Vitamin K2 Benefits in Diabetes

• juin 01 2019, par SANUSq Research team

Vitamin K2 Benefits in Diabetes

Most common knowledge around vitamin K health benefits is limited to its role in healthy blood clotting, whereas it certainly has far more to offer than this.  Unfortunately, vitamin K (specially K2) hardly gets any mention, and certainly not the accolades that it deserves.

Vitamin K refers to a group of fat-soluble vitamins, that work as essential cofactors in the activation of many proteins. These proteins are involved in the process of blood clotting and regulating calcium levels in the body.

Emerging research has investigated the role of vitamin K2 in various health conditions and found it to be promising for bone health, osteoporosis, vascular calcification and cardiovascular disease. By activating proteins that help calcium get to bones and remove it from the arteries, K2 plays a very important, but unfortunately lesser known role, in keeping bones and the heart healthy.

These benefits have been backed by clinical studies that suggest vitamin K2 supplements may lower age-associated bone loss in women and reduce the risk of fractures. Studies also demonstrate that vitamin K2 can also reduce arterial stiffness, thereby improving heart health.

Current studies now show that vitamin K2 has an effect on the endocrine system too, which helps in the prevention and treatment of type 2 diabetes. Vitamin K2 may also be helpful in reducing the risk of complications associated with diabetes such as heart diseases, arterial stiffness, peripheral vascular disease and poor bone health. 

Vitamin K2 reduces the risk of type 2 diabetes

Several studies have pointed out the role of vitamin K2 in reducing the risk of type 2 diabetes and improving insulin sensitivity.

Poor insulin sensitivity, also known as insulin resistance, is a condition when your body is not able to efficiently use the available insulin. Since cells need insulin to absorb glucose present in the bloodstream, this increases your blood sugar levels. This also causes more spikes in insulin levels, creating a vicious cycle. Insulin resistance is associated with a higher risk of developing metabolic syndrome, obesity, type 2 diabetes and cardiovascular disease. 

A 2017 review concluded that vitamin K2 improves insulin sensitivity. It also concluded that vitamin K2 had a better effect than vitamin K1 on reducing the risk of type 2 diabetes. The review underlined three major mechanisms that are involved in improving insulin sensitivity. [1]

1. Vitamin K2 increased insulin sensitivity through osteocalcin metabolism. Osteocalcin is known to influence insulin secretion and sensitivity.
2. Vitamin K2 improved insulin resistance by its ability to lower lipid profiles. Vitamin K2 supplementation reduces the accumulation of fat and lowers triglycerides levels in blood.
3. Vitamin K2 improves insulin resistance by supressing inflammation. Chronic inflammation has long been associated with the onset and development of insulin resistance and metabolic syndrome. This anti-inflammatory effect of K2 is achieved through its ability to inactivate NF-?B signalling pathway. This is one of the most important pathways involved in triggering inflammatory responses in the body.

Vitamin K2 may also reduce the risk of metabolic syndrome, which is an independent risk factor for type 2 diabetes, heart disease, inflammation, stroke and polycystic ovarian syndrome (PCOS). A 2015 study showed that a “high intake of menaquinones and high vitamin K status are associated with a lower occurrence of MetS.” [2]

A placebo-controlled trial conducted in 2011 showed that using vitamin K2 supplementation improved insulin sensitivity in healthy young men.  The study reported that "Although our study could not provide the underlying mechanism, we speculate that osteocalcin or vitamin K could modulate adipokines or inflammatory pathways other than the IL-6 pathways. Alternatively, it can directly regulate glucose disposal at skeletal muscle or adipose tissues." [3]

Effects on bone quality in type 2 diabetes

Type 2 diabetes causes high blood sugar levels, leading to oxidative damage and inflammation in the body and especially in the blood vessels. This effect takes a heavy toll on the entire vascular system – damaging both small and large blood vessels and increasing the risk of macrovascular and microvascular complications like:

• Coronary artery disease (CAD), caused by hardening and narrowing of arteries that supply blood to the heart muscle.
• Peripheral artery disease (PAD), caused by thickening and narrowing of blood vessels that supply blood to areas other than the heart and brain, such as legs, arms, and head. Narrowed and stiff arteries lead to the decreased flow of blood to these areas.
• Stroke
• Retinopathy, damage to small blood vessels of the retina
• Neuropathy, damage to peripheral nerves, of toes, feet, legs, hands and fingers) and
• Nephropathy or kidney disease

