Comprehensive Guide to Vitamins by Dr. James Meschino - HTML preview

Vitamin D

Introduction

Since the Middle Ages, cod liver oil has been used to prevent and treat rickets. In 1930, Vitamin D was isolated and shown to be the fat-soluble compound in cod liver oil that was effective against rickets.¹

In recent years, Vitamin D receptors have been discovered on tissues other than bone, and Vitamin D is now emerging as an important nutrient that may help reduce risk of colon, breast and prostate cancer due primarily to its effects on cellular differentiation and its anti-proliferative properties. Vitamin D may also help to reduce the risk of multiple sclerosis.²

Absorption and Metabolism

Vitamin D is a fat-soluble vitamin and is absorbed from the intestinal tract by means of chylomicrons (like Vitamins A and E), and is transported to the liver where it is stored. Vitamin D can also be acquired by exposure to direct sunlight (not through a window pane). Sunlight converts dehydrocholesterol to cholecalciferol (D₃) under the skin. Cholecalciferol then circulates to the liver, where like dietary Vitamin D, it can be converted to 25-hydroxycholecalciferol, which is five times more potent than cholecalciferol.

25-hydroxycholecalciferol circulates to the kidney where via further enzymatic hydroxylation it can be converted to 1, 25 dihydroxycholecalciferol, which is ten times more potent than cholecalciferol.^1,3 This form of Vitamin D (1, 25-dihydroxyvitamin D) is also known as calcitriol.

With aging, the body is less able to convert 25 hydroxycholecalciferol to 1,25 dihydroxycholecalciferol due to decreased activity of the kidney hydroxylase enzyme. Thus, circulating Vitamin D is less potent and appears to require compensation of higher Vitamin D₂ or Vitamin D₃ intake or increased sun exposure to help prevent age-related hip and other fractures.^2,4,5

Excess Vitamin D is stored in the liver. It has recently been shown that humans can tolerate much higher levels of Vitamin D intake without experiencing toxicity than previously believed to be true. In fact, higher levels (i.e., 1,000 I.U. or more per day) may be advantageous in people living above or below the 40^th degree latitude, where sunlight intensity is insufficient for long periods of the year to maintain optimal levels of serum Vitamin D (approximately 100 nmol/L) that is associated with less osteoporosis, certain cancers and multiple sclerosis.^2,6,7,8

Vitamin D formed under the skin as well as 25-hydroxyvitamin D₃ are transported through the blood attached to Vitamin D plasma binding protein, which is synthesized in the liver.¹

Functions

Vitamin D in the bloodstream stimulates the intestinal absorption of calcium and phosphorous (stimulates synthesis of calcium-binding protein in intestinal cells).

Vitamin D regulates the metabolism of calcium and phosphorous, which is vital for many functions including neuromuscular function, and mineralization of bone and teeth.¹

Vitamin D is involved in cellular differentiation of many tissues. Vitamin D receptors have been found on intestinal epithelial cells, renal cells, bone cells, skin cells, breast cells, and cells in the pancreas, connective tissue and parathyroid gland.^1,9

Vitamin D acts directly on bone aiding bone formation and in times of need, it stimulates the release of calcium from bone to help maintain blood calcium within the normal range; a function it shares with parathyroid hormone.¹

Vitamin D modulates immune system function, which appears to be important in resistance to infectious diseases and possibly multiple sclerosis prevention.^{2,10,11,12,21}

RDA (Vitamin D) – one I.U. equals 0.025 mcgs.

N.B. recent evidence suggests that older adults can reduce their risk of bone fractures by supplementing with 600-800 I.U. of Vitamin D per day to compensate for the drop off in conversion of 25 hydroxyvitamin D₃ to 1, 25-dihydroxyvitamin D₃ that accompanies aging.^5,13

Overt Vitamin D Deficiency

1. Rickets: lack of Vitamin D results in inadequate absorption of calcium and phosphorous, and consequently, faulty mineralization of bones and teeth. In children, this results in skeletal malformations from soft bones (i.e. knock knees, skull deformities).
2. Osteomalacia: in adults Vitamin D deficiency causes osteomalacia (bone softening) or adult rickets. The most common symptoms are weakening of the bone due to an increased porosity and decreased density. This can result in pain the bones in the leg and lower back, difficult walking and bone fractures.

