Recently quite a bit has been written about the apparent epidemic of vitamin D deficiency in the U.S. There have been many newspaper articles written about the need to increase vitamin D and calcium intake to prevent weak bones and fractures. As best I can tell, it is now the standard of care to measure vitamin D levels (as serum 25-hydroxy vitamin D or 25-OH vitamin D)) in all middle-age women and in elderly men and women. It seems that DEXA scans (a way to quantify bone mineralization) have become almost as common as blood glucose measurements. I have spoken to quite a number of people, mostly women, whose doctors (primary care docs and OB/GYN docs) have measured their vitamin D levels, found them to be “dangerously low,” and have prescribed supplemental calcium and vitamin D. So, do we really have an epidemic of vitamin D deficiency? I would submit that it’s mostly nonsense. I will try to explain.
First, there is no question that, weak bones (osteoporosis) are a problem in the elderly, particularly women. The prevalence of pathological fractures (those resulting from only minor trauma), particularly of the hips and spine are significantly increased in seniors and are very serious indeed. For the most part, osteoporosis in the elderly is the result of a number of factors including poor nutrition resulting in insufficient intake of vitamin D and calcium, decreased physical activity, and low levels of the sex hormones estrogen and testosterone.
Many people now take vitamin D and calcium supplements in an effort to keep their bones strong. Widespread use of these supplements led to a recent consensus statement by medical experts regarding recommendations for calcium and vitamin D supplementation- really an effort to clarify just what calcium and vitamin D requirements are at different ages (see “Extra vitamin D and calcium aren’t necessary, report says,” written by Gina Kolata, NYT November 30, 2010, page 1, A20). We will come back to the report later in my entry.
Vitamin D and Calcium absorption
Calcium absorption from the gut is different than for minerals such as sodium and potassium which are almost entirely absorbed; the absorption of calcium is incomplete and dependent on the body’s “need” for calcium. It is a good thing that calcium absorption is regulated since, unlike sodium and potassium, the kidneys cannot excrete excess calcium very well; large calcium loads can cause serious damage to the kidneys. Thus, the body normally absorbs just the right amount of calcium regardless of the dietary intake. The rate of calcium absorption is controlled by vitamin D, primarily 1,25-diOH vitamin D, the active component (25-OH vitamin D and related compounds can also modulate calcium absorption somewhat). The way this all works is that when the blood calcium drops even a slight amount, the parathyroid glands secrete parathyroid hormone which, in turn, stimulates formation of 1,25-diOH vitamin D, which in turn, stimulates intestinal calcium absorption. The process is modulated by other hormones such as growth hormone and estrogens, which have direct effects on the secretion of 1,25-diOH vitamin D. Glucocorticoids (e.g., hydrocortisone) in high doses can inhibit calcium absorption but this effect can be overcome by increasing intake of vitamin D.
Calcium absorption can be decreased in conditions that decrease fat absorption which decreases vitamin D absorption. Also, diarrheal states or any other conditions that increase intestinal motility, decrease calcium absorption. Some intestinal conditions such as celiac disease directly inhibit absorption of calcium. High fiber foods, particularly certain cereals can inhibit calcium absorption; high fiber foods contain large amounts of phosphates (specifically, an organic phosphate, phytic acid, which contains inositol hexaphosphate) which blocks calcium absorption. It is interesting that whole wheat flour contains large amounts of phytic acid but fortunately, the leavening process (adding yeast to bread), breaks down the phytic acid.
Absorption of calcium in dietary supplements (e.g., vitamins) can be affected by the chemical form of the calcium. Calcium supplements are generally either calcium carbonate or calcium citrate. Calcium carbonate, the most common form of supplemental calcium, requires an acid environment for optimal calcium absorption. Thus, diseases or drugs that decrease stomach acid inhibit calcium absorption. The citrate form of calcium is soluble and does not require an acid environment for absorption. So, if one is taking supplemental calcium that is in the carbonate form, it is usually recommended that the medication be taken along with or immediately after eating, which stimulates stomach acid production. I have not seen any good data showing just how different absorption of supplemental calcium is when taken with food or on an empty stomach. I doubt it matters much but just to be on the safe side, I suppose people should take calcium carbonate-containing supplements with meals.
Vitamin D is essential for normal growth and development. Both deficiency and excess of the nutrient can have serious consequences. Deficiency of vitamin D causes rickets, while excess can cause hypercalcemia and injury to many tissues, particularly the kidneys. Vitamin D is formed from 7-dehydrolcholesterol, a cholesterol precursor found in the skin. Ultraviolet light converts the precursor to vitamin D. Vitamin D2 (called ergo-calciferol) is formed from irradiation of the plant sterol ergosterol while vitamin D3 (called cholecalciferol) is formed from irradiation of 7-dehydrocholesterol. Both vitamin D2 and D3 are as potent as vitamin D in treatment of rickets.
