Directing Calcium To Where It Belongs
Osteoporosis is a bone disorder that mainly affects us as we age - decreasing bone strength increases the likelihood of breaking a bone, usually a hip or a vertebra. It is most common in post-menopausal women and affects over 200 million people worldwide. Women over 50 have a 1-in-3, and men a 1-in-5 chance of suffering some form of osteoporotic fracture. Calcium forms the structural hardness of bones, but getting it there is not just a simple matter of consuming enough of it.
Heart disease refers to a number of conditions that impair heart function. Many of the problems associated with heart disease arise from atherosclerosis - the build-up of plaques in the walls of the coronary arteries that supply the heart muscle itself. Heart disease is the leading cause of death in the U.S. and in Canada: 1 of every 4 deaths in the US is a result of heart disease.
So what do these two diseases have in common?
Besides their overwhelming prevalence and debilitating consequences, they are both directly related to calcium status and perhaps more importantly, the vital calcium handling co-ordinator, vitamin K2.
The relatively unknown vitamin K2 is a fat-soluble molecule that belongs to the vitamin K family, along with K1 and K3.
Vitamin K1 was the first K vitamin to be discovered back in 1929 for its role in blood ‘Koagulation’ (the German spelling) after which vitamin K is named. It wasn’t until later that K2, and its role in coordinating bone and vascular health was discovered.
Vitamin K2 modifies the structure of critical calcium-handling proteins, acting as an on-switch. Without K2, these proteins remain ‘off’ and cannot bind calcium. These vitamin K2-dependent proteins, Osteocalcin and Matrix-Gla-Protein, are key players in maintaining healthy bones and blood vessels.
K2 and Bone Remodelling
Vitamin K2 has an anabolic effect on bone formation. Just like anabolic steroids help to build muscle mass, K2 helps to increase bone density by stimulating osteoblasts - the cells responsible for building bone.
Osteocalcin (OC) is the second most common protein in bone after collagen. It is made and released by osteoblasts, the bone cells tasked with building bone. OC needs to be activated once released. This is done exclusively by K2, enabling OC to bond crystals in the bone and bring in calcium, both critical for bone formation. Bone is constantly being remodeled, broken down by osteoclast and rebuilt by the osteoblasts. It is crucial to keep up with the re-building part. Without K2-activated OC, calcium cannot mineralize into new bone and bone density declines.
This is the fallacy behind the tired and false dictum that ‘taking calcium strengthens your bones.’ It’s just not that simple. Without K2, the rate of bone breakdown exceeds the rate of bone building, raising calcium levels in the blood and weakening bones. With such a critical role in maintaining the healthy structure of our bones, it’s easy to see how a deficiency in K2 is directly linked to osteoporosis. It explains why high calcium intake doesn’t improve bone density on its own but readily accumulates in the wrong tissues, causing severe harm, with no bone benefit.
What happens to all that wayward calcium?
The deposition of calcium in blood vessels is a hallmark of cardiovascular disease. As the calcium plaques grow they can obstruct the flow of blood, eventually leading to a stroke or heart attack.
Recently, CAT scans are used to measure the amount of calcium load in coronary arteries as this provides a reliable means of assessing the extent of coronary artery disease and risk of a heart attack. Healthy young people have no calcium precipitation in the soft tissues, including blood vessels.
Why does this happen?
A severe lack of K2 means OC remains ‘off’ and calcium can’t get into bone and is then free to be turned into plaque because MGP isn’t able to remove it.
Matrix-Gla-Protein (MGP) is also used to bind to calcium ions. Unlike OC, that incorporates itself and its calcium ion into the bone structure, K2-activated MGP binds calcium in soft tissues and simply removes it, breaking down calcium plaques and deposits as they form. The two proteins chaperone calcium to where it belongs, overcoming simple chemical reactions that would have it end up in all the wrong places. (6)
This is the double-edged sword of K2 deficiency, also known as the Calcium Paradox. Without K2, calcium is slowly transferred from the bone to the soft tissues, regardless of how much calcium you ingest. This is also the reason the anticoagulant warfarin increases the risk of cardiovascular disease through excessive calcification, as it specifically causes a severe vitamin K1 and 2 deficiency.
Equally, supplementing calcium without K2 may actually increase cardiovascular risk. Without the means to deposit calcium into our bones and clearing misdirected deposits in soft tissue, we are accelerating age-related calcium disease.
What about Vitamins D3 and A?
Of course, the answer is not as simple as only taking K2. Equally important in taking care of calcium are the other fat-soluble vitamins, D3 and A. The interplay of these 3 vitamins is critical in understanding each of them individually.
Vitamin D3 is responsible for assisting in the absorption of calcium through the gut wall. This is why D3 is so often recommended to be taken with calcium to treat osteoporosis. Studies using a rodent model of osteoporosis have shown an increased benefit from K2 when used along with vitamin D3. The results included an increase in bone mineral density (BMD) and overall bone health. Additionally, a meta-analysis of all the research on K2 for osteoporosis further confirmed these benefits.
Vitamin A helps to maintain healthy bones by stimulating the production and release of OC. This means higher levels of A can lead to more mineralization of bone - IF there is enough K2 and D3 to satisfy it. It is easy to see how a lack of any of these 3 vitamins can create an imbalance. Without each of these key players, calcium deposits into all the wrong areas.
Where does one get dietary K2?
Vitamin K2 exists in many different forms. The most common forms of K2 in the diet are MK-4 and MK-7 and are used exclusively when studying K2.
