Introduction
I am reviewing in this blog why calcium, vitamin D3 and vitamin K2 are needed for bone health. Recently there has been a lot of coverage in the press regarding postmenopausal treatment of women to prevent osteoporosis. It is all based on this original publication February 26, 2013.
Essentially, there are a number of studies where researchers did a meta-analysis of several trials. They studied osteoporotic bone fracture frequency in female subjects taking 400 IU vitamin D and 1000 mg calcium daily. The researchers measured the frequency of osteoporotic fractures as the indicator for osteoporosis in these postmenopausal women. The conclusion was that there was no value in taking these supplements to prevent osteoporosis. Many other media publications carried this story.
No kidney stones in study with calcium and vitamin D3
Just two days earlier (Feb. 24, 2013) another study was released with a much larger patient base of 36,282 postmenopausal women of the Women’s Health initiative in the US who were followed up for 7 years. Initially there confusion how compliant the patients were taking their supplements. The required supplementation consisted of 1000 mg of calcium carbonate and 400 IU of vitamin D3. 7 years into the trial the researchers compared the supplement compliant group with the control group taking placebos.
Calcium and vitamin D3 supplementation significantly reduces risk of hip fractures
The study group had 35% to 38% less fractures of the hip than the placebo group. This supplementation did not cause kidney stones in the study group. This was in contrast to what previous smaller studies showed. Some physicians insisted citing the older studies that vitamin D3 and calcium supplementation would cause kidney stones. But the above study refutes the causation of kidney stones by supplementing with vitamin D3 and calcium. In other words, all of these kidney stone concern you have so often read in the media are not true.
Outline of this review
In order to make sense of supplementation as osteoporosis prevention I will first review what a normal bone metabolism requires. I will then comment on what is missing in some of the studies and why it still makes sense to supplement to prevent osteoporosis. In addition, at the end of this blog I will also recommend a sensible supplementation regimen. All this is based on a balanced review of the medical literature.
Calcium, Vitamin D3 and Vitamin K2 Needed For Bone Health
Bone metabolism
But vitamin D3, vitamin K2 and strontium together have also been shown to build up bone density within one year.
So, how does vitamin K2 deposit calcium into the bone? Vitamin K2 stimulates a hormone, called calcitonin, which is produced by specialized C cells (parafollicular cells) inside the thyroid gland and released into the bloodstream. Calcitonin arrives in the bone where it binds firmly with receptors of osteoclasts (bone remodeling cells), which stops breakdown of bone. Calcitonin is helped by another hormone, called osteocalcin, which is produced by the bone producing cells with the name osteoblasts.
Vitamin K2 controls osteocalcin, which is a calcium-regulating hormone
The physician can measure osteocalcin levels in the blood and use this as a research tool to see whether a medication is effective in building up bone mass density (BMD). Vitamin K2 control osteocalcin as a calcium-regulating hormone. If vitamin K2 is present, carboxylation of osteocalcin will lead to mineralization of the bone (new bone formation); if vitamin K2 is absent, osteoporosis sets in.
The skeleton of an average adult contains 1–1.3 kg of calcium and 99% of this is mostly in the form of hydroxyapatite.
The key vitamins for bone metabolism are vitamin D and vitamin K2
Calcium absorption from the small intestine requires vitamin D3 (Ref.1). To transport calcium from the blood into the bone we require both vitamin D3 and vitamin K2 (=menaquinone). This blog explains that several studies have shown that vitamin K2 (or MK-7) plays a double role of preventing calcification of the arteries and bringing the calcium into the bones of osteoporotic women.
Apart from Vitamin K2 that is necessary for osteoporosis prevention other factors have shown to be of importance. For instance, testosterone is an anabolic hormone (meaning a hormone that builds up) and it has clearly been shown that it is bone building: It does so by stimulating osteoblasts, which are bone producing cells that reside inside the bone.
Vitamin D3, vitamin K2, Calcitonin and osteocalcin
But vitamin D3, vitamin K2 and strontium together have also been shown to build up bone density within one year.
So, how does vitamin K2 deposit calcium into the bone? It does so by stimulating a hormone, called calcitonin, which is produced by specialized C cells (parafollicular cells) inside the thyroid gland and released into the blood stream. Calcitonin arrives in the bone where it binds firmly with receptors of osteoclasts (bone remodeling cells), which stops breakdown of bone. Calcitonin is helped by another hormone, called osteocalcin, which is produced by the bone producing cells with the name osteoblasts.
