Vitamin D Testing and Dosing

Before I start this discussion I must confess I have omitted discussing vitamin D and osteoporosis. Most practitioners consider Vitamin D as an essential ingredient in any treatment plan for osteoporosis to the degree I take it for granted and would like to skip over it. Suffice to say that low vitamin D contributes to low bone density. There was a meta-analysis of 25 studies looking at the efficacy of vitamin D supplementation on fracture risk. Though many of the studies used inadequate doses of Vitamin D, the analysis concluded that combined supplementation lowered risk of vertebral fractures. It seems clear that supplementation especially among the elderly can reduce fracture rates.

Current reference ranges for vitamin D levels are wrong. They are still based on average serum levels of what were thought to be healthy individuals with adequate vitamin D. That simply meant they didn't have rickets. We now know that a large proportion of the "healthy American population", that doesn't have overt signs of rickets, is vitamin D deficient. We can not use these normals, but must look at what normal should be based on research.

For most labs the bottom of the reference range is set too low due to the previous under appreciation of the clinical benefits of and physiological requirements for higher Vitamin D levels. The top of the range is set too low due to misinterpretations of the research resulting in a fear of vitamin D toxicity. New reference ranges need to be determined based on the current research.

I hate to get up on a soap box here but setting new standards for non patented vitamins often takes the back seat to changing standards which might increase the use of prescription drugs. There are few financial concerns lobbying for more vitamins in contrast to drug manufacturers and their lobbyists….

Vitamin D is tested using a 25(OH)D (25-hydroxyvitamin D or calcidiol) serum measurement. Current lab values are inadequate for assessing status. Until new standards for vitamin D are set officially, we recommend the following values to interpret 25(OH)D test results:

20 ng/mL: deficient

30 ng/mL: insufficient

40-65 ng/mL: optimal

80 ng/mL: excess

Vitamin D deficiency: Less than 20ng/mL

A serum 25(OH)D below 20 ng/mL (50nmol/L) indicates a vitamin D deficiency. There are some authorities on Vitamin D who say anything below 30ng/ml (75nmol/L) should be considered low. We will be conservative and say 20 ng/ml.

Vitamin D Insufficiency: Less than 30 ng/mL

A serum 25(OH)D level less than 30 ng/mL (100 nmol/L). This may still be too low. Researchers suggest that the way to know when someone has enough vitamin D is that adequate levels will suppress parathyroid hormone (PTH) levels. Elevated PTH increases the risk of the diseases we are trying to prevent through the use of Vitamin D. Various studies have reported levels of vitamin D sufficient to suppress PTH levels. Results vary slightly. Dawson-Hughes says it needs to be above 45 ng/mL while Need and Horowitz say 40ng/mL . Instead of using PTH as a marker others have simply measured loss of bone mass and calculated at what level elderly people start losing bone. They set the lower level at 37ng/mL. Again we are being conservative and will say 30 ng/mL.

Vitamin D Optimal Levels: 40-65 ng/mL (100-160 nmol/L)

A reasonable target level for vitamin D based on current research is 40-65 ng/mL (100-160 nmol/L). This range matches what most of the experts are recommending. Zittermann suggests 40-80ngl/mL (100-250nmol/L) is adequate, and Mahon in his work with multiple sclerosis recently suggested 40-100ng/mL). Again 40-65 ng/mL is a conservative goal.

But isn't too much vitamin D dangerous?

I don't remember much from my first nutrition courses in the 1970's at Cornell but I do remember that D stands for Dangerous. Too much vitamin D is supposed to be very, very dangerous. In fact my textbook from that time, which amazingly I still have in my possession, says vitamin D should never be supplemented at more than 400 IU/day. What should the upper limit be for 25(OH)D levels in the serum? There is no consistent evidence of vitamin D toxicity at levels below 80-88 ng/mL (200-220) nmol/L). In fact these levels "should be regarded as being within the physiologic ranges for humans." Zittermann thinks the levels up to 100 ng/mL are not toxic. Still let's be conservative and stick with the 65ng/mL as stated before.

Excess Vitamin D: Greater than 80ng/mL (200 nmol/L) with hypercalcemia. It is difficult to know what is too much vitamin D. People can reach 80 ng/mL just by sun exposure without vitamin D supplementation or by taking 10,000 IU/day of vitamin D without any symptoms of toxicity. Having the 25(OH)D greater than 80 ng/mL isn't itself dangerous or toxic UNLESS blood calcium levels increase. Elevated calcium called hypercalcemia is a problem. Holick, who has authored some 220 papers on Vitamin D, doesn't think toxicity occurs until over 125 ng/mL.

