High-Dose Vitamin D - One of the Best Nutritional Supplements on the Market

Very few interventions offer the power, safety, and cost-effectiveness of vitamin D supplementation.Last year, I wrote one of the most complete monographs on vitamin D that has ever been published, and I would like to share some of that information with you here, as well as provide some updates on new research that has been published in the past few months. I think that by the time you have finished reading this column, you will have a new appreciation for vitamin D and its ability to help you and your patients toward your goals of optimal health.

Of course, vitamin D is made endogenously, following exposure of the skin to the sun or other source of UV-B radiation, such as tanning beds. Most of us work indoors during the day, and when we are outside, we are shielded from the sun by clothes, hats, shade, clouds, or sunscreen lotion. The end result is that the vast majority of Americans are not getting enough vitamin D to prevent deficiency - let alone promote optimal health. Studies among Americans in different social groups have consistently shown that vitamin D is an epidemic in the U.S., with most studies reporting 40 percent to 80 percent of study populations showing deficient levels of vitamin D in their blood. Impressively, a study published in Mayo Clinic Proceedings in December 2003 showed that, among 150 patients with persistent nonspecific musculoskeletal pain, 93 percent of patients showed abnormally low levels of vitamin D in their blood. Similarly, a study published in Spine showed that 83 percent of patients with low-back pain had an abnormally low level of vitamin D according to blood tests, which accurately measure vitamin D status.

Although many doctors and patients are using multivitamin supplements these days, the vast majority of consumers are unaware that even with daily supplementation, they are almost certainly not receiving enough vitamin D. Most multivitamin supplements contain only 400-800 IU of vitamin D; notice that this is only 10 to 20 percent of what is necessary for optimal physiologic function. Indeed, research published by Robert Heaney and colleagues in the American Journal of Clinical Nutrition in January 2003 showed that the physiological requirement for vitamin D in adult men is between 3,000-5,000 IU per day. There is no way to meet physiologic demands for vitamin D based on consumption of a reasonable diet and an average multivitamin supplement. Thus, for people unable to obtain 20-30 minutes of full-body sun exposure on an almost daily basis, it has become clear that high-dose vitamin D supplementation is necessary to ensure that physiologic needs are met, and so that optimal health can be obtained and maintained.

What are the consequences of long-term vitamin D deficiency? The answer to this question has become increasingly clear in the past few years. Actually, the first evidence in support of sun exposure as a source of vitamin D was published in 1941 by Apperly, who showed in the journal Cancer Research that cancers of various types were much less frequent in populations that lived closer to the equator. Since then, additional research has shown that vitamin D deficiency is a risk factor for breast cancer, prostate cancer, and numerous autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and type-1 diabetes. The most convincing study ever published on this topic was authored by Hypponen and colleagues in the November 2001 issue of The Lancet. In this remarkable study, the investigators administered 2,000 IU of vitamin D per day to more than 10,000 infants, who were supposed to receive the vitamin D supplement every day for the first entire year of life. Thereafter, the risk of developing type-1 diabetes was calculated and a dose-response relationship was established. The results showed a positive dose-response relationship: the more regularly vitamin D was consumed, the greater the protection afforded against the development of type-1 diabetes. Children who were given vitamin D supplements on a regular basis had their risk of type-1 diabetes reduced by an amazing 88 percent! No adverse effects were noted.

In a brilliant article published in the November 2003 issue of the American Journal of Clinical Nutrition, Heaney distinguished "acute nutritional deficiencies" from "long-latency deficiency diseases" and thus helped us understand how mild, subclinical nutritional deficiencies directly contribute to the development of cancer, cardiovascular disease, and other problems that plague modern industrialized societies. Thus, when speaking of vitamin D, the manifestation of acute deficiency is rickets, whereas the long-latency diseases caused by vitamin D deficiency include cancer, hypertension, polycystic ovary syndrome, migraine headaches, chronic musculoskeletal pain, insulin resistance, and many of the autoimmune diseases. Proof of principle is found in numerous epidemiological studies and clinical trials showing that vitamin D supplementation prevents or alleviates all of the above-mentioned conditions. Let's look at a few examples from the current research; for more details and citations, please see the review article I published last year, which is also available online.¹

Alleviation of depression and the enhancement of well-being: At least three studies have shown that vitamin D has a mood-elevating effect that begins within just a few days of supplementation.^2,3

The most recent study showed that the administration of 4,000 IU per day of vitamin D was superior to a lower dose of 600 IU per day, and provided additional benefits for patients in terms of increasing feelings of overall health, sociability, and ability to deal with stress.⁴

Anti-inflammatory benefits: Three clinical trials have documented an anti-inflammatory benefit of vitamin D supplementation, suggesting that vitamin D may be used as part of a comprehensive approach for the prevention and treatment of inflammatory disorders.^5,6 In one of the studies, a modest dose of vitamin D reduced blood levels of C-reactive protein by 23 percent, which is remarkable considering that CRP is considered one of the most sensitive markers for predicting the risk of cardiovascular disease.⁷

Alleviation of chronic musculoskeletal pain: As I mentioned before in this article, vitamin D deficiency is particularly common in patients with chronic musculoskeletal pain, including the clinical picture of what is commonly labeled as "fibromyalgia." In the aforementioned article published in Spine, administration of 5,000-10,000 IU per day of vitamin D alleviated low-back pain in 95 percent of patients, 83 percent of whom had been diagnosed with vitamin D deficiency. Thus, it appears that vitamin D supplementation can alleviate pain even in patients without overt vitamin D deficiency.

