Vitamin D

 

 

Vitamin D

Vitamin D is both a hormone and a vitamin. It was identified in the 1920s after a long search for the cause and cure of rickets, which had been a significant health problem since the industrialization of northern Europe. Vitamin D is obtained from food sources and is also manufactured in the skin through the action of sunlight. There are three forms of vitamin D: vitamin D1 (calciferol), vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D2 is the form most commonly added to foods and nutritional supplements. These forms of vitamin D are converted in the liver and kidneys to the hormone, calcitriol, which is the physiologically active form of vitamin D.

What it does in the body

Bones and teeth

The most important role of vitamin D is to maintain blood calcium levels within an acceptable range. It stimulates intestinal calcium absorption and re-absorption in the kidneys, and regulates the metabolism of calcium and phosphorus, which are vital for many body functions including the normal growth and development of bones and teeth. It enables bones and teeth to harden by increasing the deposition of calcium into these structures and may also assist in the movement of calcium across body cell membranes.

Cell growth

Vitamin D is involved in normal cell growth and maturation and may play a part in cancer prevention. In test tube experiments, calcitriol seems to have anticancer properties, inhibiting the growth of human leukemia, colon cancer, skin cancer and breast cancer cells.

Immune system

Vitamin D is involved in the regulation of the immune system. It has several functions including effects on white blood cells known as monocytes and lymphocytes and seems to suppress function of several parts of the immune system.

Hormones

Vitamin D plays a role in the secretion of insulin by the pancreas, thus aiding in the regulation of blood sugar. Vitamin D suppresses both the action of the parathyroid gland and the action of a hormone from this gland and may play a role in the treatment of an overactive parathyroid.

Nervous system

Careful regulation of calcium levels is vital for normal nerve impulse transmission and muscle contraction. Vitamin D plays a role in the functioning of healthy nerves and muscles by regulating the level of calcium in the blood.

Absorption and metabolism

As with other fat soluble vitamins, fat in the intestine is necessary for vitamin D absorption. Vitamin D from food and supplements is absorbed through the intestinal walls and can be stored in the fat cells of the liver, skin, brain and bones in amounts sufficient for many months' consumption. Exposure to sunlight in spring, summer and autumn usually makes up for any shortfall in dietary vitamin D and even brief exposure to sunlight during these times is adequate. There may, however, be problems in winter months in some climates. The production of vitamin D in the body is blocked by anything which blocks ultraviolet light including skin pigment, smog, fog, sunscreen, windows and hats.

Deficiency

Vitamin D deficiency leads to increased production of parathyroid hormone and the removal of calcium from the bones. In children, this results in rickets, a disorder in which the bones are so soft that they become curved from supporting the weight of the body. The equivalent in adults is osteomalacia which involves a softening of bones and causes bone pain and tenderness and muscle weakness. Other signs of deficiency include severe tooth decay and hearing loss, which is due to a softening of the bones in the inner ear.

Studies show that elderly people, particularly those who are housebound or in institutions, may be at high risk of vitamin D deficiency. A study published in 1998 in the New England Journal of Medicine found vitamin D deficiency in 57 per cent of a group of 290 patients who were admitted to hospital. In a subgroup of the patients who had no known risk factors for vitamin D deficiency, the researchers found that 42 per cent were deficient. They concluded that vitamin D deficiency was probably a substantial problem.1

There is some concern that the increasing use of sunscreens as skin cancer preventives may increase the risk of vitamin D deficiency. This is unlikely to be a problem in children and young people who do not usually wear sunscreen every time they go outside. However, older people who may be more concerned about sun damage to skin and who may go outside less often are more likely to be at risk.

