Vitamin D Deficiency Occurs Even When Marker Is 'Normal'

TAMPA — Vitamin D deficiency is highly prevalent, even in patients whose 25-hydroxyvitamin D levels are within the “normal” range, Dr. Robert P. Heaney said at the annual meeting of the International Society for Clinical Densitometry.

That's because the reference range for serum 25-hydroxyvitamin D (25[OH]D) levels is too low, said Dr. Heaney of Creighton University, Omaha, Neb. “Within the reference range, there is malabsorption of calcium and preventable fractures. These are as much expressions of nutritional deficiency as are the bleeding gums of scurvy.”

The Institute of Medicine reevaluated the nutrient intake recommendations for bone-related nutrients, including vitamin D, in the mid-1990s. The role of vitamin D intake in preventing rickets had long been recognized, and it was known that vitamin D was necessary for calcium absorption. Ten years ago, the unknowns were the vitamin D intake for optimal calcium absorption, possible links between vitamin D and other diseases, and how to determine whether a patient's intake was sufficient.

“We've learned a lot since then,” said Dr. Heaney. “We know that 25(OH)D is the functional status indicator, and we know that at levels below 20 nmol/L or 8 ng/mL, we get rickets and osteomalacia.”

The controversy lies in deciding where the normal range of serum 25(OH)D should be for optimal bone health. Although the low end of the reference range may vary from 38 to 50 nmol/L, an individual is at risk for osteoporosis at serum 25(OH)D levels below 80 nmol/L, according to Dr. Heaney, who argues that normal levels of serum 25(OH)D begin at 80 nmol/L. At levels between 20 and 80 nmol/L, increased bone remodeling, reduced calcium absorption, increased risk of falls, and increased risk of fractures occur.

Individuals might have inadequate vitamin D status even when serum 25(OH)D levels are well within the reference range. A study Dr. Heaney and colleagues conducted assessed serum 25(OH)D levels and calcium absorption in 34 healthy, postmenopausal women. The study showed that women whose serum 25(OH)D levels were at the lower end of the reference range had lower calcium absorption than women with higher levels. The study was conducted over 2 consecutive years in Omaha, in early spring, when serum vitamin D levels would be at their lowest levels.

Participants were given oral 500-mg calcium supplements, and calcium absorption and serum 25(OH)D levels were measured. One year, the participants were predosed with vitamin D supplementation, and the other year, they were not (Am. Coll. Nutr. 2003;22:142–6).

Vitamin D supplementation resulted in an increase in serum 25(OH)D from 50 to 83 nmol/L. Both of those values are considered to be within the reference range, but the two levels had different effects on calcium absorption efficiency.

At the lower serum 25(OH)D level of 50 nmol/L, calcium absorption efficiency was 22%, compared with 37% at the higher serum 25(OH)D level. Higher serum 25(OH)D levels were also associated with higher serum calcium concentrations and decreased serum parathyroid hormone levels.

Other studies have shown higher bone mineral density levels, decreased risk of fractures, or decreased risk of falling with levels of serum 25(OH)D above 80 nmol/L.

“Within the range of 25(OH)D levels commonly encountered, calcium absorption rises as 25(OH)D rises,” said Dr. Heaney. “Raising serum 25(OH)D levels from 50 to [about] 80 nmol/L improves calcium absorption, raises [bone mineral density], and reduces both fall and fracture risk.”

Sources of vitamin D are not equivalent. The high-dose (50,000 IU) vitamin D supplement that is available by prescription is ergocalciferol, or D2, which is less potent than cholecalciferol, or D3. Over-the-counter preparations of vitamin D in the form of cholecalciferol are available at lower doses.

A typical over-the-counter vitamin D supplement might contain 400 IU, but supplementation to increase serum 25(OH)D levels within an effective range usually requires much higher doses. Intake of 1,000 IU of vitamin D raises serum 25(OH)D by approximately 15–25 nmol/L.

In studies conducted by Dr. Heaney, dosages of 5,000–10,000 IU/day for a 4- to 5-month period in healthy adults have not caused elevated calcium levels in serum or urine. Vitamin D dosages in that range produce serum 25(OH)D levels comparable to those seen in outdoor workers at summer's end.

Vitamin D intoxication should not be an issue unless the individual has regular dosages in excess of 10,000 IU per day.

“Our conclusion is that the safe upper limit level ought to be 10,000 IU per day,” said Dr. Heaney. “I don't think many people would ever need that much, but it is nice to know that there is a therapeutic margin of safety.”

