Use of vitamin D in clinical practice

Alternative Medicine Review, March, 2008 by John J. Cannell, Bruce W. Hollis

Abstract

The recent discovery--from a meta-analysis of 18 randomized controlled trials--that supplemental cholecalciferol (vitamin D) significantly reduces all-cause mortality emphasizes the medical, ethical, and legal implications of promptly diagnosing and adequately treating vitamin D deficiency. Not only are such deficiencies common, and probably the rule, vitamin D deficiency is implicated in most of the diseases of civilization. Vitamin D's final metabolic product is a potent, pleiotropic, repair and maintenance, seco-steroid hormone that targets more than 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. One of the most important genes vitamin D up-regulates is for cathelicidin, a naturally occurring broad-spectrum antibiotic. Natural vitamin D levels, those found in humans living in a sun-rich environment, are between 40-70 ng/mL, levels obtained by few modern humans. Assessing serum 25-hydroxy-vitamin D (25(OH)D) is the only way to make the diagnosis and to assure treatment is adequate and safe. Three treatment modalities exist for vitamin D deficiency: sunlight, artificial ultraviolet B (UVB) radiation, and vitamin D supplementation. Treatment of vitamin D deficiency in otherwise healthy patients with 2,000-7,000 IU vitamin [D.sub.3] per day should be sufficient to maintain year-round 25(OH)D levels between 40-70 ng/mL In those with serious illnesses associated with vitamin D deficiency, such as cancer, heart disease, multiple sclerosis, diabetes, autism, and a host of other illnesses, doses should be sufficient to maintain year-round 25(OH)D levels between 55-70 ng/ mL. Vitamin D-deficient patients with serious illness should not only be supplemented more aggressively than the well, they should have more frequent monitoring of serum 25(OH) D and serum calcium. Vitamin D should always be adjuvant treatment in patients with serious illnesses and never replace standard treatment. Theoretically, pharmacological doses of vitamin D (2,000 IU/kg/day for three days) may produce enough of the naturally occurring antibiotic cathelicidin to cure common viral respiratory infections, such as influenza and the common cold, but such a theory awaits further science. (Altern Med Rev 2008; 13(1):6-20)

Introduction

A recent meta-analysis of 18 randomized controlled trials (RCT) found that cholecalciferol (vitamin D) significantly reduced total mortality. (1) This discovery is all the more remarkable because of the relatively low doses of vitamin D used (mean close 528 IU (13 mcg)) and because the finding persisted across a number of subgroup analyses. In spite of the low doses used and the short duration of the trials, vitamin D's mortality reduction was seven percent. (2) Indeed, the recent discovery that statins significantly increase 25-hydroxy-vitamin D (25(OH)D) levels raise the possibility that some--or all--of the mortality reduction of statins may be mediated through increases in vitamin D levels. (3,4)

Lappe et al recently reported the first RCT of vitamin D in preventing internal cancers and found a 60-percent reduction in such cancers by increasing baseline 25(OH)D levels from 29 ng/mL to 38 ng/mL with 1,100 IU (28 mcg) per day. (5) Baseline and treatment-induced serum 25(OH)D levels were strong and independent predictors of cancer risk. Lappe et al's study left open the possibility that higher doses and higher treatment-induced 25(OH)D levels might prevent even more cancers. (Note that 25(OH)D levels are reported in the literature as either ng/mL or nmol/L; 1.0 ng/mL equals 2.5 nmol/L.)

Besides cancer, vitamin D deficiency is associated with cardiovascular disease, hypertension, stroke, diabetes, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, osteoporosis, periodontal disease, macular degeneration, mental illness, propensity to fall, and chronic pain. (6-10) A recent review presented considerable evidence that influenza epidemics, and perhaps even the common cold, are brought on by seasonal deficiencies in antimicrobial peptides (AMP), such as cathelicidin, secondary to seasonal deficiencies in vitamin D. (11) Results of an RCT support the theory, finding 2,000 IU of vitamin D/day for one year virtually eliminated self-reported incidence of colds and influenza (Figure 1). (12) Even the current triple childhood epidemics of autism (13) (Figure 2), asthma, (14) and type 1 diabetes, (15) all of which blossomed after sun-avoidance advice became widespread, might be the tragic and iatrogenic sequela of gestational or early childhood vitamin D deficiencies brought on by medical advice to avoid the sun.

[FIGURE 1 OMITTED]

Claims that vitamin D may help prevent such a wide variety of diseases seem incredible until one realizes vitamin D is not a vitamin; rather, it is the only known substrate for a potent, pleiotropic, repair and maintenance, seco-steroid hormone with a single endocrine function, but multiple autocrine functions. Previously, many practitioners thought vitamin D's activity was principally its endocrine function--the regulation of serum calcium--and was thus mainly involved in bone metabolism. Indeed, the classic endocrine function of vitamin D begins when the kidney hydroxylates 25(OH)D into 1,25[(OH).sub.2]D, which then acts, both directly and indirectly, to maintain serum calcium.