Vitamin K2 controls osteocalcin, which is a calcium-regulating hormone
Osteocalcin levels in the blood can be measured and used as a research tool to see whether a medication is effective in building up bone mass density (BMD). Vitamin K2 controls osteocalcin as a calcium-regulating hormone. If vitamin K2 is present, carboxylation of osteocalcin will lead to mineralization of the bone (new bone formation); if vitamin K2 is absent, osteoporosis sets in.
Vitamin K2 also prevents heart attacks and strokes
Vitamin K2 has a second function: it removes calcium from the arterial walls and tissues. How does it do this?
Matrix GLA protein is found in tissues of the heart, lungs, kidneys and blood vessels. When vitamin K2 stimulates carboxylation of this protein, it will function like a broom and clean out calcium deposits (calcification) from blood vessels and organ tissues. As vitamin K2 is needed for this carboxylation process, it appears that nature had in mind to remove calcium from soft tissue organs and blood vessels and form hydroxyapatite in the bone for bone strength.
Vitamin K2 is the key to deposit calcium into the bone
It seems that vitamin K2 is the key vitamin necessary to do this job. Another player is magnesium, which is part of of the normal function of more than 300 cellular enzyme systems. In terms of hormones the three hormones parathyroid hormone (PTH), vitamin D3 and calcitonin need to interact normally, all requiring magnesium as cofactor. In addition, zinc, copper, boron, and manganese are also essential as trace minerals. They act as cofactors with regard to specific enzymes of the bone metabolism (Ref. 1).
Bioidentical hormone replacement essential after menopause and andropause
In the aging person hormonal deficiencies are also factors for causing osteoporosis to develop. As this link shows, Dr. John Lee found bioidentical progesterone topical cream very helpful in women with respect to increasing bone mass density by 15% over 3 years.
When bloods tests show testosterone depletion men need to replace what is missing with bioidentical testosterone. So, bioidentical hormone replacement in both men and women is part of a bone health management program to prevent osteoporosis.
Some trials that demonstrate how you can build up bone
- In this paper parathyroid hormone was used in combination with 1000 mg of calcium and 400 IU of vitamin D3 in a group of postmenopausal women with osteoporosis. Within 3 month of treatment there was an increase of bone mass density in the lower back (lumbar spine) of 4.7%, which translates into a yearly increase of bone mass density of 18.8%. In the past when physicians tested other agents for bone regeneration, this type of result never occurred. There is a variation of this hormone, a parathyroid hormone look-alike with the name Teriparatide (PTH 1-34). The patient administers this once daily as an injection of 20 mcg up to 2 years. Physicians found this useful in treating fractures of the vertebrae and other fractures in osteoporotic postmenopausal women (Ref.2).
Effect of Vitamin K2, estrogen and calcium citrate supplementation
- This publication tells the story of how bone was built up just by adding vitamin K2 to the diet in a varied patient population from children to middle aged and older individuals with a variety of osteoporotic conditions in Mumbai, India.
- In this paper the various effects of estrogens, selective estrogen receptor modulators, calcitonin and strontium ranelate were investigated with regard to their ability to build up bone when severe bone loss was caused by end stage osteoarthritis.
- Postmenopausal women who received 800mg/day of calcium citrate, along with various levels of intensity of a structured exercise program, increased their muscle mass by 11% to 21% and increased their BMD by approximately 2%.
Calcitonin and calcium strontium
- Calcitonin is very effective in reducing bone pain when the patient has compression fractures from osteoporosis; the physician can prescribe it as an intranasal spray of 200 units daily (Ref. 2). However, on March 5, 2013 the FDA announced that salmon calcitonin would not be safe for humans as there is a slight risk that cancer can develop as a “side-effect”.
- According to Ref. 2 physicians sometimes use strontium ranelate in Europe for the treatment of postmenopausal osteoporosis. Researcher showed that strontium ranelate builds up bone and decreases the amount of bone resorption. Side effects include nausea and diarrhea.
The team players of bone metabolism to build strong bone
We are now in a position to analyze why the researchers of the first paper (citation above) concluded that calcium and vitamin D3 supplementation were not enough to make a statistical difference in the treatment of postmenopausal women in comparison to placebos. As explained bone metabolism is a complex process involving several team players, where the key player is vitamin K2, which the researchers of that study ignored completely. The examples I mentioned above in point form show that exercise and calcium are also important. Vitamin K2 by itself worked quite well as it is so powerful. Hormones like PTH and calcitonin are effective, but more difficult to take for the average consumer and the FDA now has banned calcitonin.
