Vitamin D, 25-hydroxy - Kresser Institute Membership Site

Marker Name: Vitamin D, 25-hydroxy

REFERENCE RANGES FOR SERUM 25-HYDROXYVITAMIN D:

Laboratory reference range: 30–100 ng/mL

Functional reference range: 35–60 ng/mL

DESCRIPTION:

25-hydroxyvitamin D, also known as calcidiol or calcifediol, is one of the two main biologically active forms of vitamin D.¹ Biologically active vitamin D has several important functions. It facilitates calcium absorption in the gastrointestinal tract and maintains calcium and phosphate levels in the blood.² Adequate vitamin D levels are important for bone formation in children and adolescents and to prevent bone demineralization in older individuals.^1,3 Adequate vitamin D is required for normal function of muscle tissue, nervous tissue, and cells of the immune system.⁴ Research suggests that deficiencies in vitamin D may contribute to hypertension, cardiovascular events, and cancer.⁴ Likewise, inadequate vitamin D levels may contribute to the etiology of both type 1 and type 2 diabetes and can interfere with normal pregnancy outcomes.⁴

Three of the five forms of vitamin D are biologically inert: vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), and 7-dehydrocholesterol. In fact, the forms of vitamin D derived from dietary sources, supplements, and skin exposure to UV light are all biologically inert. Vitamin D is found in limited amounts in most foods; when present, it is most often in the form of vitamin D3.² Vitamin D2 and vitamin D3 are obtained from vitamin D-fortified foods and vitamin D supplements. Ultraviolet light striking the skin non-enzymatically converts circulating 7-dehydrocholesterol into vitamin D3.¹Vitamin D2 and vitamin D3 are converted to 25-hydroxyvitamin D, an active form of the vitamin, in the liver. 25-hydroxyvitamin D can then act on tissues in the body or be converted to 1,25-hydroxyvitamin D, another active form of the vitamin, in the kidney.^1,5 Both 1,25-hydroxyvitamin D and 25-hydroxyvitamin D are enzymatically degraded and excreted with the bile in the gastrointestinal tract.⁶ The half-life of 25-hydroxyvitamin D is three to four weeks, while the half-life of 1,25-hydroxyvitamin D is roughly four hours.³

1,25-dihydroxyvitamin D (calcitriol) is more biologically active than 25-hydroxyvitamin D; however, serum 25-hydroxyvitamin D is the most abundant active form of vitamin D in the blood and the best indicator of a person’s vitamin D status in most circumstances.^2,3,7 Serum 25-hydroxyvitamin D may not accurately reflect true vitamin D status in people with chronic renal failure or type 1 vitamin D rickets or in those taking therapeutic calcitriol.⁷ There is wide variability in reported 25-hydroxyvitamin D levels between laboratories and between assay methods, which could impact clinical decision-making.⁷

The most common cause of elevated serum 25-hydroxyvitamin D levels is excess intake of vitamin D. Excess sun exposure does not lead to increased 25-hydroxyvitamin D levels, since sustained heating of the skin will photodegrade the vitamin and its precursor.² Hyperparathyroidism greatly affects calcium levels but does not usually increase 25-hydroxyvitamin D levels. In fact, secondary hyperparathyroidism can paradoxically lower 25-hydroxyvitamin D levels in some cases.⁸

Low vitamin D levels may be characterized as insufficiency or deficiency, the latter reflecting lower 25-hydroxyvitamin D levels than the former.^3,9 Low 25-hydroxyvitamin D arises from decreased consumption of vitamin D, inadequate synthesis of precursors in the skin, decreased synthesis in the liver, increased breakdown, or loss from the kidneys.¹ Certain drugs, most notably anti-epileptic drugs, can cause abnormally low 25-hydroxyvitamin D levels. Since vitamin D is fat soluble, obese individuals may have a relative lack of bioavailable 25-hydroxyvitamin D because it is sequestered in fatty tissue.⁷ Likewise, obese individuals undergoing bariatric surgery may not be able to absorb adequate amounts of vitamin D through the gut.¹⁰

25-hydroxyvitamin D is often the sole test used to initially diagnose vitamin D deficiency. 1,25-dihydroxyvitamin D may be assayed to explore possible reasons for vitamin D deficiency.¹¹ When abnormalities in 1,25-dihydroxyvitamin D are being considered, parathyroid hormone, serum calcium, and serum phosphate may be tested.

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:²

Excessive intake

Low in:^2,10

Normal pregnancy
Breastfeeding infants
Inadequate sunlight exposure
Obesity
Fat malabsorption
Hypoparathyroidism
Secondary hyperparathyroidism
Small bowel disease
Gastric bypass surgery
Pancreatic insufficiency
Advanced liver disease
Nephrotic syndrome
Thermal burn injury with extensive skin damage
Hereditary vitamin D-resistant rickets (vitamin D-dependent rickets, type 2)
Cystic fibrosis
Drugs
- Anticonvulsants (e.g., phenobarbital, phenytoin, carbamazepine)
- Isoniazid
- Corticosteroids
- Theophylline
- Rifampin

FUNCTIONAL RANGE INDICATIONS:

High in:

Excessive intake

Low in:

Nonpathological in some nonwhite populations (must check PTH and 1,25D to determine true biological vitamin D activity)

References: