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Is vitamin D metabolism altered in dogs with cancer?

Posted on: October 4, 2017   by  Missy Sturges

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A recent study published in the Journal of Veterinary Internal Medicine evaluated the impact of cancer on vitamin D status in dogs.

Like humans, our furry companions are living longer than ever before, and thus experience an increased risk of developing cancer throughout their lifetime. In fact, dogs develop more types of cancer than all other companion animals.

Approximately 1 in 4 dogs are diagnosed with cancer each year. In addition, cancer is responsible for 47% of canine deaths, making this disease the leading cause of canine mortality.

Vitamin D plays a crucial role in cancer prevention and treatment. For example, vitamin D regulates cell differentiation and cell growth, two important components in cancer prevention. In addition, vitamin D can recognize when cells become dysfunctional and initiate cell apoptosis, or programmed cell death.

Research continues to support the role of vitamin D in cancer prevention and treatment among humans. In fact, low vitamin D status has been linked with cancer development, impaired treatment outcome and mortality in people.

Research evaluating the role of vitamin D status in cancer among dogs is in its infancy. One study suggested that dogs with vitamin D levels below 40 ng/ml (100 nmol/l) experienced a 3.9 fold increased risk of developing cancer. Research has also shown that dogs with cancer are more likely to be vitamin D deficient than their healthy counterparts.

Unfortunately, canine vitamin D metabolism differs from humans and is not well understood.  Additionally,  the reference range for vitamin D status in canines varies significantly, depending on the laboratory used. These factors make it difficult to draw conclusions based off the available data.

Therefore, researchers recently conducted a study to evaluate whether various forms of cancer may affect a dog’s vitamin D status. They also aimed to identify other factors that may impact vitamin D levels among healthy dogs and dogs with cancer.

All dogs included in the study were client owned. Those were considered healthy when they presented a normal medical history, physical exam, complete blood count and biochemical profile. Dogs with newly diagnosed cancer were evaluated at the Mona Campbell Centre for Animal Cancer at the Ontario Veterinary College’s Health Centre to confirm their diagnosis.

Those who received supplements containing calcium or vitamin D, received corticosteroid treatment within two weeks of enrollment, were less than 2 years old or were diagnosed with systemic or infectious diseases (aside from cancer) were excluded from the study. A total of 92 dogs met this criteria, and thus were included in the analysis. Of these dogs, 21 had osteosarcoma, 27 had lymphoma, 21 had mast cell tumors and 23 acted as healthy controls.

The researchers recorded the dog’s dietary vitamin D intake, breed, age, sex, neuter status, body weight, body condition score (BCS) and muscle condition score (MCS). All healthy dogs were followed for one year after enrollment to confirm sustained health. All dogs received a blood draw to measure ionized calcium and parathyroid levels. Ionized calcium is routinely measured to observe blood calcium levels.  They also measured the following vitamin D metabolites:

  • Calcidiol or 25(OH)D: The form of vitamin D that has undergone the first activation step in the liver to become a prohormone. This is the form of vitamin D widely measured to determine vitamin D status.
  • Calcitriol or 1,25(OH)2D3: The hormonally active form of vitamin D.
  • 24,25(OH)2D: A metabolite associated with CYP24A1, an enzyme that breaks down circulating 25(OH)D and 1,25(OH)2D3 . Research suggests CYP24A1 is upregulated in dogs with cancer, resulting increased 24,25(OH)2D and decreased 25(OH)D levels.

Here is what the researchers found:

  • The average vitamin D status of healthy dogs was 51.3 ng/ml (128.25 nmol/l); whereas dogs with osteosarcoma had an average of 41.9 ng/ml (104.75 nmol/l), lymphoma had 41.1 ng/ml (102.75 nmol/l) and mast cell tumor had 44.9 ng/ml (112.25 nmol/l).  
  • Dogs with osteosarcoma had significantly higher body weight than dogs with lymphoma (p < 0.05).
  • Cancer type, serum calcium and 24,25(OH)2 levels were significantly associated with 25(OH)D status (p = 0.004, p = 0.047 and p = 0.001, respectively).
  • Cancer was independently associated with serum calcium levels (p = 0.005).
  • As serum calcium levels increased in dogs with cancer, so did their 25(OH)D levels; however, serum 25(OH)D levels decreased as serum calcium levels increased in healthy dogs.
  • Vitamin D status was not affected by the dog’s age, sex, neuter status, body weight, BCS, MCS or their plasma parathyroid levels (p > 0.05).

The researchers concluded,

“Results support a relationship between cancer and altered vitamin D metabolism in dogs, mediated by plasma ICa concentrations. The CYP24A1 activity and plasma [ionized calcium] should be measured in studies examining plasma 25(OH)D concentrations in dogs.”

Research continues to support the role of vitamin D status in canine health, showcasing the need for more clarity regarding vitamin D requirements for dogs, beyond prevention of rickets.

In order to determine whether vitamin D supplementation may prevent or help treat cancer in dogs, clinical trials are required.

Citation

Sturges, M. Is vitamin D metabolism altered in dogs with cancer? The Vitamin D Council Blog & Newsletter, 2017.

Source

Weidner, N. Influence of Various Factors on Circulating 25(OH) Vitamin D Concentrations in Dogs with Cancer and Healthy Dogs. Journal of Veterinary Internal Medicine, 2017.

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