Vitamin K2 research
There are two types of vitamin K, those being K1 and K2. Phylloquinone is vitamin K1, which is found in green leafy vegetables, and its primary function is to promote blood clotting. Coumadin “thins the blood” by antagonizing the action of vitamin K.
Menaquinone is vitamin K2 and there are multiple varieties, which are designated as MK-4 to MK-14. The most commonly discussed and supplemented variety is the short chain MK-4, which is found in meat. The longer chain menaquinones are attracting more attention as supplements and include MK-7, MK-8, MK-9, which are found in fermented foods such as cheese and curds. Important to note that the anti-inflammatory diet does NOT discourage the consumption of meat, cheese, or fermented foods.
While vitamin K2 also influences blood clotting proteins like K1, the menaquinones (K2) uniquely influence calcium metabolism in relation to bone and cardiovascular health. Recent studies suggest that vitamin K2 may be protective against cancer expression (1,2).
Bone producing cells called osteoblasts produce a substance called osteocalcin that participates in building bone density; however to do this effectively, it must be first activated by vitamin K2 (3,4). Studies suggest that reduced levels of K2-activated osteocalcin is a marker of bone mineral density as it is correlated with hip bone mineral density and fracture risk in elderly women (4).
In artery walls, a vitamin K2-activated vessel wall protein is produced that functions to inhibit arterial calcification (5,6). When vessels with atherosclerosis have been examined, it was discovered that there were significantly decreased levels of this protein referred to as vascular MGP (7). Important to notes is that research suggests that vitamin K2 intake is protective against coronary heart disease, while the same correlation has not been found for vitamin K1 (6). It is known that most subjects in the healthy population are not optimally protected against vascular calcification due to the presence of reduced levels of vascular MGP, suggesting that vitamin K2 supplementation may be an effective preventive strategy (8).
Patients on anticoagulant therapy should not take K2 without supervision and monitoring by their attending physician. Researchers suggest that 50 mcg may be a safe upper limit of vitamin K2 supplementation for properly monitored patients taking anti-coagulants (9).
Vitamin D research
For the average individual, 4000 IU per day will help to maintain optimal serum levels of vitamin D as measured by 25(OH)D. You can acquire this amount in Ultra K2D3 along with vitamin K2, which supports bone and vascular health.
In recent years, the importance of vitamin D has captured the attention of health care providers. We now know that vitamin D toxicity is exceedingly rare and that vitamin D is required for health expression in multiple body systems and not just for bone metabolism as previously thought.
It is likely that many of us are deficient in vitamin D, and this is thought to be related to the expression of many conditions, such as low back pain, epilepsy, cancer, osteoporosis, osteoarthritis, chronic aches and pains, type I diabetes, type II diabetes, cardiovascular disease, rheumatoid arthritis, osteoarthritis, multiple sclerosis, inflammatory bowel disease, hypertension, syndrome X and depression (10,11).
It is estimated that $50 billion is spent each year to treat conditions associated with vitamin D insufficiency, and some 50,000-70,000 Americans are thought to die prematurely of cancer each year caused by an inadequate intake of vitamin D (12). Consider that we are supposed to get most of our vitamin D from the sun, and many people have been feared out of the sun due to concerns about skin cancer. Compared to the $50 billion spent on conditions caused by vitamin D insufficiency, it is estimated that only about $5-7 billion is spent in medical costs due to excess sunlight exposure. With this in mind, it is thought that about 20-30 minutes of full body exposure to mid-day sunshine will provide optimal levels of vitamin D (12).
When sunlight hits the skin, cholesterol is converted into vitamin D. In times past, we got our vitamin D largely from the sun, however, in modern times, we spend far too much time indoors, and so we do not typically get enough sun. For example, we know that vitamin D levels for people living in Florida, Boston, and Canada are similar, which means that we all need to be aware that an inadequate level of vitamin D is likely for many of us, no matter where we live. Even individuals living in desert environments can be deficient in vitamin D if sun exposure is avoided (13).