Interestingly, diabetes also affects your bone health. It is known to influence bone mineral density (BMD) and bone structure. Both type 1 and type 2 diabetes increase the risk of osteoporosis, and bone fractures. A study published in Nutrition Reviews found that vitamin K2 supplements may improve bone quality in type 2 diabetics. [4]

Many studies show that you need vitamin K2, along with D3, to keep your bones healthy and strong. The combination of calcium, K2 and D3 improves bone mineral density and reduces risk of fractures. In Japan, vitamin K2 is considered as a standard care to treat osteoporosis. This 2013 study showed that vitamin K2 supplements improved many parameters of bone health such as mineral density and strength in post-menstrual women without existing osteoporosis. [5] In another study, vitamin K2 supplements improved lumbar bone density and reduced the rate of fractures. [6]

How does K2 improve bone health? Vitamin K2 is responsible for activating many inert proteins involved in blood clotting and controlling where calcium ends up in the body. By activating proteins that help calcium go to bones and get removed from the arteries, vitamin K2 plays a highly important role in protecting both bone and heart health.

Vitamin K2 activates osteocalcin, a protein that is great at binding to calcium and integrating the mineral to the bone matrix but only when it is activated. Osteocalcin needs to undergo a chemical change, called gamma-carboxylation, that makes it active. This process requires vitamin K2.

Vitamin K2, vascular calcification and artery stiffening in diabetic patients

Type 2 diabetic patients are at an increased risk of calcification of the blood vessels, which leads to peripheral artery disease (PAD) and arterial stiffness. Vascular calcification also contributes to the development of type 2 diabetes complications, such as retinopathy, neuropathy and nephropathy.

The risk of cardiovascular disease is significantly raised in patients with type 2 diabetes. The role of Vitamin K2 in heart disease and diabetes has been extensively studied. It keeps the calcium mobile and prevents its accumulation in the arteries. How it works?

Vitamin K2 is required to fully activate a protein called Matrix Gla-protein (MGP), which is considered as one of the most potent inhibitors of calcification in the arteries. Simply put, activated MGP plays a significant role in preventing build-up of calcium within the blood vessels, including coronary arteries and aorta. What happens if you are K2-deficient? This situation will raise the levels of inactive MGP (dp-ucMGP) in circulation.

High levels of dp-ucMGP floating in the blood is not only a strong indicator of poor vitamin K2 levels but is also a risk factor for arterial calcification and vascular stiffness. Increased levels of inactivated MGP is associated with many parameters related to arterial health in both healthy individuals [7] [8] and patients with type 2 diabetes.

In people with type 2 diabetes in particular, it increases the risk of cardiovascular disease [9], artery stiffening [10] and calcification of peripheral arteries in patients with diabetes [11]

In addition to this association, studies show that high intake of K2 can reduce arterial calcification. [12] This effect is due to the ability of K2 to activate MGP. Another study showed that long-term K2 supplementation (MK-7) can “improve arterial stiffness in healthy postmenopausal women.” [13]

Vitamin K2 Vs Vitamin K1

As mentioned earlier, the 2017 review published in the “Diabetes Research and Clinical Practice” reported that vitamin K2 works better than K1 in reducing the risk of type 2 diabetes. [2] Similarly, many other studies also confirm that vitamin K2 may be better than K1 in improving bone and cardiovascular health.

The fact is both vitamins K1 and K2 are absorbed and distributed across various tissues in different ways. One may work differently than the other, the reason why both these vitamins offer different health benefits. While you need both K1 and K2 vitamins for healthy blood clotting, you also want to pay attention to K2 as its deficiency may be detrimental to the bone and heart heath.

Let’s quickly go through how K1 is different to K2. 

