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The synergistic relationship between vitamin D and vitamin K

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What is vitamin K?

Vitamin K describes a family of compounds with a common chemical structure. These compounds include vitamin K1 (phylloquinone) and multiple forms of vitamin K2 (menoquinones/MK), all of which are fat soluble.

vitamin-k-structure

Figure 1: The structure of vitamin K1 (phylloquinone) and vitamin K2 (MK)

Vitamin K primarily functions as a coenzyme, a protein that speeds up a reaction, for the synthesis of proteins involved in blood clotting and bone metabolism. Prothrombin is a vitamin K dependent protein vital for blood coagulation. This explains why patients on anticoagulants, such as Warfarin, must avoid vitamin K supplementation.

Osteocalcin is also a vitamin K dependent protein that plays a role in bone building and mineralization. Although, little is known about vitamin K’s function in bone.

In recent years, researchers have taken an interest in a matrix Gla-protein (MGP), yet another vitamin K dependent protein, present in blood vessel walls, bone and cartilage. Researchers have found that MGP may help reduce abnormal calcification.

Relationship between vitamin D and vitamin K:

Traditionally, vitamin D has been known for its role in bone health, allowing for proper bone mineralization to occur. However, in the past decade, researchers have discovered that maintaining healthy vitamin D levels provides a myriad of benefits for human health, ranging from reducing one’s risk of cancer to aiding in the treatment of multiple sclerosis. These profound effects are primarily attributed to vitamin D’s combination of anti-inflammatory and anti-microbial properties.

Vitamin D toxicity poses a risk to one’s health when supplementing with very large doses, such as 40,000 IU of vitamin D daily. Toxicity results from excessively high calcium levels, known as hypercalcemia.

To maximize the benefits of vitamin D supplementation while also minimizing the potential risk of toxicity, some experts believe that vitamin K supplements should be taken adjunctively to vitamin D. As mentioned previously, vitamin K activates the MGP, a protein that helps direct calcium to the desirable places (bone) and lead calcium away from the undesirable places (arteries). Thus, one would expect the risk of hypercalcemia to decrease when supplementing with vitamin K.

Health outcomes that may benefit from both vitamin D and vitamin K

Hypertension

A longitudinal study published in September, 2016 assessed the vitamin D levels and uncarboxylated matrix Gla-protein levels (MGP) of 257 men and women between the ages of 55-65 who were free of cardiovascular disease and hypertension.2 The uncarboxylated MGP levels indicate the lack of vitamin K, because the MGP becomes carboxylated from vitamin K. Thus, a high level of uncarboxylated MGP represents a low level of vitamin K.

The researchers followed the participants’ health for six years. Over this time, approximately half of the cohort developed hypertension. The researchers determined that both low vitamin D and high uncarboxylated MGP levels were associated with an increased risk for developing hypertension (HR: 1.72) after adjusting for age, body mass index and type II diabetes. The risk of developing hypertension was much more profound with both low vitamin D and high uncarboxylated MGP levels compared to the risk with solely low vitamin D levels or solely high uncarboxylated MGP levels (HR 1.08 and 1.43, respectively).

Hip Fractures

Since both vitamin D and vitamin K play a role in bone mineralization, researchers conducted a study to see if low vitamin K1 and vitamin D levels were associated with an increased risk of hip fracture among the elderly population in Oslo, Norway.3 The researchers compared the vitamin D levels of 111 hip fracture patients and 73 healthy participants.

The study concluded that low vitamin K1 and vitamin D levels are independently and synergistically associated with an increased risk of hip fractures after adjusting for confounding factors.

Atherosclerosis

In 2015, researchers conducted a RCT with 42 non-dialysis CKD patients. Twenty nine patients were randomly assigned to receive a daily oral dose of 90 μg of vitamin K2 plus 400 IU of vitamin D per day for about 270 days.4 The remaining thirteen patients were assigned to receive 400 IU of vitamin D.

The researchers discovered that vitamin K supplementation in conjunction to vitamin D supplementation reduced the progression of atherosclerosis in patients with chronic kidney disease (CKD) significantly more so than supplementing with vitamin D alone.