The test that best determines our vitamin D status is serum 25(OH)D. LabCorp is one of the nations largest clinical laboratories. Before February 2006, LabCorp’s normal range for 25(OH)D was 8-46 ng/mL. However, based on published evidence, the normal range was changed to 32-100 ng/ml.
In a review article written by Dr. Michael Holick from Boston University, one of the nation’s leading vitamin D researchers, we are told that:
“Patients often complain of aching bones and muscle discomfort. Such patients are often misdiagnosed with fibromyalgia, chronic fatigue syndrome, myositis, or other nonspecific collagen vascular diseases. It is estimated that 40-60%of patients with fibromyalgia may have some component of vitamin D deficiency and osteomalacia. It has been reported that 88% of Danish Arab women with muscle weakness and pain were vitamin D deficient. More than 90% of 150 children and adults 10–65 y of age who presented with nonspecific muscle aches and bone aches and pains at a Minnesota hospital were found to be vitamin D deficient” (14).
To appreciate the degree to which those suffering pain are deficient in vitamin D, we only need to look at a couple of specific studies that examined vitamin D levels. For example, researchers were interested in finding out if fibromyalgia patients were at risk for developing osteoporosis or osteomalacia, and so they examined vitamin D levels.
All 40 fibromyalgia patients and several “normal” control subjects were deficient in vitamin D. Of the fibromyalgia patients, 18 averaged a mere 6 ng/mL of 25(OH)D, and 22 patients averaged less than 15 ng/mL (15). This study did not treat the fibromyalgia with vitamin D, however, these results suggest that all fibromyalgia patients, or those with widespread chronic pain, should have the 25(OH)D levels assessed.
In another study, 25(OH)D levels were measured in 360 Saudi Arabian subjects with chronic low back pain [90% of subjects were female] (13). Nearly all 360 subjects were deficient in vitamin D – and it is important to keep in mind that these are individuals living in Saudi Arabia, a very sunny country.
The “normal” 25(OH)D range for this study was 9-37.5 ng/mL, which means that the normal range actually represented a deficient or insufficient range, when compared with the current normal values outlined in Table 2. In this study with Saudia Arabian subjects, only 61 had serum 25(OH)D levels between 9-37.5 ng/mL. A total of 121 individuals had values between 6-8.9 ng/mL; 106 subjects were between 4-5.9 ng/mL; and 72 subjects had less than 4 ng/mL. Essentially, all 360 subjects were deficient in vitamin D (13).
The intervention for this group will be surprising for many who have been mislead about vitamin D toxicity issues. The subjects who weighed less than 110 pounds took 5,000 IU of vitamin D for 3 months, and those weighing over 110 pounds, took 10,000 IU of vitamin D for three months. No one suffered from a vitamin D overdose; in fact, 95% of subjects registered either an improvement or elimination of their low back pain (13). The authors made the following statements regarding vitamin D deficiency and low back pain:
“The result of observations in the community tested for this study showed a high prevalence of vitamin D deficiency in patients presenting initially and predominantly with low back pain. Furthermore, there is a remarkable clinical and biochemical response to oral therapy with vitamin D. The most obvious recommendation for areas with endemic vitamin D deficiency is to screen all patients with low back pain for vitamin D deficiency by measurement of serum 25(OH)D” (13).
Recommended amounts of vitamin D supplementation
If we are not getting into the sun, the researchers are telling us we need to take vitamin D supplements. This topic has been a source of confusion because of the fears associated with vitamin D toxicity. Until recently, the upper limit was set at 2,000 IUs per day.
Dr. Reinhold Vieth, one of the more prolific vitamin D researchers, criticized the old 2,000 IU as arbitrary (16). Vieth stated:
“The process of ignoring evidence of the true nutrient requirement has resulted in an unrealistically low UL for vitamin D. This low UL (2000 IU) is itself harmful. The low UL has been, and continues to be, the major hindrance to solving the problem of vitamin D insufficiency in adults” (16).
