Vitamin D

BACKGROUND

The major function of Vitamin D in humans is to maintain appropriate serum calcium concentrations by enhancing the ability of the small intestine to absorb calcium from the diet. Vitamin D also plays a role in enhancing absorption of phosphorus from the diet, but the blood concentration of phosphorus is not well regulated and varies according to supply and the renal excretory threshold.

Vitamin D maintains the blood calcium at supersaturating levels such that it is deposited in the bone as calcium hydroxyapatite. When dietary calcium is inadequate for the body's needs, 1,25-dihydroxyvitamin D [1,25(OH) 2 D or calcitriol] – the active form of vitamin D – together with parathyroid hormone, can mobilise stem cells in bone marrow to become mature osteoclasts which in turn increase the mobilisation of calcium stores from bone. However, there is a limited capacity to mobilise sufficient calcium from bone to have a significant effect on blood calcium levels.

Vitamin D occurs in two forms. One is produced by the action of sunlight on skin (D 3 or cholecalciferol) and the other is found in a limited range of foods (D 2 or ergocalciferol). With current food supplies and patterns of eating, it is almost impossible to obtain sufficient vitamin D from the diet alone (Fuller & Casparian 2001). Vitamin D in foods is fat soluble and is biologically less active. Its metabolite, 1.25-dihydroxyvitamin D (1,25(OH 2 )D, or calcitriol) is the biologically active hormone responsible for its physiological actions. In the circulation, vitamin D appears as 25-hydroxyvitamin D (25(OH)D) which is five times more potent than cholecalciferol.

Vitamin D status is generally maintained in the population by exposure to sunlight (Glerup et al 2000, Holick 1996, Rasmussen et al 2000). If sunlight exposure is adequate, dietary vitamin D can be considered unnecessary (Holick 2001). In skin, 7-dehydrocholesterol is converted to pre-vitamin D 3 by a narrow band of solar ultraviolet radiation (290–320 nm) which undergoes isomerisation in a temperature-dependent manner to vitamin D 3.

Thus, vitamin D is not a nutrient in the usual sense, since under normal conditions it is supplied mainly by the skin. In addition, its physiological actions are attributable to the active metabolite, 1,25-dihydroxyvitamin D which, because it is synthesised in the kidneys and acts elsewhere, is often called a hormone.

1 µg cholecalciferol is equal to 0.2 µg 25(OH)D.

Vitamin D is also sometimes expressed in International Units where 1 IU equals 0.025 µg cholecalciferol or 0.005 µg 25(OH)D.

Seasonal changes have been shown to have a significant effect on the cutaneous production of cholecalciferol (Pettifor et al 1996, Webb et al 1990). In the winter months in temperate latitudes, solar UV light in the wavelength range of 290–320 nm is absorbed by the atmosphere. People also spend less time outdoors and wear more clothing. For this reason, vitamin D deficiency is more common in the winter months (Holick 1995).

Despite the sunny climate, a seasonal variation in vitamin D levels also occurs in Australia. In the Geelong Osteoporosis Study, the mean vitamin D levels for winter were 58 nmol/L compared with 70 nmol/L in summer (Pasco et al 2001). However, after regular sun exposure, people under the age of 50 can produce and store approximately 6 months' worth of vitamin D, so vitamin D stored in the body is available during the winter when production is minimal (Holick 1996). However, in older people, the efficiency of cutaneous synthesis of vitamin D is significantly less than that in younger people (Holick et al 1989, Need et al 1993).

Other environmental factors such as the angle of the sun, distance from the equator, the amount of cloud cover and the amount of particulate matter in the atmosphere (Holick 1995, Kimlin et al 2003, Madronich et al 1998) can affect the amount of vitamin D produced. Comparative data indicate that Northern and Southern latitudes are not equivalent. It has been estimated that ultraviolet levels in summer are up to 40% higher in New Zealand than in the equivalent Northern latitudes (Madronich et al 1998).

Deficiency of Vitamin D results in inadequate mineralisation or demineralisation of the skeleton. This can lead to rickets in young children, causing bowed legs and knocked knees. A study in China showed that vitamin D given as a supplement over 2 years increased both total body bone mineral content and bone mineral density in older children (Du et al 2004). In adults, deficiency can lead to increased bone turnover and osteoporosis and less commonly to osteomalacia for which the associated secondary hyperparathyroidism enhances mobilisation of calcium from the skeleton, resulting in porotic bone. Vitamin D may also affect fracture rates via mechanisms other than its influence on bone mass. Bischoff-Ferrari et al (2004) showed that on the basis of five RCTs involving 1,237 participants, vitamin D reduced the number of falls by 22% compared with patients receiving calcium or placebo.

Vitamin D is also thought to play a role in maintaining the immune system (Brown et al1999, DeLuca 1998) and helping maintain healthy skin (DeLuca 1998, Jones et al 1998) and muscle strength (Brown et al 1999).

