in behavior or coat quality may also occur.18

It’s always best to observe your dog the first few times you give melatonin. Be sure to call your veterinarian or visit your nearest emergency vet right away if significant adverse reactions of any kind occur.18

Can Be Given With

Even though melatonin supplements are available over the counter, you should still consult with your veterinarian before adding it to your dog’s regimen and ensure that it is safe to use with their current treatment plan.18 Melatonin is likely safe to use with most other supplements and has been tested in conjunction with other compounds in previous research studies.6

Melatonin was found safe to use with chemotherapy in studies involving humans and is a promising adjuvant therapy. 5, 12, 15 There is evidence supported by data that melatonin in combination with chemotherapy has synergistic properties that resolve drug resistance and fight tumor progression.21 One of the predominant reasons that drug resistance develops in cancer cells is because of genetic mutations that allow cells to better resist instability caused by chemotherapeutic drugs. Interestingly, melatonin has been found to correct for these alterations, ultimately improving the efficacy of such treatments.

Some precautions will need to be taken with some chemotherapy agents, and it’s likely that cancer-specific therapies will be necessary for maximum efficacy.21

When to Not Use

While melatonin is largely safe for use, there are a few cases in which you should exercise caution:

  • If your dog is taking immunosuppressive drugs, including steroids2
  • If your dog takes anticoagulants or anti-platelet medications2
  • If your dog takes fluoxetine (Prozac®)22
  • Diabetics – may influence the amount of insulin they need2
  • Epilepsy2
  • Chemotherapy drugs in conjunction with melatonin is not well studied in dogs, so it’s best to discuss in detail with your veterinarian if your dog is receiving this treatment before introducing melatonin

As with most supplements, be wary of using melatonin with dogs that are pregnant or nursing and discontinue use if any allergic reactions occur.18

How to Give

Melatonin is linked to your dog’s natural circadian rhythm, which is an important part of his overall biological function. Melatonin can disrupt this if given at a time incongruent with when it would normally and naturally be produced, so it is best to give it to your dog at night.

Melatonin is relatively inexpensive and widely available in varying forms. Depending on type and brand, melatonin can come in a solid tablet, capsule, or liquid.18 As with any oral supplement, you can give it to your dog with a bit of food to help prevent digestive upset. If administered by your veterinarian in a clinical setting, melatonin may be given as an implant under your dog’s skin.18

The dosage of melatonin varies based on your dog’s weight, health condition, and any other medications and supplements that he is receiving. Doses are typically between 1 and 6mg, but may vary.2, 23

What If I Miss a Dose?

It’s okay to miss a dose every once in a while. If you remember soon after, then you can give the dose to your dog at that time. However, if enough time has passed that your dog is close to receiving their next dose, then skip the dose you missed and go back to your regular dosing schedule. Never double dose your dog or give extra doses.18

Storage and Handling

Unless supplement instructions state otherwise, store at room temperature away from exposure to light and in an air-tight container.18

Our Take

Melatonin appears to be a highly underrated, understudied, and undervalued supplement given its potential. Its high availability and low cost make it an accessible addition to your dog’s treatment plan, though owners should be mindful when selecting a brand, with human-grade supplements preferred over pet-grade.

Research surrounding melatonin’s effects on dogs and dog cancer are limited, but shouldn’t necessarily deter you from considering it and consulting with your veterinarian. It may be just what your dog needs to sleep well and support his fight against cancer.