The most important indicator of too much vitamin D is elevated calcium AND high serum 25(OH)D, greater than 90 ng/mL Vitamin D hypervitaminosis is extremely rare and is usually seen with industrial accidents when milk is way over fortified. For infants to become hyper vitamin D typically requires daily doses for 1-4 months of 40,000 IU/day. In adults, toxicity generally requires several months of supplementing 100,000 IU/ day. There are some people who will become hypercalcemic from vitamin D without an elevated 25(OH)D. This is why calcium levels needs to be monitored.

Some authors suggest weekly calcium monitoring of patients receiving High Dose vitamin D treatments. There are several diseases which cause vitamin D hypersensitivity. In these cases vitamin D is more rapidly converted into the active form of the vitamin calcitriol and causes disproportionate increases in calcium.

As humans we have spent thousands of years adapting to a natural environment which included regular and ample sunlight. Full body exposure on clear days near the equator, will generate the equivalent of 4,000-20,000 IU of vitamin D. How much vitamin D people make varies a great deal on their skin pigmentation. In fair skinned people sunburn may produce 50,000 IU. How much oral vitamin D a person should take depends on where they live (the latitude), sun exposure, body weight, skin pigmentation, dietary sources, and efficiency of absorption and medications that may interfere.

Suggested doses for supplementation for people with low Vitamin D levels: For adults 4,000 IU/day is a safe level of supplementation. I know that's ten times the dose I was taught 25 years ago but this is what the current research says. There have been studies in which pregnant women were given 100,000 IU/day for extended periods of time without ill effect to mother or child. Data from numerous studies in which pregnant women were supplemented with vitamin D show it results in superior health status for the mother and infant. Based on this data, "the current recommendations of 200-400 IU of vitamin D per day are scientifically unjustifiable and ethically questionable." Ideal doses for pregnant women are somewhere between 1,000 and 4,000 IU/day. I confess these doses are new to me and I would suggest periodic testing of 25(OH)D and calcium if taking high doses while pregnant. In Finland the suggested daily dose for infants and children was 4-5,000 IU/day, a dose which not only appears safe but protects against Type I diabetes. Doses of 1,000 IU/day are safe for children and infants; higher doses should still probably be monitored.

It would be nice if we could still obtain our vitamin D from sunlight. Here in Denver it's getting hard to conceive of doing this, especially in the colder months. Our current concerns about developing skin cancer may limit our ability to produce vitamin D even in the summer. Typical sunscreens block vitamin D production by 97-100%. Most of us work indoors and even when outdoors keep our clothes on, most of the time. Sunlight is no longer a reliable source for most of us. Food sources provide little vitamin D. Cod liver oil does contain decent amounts of D, but it would still take 3 Tablespoons a day to reach the 4,000 IU dose required to bring up one's status. This doesn't sound like fun and I'm not even going to suggest it to anyone.

Vitamin D deficiency and insufficiency is fast becoming epidemic in the developed world and attempts at supplementation have been at inadequate levels to prevent long term health consequences. For example, 57% of 290 inpatients in Massachusetts , many of whom were getting "adequate dietary intake" were Vitamin D deficient. In Minnesota 93% of patients with chronic musculoskeletal pain were deficient. Or 48% of patients with multiple sclerosis, 50% of patients with fibromyalgia and systemic lupus, 42% of healthy adolescents , and 42% African American Women and more than 62% of obese patients. These percentages are consistent with numbers from

Europe , Australia , Israel , Turkey and Saudi Arabia . In Saudi Arabia , 83% of patients with chronic back pain were deficient. The research provides us with no end of examples tying low vitamin D with illness: 73% of Austrian patients with ankylosing spondylitis, 58% of Japanese women with Grave's disease, and so on.

Something between 23,000 and 47,000 cancer deaths might be prevented in the United States each year if we used simple interventions, either sunlight or supplementation, to raise vitamin D to adequate levels.

Scientists knew for years that folic acid would prevent neural tube defects and deaths from heart disease. The years it took from when this information was known by researchers until it was applied by the medical community resulted in untold numbers of lives lost. Given the weight of evidence in support of using vitamin D, let us not repeat the same mistake of waiting too long.

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