Vitamin D (and vitamin D2 and D3) is not metabolically active. Rather, it is activated by first being converted to 25-OH vitamin D and then to 1,25-dihydroxy vitamin D. The first conversion takes place in the liver and the second in the kidneys. Both 25-OH vitamin D and 1,25-diOH vitamin D are metabolically active but the latter much more so (about 1000X more active). Vitamin D is a fat soluble vitamin which can be stored in the body fat for many months and be slowly converted into the active metabolites. This is a big problem in cases of vitamin D over dosage. As a fat soluble vitamin (just like vitamins A, E, and K), vitamin D anbsorption is affected by conditions that inhibit fat absorption, such as certain intestinal diseases and deficiencies in the intestinal enzymes responsible for fat absorption. Thus, it is important to consider the possibility of vitamin D deficiency in all patients who have fat malabsorption. Likewise, people who ingest very low fat diets, may have somewhat decreased dietary or supplemental vitamin D absorption. Of course, adequate exposure to sunlight, results in synthesis of all the vitamin D normally required. Some drugs do affect conversion of vitamin D to 25-OH vitamin D (e.g., cimetidine, some anticonvulsants) and as one would expect, liver disease can affect synthesis of 25-OH vitamin D as well. Kidney disease can affect synthesis of 1,25-diOH vitamin D.
For people taking vitamin D supplements, it is generally recommended that they be taken with food. One recent study showed that vitamin D absorption was significantly increased when taken with the biggest meal of the day (Mulligan GB, Licata A: Taking vitamin D with the largest meal improves absorption and results in higher serum levels of 25-hydroxyvitamin D. J Bone Min Res 2010;4:928-30). I am not sure how to interpret the results of the study. There were only 17 study subjects and all had normal 25-hydroxyvitamin D levels at baseline. I don’t doubt the fact that taking vitamin D supplements with meals, particularly high fat meals, increases vitamin D absorption. What I question is whether it matters much for most people? If levels of 25-OH vitamin D levels are normal, is higher better? I have not seen any data to show any health benefits. In fact, recent studies show no relationship between serum 25-hydroxy vitamin D levels and mortality rate. Anyway, I suppose that for both calcium and vitamin D supplements, it makes sense to take them with food.
The Expert Committee Report
So, back to the recent expert report on vitamin D and calcium supplements. The bottom line is that most people do not need vitamin D and calcium supplements and they may, in fact be harmful. There are data to suggest that extra calcium can increase the risk of heart disease and compelling data to show that extra calcium increases risks for kidney stones and permanent kidney damage. The Institute of Medicine convened an expert committee to examine the available data to determine just how much vitamin D and calcium people really need. Much of the “push” to treat with calcium and vitamin D supplements was based on the misguided notion that levels of serum 25-OH vitamin D below 30 ng/ml were low. Based on this standard 80+% of people in the U.S. were vitamin D deficient. In fact, the committee concluded that levels between 20-30 ng/ml were just fine (in the “old days” the lower limit of normal for serum 25-OH vitamin D was about 15 ng/ml and I suspect that has not changed at all). Note: breast-fed babies DO need supplemental vitamin D.
What did change was the availability of new drugs called bisphosphonates to treat osteoporosis. The pharmaceutical companies, perhaps aided by the endocrinologists, pushed and pushed for more aggressive treatment of patients with weak bones. A new disease entity was created- osteopenia. This was defined as a condition in which the DEXA scan results showed normal but below average bone mineralization. To be sure, people with osteopenia are more likely to develop osteoporosis than those with higher bone mineral densities, but there was no scientific justification for treating large numbers of patients with bisphosphonates (and supplemental calcium and vitamin D) to improve their bone health. We certainly had the opportunity to learn about the complications that can develop with use of bisphsphonates (e.g., jaw necrosis).
The expert committee updated the recommended dietary allowance (RDA) for calcium and vitamin D emphasizing that most people in the U.S. already receive enough of both nutrients to manage just fine without supplements. For example, in women ages 51-70 years, the committee recommended calcium RDA of 1200 mg/d with a maximum of 2000 mg/d; the recommended vitamin D RDA for people 9-70 years was 600 IU with a maximum of 4000 IU. I know many people whose physicians have recommended that they take 20,000 IU or more of vitamin D daily to treat either their osteopenia or “low” 25-OH vitamin D levels. Crazy stuff
In summary, osteoporosis is a serious medical condition that can be caused in part by low calcium and/or vitamin D levels and that can predispose people to bone fractures. Most people in the U.S. are not deficient in either calcium or vitamin D and can maintain normal levels just by eating well and maybe, getting sun exposure now and then. If a person has a legitimate need for calcium and/or vitamin D supplementation, taking the supplements with food results in better absorption than if taken on an empty stomach. Physicians would do well to read the recent Institute of Medicine report on vitamin D and calcium supplementation.
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