N.B. The main cause of primary Vitamin D deficiency is lack of sunlight, hence milk fortification with Vitamin D is used in many countries to help safeguard against frank Vitamin D deficiency. In the U.S., one quart of milk is fortified with 400 I.U. of Vitamin D.¹

Supplementation Studies and Clinical Applications

Osteoporosis Prevention and Management

Human intervention studies demonstrate that postmenopausal women and older individuals can reduce their risk of hip fractures by approximately 43 percent with Vitamin D supplementation at 800 I.U.^2,4,5,13

Cancer Prevention

Individuals with higher blood levels of Vitamin D (at or above 100 nmol/L) tend to have a lower risk of colon, breast and prostate cancer. In subjects living above or below the 40^th latitude, Vitamin D supplementation of 400-1,000 I.U. per day is often required to achieve this blood level of Vitamin D. Generally speaking, 400 I.U. of Vitamin D supplementation raises serum 25-hydroxyvitamin D levels by about 45 nmol/L.

N.B. In experimental studies, Vitamin D has been shown to suppress cancer cell proliferation, induce cancer cell apoptosis and differentiation, demonstrating a strong potential role in the prevention and management of colon, breast and prostate cancer.^{2,6,7,8,14-17}

Dosage Ranges

Prevention of Osteoporosis and possibly certain cancers in adults over 40 years of age: consider 400-1,000 I.U. per day, especially if living in regions above or below the 40^th degree latitude.^{2,5,8,11,13-17,19,20}

Vitamin D Side Effects and Toxicity

Hypercalcemia is always accompanied by a serum 25 hydroxyvitamin D concentration of greater than 220 nmol/L.

Most authorities recommend that adults not supplement with more than 1,000 I.U. per day (of Vitamin D), however, evidence suggests that levels as high as 4,000 I.U., per day is non-toxic and may actually be beneficial in osteoporosis prevention and management, as well as for other health-promotion purposes (see reference 2 for complete details of this position).^1,2 In fact, of all published cases of Vitamin D toxicity for which a Vitamin D amount is known, only one occurred at a dose under 40,000 I.U. per day.² Nevertheless, people wishing to take more than 1,000 I.U. per day for long periods of time require proper monitoring of block levels and liver function tests.

People with hyperparathyroidism should not take Vitamin D supplements without consulting a physician, nor should people with sarcoidosis.

Signs and symptoms of Vitamin D toxicity include headaches, nausea, vomiting, polyuria, polydipsia, weight loss, kidney stones, calcification of soft tissues and some other more rare symptoms (i.e., blindness, deafness).^1,2

Drug-Nutrient Interactions

It is well known that cortisone or predisone therapy (glucocorticoids) interfere with the metabolism of Vitamin D and are associated with increased risk of osteoporosis. Barbituates and anticonvulsants also cause increased degradation of Vitamin D and its metabolites¹ and increase osteoporosis risk.^22,23

Other drugs that reduce Vitamin D nutritional status include:

Allopurinol¹⁹

Bile Acid Sequestrants (eg. Cholestyramine and colestipol)^18,24

Cimetidine and other H-2 Antagonists^18,25

Oral Contraceptives¹⁸

Heparin¹⁸

Hydroxychloroquine¹⁸

Indapamide¹⁸

Isoniazid^18,26

Mineral oil^18,27

Neomycin¹⁸

Thiazide Diuretics¹⁸

Rifampin – may reduce blood vitamin D levels by 70%²⁸

Orlistat – reduces blood levels of Vitamin D²⁹

Vitamin D supplements may antagonize the calcium channel blocker drug known as Verapamil, which is used to treat angina pectoris, heart arrhythmias, and hypertension.¹⁸

Standard Textbooks of Nutritional Science:

- Shils M, Shike M, Olson J, Ross C. Modern Nutrition in Health and Disease. 9^th ed. Baltimore, MD: Lippincott Williams & Wilkins; 1993.

- Escott-Stump S, Mahan LK, editors. Food, Nutrition and Diet Therapy. 10^th ed. Philadelphia, PA: W.B. Saunders Company; 2000.

- Bowman B, Russell RM, editors. Present Knowledge in Nutrition, 8^th ed. Washington, DC:.ILSI Press; 2001.