Clinical implementation of vitamin D supplementation at physiologic doses is easy and effective. Since the vast majority of multivitamin supplements do not contain a high enough level of vitamin D to meet the requirement of 3,000-5,000 IU per day, patients and doctors have to get in the habit of using a separate vitamin D supplement to complement their other supplements of vitamins, minerals, and fatty acids. Vitamin D is available in pills as well as liquid drops. For the sake of ease of use, as well as cost-effectiveness and enhanced absorption, microemulsified drops appear to be the best form of vitamin D supplementation, and of course, this is especially true when working with infants and children who cannot swallow pills. One or two drops (depending on the dosage desired) can be placed directly into the mouth, on food, or in water. There is essentially no taste to vitamin D, and it never causes stomach upset. Daily doses that I recommend for patients are 1,000-2,000 IU for infants, 2,000 IU for children, and 4,000 IU for adults.

In each of the major studies using 4,000-10,000 IU per day of vitamin D for periods up to six months, no adverse effects have ever been reported. However, doctors and patients need to be aware that certain drugs (namely thiazide diuretics) and certain conditions known as "vitamin D hypersensitivity syndromes," seen with conditions such as sarcoidosis, tuberculosis, Crohn's disease, adrenal insufficiency, and thyroid disease, increase the risk for elevated blood calcium levels (hypercalcemia), which is the only mechanism of toxicity for the vitamin. Thus, when working with these higher-risk patients, serum calcium levels should be checked more frequently (every 1-2 months) and supplementation should be initiated slowly and increased over time. The ultimate goal is to ensure safety (by measuring serum calcium) and effectiveness (by measuring 25-OH-vitamin D levels in the blood). According to our research, the optimal range for 25(OH)D is 40-65 ng/mL (100-160 nmol/L).

In summary, human physiology has adapted though millions of years of living in a natural environment to depend on a plentiful supply of vitamin D. In modern times, our indoor lifestyles and use of abundant clothing and sunscreen have made oral supplementation with vitamin D a necessity, to replace what our bodies need but are not receiving - namely, vitamin D in a dosage range of at least 3,000-5,000 IU per day. For adults, two drops per day of vitamin D is the easiest and most cost-effective way to ensure that vitamin D needs are being met, and products that are microemulsified have excellent absorption and increase the effectiveness of supplementation.⁸ In addition to alleviating back pain, depression, and inflammation, as discussed previously, clinical trials have also proven the effectiveness of vitamin D supplementation in the treatment of hypertension,^9,10 polycystic ovary syndrome,¹¹ and migraine headaches.^12,13 Thus, on the grounds of safety, convenience, and cost-effectiveness, vitamin D has an important role in preventive medicine and interventional nutrition, and should be a regular part of the treatment plan of essentially all patients.

References

1. Vasquez A, Manso G, Cannell J. The clinical importance of vitamin D (cholecalciferol): a paradigm shift with implications for all healthcare providers. Alternative Therapies in Health and Medicine 2004;10:28-37. Available at www.bioticsresearch.com/vitD.htm.
2. Gloth FM 3rd, Alam W, Hollis B. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. J Nutr Health Aging 1999;3(1):5-7.
3. Lansdowne AT, Provost SC. Vitamin D3 enhances mood in healthy subjects during winter. Psychopharmacology (Berl) 1998;135:319-23.
4. Vieth R, Kimball S, Hu A, Walfish PG. Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Nutr J 2004;3(1):8.
5. Van den Berghe G, Van Roosbroeck D, Vanhove P, et al. Bone turnover in prolonged critical illness: effect of vitamin D. J Clin Endocrinol Metab 2003;88(10):4623-32.
6. Tetlow LC, Woolley DE. The effects of 1 alpha,25-dihydroxyvitamin D(3) on matrix metalloproteinase and prostaglandin E(2) production by cells of the rheumatoid lesion. Arthritis Res 1999;1:63-70.
7. Timms PM, Mannan, et al. Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM 2002;95:787-96.
8. Bucci LR, Pillors M, Medlin R, et al. Enhanced Blood Levels of Coenzyme Q-10 From an Emulsified Oral Form. In Faruqui SR and Ansari MS (editors): Second Symposium on Nutrition and Chiropractic Proceedings, April 15-16, 1989, in Davenport, Iowa.
9. Pfeifer M, Begerow B, Minne HW, et al. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab 2001;86(4):1633-7.
10. Krause R, Buhring M, Hopfenmuller W, et al. Ultraviolet B and blood pressure. Lancet 1998;352(9129):709-10.
11. Thys-Jacobs S, Donovan D, Papadopoulos A, et al. Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids 1999;64(6):430-5.
12. Thys-Jacobs S. Alleviation of migraines with therapeutic vitamin D and calcium. Headache Nov-Dec 1994;34(10):590-2.
13. Thys-Jacobs S. Vitamin D and calcium in menstrual migraine. Headache October 1994;34(9):544-.