Vieth has previously written about the physiologic dose of vitamin D, stating that,
“long-term use of the official toxic dose, ‘the lowest observed adverse effect level,’ (4000 IU) of vitamin D 3 per day, is in reality a physiologic dose that has no effect on calcium levels in serum or urine” (17).
When 4,000 IU were supplemented for 2-5 months, serum 25(OH)D levels reached only 38 ng/mL (18), which is likely why Vieth refers to 4,000 IU as a physiologic dose.
In a recent study, Vieth et al. supplemented subjects with 4000 IU of vitamin D per day for approximately 2-6 months. Levels of 25(OH)D were elevated from 19 ng/mL to 45 ng/mL, and this was associated with less depression and a greater feeling of well being (19).
Vieth and others contend that 10,000 IU of vitamin D per day is the appropriate upper limit (16). Indeed, when vitamin D was supplemented at 10,000 IUs for several months, serum 25(OH)D levels reach 56 ng/mL or less (20). Remember, the healthy range of 25(OH)D is 32-100 ng/mL. Vieth states that,
“all cases of vitamin D toxicity in the literature seen by us have involved vitamin D2 (ergocalciferol), a product not normally present in humans. While poisonings have ocurred with cholecalciferol (vitamin D3), the physiologic molecule, all of those cases involved intake on an industrial scale, with unintended, prolonged daily consumption far beyond >40,000 IU ” (17).
According to the evidence, it seems that 4000 IU of vitamin supplementation is appropriate for those not getting adequate sun exposure. I personally take at least 4,000 IU per day. There is no evidence that this amount is problematic, unless we are suffering from one of the hypercalcemic issues discussed earlier.
mportant to understand is that your margin of safety is very large when it comes to vitamin D supplementation, unless you are suffering from certain diseases that increase blood levels of calcium (high blood calcium is called hypercalcemia).
Approximately 90% of those who have hypercalcemia have primary hyperparathyroidism. Cancer can lead to hypercalcemia, the most common being primary bone cancer, such as multiple myeloma or cancers that have spread to bone (most common are breast, prostate, lung, thyroid and kidney cancer). A variety of granulomatous diseases can also cause hypercalcemia such as sarcoidosis, tuberculosis, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, Crohn’s disease, Wegener’s granulomoatosis, and a few others. Hyperthyroidism and other less common conditions can also lead to hypercalcemia. Symptoms of hypercalcemia can influence the neuropsychiatric, renal, cardiovascular, gastrointestinal, and musculoskeletal systems (21).
Symptoms of hypercalcemia
Neuropsychiatric:depression, anxiety, cognitive dysfunction, headaches, fatigue
Renal:polyuria, polydipsia, nocturia (maybe kidney stones for some)
Cardiovascular:short QT interval
Gastrointestinal: constipation, anorexia, abdominal pain
Musculoskeletal:muscle weakness, aches/pains, fractures
For a detailed description of the conditions that can cause hypercalcemia and the symptoms of hypercalcemia, please click here to access an online text published by the Cleveland Clinic (21).
The other group of individuals at risk for hypercalcemia are those taking thiazide diuretics for high blood pressure or water retention. Thiazide diuretics are called “thiazide” diuretics, because they contain the drug hydrochlorothiazide. If you are taking high blood pressure medication or a water pill, check with your doctor to make sure it is not a thiazide diuretic. Here is a list: Aldactazide, Dyazide, Inderide, Moduretic, Aldoril, Esidrix, Lopressor, Oretic, Capozide, Ezide, Loqua, Timolide, Carozide, HydroDIURIL, HCTMaxzide, Vaseretic, Diaqua, Hydro Par, and Microzide.
For those who do not have the diseases that cause hypercalcemia and if you are not taking thiazide diuretics, vitamin D supplementation is quite safe. If you wish to supplement with vitamin D and you have a potential contraindication, it is still possible to supplement so long as your vitamin D and calcium levels are monitored.