- Kreutler PA, Czajka-Narins DM, editors. Nutrition in Perspective. 2^nd ed. Upper Saddle River, NJ: Prentice Hall Inc.; 1987. Veith R. Vitamin D supplementation, 25-hydroxy Vitamin D concentrations and safety. Am J Clin Nutr 1999; 69(5):842-56.

Lore F, et al. Vitamin D metabolites in postmenopausal osteoporosis. Horm Metab Res 1984;16:161-6.

Optimal Calcium Intake: NIH consensus conference. JAMA 1994;272(24):1942-8.

Dawson-Hughes B, et al. Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of the Vitamin D. Am J Clin Nutr 1995;61:1140-5.

Garland FC, et al. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med 1970;19:614-22.

Garland CF, et al. Can colon cancer incidence and death rates be reduced with Calcium and Vitamin D? Am J Clin Nutr 1991 ;54(Suppl-1):193S-201S.

Gahn PH, et al. Circulating Vitamin D metabolites in relation to subsequent development of prostate cancer. Epidemiol Biomarkers Prev 1995;5(2):121-6.

Shabahang M, et al. Growth inhibition of HT-29 human colon cancer cells by analogues of 1,25 dihydroxy vitamin D3. Cancer Res 1994;54:407-64.

Crowle AJ, et al. Inhibition by 1,25 dihydroxy vitamin D3, of the multiplication of virulent tubercle bacilli in cultured human macrophages. Infect Immun, 1987;55:2945-50.

DeLuca HF. The Vitamin D story: A collaborative effort of basic science and clinical medicine. FASEB J 1988;2:224-36.

Fukazawa T, et al. Association of Vitamin D receptor gene polymorphism with multiple sclerosis in Japanese. J Neurol Sci 1999;166(1):47-52.

Chapuy MC, et al. Effect of Calcium and chole-calciferol treatment for three years on hip fractures in elderly women. Br Med J 1994;308:1081-2.

Feldman D, et al. Vitamin D and prostate cancer. Adv Exp Med Biol 1995; 375:53-63.

Rozen F, Yang XF, Huynh H, Pollak M. Antiproliferative action of Vitamin D - related compounds and insulin-like growth factor - binding protein 5 accumulation. J Natl Cancer Instit 1997;89(3):652-6.

Mehta RG, et al. Prevention of preneoplastic mammary lesion development by a novel Vitamin D analogue, 1-alpha-hydroxyvitamin D5. J Natl Cancer Instit 1997; 89(3):212-8.

Martinez ME, et al. Calcium, Vitamin D and the occurrence of colorectal cancer among women. J Natl Cancer Instit 1996;88(19):1375-82.

Healthnotes, 2000 Inc. Available from: URL: http://www.healthnotes.com. Dawson-Hughes B, et al. Effect of calcium and Vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997;337:670-6.

Dawson-Hughes B. Calcium and Vitamin D requirements of elderly women. J Nutr 1996; 126(Suppl4):1165S-7S.

Hayes C, et al. Vitamin D and multiple sclerosis. Proc Soc Exper Biol Med 1997;216:21-7.

Zerwekh JE, et al. Decreased serum 24,25-Dihydroxyvitamin D concentration during long-term anticonvulsant therapy in adult epileptics. Ann Nerol 1982;12(2):184-6.

Chesney RW, et al. Decreased serum 24,25-dihydroxyvitamin D3 in children receiving glucocorticoids. Lancet 1978;2(8100): 1123-5.

Knodel LC, et al. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2(1):10-32.

Odes HS, et al. Effect of cimetidine on hepatic vitamin D metabolism in humans. Digestion 1990;46(2):61-4.

Toppet M, et al. Sequential development of vitamin D metabolites under isoniazid and rifampicin therapy. Arch Fr Pediatr 1998;45(2):145-8.

Diarrhea and constipation. In: Berkow R, Fletcher AJ Beers MH, et al, editors. The Merck Manual of Diagnosis and Therapy. 16^th ed. Rahway, NJ: Merck Research Laboratories; 1992.

Brodie MJ, et al. Rifampicin and vitamin D metabolism. Clin Pharmacol Ther 1980;27(6):810-4.

James WP, Avenell A, Broom J, et al. A one-year trial to assess the value of Orlistat in the management of obesity. Int J Obes Relat Metab Disord 1997;21 (Suppl3):24S-30S.