There is increasing recognition that a significant number of Australians and New Zealanders may have less than optimal 25(OH)D status, however limited published information of the prevalence of vitamin D deficiency in Australia is available, other than from relatively small subpopulations (Nowson & Margerison 2002, Pasco et al 2004). Some information is available currently in unpublished form, from the national surveys of 1997 and 2002 in New Zealand (Green et al 2004a,b). Recent analyses of blood samples from these surveys showed that 31% of New Zealand children aged 5–14 years whose bloods were sampled in 2002 had a serum 25(OH)D concentration indicative of vitamin D insufficiency. Between 0% (for 5–6 year olds of European background) and 14% (for girls aged 11–14 years of Pacific Island backgrounds) had vitamin D deficiency. For adolescents at or above 15 years and adults whose bloods were sampled in 1997, the prevalence of deficiency, defined as <17.5 nmol/L, was 2.8%, but the prevalence of insufficiency, defined as <37.5 nmol/L, was 27.6%. Vitamin D concentrations were lower in winter than summer and lower in Pacific peoples and Mäori than those of European and other origins.

The groups thought to be at particular risk in Australia and New Zealand include older persons living in the community, those in residential care with limited mobility for whom frank deficiency may be 22–67% and mild deficiency may be 45–84%, dark-skinned peoples and veiled women who have limited exposure to sunlight (as many as 80% having mild deficiency) and breast-fed infants of these groups of women. Some of these groups (eg the institutionalised elderly) are often not represented in National Surveys.

Adolescents and young children growing rapidly who are on marginal calcium intakes may also have increased requirements for vitamin D that may not be met in winter, when reduced exposure to sunlight depletes the body's stores of vitamin D. There is also some evidence that up to 8% of younger women (20–39 years) may have a frank vitamin D deficiency at the end of winter and 33% may have a marginal deficiency. People who wear protective clothing, always use sunscreen and those who have intestinal, hepatic, renal or cardiopulmonary disease or are taking anticonvulsants may also be at increased risk (Compston 1998, Fitzpatrick et al 2000, Fuller & Casparian 2001, Thomas et al 1998).

Very few foods contain significant amounts of vitamin D (Holick 2001, Vieth 1999). In Australia, fortified margarine appears to be the major dietary source of vitamin D, together with fatty fish such as salmon, herring and mackerel, and eggs (Baghurst & Record 2002).

Accurate estimates of dietary intakes of vitamin D in Australia and New Zealand are not yet available as local food databases are limited. Some estimates have been made using a mix of local and overseas information on food composition with figures between 2-3mg/day for adults (Baghurst & Record 2002, LINZ 1992). Currently in Australia, vitamin D fortification is mandated for edible oil spreads (table margarine) and voluntary for modified and skim milks, powdered milk, yoghurts and table confections and cheese. In New Zealand, fortification of margarine or milk products with vitamin D is not mandated, however since 1996, voluntary fortification of margarine, fat spreads and their reduced fat counterparts has been permitted. It is also permitted to add vitamin D to dried milk, dried skim milk and non-fat milk solids, skim milk and reduced fat cows' milk, legume beverages and 'food' drinks.

Serum 25(OH)D is the indicator of choice for assessing requirements since it accounts for both dietary and cutaneous sources of the vitamin. However, there is some disagreement in the literature and clinical practice over quantification of the optimal range. A 25(OH)D below 27.5 nmol/L is consistent with vitamin D deficiency in infants, neonates and young children (Specker et al 1992) and is thus used as the key indicator for determining a vitamin D reference value. Little information is available on the levels required to maintain normal calcium metabolism and peak bone mass in children, or young and middle-aged adults but in a recent position statement a Working Group of the Australian and New Zealand Bone and Mineral Society, the Endocrine Society of Australia and Osteoporosis Australia (2005) defined mild deficiency for adults as serum 25-OHD levels between 25 and 50nmol/L; moderate deficiency as between 12.5 and 25nmol/L and severe, below 12.5nmol/L based on various indicators such as increases in parathyroid hormone secretion and various bone indicators. There is mounting evidence for the elderly to support increased dietary requirements for the maintenance of normal metabolism and maximum bone health (Dawson-Hughes et al 1991, Krall et al 1989, Lips et al 1988) and some researchers recommend levels of 75–100 nmol/L, especially for the elderly, on the basis of optimising bone (Dawson-Hughes 2004, Dawson-Hughes et al 1997, Heaney 1999, 2004, Kinyamu et al 1998, Sahota 2000, Vieth et al 1999, Vieth 2004).

When 25(OH)D concentrations are in the deficient range, serum PTH levels are inversely proportional to 25(OH)D levels, and can therefore also be a valuable indication of inadequate vitamin D status, as can skeletal health including bone development and prevention of rickets in infants and children and bone mineral content, bone mineral density and fracture risk in adults.

The recommendations herein assume no, or minimal, exposure to sunlight as sunlight exposure factors and environmental factors can vary widely between individuals across Australia and New Zealand. An assessment of the effect of environmental and personal factors in reducing this requirement is also given, although data are limited.