Vitamin D, Nutritional Deficiency, and the Medical Paradigm

Robert P. Heaney

Creighton University Omaha, Nebraska 68131

Address all correspondence and requests for reprints to: Robert P. Heaney, M.D., Creighton University, 601 North 30th Street, Suite 4841, Omaha, Nebraska 68131. E-mail: rheaney{at}creighton.edu.

A century ago, at the birth of nutrition as a science, the prevailing medical paradigm held that all disease was caused by harmful external influences—bacteria or toxins, principally. The idea that not eating something could make one sick was initially inconceivable. The recognition of the role of thiamin in preventing beri-beri and the discovery of niacin and vitamin A (among other micronutrients) forced a change in that view. But public health measures in the first half of the 20th century eradicated the most extreme of the vitamin deficiencies in the industrialized nations, and the physician’s actual experience of deficiency disease dropped to near zero. Perhaps as a result, the medical profession’s approach to nutrition today is still dominated by the external agent paradigm, as witnessed in the national campaigns for cholesterol, saturated fat, and salt. Those who think more seriously in terms of the continuing importance of deficiency per se are often derogated or relegated to the quackery fringe (1). The result, at the very least, is inattention to the real deficiencies that may masquerade as other disorders, or that may simply be ignored altogether.

This issue of JCEM contains an instance of the latter phenomenon. In a report on Northern Italian centenarians, Passeri et al. (2) note that 99 of the 104 individuals examined had undetectable levels of serum 25-hydroxyvitamin D [25(OH)D] (i.e. less than 5 nmol/liter), and the lone individual with a value approaching the lower end of the optimal range (3) was receiving 400,000 IU vitamin D2 im every 6 months, for a daily average of approximately 2200 IU [probably equivalent to not much more than 1000 IU of the more potent vitamin D3 (4)]. The fact that less than 1% of this vulnerable population was receiving even marginally appropriate nutritional prophylaxis is an indictment, not so much of Northern Italian health care as of medicine generally for its failure to recognize and deal effectively with deficiency involving whole cohorts of individuals.

This Northern Italian study, which is probably the most egregious recent example, is not by any means the only published report of vitamin D deficiency in recent years. Thomas et al. (5) reported that 57% of all adults admitted to the Massachusetts General Hospital in Boston had 25(OH)D values below the lower end of the laboratory reference range, and, had a more appropriate criterion (3) been applied, more than 85% of them would have been deficient. Abrams (6) has described the sad recurrence of rickets in children, and Glerup et al. (7) in Denmark reported widespread vitamin D deficiency, particularly in individuals covering most of their skin for religious or cultural reasons.

This is not simply a matter of equating abnormal test values with disease. There are clear physiological and morbid consequences of low serum vitamin D. In the article by Passeri et al. (2), 14% of the subjects had sustained hip fractures after age 94 yr. In a recently reported trial from Great Britain, osteoporotic fractures were reduced by 33% in a randomized controlled trial of modest levels of vitamin D supplementation (8). What is particularly noteworthy about the British study is that the unsupplemented individuals had 25(OH)D values that, while less than many experts now consider optimal (3), were nevertheless well above the bottom end of the reference range. Additionally, Heaney et al. (9) have just this year published measurements of calcium absorption efficiency at different regions of the reference range for serum 25(OH)D, showing that calcium absorption does not plateau until 25(OH)D exceeds approximately 80 nmol/liter.

Vitamin D, in fact, may be somewhat of an exception to medicine’s selective ignoring of the value of preventive nutrition. If Passeri et al. (2) had not been at least concerned about vitamin D in their centenarians, they would not have bothered to measure it. And the Food and Nutrition Board of the Institute of Medicine in the United States, in 1997 (10), while caviling over a few milligrams in the calcium recommendation, had no apparent trouble in tripling the vitamin D requirement for the elderly (probably the largest increase in an intake recommendation in the history of the RDAs).

Hence, the good news is that the problem is now out in the open and physicians seem much more aware of it than they had been in the past. But physicians necessarily deal with individuals. What the Passeri paper shows is that entire segments of the population are affected. A broader public health approach is needed.

However, even at the level of the individual physician-patient encounter, something more than just awareness will be required. Although serum 25(OH)D assays have improved over the past 20 yr, they still are not well standardized, and results are often hard to compare or interpret. Perhaps even worse is the virtual absence of good vitamin D preparations (oral or parenteral) in North America. Cholecalciferol (vitamin D3), the preferred form of the vitamin, is hard to find, and the few pharmacists who stock it typically do so as a "behind the counter" product. The im ergocalciferol (D2) preparation has become difficult to obtain in recent months. Moreover, calcidiol [25(OH)D3], an extremely effective, rapidly acting, and safe form of vitamin D, has been withdrawn by its manufacturer.

Thus, we are left, on the one hand, with belated recognition of the importance of vitamin D deficiency, particularly in the elderly, and on the other, with weak and inconsistent analytical technology for measuring vitamin D status in patients and with the virtual absence of good therapeutic products to manage what we measure.

Vitamin D is inexpensive to manufacture and to administer. (Maybe that is a part of the reason for the problem.) By contrast, the cost of vitamin D deficiency, while yet to be fully reckoned, may well be massive. J. Cannell (submitted for publication) has written that measures such as this editorial will not change the situation, and that only tort litigation will work. One can only hope that he is wrong. Either way, something needs to change.

Footnotes

Abbreviation: 25(OH)D, 25-Hydroxyvitamin D.

Received September 18, 2003.

Accepted September 18, 2003.

References

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