Vitamin D deficiency is more common in winter in cold climates. This decline may lead to an increased risk of bone loss in elderly men and women according to a 1997 study by researchers at Tufts University in Boston. They examined vitamin D levels in 182 men and 209 women aged over 65. Levels were found to be lower in women. In wintertime levels were lower than in summertime. Travel, vitamin D intake and time spent outdoors increased the vitamin D concentrations.2

Other groups at risk of deficiency include alcoholics, those with gastrointestinal malabsorption disorders such as celiac disease, those taking anticonvulsant drugs, those who don't drink milk or get much sunlight, those with absorption problems and darker skinned people living in colder climates. As vitamin D is converted in the liver and kidneys to calcitriol, its active form, sufferers of kidney and liver diseases may also be at risk of vitamin D deficiency.

Osteoporosis

Vitamin D regulates bone mineral density and a deficiency may lead to osteoporosis, a disease in which bones become lighter, less dense and more prone to fractures. (See page 653 for more information.) People with a certain type of vitamin D receptor may be more susceptible to osteoporosis. As the structure of the vitamin D receptor is genetically determined, this may eventually lead to a test to identify women at risk of the disease. Research suggests that women with different types of vitamin D receptor respond differently to vitamin D supplements given to build bone.3

Arthritis

Osteoarthrtitis

New research suggests that people with osteoarthritis who have low vitamin D intakes suffer more severe symptoms than those whose intakes are high. In a study done in 1996 researchers at Boston University studied more than 500 elderly people with osteoarthritis of the knee. They found that those with the lowest intakes and blood levels of vitamin D were three times more likely to see their disease progress than people with high intakes and blood levels. Vitamin D may help reduce the cartilage damage seen in osteoarthritis.4

Rheumatoid arthritis

Severe rheumatoid arthritis is associated with bone loss. In a 1998 study, German researchers investigated the links between disease activity and serum levels of vitamin D in 96 patients. They found that high disease activity was associated with alterations in vitamin D metabolism and increased bone breakdown. Low levels of vitamin D may also increase the proliferation of white blood cells and may accelerate the arthritic process in rheumatoid arthritis.5 Vitamin D supplements are likely to be useful in retarding these adverse effects of alterations in metabolism.

Cancer

Low levels of vitamin D have been linked to several cancers including those of the colon, prostate and breast. Laboratory experiments show that vitamin D can inhibit the growth of human prostate cancer6 and breast cancer cells7. Lung cancer and pancreatic cancer8 cells may also be susceptible to the effects of vitamin D. Sunlight also seems to be protective against several types of cancer, including ovarian9 and breast cancers, and this effect may be mediated by vitamin D levels.

Colorectal cancer

Several studies have suggested a link between low dietary vitamin D intake and colorectal cancer risk. In a 1996 study, researchers conducted a population-based case-control study to examine this relationship among 352 people with colon cancer, 217 people with rectal cancer, and 512 healthy people in Stockholm, Sweden. The researchers used questionnaires to assess the vitamin D intake for the preceding five years. The results showed that those with the highest vitamin D intakes were around half as likely to get cancers of the colon or rectum than those with the lowest intakes.10

Results from the Harvard Nurses Health Study published in 1996 suggest a link between vitamin D and colorectal cancer. The study involved 89,448 female nurses and covered the time period from 1980 to 1992 during which 501 cases of colorectal cancer were documented. The results showed a link between intake of total vitamin D and risk of colorectal cancer.11

Prostate cancer

Low vitamin D levels are linked to an increased risk of prostate cancer. In a study published in 1996, researchers at Brigham and Women's Hospital in Boston collected blood plasma samples from 14,916 participants in the Physicians' Health Study and measured vitamin D levels. Their analysis included 232 cases diagnosed up to 1992 and 414 age-matched control participants. The results showed a slightly reduced risk of prostate cancer in those with high vitamin D levels.12

The way a man's body utilizes vitamin D could affect his risk of prostate cancer. A 1996 National Institute of Environmental Health Sciences study has found that men with a particular type of vitamin D receptor gene are less likely than others to develop the type of prostate cancer that requires surgery. Researchers looked at the receptor genes in 108 cancer patients and 170 men without cancer. The results showed that 22 per cent of cancer patients had two copies of a particular gene, while only 8 per cent of the cancer-free men did. These findings support the theory that vitamin D plays an important role in prostate cancer.13