Importance of vitamin D3 as a supplement
Vitamin D3 is important for absorption of calcium from the intestine, but also for depositing calcium into the bone in addition to vitamin K2. The WHI study mentioned above is highly significant because of a 1/3 reduction of hip fractures after 7 years of vitamin D3 and 1000 mg of calcium per day supplementation. If you add vitamin K2, exercise and bioidentical hormone replacement in postmenopausal women who need it, the prevention of hip fractures, wrist fractures and vertebral compression fractures likely will be as high as 50% in those who are taking their supplements regularly (compliance issues like forgetting the supplements or deliberately not taking them were mentioned in several of the studies).
Vitamin K2 helps to reduce heart attacks, strokes and osteoporosis
With the right supplementation, which includes vitamin K2 as mentioned above, you achieve that you lower your heart attack and stroke risk as the vitamin K2 removes the calcium from the blood vessels and deposits it into the bones, while at the same time strengthening your bones. Attention to proper nutrition, exercise and your hormone balance (using only bio-identical hormones to replace what’s missing) will also reinforce osteoporosis prevention. The bonus of using bioidentical hormone replacement therapy is that you prevent heart attacks and strokes in addition to preventing osteoporosis. I think that this is a good deal!
An easy-to-follow osteoporosis prevention program
The best combination is 1000 mg (or 1200 mg as per National Osteoporosis Foundation recommendation) of calcium per day together with 400 to 800 IU of vitamin D3 (for cancer prevention you may want to take 4000 IU to 5000 IU of vitamin D3 per day instead monitored by a 25-hydroxyvitamin D blood level test through your physician) and 100 to 200 micrograms of vitamin K2 (also called MK-7). In the age group above 50 several hormones can be missing.
Hormone depletion in menopause and andropause
That’s why the doctor recommends bioidentical testosterone in men and bioidentical progesterone/estrogen combinations in women with hormone depletion. This works best, if you also watch your weight and cut down your alcohol consumption to a minimum. Cutting alcohol out completely would be even better. In addition, exercise regularly as this builds up bone and muscle strength. It also helps, if you stick to a balanced diet (Mediterranean or Zone type diet). These diets are low-glycemic, low fat, wheat free and without sugar).
If you want to age gracefully, you need not only a healthy heart and a healthy brain. You also need healthy bones as this prevents disabilities.
References
- McPherson: Henry’s Clinical Diagnosis and Management by Laboratory Methods, 22nd ed. Copyright © 2011 Saunders, An Imprint of Elsevier
- Rakel: Integrative Medicine, 3rd ed. Copyright © 2012 Saunders, An Imprint of Elsevier
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I received the following feedback (Originally on Nov. 10, 2013)
Dr. Ray, I read your March 17 Blog entry which suggested 100 ug of Vitamin K2 with 5000 IU of D3. I have atherosclerosis and have radically changed my diet (plant only), but also now take an average of about 3000 IU of Vitamin D3. Dr. Kate Rhéaume-Bleue (book on K2) recommended taking about 200 ug per day of K2, but increasing K2 to about 1,000 ug if taking around 5,000 IU of D3 to ensure proper activation of MGP. What is your opinion with regard to a D3/K2 ration? Thank you
Answer from Dr. Ray (Originally on Nov. 12, 2013, modified April 29, 2021)
I appreciate your question about what doses of vitamin K2 to take. There are varied recommendations, but I like to go by human trials and what they have actually shown. In this review in 2010 from the Life Extension Magazine a study is cited that showed that only 45 micrograms of vitamin K2 was enough to get the calcium out of the arterial walls and into the bones.
200 micrograms of Vitamin K2 daily
Dr. Mercola reviewed the literature and found that most investigators were now using 180 to 200 micrograms. In the past I took 100 micrograms of vitamin K2 per day. However, a few years ago I increased it to 200 micrograms per day. With regard to vitamin D3 absorption my anti-aging doctor found that I have an absorption problem regarding vitamin D3. This is why I need 10,000 IU of vitamin D3 daily. This brings my vitamin D blood level up into the high normal range (between 50 and 80 ng/mL). Toxic vitamin D blood levels start only above 150 ng/mL.
Avoid sugar and too much starch consumption
Remember that other risks for cardiovascular disease are sugar and starch consumption. The liver turns this into triglycerides and too much LDL cholesterol, which plugs up your arteries. Avoid wheat because of the gliadin content. This causes an addiction to wheat and sugary foods. Here is a summary how leaky gut syndrome and autoimmune illnesses may develop from this. If you want to consume beef, reduce your consumption to once or twice per week. It id best to stick to only eat grass fed, antibiotic free beef). But I rather prefer to eat organic chicken, turkey and lean pork. I understand that you have a plant only based diet, but I would recommend to you to reconsider that. Ask your doctor to check your ferritin from time to time. This way you do not miss an iron deficiency that may develop. For other readers: Don’t forget your vegetables (organic, please).
About Ray Schilling
