• Erin Bannink, DVM, DACVIM

Vitamin D: What Your Dog Wants You to Know

Updated: Apr 30, 2019


Vitamin D is important for dogs too. And they rely entirely on you to get what they need. Dogs can't make vitamin D. They need to eat it in their food. At least 90% of the patients I test in my practice have low vitamin D levels which are not adequate to maintain hormone balance and optimal body functions. Vitamin D deficiency has been linked to autoimmune disease, skin disease (including atopy in dogs), cancer, poor immune function and depression (in people). Simple vitamin D supplementation can correct these imbalances. This will improve immune function, hormone health and ability to recover from cancer.

Here are some scientific facts about vitamin D and cancer that your dog really wants you to know!


Vitamin D and cancer

Vitamin D plays an important role in many physiological functions. Directly relating to cancer, vitamin D is important in normal cell maturation (cellular differentiation), replication (proliferation), appropriate cell death (apoptosis), and the formation of new blood vessels (angiogenesis) which are required for cancerous masses to receive the nutrients they need to continue growing. Vitamin D also plays a role in controlling inflammation in the body. We know that chronic low-grade inflammation is one of the main contributing factors to cancer development and progression.

A number of mechanisms have been outlined involving vitamin D, vitamin D receptor (VDR) expression and cancer progression. And the protective effect of vitamin D against development and progression of cancer has been documented in people with a variety of cancer types.

In a 2016 veterinary study, low serum vitamin D levels were shown to be associated with an increased risk of developing cancer in canine patients. Specifically this study identified an increased risk of hemangiosarcoma in dogs who had a hemoabdomen (bleeding into the belly). The results of this study suggest that Vitamin D levels over 100 ng/mL might provide some protective effect against hemangiosarcoma, although larger studies are needed to see if this is true when a larger number of dogs are evaluated and followed over a long period of time.

The optimal serum vitamin D3 level was determined to be 100 -120 ng/mL based on achieving a balance in hormone levels ( iPTH and c-CRP) at these values.

In my practice, Vitamin D levels are routinely monitored in my cancer patients. Despite most of my patients receiving a nutritionally "balanced" diet based on AAFCO requirements, an alarmingly high percentage of them (I would estimate almost 90%) have low vitamin D levels, often in the 30-50 ng/mL range. Oral vitamin D3 supplementation is initiated in these patients with a target range of 100-120 ng/mL, although higher serum concentrations have been maintained in individual patients with no accompanying hypercalcemia to date.

Vitamin D and Osteosarcoma (OSA)

Despite the fact that decrease vitamin D levels have been correlated with increased incidence of human osteosarcoma, a recently published study showed similar blood vitamin D levels in canine osteosarcoma patients and age-matched controls. This may suggest that vitamin D3 does not play a similar role in development of canine OSA. It should be noted, however, that the blood vitamin D levels in all patients evaluated were severely deficient. Serum levels of these OSA patients and age-matched controls were 34.95 ng/mL and 33.85 ng/mL, respectively. This is significantly below the optimal serum levels established in the previously mentioned study of 100-120ng/mL, suggesting that vitamin D3 supplementation is indicated in most canine OSA patients at least to establish optimal PTH/vitamin D-related hormonal balance.

Other studies do suggest a protective role for vitamin D. Vitamin D protected against the development of experimentally induced osteosarcoma in a mouse study. Vitamin D inhibited migration activity and ability to invade new tissues in OSA cells in a laboratory study. Vitamin D was also shown to have synergistic action with the chemotherapy agent Cisplatin in dogs with various naturally occurring tumors, including OSA.

Vitamin D and Mast Cell Tumors (MCT)

Low vitamin D levels have been suggested as a risk factor for mast cell tumor development in dogs.

Mast cell tumors were shown to have more vitamin D receptors than normal mast cells and as tumor grade increased (higher grade is associated with more aggressive behavior), the number of vitamin D receptors increased. This suggests that Vitamin D therapy might play a role in treatment of mast cell cancer by using these receptors as a target for therapy.

A study looking at the effects of combining high dose vitamin D with chemotherapy showed that two to six- times less chemotherapy dose was needed to kill cancerous mast cells when vitamin D (in the form of Calcitriol) was given in combination with chemotherapy drugs. Additionally, this study documented that high dose vitamin D therapy could induce remission in dogs with mast cell cancer (4 out of 10 had their tumors shrink with high dose vitamin D therapy). The problem was that most of the dogs had toxic side effects from the high doses of Vitamin D used. So, more research needs to be done on how we might use Vitamin D therapeutically for this disease. But this study suggests that there may be some benefit to Vitamin D administration with chemotherapy.