Multiple sclerosis

There is some suggestion that abnormalities in vitamin D metabolism may be linked to multiple sclerosis. The hormonal form of vitamin D can prevent a disease similar to multiple sclerosis in mice. Multiple sclerosis is more prevalent in areas where there is less exposure to sunlight and some researchers believe that vitamin D protects against the disease.14

Diabetes

Vitamin D deficiency impairs glucose metabolism by reducing insulin secretion. This is likely to increase the risk of diabetes mellitus. Vitamin D supplements are likely to be useful in preventing diabetes in areas where vitamin D deficiency is common.15

In a 1997 study looking at the links between environmental factors and Type II diabetes, vitamin D levels were assessed in 142 Dutch men aged from 70 to 88 years of age. Thirty-nine per cent were found to have low vitamin D levels and tests showed that low vitamin D levels increased the risk of glucose intolerance.16

Heart disease

Low vitamin D levels may also increase the risk of atherosclerosis. Research published in 1997 in the American Heart Association journal Circulation suggests that a low level of vitamin D increases the risk of calcium build-up in atherosclerotic plaques and that higher levels reduce the risk of build-up. Researchers at UCLA School of Medicine measured the vitamin D levels in the blood of 173 men and women at risk of heart disease and also measured the build-up of calcium in coronary arteries (a common finding in coronary artery disease). The results suggest that calcium may regulate calcium deposition in the arteries as well as in the bone.17

Other effects

Vitamin D deficiency may also play a role in inflammatory bowel disease, tuberculosis, stroke and high blood pressure.

Sources

Fish liver oils, sardines, herring, salmon, tuna, liver, eggs and some dairy products are good dietary sources of vitamin D. Milk is often fortified with vitamin D and is a good source, but dairy products other than milk are not usually fortified with vitamin D.

Medicinal cod liver oil 1 tbsp 2271 IU

Pink salmon, canned 100g 624 IU

Tuna, canned in oil 1 can 404 IU

Whole milk, dried 1 cup 380 IU

Oysters 6 oysters 269 IU

Mackerel, canned in oil 100g 252 IU

Shiitake mushrooms, dried 4 mushrooms 249 IU

Sardines, canned in tomato sauce 1 sardine 182 IU

Fortified milk, evaporated ½ cup 97.9 IU

Whole milk, fortified 1 cup 92.7 IU

Skim milk, fortified 1 cup 92.7 IU

Chocolate milk, fortified 1 cup 92.7 IU

Beef salami 1 slice (23g) 80.3 IU

Low fat milk, dried ¼ cup 79.0 IU

Sardines, canned in oil 2 sardines 65.3 IU

Herring, smoked 1 fillet 48.0 IU

Natural raisin bran 30g 45.6 IU

Shrimp 4 large 42.6 IU

All Bran 30g 42.0 IU

Bran flakes 30g 42.0 IU

Corn flakes 30g 42.0 IU

Special K 30g 42.0 IU

Egg yolk 1 large 24.6 IU

Pork sausages 1 sausage, 10cm long 14.6 IU

Recommended dietary allowances

USA

Men 200 IU
(over 50) 400 IU
(over 70) 600 IU

Women 200 IU
(over 50) 400 IU
(over 70) 600 IU

Pregnancy 200 IU

Lactation 200 IU

UK

Men 400 IU

Women 400 IU

Australia

Men 200 IU

Women 200 IU

Pregnancy 400 IU

Lactation 400 IU

The tolerable upper intake limit has been set at 2000 IU per day.

Supplements

Vitamin D supplements are often available in the form of cod liver oil. Anyone on long-term anticonvulsant drug therapy, older people, and those who follow a strict vegan diet may benefit from supplements.