MK-4 is produced by animals that convert K1 from the plants in their diet into MK-4, while MK-7 is the form of K2 produced by bacteria and is found in fermented foods.
Dietary K2 is found mostly in cheese, eggs, butter, red meat, and chicken. In the U.S., chicken is the primary source of K2 (MK-4), while in some eastern countries like Japan, a dish of fermented soybeans - called natto - is the primary source, and contains massive amounts of K2 (MK-7).
It has been suggested that gut bacteria may provide a viable source of K2. However, K2 is absorbed in the small intestine with the help of bile, while the K2-producing bacteria reside in the large intestine, an environment that lacks the bile needed for absorption.
What does this mean?
We must get adequate K2 from our diet; it’s not plausible to expect our gut to provide enough for us. Eating animal products from grass-fed sources is one way to ensure a higher intake of K2. In factory farm settings, animals are often fed a diet deficient in K1 - such as grains and corn - which means they don’t produce much, if any, K2. Choosing sources of animal products that allow the animals to roam in their environment and eat from the land will ensure your diet has more K2 and other important vitamins and minerals.
To ensure that you are getting enough, adding a K2 supplement has been shown to be safe and effective in treating and preventing K2 deficiency.
How do we know if we’re deficient?
K2 can be recycled by the body after modifying OC or MGP, but there is a limit to how many times this can happen. Also, very little K2 is stored in the body. Because of its frequent turnover a steady supply of dietary K2 is needed to keep up with the demands of K2-dependent proteins.
Because K2 is the only molecule capable of modifying OC and MGP, levels of unmodified OC and MGP are good indicators of K2 levels in the body. When unmodified OC/MGP is high there is a deficiency of K2.
Unfortunately, at this time, the best tests for determining K2 deficiency are expensive and usually only used in experimental studies. There are other, less accurate alternatives for measuring K2 but due to the prevalence of K2 deficiency, it may be best to adjust our focus to a diet rich in fermented dairy products, grass-fed foods, and/or a K2 supplement.
Where’s the proof?
Evidence for K2 deficiency comes from levels of un-activated MGP. Studies have shown that in Western populations, levels of modified (carboxylated) MGP are somewhere between 60 and 70% of the total MGP level, illustrating a real deficiency of K2.
Furthermore, a study from 2007 found that the majority of apparently healthy people had high levels of unmodified OC and MGP, caused by a lack of K2.
If this is common in healthy individuals imagine how bad it can get in people dealing with osteoporosis and cardiovascular disease, as well as a number of other conditions that have been linked to K2 deficiency such as diabetes, some forms of cancer, kidney disease, dental cavities, and even skin wrinkles.
How much should I take?
The Adequate Intake (AI) of vitamin K is 120 ug/day and 90 ug/day for men and women over the age of 18, respectively (9). According to the National Institute of Health, AI’s are the levels assumed to ensure nutritional adequacy and are determined when there is insufficient evidence to develop a Recommended Daily Allowance (RDA).
Compared to the doses that are used in rat and human studies, these values are low, which begs the question, ‘Are the results of scientific studies unrealistic because they used such high doses?’
I don’t think so. The problem may be that we have set the AI bar too low.
First off, it is important to understand how the AI is determined. For vitamin K, K2 was not taken into consideration when determining the AI for vitamin K. The current guidelines are based solely on the median intake of Vitamin K1 in healthy individuals, and were developed before the importance of K2 was fully understood.
This means that the amount of vitamin K2 needed for bone and vascular health wasn’t taken into account when determining the AI. In recent years the International Life Sciences Institute has recommended that K2 be considered when establishing the Vitamin K RDA.
Additionally, the AI does not represent the amount of K needed to replenish the levels in those who are deficient. According to Dr. Cees Vermeer, a leading expert in the study of vitamin K2, almost everyone is deficient in this vitamin. With many studies showing efficacy and safety at doses of up to 45 mg/day of K2, it appears we have undershot the necessary intake of this critical vitamin.
Choosing a K2 supplement can be tricky; do I take MK-4 or MK-7?
While MK-4 in our diet comes from animal sources, the MK-4 in supplements is a synthetic version that requires large doses - 45 milligrams/day - to get the therapeutic benefits. On the other hand, MK-7 supplements are extracted from bacteria and require much lower doses to get the same effect - only 120 micrograms/day. Due to restrictions on vitamin K supplements in Canada, you won’t find any products with more than 120 micrograms per capsule. At such a low dose you would need to take almost 400 capsules of MK-4 every day to get the full benefits! It is for this reason that using a MK-7 supplement is more appropriate for alleviating K2 deficiency.
When supplementing Vitamin K it is important to do so during or after eating a meal containing fat, as this is needed for it to absorb in the gut. (Vitamin D-K2 Balance uses olive oil as the base to encourage absorption).
What do we suggest?
The best remedy for a potential K2 deficiency is to add a K2 supplement to your daily regimen. True Protocol's Vitamin D-K2 Balance contains the three essential fat-soluble vitamins (including the MK-7 form of K2) in proportionate amounts to maximize bone mineralization of calcium and reduce unhealthy soft-tissue calcification.
The first step towards resolving the epidemic of bone and heart disease requires a thorough understanding of these issues. With this knowledge, we can confidently share ways to prevent and fight these diseases. The importance of vitamins K2, D3, and A has been shown repeatedly and hold the promise to better health.
For a more intensive review of the history and benefits of vitamin K2, I would encourage you to read ‘Vitamin K2 and the Calcium Paradox’, by Dr. Kate Rheaume-Bleue.