Vitamin D and lymphoma (LSA)

In people, patients with non-Hodgkin's Lymphoma who had low vitamin D levels came out of remission more quickly than those with normal vitamin D levels. This association with prognosis has been proven for Diffuse Large B-Cell Lymphoma and T-cell lymphoma, which are the most common types of lymphoma diagnosed in dogs, in a number of studies.

Diffuse Large B-Cell Lymphoma (DLBCL) is the most common type of lymphoma we see in dogs. Supplementation to achieve normal Vitamin D levels is associated with improved outcome in human patients with DLBCL who were being treated with immunochemotherapy. Patients who reached normal blood levels of vitamin D stayed in remission longer than those whose levels increased but were still below normal recommended levels.

Vitamin D and other "Blood" Cancers

Additionally, for human patients with Chronic Lymphocytic Leukemia (CLL) low vitamin D was shown to predict shorter survival time and short time until treatment is needed after initial diagnosis. CLL is the most common type of leukemia diagnosed in dogs and cats. Multiple Myeloma, a different type of cancer arising from cells in the immune system called plasma cells, was shown to be more aggressive in patients with low vitamin D levels.

A recent well-executed study published in 2017 showed that modest vitamin D and Calcium supplementation in older women did protect them from developing blood-borne cancers (leukemias).


Vitamin D Supplementation:

We can see from this sampling of the hundreds of studies on Vitamin D and cancer that management of Vitamin D levels in cancer patients would be an important part to a whole-being approach to cancer care.

Vitamin D3 is the best option to supplement Vitamin D levels and is relatively safe. Vitamin D can also be found in certain foods. Vitamin D3 is derived from meat sources. Plants (like mushrooms) contain Vitamin D2. While Wild caught fish and organic beef liver can be good sources of vitamin D3, in patients with very low levels requiring aggressive supplementation I recommend a clean Vitamin D3 supplement that can be accurately dosed. We use a liquid formulation that is readily absorbed and easy to titrate for accurate dosing. Additionally, these vitamin D3 supplements allow you to avoid the potential issues of mercury and other undesirable pollution related toxins that feeding huge amounts of fish, like salmon, could carry.

Sardines can be a nice option for dietary supplementation, as they are smaller fish, so considered "cleaner", and contain a healthy dose of Vitamin D3. We often use sardines as a carrier for herbal medications and as a food addition to entice picky eaters. I've listed some other food sources of Vitamin D3 at the end of this article.

What About Vitamin D Toxicity?

The concern for iatrogenic (treatment-caused) vitamin D toxicity, primarily dangerous elevations in blood calcium levels (hypercalcemia), is often cited as a caution against oral vitamin D3 supplementation. Specially because optimal dosing and clear information about serum levels at which vitamin D toxicosis occurs in dogs has been lacking in the past. The fear of this, however, is largely unfounded. There are some important things to understand about Vitamin D and the risk of toxicity.

Although the precise threshold of Vitamin D3 associated with hypercalcemia in animals has not been established, based on a number of animal studies the blood vitamin D3 concentrations associated with toxicity have all been in excess of 930 ng/mL. This would be difficult to achieve with oral supplementation and is well above our target range of 120ng/mL. Most of the reported toxicities have occurred through accidental ingestion and errors in food mixing at dog food packaging plants which resulted in uneven distribution of the huge amounts of Vitamin D added to large batches of dog food mix.

Current human data support the viewpoint that, for people, blood Vitamin D3 concentration must rise well over 1500 ng/mL to produce vitamin D toxicity. An upper limit of 624 ng/mL has been suggested as a prudent limit to ensure a wide margin of safety. In another review article published in 2008, it was stated that effective supplementation of vitamin D3 for many health goals in humans requires serum vitamin D3 levels of 199.68 ng/mL or higher. In this study, toxicity was reported to occur (in humans) at blood levels of 1248 ng/mL or more. To achieve these levels, supplementation of 1000-2000 IU daily is typical and toxicity was reported only with extremely excessive oral intakes, typically above 20,000 IU/day.

Based on this information and the fact that vitamin D toxicity associated with oral supplementation of vitamin D3 has not been extensively evaluated, it seems that concern for hypervitaminosis D due to oral vitamin D3 supplementation in dogs is overemphasized.