Toxic effects of excess intake

High daily doses of dietary vitamin D over an extended period of time can produce excessive calcium levels in the blood with symptoms of unusual thirst, metallic taste, bone pain, fatigue, sore eyes, itching skin, vomiting, diarrhea, urinary urgency, abnormal calcium deposits in blood vessel walls, liver, lungs, kidney and stomach. High doses also cause the build-up of calcium in the muscles which impairs their function. Doses of less than 1000 IU daily are unlikely to cause any adverse effects and prolonged exposure to sunlight does not cause toxic effects.

Large doses of vitamin D can irritate the urinary tract. There may be a link between excessive vitamin D intake and heart attacks, atherosclerosis and kidney stones in people who are susceptible.

Very high doses of vitamin D supplements may actually increase the risk of osteoporosis. In an article published in 1997, researchers at the Cedars Sinai Medical Center in Los Angeles reported four cases of osteoporosis linked to excessive use of vitamin D supplements. Each of the four patients had high levels of calcium and vitamin D metabolites in their urine and were taking dietary supplements which contained unidentified amounts of vitamin D. When the patients stopped taking the supplements, bone mineral density increased. Excessive vitamin D supplementation for six months or longer upsets calcium balance and affects bone mineral density.18

Therapeutic uses of supplements

Supplements are used to treat vitamin D deficiency and its symptoms.

Osteoporosis

Vitamin D is recommended in the treatment of osteoporosis in postmenopausal women. Several research studies suggest that vitamin D supplements reduce the occurrence of fractures in elderly people.

In a study published in 1997, researchers at Tufts University in Boston assessed the effects of calcium (500 mg per day) and vitamin D (700 IU per day) in 176 men and 213 women aged 65 years or older. When bone density was measured after a three-year period, those taking the supplements had higher bone density at all body sites measured. The fracture rate was also reduced by 50 per cent in those taking the supplements.19

Vitamin D supplements may also be useful in preventing bone loss in patients taking corticosteroid drugs. In a study published in 1996, researchers at the University of Virginia found that calcium and vitamin D supplements helped prevent the loss of bone mineral density in those taking the drugs for arthritis, asthma and other chronic diseases.20

However, other studies have not shown any reduction in fracture rates in those taking vitamin D supplements. A 1996 study which was carried out in Amsterdam looked at the effects of either vitamin D or a placebo on 2500 healthy men and women over the age of 70 who were living independently. The participants received a placebo or a daily dose of 400 IU of vitamin D for a three-and-a-half-year period. Dietary calcium intake was the same in both groups. Forty-eight fractures were observed in the placebo group and 58 in the vitamin D group.21

Other uses

Synthetic vitamin D analogs are used to treat the skin disorder, psoriasis, and are also being investigated for their ability to prevent and treat cancer.

Because of its effects on the immune system, many researchers are investigating the possibility of using vitamin D and related compounds to treat autoimmune disorders and to suppress rejection of transplanted organs.

Interactions with other nutrients

Vitamin D is necessary for calcium and phosphorus absorption and metabolism. Pantothenic acid is necessary for the synthesis of vitamin D.

Interactions with drugs

The cholesterol-lowering drug, cholestyramine, and mineral oil laxatives interfere with the absorption of vitamin D. Alcohol interferes with the conversion of vitamin D to its biologically active form.

People taking certain anticonvulsant drugs, such as phenytoin, may decrease the activity of vitamin D by increasing its metabolism. People taking this drug are likely to be at increased risk of osteoporosis and have high vitamin D requirements

Cautions

Vitamin D supplements should not be given to those with high calcium levels or high phosphorus levels, and should be given with caution to those suffering from cardiac or kidney diseases.