  1. Masters A, Seithikurippu R, Seixas A, Girardin JL, McFarlane SI. Melatonin, the hormone of darkness: From sleep promotion to ebola treatment. Brain Disorders & Therapy. 2015;04(01). doi:10.4172/2168-975x.1000151
  2. Jordan P. Melatonin for dogs: More than just a good night’s sleep. Dogs Naturally. Published June 9, 2022. Accessed December 11, 2022.
  3. Serrano C, Guzmán S, Arias JI, Torres CT. Melatonin decreases in vitro viability and migration of spheres derived from CF41.Mg canine mammary carcinoma cells. BMC Vet Res. 2019;15(1):390.
  4. Meng X, Li Y, Li S, et al. Dietary sources and bioactivities of Melatonin. Nutrients. 2017;9(4):367. doi:10.3390/nu9040367
  5. Li Y, Li S, Zhou Y, et al. Melatonin for the prevention and treatment of cancer. Oncotarget 2017;8(24):39896-39921.
  6. Khoory R, Stemme D. Plasma melatonin levels in patients suffering from colorectal carcinoma. J Pineal Res. 1988;5(3):251-258. doi:10.1111/j.1600-079x.1988.tb00651.x
  7. Ahabrach H, El Mlili N, Errami M, Cauli O. Circadian Rhythm and Concentration of Melatonin in Breast Cancer Patients. Endocr Metab Immune Disord Drug Targets. 2021;21(10):1869-1881. doi:10.2174/1871530320666201201110807
  8. Lissoni P, Chilelli M, Villa S, Cerizza L, Tancini G. Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: A randomized trial. J Pineal Res 2003; 35:12-15.
  9. Custódio PR, Colombo J, Ventura FV, Castro TB, Zuccari DAPC. Melatonin treatment combined with TFG-β silencing inhibits epithelial-mesenchymal transition in CF41 canine mammary cancer cell line. Anticancer Agents Med Chem. 2020;20:989-997.
  10. Olivieri F. Delta tocotrienol and melatonin in management of mast cell canine tumor. Biomed J Sci Tech Res. 2020;28(4):218210-21821.
  11. Lopes JR, Maschio LB, Jardin-Perassi BV, et al. Evaluation of melatonin treatment in primary culture canine mammary tumors. Oncol Rep. 2015;33(1):311-319.
  12. Capote-Mareno A, Ramos E, Egea J, López-Muñoz F, Gil-Martín E, Romero A. Potential of melatonin as adjuvant therapy of oral cancer in the era of epigenomics. Cancers 2019:11;1712.
  13. Pourhanifeh MH, Mahdavinia M, Reiter RJ, Asemi Z. Potential use of melatonin in skin cancer treatment: A review of current biological evidence. J Cell Physiol 2019;DOI:10.1002/jcp.28129.
  14. Hagström A, Kal Omar R, Williams PA, Stålhammar G. The rationale for treating uveal melanoma with adjuvant melatonin: a review of the literature. BMC Cancer. 2022;22(1):398.
  15. Mortezaee K, Najafi M, Farhood B, Ahmadi A, Potes Y, Shabeeb D, Musa AE. Modulation of apoptosis by melatonin for improving cancer treatment efficiency: an updated review. Life Sci 2019;228:228-241.
  16. Palmer ACS, Zortea M, Soua A, et al. Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: a randomized, double-blind placebo-controlled trial. PLoS ONE 2020;15(4):e0231379.
  17. Lissoni P, Paolarossi F, Tanchini G, et al. Is there a role for melatonin in the treatment of neoplastic cachexia. Eur J Cancer. 1996; 32A(8):1340-1343.
  18. Gollakner R. Melatonin. VCA Animal Hospitals. 2022. Accessed November 17, 2022.
  19. Buzby J. Canine cognitive dysfunction in dogs: signs, symptoms, solutions. Dr. Buzbys ToeGrips Dog Nail Grips. Published September 27, 2021. Accessed December 22, 2022.
  20. FDA. Paws off xylitol; it’s dangerous for dogs. U.S. Food and Drug Administration. Published July 7, 2021. Accessed December 11, 2022.
  21. Najafi M, Salehi E, Farhood B, et al. Adjuvant chemotherapy with melatonin for targeting human cancers: A review. J Cell Phys 2018; 234:2356-2372.
  22. Fluoxetine and melatonin interactions. Accessed December 11, 2022.
  23. LaRock A. Melatonin dosage for Dogs Calculator and chart: How much to provide. Emergency Vets USA. Published December 2, 2021. Accessed December 11, 2022.


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