Regardless, until more clear dosing regimens are established periodic monitoring of serum vitamin D3 and calcium levels is prudent in patients receiving oral vitamin D3 supplementation in the upper limit of the “normal” range. Additionally, urine calcium/creatinine ratios have been measured in dogs and may be a way to detect early vitamin D toxicity in patients for whom this is a significant concern. This test identifies high calcium in the urine before serum calcium elevation, and associated risk to kidney function, is detectable.

Optimal Strategies for Achieving normal Vitamin D levels

There is currently no standard for the protocols for achieving optimal vitamin D blood levels in dogs. In my practice, the most common approach is to add a daily dose of vitamin D3 to food based on current blood levels and monitor blood levels every 1-2 months to determine whether additional adjustments are needed. Most dogs seem to respond well to this approach.

However, there are a few patients who fail to achieve increases in their vitamin D levels. For these patients a more aggressive approach may be beneficial. In human oncology, a number of previously published studies have reported that reliable normalization of vitamin D levels has been challenging in cancer patients, even with aggressive daily dosing of over 20,000 IU daily. A recent study published in 2017 outlined a protocol of megadosing Vitamin D once weekly (50,000 IU) for 12 weeks, which resulted in 97% of patients achieving normal blood levels. Even at this aggressive dosing, no toxicity was seen: no patient developed hypercalcemia and no patient developed kidney stones.

Based on my clinical experience and articles like this one, vitamin D supplementation more aggressive than low dose oral daily supplementation may be needed to achieve normal blood levels in some dogs. While vitamin D supplementation appears to be relatively safe based on published research, toxicities can occur. I always recommend working with your veterinarian when formulating a vitamin D supplementation regimen in order to monitor blood levels, determine if target blood levels are being achieved with the current protocol, and to monitor for any toxicities.


Some Food Sources of Vitamin D3

Wild Sustainably-Caught salmon (400 IU in 3 oz)

Wild Sustainably-Caught mackerel (400 IU in 3 oz)

Organic Beef liver (42 IU in 3 oz)

Canned sardines (164 IU in 3 oz)

Codliver oil

1 tsp: 440 IU

REFERENCES:

Serum 25-hydroxyvitamin D concentrations in dogs - correlation with health and cancer risk.

Serum 25-hydroxyvitamin D concentrations in dogs with osteosarcoma do not differ from those of age- and weight-matched control dogs.

Synergistic Action of Genistein and Calcitriol in Immature Osteosarcoma MG-63 Cells by SGPL1 Up-Regulation.

Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells.

In vitro and in vivo evaluation of combined calcitriol and cisplatin in dogs with spontaneously occurring tumors.

An immunohistochemical study of vitamin D receptor expression in canine cutaneous mast cell tumours.

Calcitriol (1,25-dihydroxycholecalciferol) enhances mast cell tumour chemotherapy and receptor tyrosine kinase inhibitor activity in vitro and has single-agent activity against spontaneously occurring canine mast cell tumours.

Cross-sectional study to investigate the association between vitamin D status and cutaneous mast cell tumours in Labrador retrievers.

An immunohistochemical study of vitamin D receptor expression in canine cutaneous mast cell tumours.

Calcitriol (1,25-dihydroxycholecalciferol) enhances mast cell tumour chemotherapy and receptor tyrosine kinase inhibitor activity in vitro and has single-agent activity against spontaneously occurring canine mast cell tumours.

Vitamin D-dependent induction of cathelicidin in human macrophages results in cytotoxicity against high-grade B cell lymphoma.

25(OH) vitamin D deficiency in lymphoid malignancies, its prevalence and significance. Are we fully aware of it?

Vitamin D deficiency and supplementation in patients with aggressive B-cell lymphomas treated with immunochemotherapy.

Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma.

Vitamin D insufficiency and prognosis in non-Hodgkin's lymphoma.

Vitamin D insufficiency predicts time to first treatment (TFT) in early chronic lymphocytic leukemia (CLL).

Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia.

Impact of vitamin D deficiency on the clinical presentation and prognosis of patients with newly diagnosed multiple myeloma.

Incidence of hematologic malignancy and cause-specific mortality in the Women's Health Initiative randomized controlled trial of calcium and vitamin D supplementation.

Pharmacokinetics of vitamin D toxicity.

Vitamin D: criteria for safety and efficacy.

Fasting urinary calcium-to-creatinine and oxalate-to-creatinine ratios indogs with calcium oxalate urolithiasis and breed-matched controls.

Validation of a vitamin D replacement strategy in vitamin D-insufficient patients with lymphoma or chronic lymphocytic leukemia

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