TAMPA — Vitamin D deficiency is highly prevalent, even in patients whose 25-hydroxyvitamin D levels are within the “normal” range, Dr. Robert P. Heaney said at the annual meeting of the International Society for Clinical Densitometry.

That's because the reference range for serum 25-hydroxyvitamin D (25[OH]D) levels is too low, said Dr. Heaney of Creighton University, Omaha, Neb. “Within the reference range, there is malabsorption of calcium and preventable fractures. These are as much expressions of nutritional deficiency as are the bleeding gums of scurvy.”

The Institute of Medicine reevaluated the nutrient intake recommendations for bone-related nutrients, including vitamin D, in the mid-1990s. The role of vitamin D intake in preventing rickets had long been recognized, and it was known that vitamin D was necessary for calcium absorption. Ten years ago, the unknowns were the vitamin D intake for optimal calcium absorption, possible links between vitamin D and other diseases, and how to determine whether a patient's intake was sufficient.

“We've learned a lot since then,” said Dr. Heaney. “We know that 25(OH)D is the functional status indicator, and we know that at levels below 20 nmol/L or 8 ng/mL, we get rickets and osteomalacia.”

The controversy lies in deciding where the normal range of serum 25(OH)D should be for optimal bone health. Although the low end of the reference range may vary from 38 to 50 nmol/L, an individual is at risk for osteoporosis at serum 25(OH)D levels below 80 nmol/L, according to Dr. Heaney, who argues that normal levels of serum 25(OH)D begin at 80 nmol/L. At levels between 20 and 80 nmol/L, increased bone remodeling, reduced calcium absorption, increased risk of falls, and increased risk of fractures occur.

Individuals might have inadequate vitamin D status even when serum 25(OH)D levels are well within the reference range. A study Dr. Heaney and colleagues conducted assessed serum 25(OH)D levels and calcium absorption in 34 healthy, postmenopausal women. The study showed that women whose serum 25(OH)D levels were at the lower end of the reference range had lower calcium absorption than women with higher levels. The study was conducted over 2 consecutive years in Omaha, in early spring, when serum vitamin D levels would be at their lowest levels.

Participants were given oral 500-mg calcium supplements, and calcium absorption and serum 25(OH)D levels were measured. One year, the participants were predosed with vitamin D supplementation, and the other year, they were not (Am. Coll. Nutr. 2003;22:142–6).

Vitamin D supplementation resulted in an increase in serum 25(OH)D from 50 to 83 nmol/L. Both of those values are considered to be within the reference range, but the two levels had different effects on calcium absorption efficiency.

At the lower serum 25(OH)D level of 50 nmol/L, calcium absorption efficiency was 22%, compared with 37% at the higher serum 25(OH)D level. Higher serum 25(OH)D levels were also associated with higher serum calcium concentrations and decreased serum parathyroid hormone levels.

Other studies have shown higher bone mineral density levels, decreased risk of fractures, or decreased risk of falling with levels of serum 25(OH)D above 80 nmol/L.

“Within the range of 25(OH)D levels commonly encountered, calcium absorption rises as 25(OH)D rises,” said Dr. Heaney. “Raising serum 25(OH)D levels from 50 to [about] 80 nmol/L improves calcium absorption, raises [bone mineral density], and reduces both fall and fracture risk.”

Sources of vitamin D are not equivalent. The high-dose (50,000 IU) vitamin D supplement that is available by prescription is ergocalciferol, or D2, which is less potent than cholecalciferol, or D3. Over-the-counter preparations of vitamin D in the form of cholecalciferol are available at lower doses.

A typical over-the-counter vitamin D supplement might contain 400 IU, but supplementation to increase serum 25(OH)D levels within an effective range usually requires much higher doses. Intake of 1,000 IU of vitamin D raises serum 25(OH)D by approximately 15–25 nmol/L.

In studies conducted by Dr. Heaney, dosages of 5,000–10,000 IU/day for a 4- to 5-month period in healthy adults have not caused elevated calcium levels in serum or urine. Vitamin D dosages in that range produce serum 25(OH)D levels comparable to those seen in outdoor workers at summer's end.

Vitamin D intoxication should not be an issue unless the individual has regular dosages in excess of 10,000 IU per day.

“Our conclusion is that the safe upper limit level ought to be 10,000 IU per day,” said Dr. Heaney. “I don't think many people would ever need that much, but it is nice to know that there is a therapeutic margin of safety.”