Vitamin K1 or phylloquinone

• Mainly found in green leafy vegetables such as kale, spinach, collard greens, mustard greens, swiss chard, broccoli and Brussel sprouts.
• Required for healthy blood clotting. It is transported to the liver, where it helps activate proteins, called clotting factors, within the liver. 
• Structurally different that K2 in that it has a smaller side chain.
• Deficiency can lead to easy bruising and excessive bleeding 

Vitamin K2 or menaquinones

• Comprises of a group of molecules called menaquinones or MKs. The numbers mentioned with MK4 or MK7 refers to the number of side chains.
• Found in fermented foods such as Natto (fermented soyabeans), curd and sauerkraut. It is also found in animal-based products such as cheese, butter, egg yolks, goose liver and chicken.
• Also produced by the gut bacteria, but in very small quantities.
• Menaquinones have a longer side chain, which helps K2 stay longer in the bloodstream. This means K2 is more efficiently absorbed by tissues throughout the body, such as bone, blood vessels and other tissues.
• Besides its involvement in blood clotting process, vitamin K2 also plays an integral role in maintaining a healthy bone and cardiovascular system. 

Vitamin K2 Deficiency

It is true that some of the K1 that you get from food is converted into K2. But is eating foods rich in vitamin K1 enough to ward off vitamin K2 deficiency? The fact is your body is not very good at making this conversion. It is also hard to get sufficient amounts of vitamin K2 naturally through diet alone.  And if you are not eating fermented foods or foods that are rich in K2, you are likely to develop a deficiency.

In addition, certain factors make you more prone to developing a poor K2 status, such as:

• Age
• People with conditions such as high blood pressure, type 2 diabetes, heart disease and chronic kidney disease
• Certain medications such as statins (cholesterol lowering drugs), blood thinners like warfarin, and antibiotics.
• Impaired digestive health and conditions like celiac disease, Crohn’s disease, ulcerative colitis, abdominal surgeries and gut dysbiosis. These gastrointestinal issues interfere with K2 absorption
• Poor liver function
• Diet low in fat

Are you taking calcium and vitamin D3 supplements for your bone health? Then taking vitamin K2 supplements is especially important. While D3 helps in the absorption of calcium and phosphorus, minerals that are important for making strong, healthy bones, K2 helps controls the movement of calcium in the body. As discussed throughout this blog post, vitamin K2 directs calcium to be integrated into the bone matrix (by activating osteocalcin) and removes calcium from the arteries, failing which calcium gets deposited in arteries and other soft tissues, increasing the risk of CAD, PAD and stroke.

So, it is all about maintaining a healthy balance between calcium, vitamin D3 and vitamin K2, not to mention that magnesium also plays a stellar role when it comes to improving your bone health and even reducing your risk of fractures. It is a good example of how nutrients don’t work alone but often in complete synergy with each other, supporting and bringing out each other’s benefits.

You can take high-quality vitamin K2 supplements, which are quite safe in terms of any toxicity or side effects, but it is advisable to consult your healthcare practitioner before taking any supplement as they may interfere with any existing health condition or any medication you are currently taking. But always weigh up the advantages, and pros and cons for yourself. Do your own research and never rely solely on what others tell you. Even your doctor does not know everything.

References:

1. Li Y et al. Effect of vitamin K2 on type 2 diabetes mellitus: A review. Diabetes Res Clin Pract. 2017
2. Dam et al. Association Between Vitamin K and the Metabolic Syndrome: A 10-Year Follow-Up Study in Adults. The Journal of Clinical Endocrinology & Metabolism. 2015
3. Choi et al. “Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial,” Diabetes Care. 2011
4. Iwamoto J et al. Bone quality and vitamin K2 in type 2 diabetes: review of preclinical and clinical studies. Nutr Rev. 2011
5. Knapen et al. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013
6. Iwamoto et al. High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Nutr Res. 2009
7. Mayer et al. Desphospho-uncarboxylated matrix Gla protein is associated with increased aortic stiffness in a general population. J Hum Hypertens. 2016
8. Dalmeijer et al. Circulating matrix Gla protein is associated with coronary artery calcification and vitamin K status in healthy women. The Journal of nutritional biochemistry. 2013.
9. Dalmeijer et al. Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic patients. Diabetes Care. 2013
10. Sardana et al. Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus. Am J Hypertens. 2017
11. Liabeuf et al. High dp-ucMGP levels were independently associated with below-knee arterial calcification score in patients with type 2 diabetes and normal or slightly altered kidney function. Cardiovascular Diabetology. 2014
12. Beulens et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2009
13. Knapen et al. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. 2015

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