PCOS and Oxidative Stress

Oxidative stress results from an imbalance of free radicals and antioxidants. Free radicals inflict damage to DNA; whereas antioxidants protect against free radicals. Oxidative stress is thought to be involved in the development of various diseases and conditions, such as cancer, Alzheimer’s disease, atherosclerosis, autism and chronic fatigue.

A randomized controlled trial published in July 2016 assessed the effects of vitamin D, vitamin K and calcium co supplementation among 60 vitamin D deficient women with Polycystic Ovary Syndrome (PCOS), a common condition in which a woman experiences hormonal imbalances.5 The researchers assessed hormone levels, oxidative stress, antioxidant levels, among other outcomes.

They found that 8 weeks of supplementation with 200 IU vitamin D, 90 μg vitamin K and 500 mg of calcium twice a day resulted in a significant decrease of oxidative stress and  serum-free testosterone, while total antioxidant capacity significantly increased compared to the placebo group.

The study did not possess enough study groups to determine whether the beneficial effects were attributed to one vitamin/mineral, or the combination of taking all. However, the improvement of oxidative stress and anti-oxidant levels warrants further research.

What can you do?

Research indicates that vitamin D and vitamin K work synergistically to optimize one’s health, especially concerning bone and heart health. Thus, it is important to take the proper steps to ensure that you are maintaining healthy levels of both vitamin K and vitamin D.

Unlike most vitamins and minerals, vitamin D cannot be found in adequate amounts from dietary sources. We must rely on either safe, sensible sun exposure or supplementation on a daily basis to ensure vitamin D sufficiency. The Vitamin D Council recommends supplementing with 5000 IU of vitamin D3 daily on days that you cannot get adequate sun to achieve a status between 40-60 ng/ml. After two months of supplementation, it is important to  measure your vitamin D levels and adjust your supplementation regimen accordingly.

On the other hand, vitamin K can be found in the following foods:

  • Vitamin K1: green leafy vegetables
  • Vitamin K2: hard cheeses, such as gouda or brie, Natto (Japanese fermented soybeans) and organ meats

In addition, the human gut produces vitamin K2.

vitamin-k-sources

Figure 2: Dietary sources of vitamin K, *DV=daily value

The adequate intakes (AIs) for vitamin K are as follows:

vitamin-k-ai

Figure 3: Adequate Intakes for Vitamin K6

Therefore, while reviewing the foods that contain vitamin K and the amount that you need, you can approximate whether you receive adequate vitamin K from your diet. If you do not, the Vitamin D Council recommends increasing your intake of the dietary sources listed above or begin supplementing.

Biotech’s Vitamin D3 Plus offers a perfect option to those who want to ensure they maintain adequate vitamin D levels while also receiving vitamin D’s cofactors.

Citation

Tovey, A. & Cannell, JJ. The synergistic relationship between vitamin D and vitamin K. The Vitamin D Council Blog & Newsletter, 2016.

Sources

1. Passwater, R. New Discoveries about the Role of Vitamin K in Health, Part 3: Brain and Nerve Function, Cognitive Function, Memory, Alzheimer’s Disease and Parkinson’s Disease. Whole Foods Magazine, 2014.

2. Ballegooijen, V. et al. The Synergistic Association between Vitamin D and Vitamin K with Incident Hypertension. Journal of Hypertension, 2016.

3. Torbergsen, A. et al. Vitamin K1 and 25(OH)D are independently and synergistically associated with a risk for hip fracture in an elderly population: a case control study. Clinical Nutrition, 2015.

4. Kurnatowska, I. et al. Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5. Polish Archives of Internal Medicine, 2015.

5. Razavi, M. et al. The Effects of Vitamin D-K-Calcium Co-Supplementation on Endocrine, Inflammation, and Oxidative Stress Biomarkers in Vitamin D-Deficient Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Hormone and Metabolic Research, 2016.

6. Vitamin K Fact Sheet for Professionals. National Institutes of Health Office of Dietary Supplements, 2016.

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