1 Thomas MK; Lloyd Jones DM; Thadhani RI; Shaw AC; Deraska DJ; Kitch BT; Vamvakas EC; Dick IM; Prince RL; Finkelstein JS. Hypovitaminosis D in medical inpatients. N Engl J Med, 1998 Mar, 338:12, 777-83

2 Dawson Hughes B; Harris SS; Dallal GE Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women. Am J Clin Nutr, 1997 Jan, 65:1, 67-71

3 Graafmans WC; Lips P; Ooms ME; van Leeuwen JP; Pols HA; Uitterlinden AG. The effect of vitamin D supplementation on the bone mineral density of the femoral neck is associated with vitamin D receptor genotype. J Bone Miner Res, 1997 Aug, 12:8, 1241-5

4 McAlindon TE; Felson DT; Zhang Y; Hannan MT; Aliabadi P; Weissman B; Rush D; Wilson PW. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study. Ann Intern Med, 1996 Sep, 125:5, 353-9

5 Oelzner P; Müller A; Deschner F; Hüller M; Abendroth K; Hein G; Stein G. Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis. Calcif Tissue Int, 1998 Mar, 62:3, 193-8

6 Feldman D; Skowronski RJ; Peehl DM Vitamin D and prostate cancer. Adv Exp Med Biol, 1995, 375:, 53-63

7 Brenner RV; Shabahang M; Schumaker LM; Nauta RJ; Uskokovic MR; Evans SR; Buras RR The antiproliferative effect of vitamin D analogs on MCF-7 human breast cancer cells. Cancer Lett, 1995 May, 92:1, 77-82

8 Colston KW; James SY; Ofori Kuragu EA; Binderup L; Grant AG. Vitamin D receptors and anti-proliferative effects of vitamin D derivatives in human pancreatic carcinoma cells in vivo and in vitro. Br J Cancer, 1997, 76:8, 1017-20

9 Lefkowitz ES; Garland CF Sunlight, vitamin D, and ovarian cancer mortality rates in US women. Int J Epidemiol, 1994 Dec, 23:6, 1133-6

10 Pritchard RS; Baron JA; Gerhardsson de Verdier M. Dietary calcium, vitamin D, and the risk of colorectal cancer in Stockholm, Sweden. Cancer Epidemiol Biomarkers Prev, 1996 Nov, 5:11, 897-900

11 Martínez ME; Giovannucci EL; Colditz GA; Stampfer MJ; Hunter DJ; Speizer FE; Wing A; Willett WC Calcium, vitamin D, and the occurrence of colorectal cancer among women. J Natl Cancer Inst, 1996 Oct, 88:19, 1375-82

12 Gann PH; Ma J; Hennekens CH; Hollis BW; Haddad JG; Stampfer MJ Circulating vitamin D metabolites in relation to subsequent development of prostate cancer. Cancer Epidemiol Biomarkers Prev, 1996 Feb, 5:2, 121-6

13 Taylor JA; Hirvonen A; Watson M; Pittman G; Mohler JL; Bell DA Association of prostate cancer with vitamin D receptor gene polymorphism. Cancer Res, 1996 Sep, 56:18, 4108-10

14 Hayes CE; Cantorna MT; DeLuca HF Vitamin D and multiple sclerosis. Proc Soc Exp Biol Med, 1997 Oct, 216:1, 21-7

15 Boucher BJ; Mannan N; Noonan K; Hales CN; Evans SJ Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. Diabetologia, 1995 Oct, 38:10, 1239-45

16 Baynes KC; Boucher BJ; Feskens EJ; Kromhout D Vitamin D, glucose tolerance and insulinaemia in elderly men. Diabetologia, 1997 Mar, 40:3, 344-7

17 Watson KE; Abrolat ML; Malone LL; Hoeg JM; Doherty T; Detrano R; Demer LL Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation, 1997 Sep, 96:6, 1755-60

18 Adams JS; Lee G. Gains in bone mineral density with resolution of vitamin D intoxication. Ann Int Med, 1997 Aug; 127:3, 203-6

19 Dawson Hughes B; Harris SS; Krall EA; Dallal GE 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 Sep, 337:10, 670-6

20 Buckley et al.Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996 Dec 15;125(12):961-968

21 Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM. Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med 1996 Feb 15;124(4):400-406