TAMPA — Vitamin D deficiency is highly prevalent, even in patients whose 25-hydroxyvitamin D levels are within the “normal” range, Dr. Robert P. Heaney said at the annual meeting of the International Society for Clinical Densitometry.

That's because the reference range for serum 25-hydroxyvitamin D (25[OH]D) levels is too low, said Dr. Heaney of Creighton University, Omaha, Neb. “Within the reference range, there is malabsorption of calcium and preventable fractures. These are as much expressions of nutritional deficiency as are the bleeding gums of scurvy.”

The Institute of Medicine reevaluated the nutrient intake recommendations for bone-related nutrients, including vitamin D, in the mid-1990s. The role of vitamin D intake in preventing rickets had long been recognized, and it was known that vitamin D was necessary for calcium absorption. Ten years ago, the unknowns were the vitamin D intake for optimal calcium absorption, possible links between vitamin D and other diseases, and how to determine whether a patient's intake was sufficient.

“We've learned a lot since then,” said Dr. Heaney. “We know that 25(OH)D is the functional status indicator, and we know that at levels below 20 nmol/L or 8 ng/mL, we get rickets and osteomalacia.”

The controversy lies in deciding where the normal range of serum 25(OH)D should be for optimal bone health. Although the low end of the reference range may vary from 38 to 50 nmol/L, an individual is at risk for osteoporosis at serum 25(OH)D levels below 80 nmol/L, according to Dr. Heaney, who argues that normal levels of serum 25(OH)D begin at 80 nmol/L. At levels between 20 and 80 nmol/L, increased bone remodeling, reduced calcium absorption, increased risk of falls, and increased risk of fractures occur.

Individuals might have inadequate vitamin D status even when serum 25(OH)D levels are well within the reference range. A study Dr. Heaney and colleagues conducted assessed serum 25(OH)D levels and calcium absorption in 34 healthy, postmenopausal women. The study showed that women whose serum 25(OH)D levels were at the lower end of the reference range had lower calcium absorption than women with higher levels. The study was conducted over 2 consecutive years in Omaha, in early spring, when serum vitamin D levels would be at their lowest levels.

Participants were given oral 500-mg calcium supplements, and calcium absorption and serum 25(OH)D levels were measured. One year, the participants were predosed with vitamin D supplementation, and the other year, they were not (Am. Coll. Nutr. 2003;22:142–6).

Vitamin D supplementation resulted in an increase in serum 25(OH)D from 50 to 83 nmol/L. Both of those values are considered to be within the reference range, but the two levels had different effects on calcium absorption efficiency.

At the lower serum 25(OH)D level of 50 nmol/L, calcium absorption efficiency was 22%, compared with 37% at the higher serum 25(OH)D level. Higher serum 25(OH)D levels were also associated with higher serum calcium concentrations and decreased serum parathyroid hormone levels.

Other studies have shown higher bone mineral density levels, decreased risk of fractures, or decreased risk of falling with levels of serum 25(OH)D above 80 nmol/L.

“Within the range of 25(OH)D levels commonly encountered, calcium absorption rises as 25(OH)D rises,” said Dr. Heaney. “Raising serum 25(OH)D levels from 50 to [about] 80 nmol/L improves calcium absorption, raises [bone mineral density], and reduces both fall and fracture risk.”

Sources of vitamin D are not equivalent. The high-dose (50,000 IU) vitamin D supplement that is available by prescription is ergocalciferol, or D2, which is less potent than cholecalciferol, or D3. Over-the-counter preparations of vitamin D in the form of cholecalciferol are available at lower doses.

A typical over-the-counter vitamin D supplement might contain 400 IU, but supplementation to increase serum 25(OH)D levels within an effective range usually requires much higher doses. Intake of 1,000 IU of vitamin D raises serum 25(OH)D by approximately 15–25 nmol/L.

In studies conducted by Dr. Heaney, dosages of 5,000–10,000 IU/day for a 4- to 5-month period in healthy adults have not caused elevated calcium levels in serum or urine. Vitamin D dosages in that range produce serum 25(OH)D levels comparable to those seen in outdoor workers at summer's end.

Vitamin D intoxication should not be an issue unless the individual has regular dosages in excess of 10,000 IU per day.

“Our conclusion is that the safe upper limit level ought to be 10,000 IU per day,” said Dr. Heaney. “I don't think many people would ever need that much, but it is nice to know that there is a therapeutic margin of safety.”