Melatonin and Lignans Treatment for Atypical Cushing’s Disease in Dogs

Melatonin and Lignans Treatment for Atypical or Subclinical Cushing's Disease in DogsCushing’s Disease, also known as Hyperadrenocorticism (HAC), is a disorder very commonly found in geriatric dogs.

When the dog shows the classic signs of Cushing’s disease in physical symptoms and standard blood tests, yet still has a normal response to specific Cushing’s tests, it is called Atypical Cushing’s Disease.

Melatonin and Lignans Protocol for Atypical Cushing’s Disease in Dogs

When a dog is diagnosed with Atypical Cushing’s Disease, our clinic recommends a natural and holistic protocol. This protocol consists of supplementation with melatonin and lignans.


  • 1.5 mg once or twice daily for dogs under 25 lbs
  • 3 mg once or twice daily for average to medium sized dogs
  • 6 mg once or twice daily for dogs over 100 lbs
  • Note: Research recommends not exceeding a melatonin dosage of 3 to 6 mg every 8 to 12 hours.


  • HMR Lignans 10 mg – 40 mg daily for small to large dogs

We have found the most cost effective place to purchase these supplements to be Swanson Vitamins.

The Research Behind the Melatonin and Lignan’s Recommendation


Melatonin is a hormone produced by the pineal gland that helps regulate hormones and the body’s circadian rhythm. It is being used in veterinary medicine as a natural treatment for coat loss in dogs, cats and ferrets. Researchers are not exactly sure how melatonin helps thicken and regrow fur.  Some researchers think it may be the relationship between melatonin, sunlight, and the body’s circadian rhythm.  Other’s feel that melatonin’s antioxidant properties help promote hair growth. Melatonin has also been shown to help a pet gain back weight after surgery, stress or illness and help with anxiety, insomnia, and noise phobias. Mink farmers have been known to use melatonin to promote thick coats in the winter.

Research recommends not exceeding a melatonin dosage of 3 to 6 mg every 8 to 12 hours.

A general guideline for dosing melatonin is:

  • 1.5 mg for dogs under 25 lbs one or twice daily
  • 3 mg for an average medium to large sized dog once or twice daily
  • 6 mg if the dog’s weight exceeds 100 lbs once or twice daily

If given once daily, the recommendation is to dose in the evening.


When ingested, plant lignans are converted in the body to other lignans such as enterolactone. Enterolactone is a major-endogenous-mammilian lignan formed by the action of intestinal bacteria on plant lignans when they are ingested, and acts as a phytoestrogen in the body.

There are two kinds of lignans, SDG (secoisolariciresinol diglucoside) lignans extracted from flax hulls and which HMR (7-hydroxymatairesinol) lignans which are extracted from the Norwegian spruce tree.

The main differences between the two types of lignans is that with the SDG flax hull lignan, cleavage of sugar chains must occur by the gastrointestinal bacteria before the enterolactone is formed. With the HMR Norwegian Spruce tree lignan, conversion to enterolactone by gastrointestinal bacteria is immediate upon ingestion.

Reports show that HMR lignan is completely and quickly absorbed from the gastrointestinal tract, while SDG lignan is not completely absorbed. This indicates that enterolactone formed by HMR lignans is absorbed better and more quickly than that of the SDG flax hull lignan, allowing for the use of lower dosages.

According to the University of Tennessee College of Veterinary Medicine, the suggested doses are:

  • SDG flax hull lignans  – 1mg per lb of body weight
  • HMR lignans – total doses of 10 mg – 40 mg daily should be adequate for small to large dogs


Side Effects, Warnings and Interactions

Lignan Side Effects, Warnings, and Interactions

If using SDG flax hull lignans, stool frequency and occasional diarrhea may occur because of its fiber component. (HMR Norwegian Spruce lignans contain very little fiber, so using this type of lignan should not cause issues with stool frequency and diarrhea.)  According to the University of Tennessee College of Veterinary Medicine, no adverse effects to the use of SDG flax lignan have been reported based on their suggested dose of 1mg/lb of body weight daily. They report limited feedback on the use of HMR lignan, citing only human studies showing that single doses of 1,200 mg did not cause any side effects in humans and that a 13-week study in rodents at a dose of 2,600mg/kg of HMR lignan did not cause any toxic effects.

Melatonin Side Effects, Warnings, and Interactions

There have been no reports of significant side effects of melatonin use in dogs. There have been a few reports of minor gastric upset and sleepiness. Melatonin has been shown to slightly alter the time an un-spayed female comes into heat. Melatonin may also interact with corticosteroids and some internal body process. Melatonin is not recommended for use in breeding dogs because it has been shown to sometimes alter mating desire and when a dog comes into heat.

It is very important not to exceed the recommended amount of melatonin.  Be very careful when choosing your melatonin product. Many of the melatonin products sold for humans are much stronger than the recommended amount for dogs. Signs of overdosage include diarrhea, vomiting, high blood pressure, incoordination, and even possibly seizures.

The information on this site is meant to be for educational purposes only and is in no way to be taken to be or substituted for the provision or practice of veterinary advice, help, diagnosis, services or treatment. The information should not be considered complete and should not be used in place of a visit, call, consultation or advice of your veterinarian. Should you have any health care-related questions, please call or see your veterinarian.




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