User login
Which regimen treats vitamin D deficiency most effectively?
SEVERAL VITAMIN D REPLACEMENT REGIMENS ARE EFFECTIVE. Cumulative dosing may be more important than frequency of dosing (strength of recommendation [SOR]: C, inconsistent results from randomized controlled trials [RCTs] of disease-oriented outcomes).
Vitamin D3 (cholecalciferol) may increase serum 25-hydroxy vitamin D (25[OH]D) concentrations more effectively than vitamin D2 (ergocalciferol) (SOR: C, a single RCT of disease-oriented outcomes).
Evidence summary
The total cumulative dose of vitamin D may be more significant than frequency of dosing. An RCT evaluated 38 postmenopausal women (median age 61.5 years) randomized into 3 groups (placebo or daily oral vitamin D2 in either 5000 or 10,000 IU doses).1 Only 1 patient had a baseline serum 25(OH)D level greater than 34 ng/mL. After 3 months, 8% of the placebo group, 50% of the 5000 IU daily group, and 75% of the 10,000 IU daily group had levels greater than 34 ng/mL. The cumulative D2 doses were 0, 450,000, and 900,000 IU, respectively. The number needed to treat (NNT), compared with placebo, was 3 (95% confidence interval [CI], 1-15) for the 5000 IU daily group and 2 (95% CI, 1-3) for the 10,000 IU daily group.
In another RCT that evaluated 48 women (average age 81±8 years) with hip fracture, the same cumulative dose of vitamin D3 (1500 IU orally per day, 10,500 IU per week, or 45,000 IU per month) approximately doubled serum 25(OH)D levels over the 2-month study period. After a cumulative dose of 90,000 IU, serum 25(OH)D levels rose from 15.7 ng/mL at baseline to 33.2, 29.2, and 37.1 ng/mL, respectively, for the daily, weekly, and monthly dose groups. These levels didn’t differ significantly from each other.2
But frequent dosing also shows effects
On the other hand, an RCT of 338 nursing home patients concluded that dosing frequency makes a difference. Patients (78% female; mean age 84±6.2 years) were randomized to 4 treatment arms: placebo (n=172), daily oral doses of vitamin D3 of 600 IU (n=55), weekly oral doses of 4200 IU (n=54), or monthly oral doses of 18,000 IU (n=57).
After 4 months, the 600 IU daily dose increased mean serum 25(OH)D levels the most, by 18.9 ng/mL; the 4200 IU weekly dose increased levels by 16.3 ng/mL, and the 18,000 IU monthly dose increased levels the least, by 11 ng/mL (P<.01 between groups). Serum 25(OH)D levels in the placebo group didn’t change. The average patient age of 84 years and high dropout rate (18.3% died or withdrew) limit this study.3
Oral D3 may be the best bet
The best route and form of vitamin D may be oral D3. A prospective intervention study randomized 32 female nursing home patients (66-97 years of age) to 4 treatment arms: oral D3, intramuscular (IM) D3, oral D2, or IM D2 (8 women per arm).4 Oral D3 in a dose of 300,000 IU increased 25(OH)D levels more effectively than the same dose of IM D3, oral D2, or IM D2.
All subjects had serum 25(OH)D levels below 32 ng/mL at baseline. One month after a single 300,000 IU dose, serum 25(OH)D levels increased by 47.8±7.3 ng/mL in the oral D3 group. Comparable differences (baseline to 1 month after treatment) in serum 25(OH)D levels for the other 3 arms were 15.9±11.3 ng/mL for IM D3; 17.3±4.7 ng/mL for oral D2; and 5±4.4 ng/mL for IM D2; P<.001 comparing 30-day serum 25(OH)D levels in the oral D3 group with the other 3 groups.4
Recommendations
The Institute of Medicine (IOM’s) 2011 report on dietary requirements for calcium and vitamin D doesn’t address the ideal treatment of deficiency, but it states that adequate levels of serum 25(OH)D are 20 ng/mL—not 30 ng/mL. The IOM advises that the upper limit of safe vitamin D intake is 4000 IU per day for people 9 years and older, and is lower for infants and young children.5
An online textbook recommends treating vitamin D deficiency (serum 25[OH]D levels below 20 ng/mL) with 50,000 IUs of vitamin D2 or D3 orally once a week for 6 to 8 weeks, followed by a maintenance dose (such as 800 to 1000 IUs of vitamin D3 daily). The same textbook recommends treating nutritional insufficiency (serum 25[OH]D levels between 20 and 30 ng/mL) with 800 to 1000 units of vitamin D3 daily. The authors recommend vitamin D3 over vitamin D2 for supplementation.6
1. Mastaglia S, Mautalen C, Parisi M, et al. Vitamin D2 dose required to rapidly increase 25(OH)D levels in osteoporotic women. Eur J Clin Nutr. 2006;60:681-687.
2. Ish-Shalom S, Segal E, Salganik T, et al. Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients. J Clin Endocrinol Metab. 2008;93:3430-3435.
3. Chel V, Wijnhoven H, Smit J, et al. Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. Osteoporosis Int. 2008;19:663-671.
4. Romagnoli E, Lascia M, Cipriani C. Short- and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93:3015-3020.
5. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53-58.
6. Dawson-Hughes B. Treatment of vitamin D-deficient states. UpToDate [online database], version 18.3. Waltham, Mass: UpToDate; June 2010.
SEVERAL VITAMIN D REPLACEMENT REGIMENS ARE EFFECTIVE. Cumulative dosing may be more important than frequency of dosing (strength of recommendation [SOR]: C, inconsistent results from randomized controlled trials [RCTs] of disease-oriented outcomes).
Vitamin D3 (cholecalciferol) may increase serum 25-hydroxy vitamin D (25[OH]D) concentrations more effectively than vitamin D2 (ergocalciferol) (SOR: C, a single RCT of disease-oriented outcomes).
Evidence summary
The total cumulative dose of vitamin D may be more significant than frequency of dosing. An RCT evaluated 38 postmenopausal women (median age 61.5 years) randomized into 3 groups (placebo or daily oral vitamin D2 in either 5000 or 10,000 IU doses).1 Only 1 patient had a baseline serum 25(OH)D level greater than 34 ng/mL. After 3 months, 8% of the placebo group, 50% of the 5000 IU daily group, and 75% of the 10,000 IU daily group had levels greater than 34 ng/mL. The cumulative D2 doses were 0, 450,000, and 900,000 IU, respectively. The number needed to treat (NNT), compared with placebo, was 3 (95% confidence interval [CI], 1-15) for the 5000 IU daily group and 2 (95% CI, 1-3) for the 10,000 IU daily group.
In another RCT that evaluated 48 women (average age 81±8 years) with hip fracture, the same cumulative dose of vitamin D3 (1500 IU orally per day, 10,500 IU per week, or 45,000 IU per month) approximately doubled serum 25(OH)D levels over the 2-month study period. After a cumulative dose of 90,000 IU, serum 25(OH)D levels rose from 15.7 ng/mL at baseline to 33.2, 29.2, and 37.1 ng/mL, respectively, for the daily, weekly, and monthly dose groups. These levels didn’t differ significantly from each other.2
But frequent dosing also shows effects
On the other hand, an RCT of 338 nursing home patients concluded that dosing frequency makes a difference. Patients (78% female; mean age 84±6.2 years) were randomized to 4 treatment arms: placebo (n=172), daily oral doses of vitamin D3 of 600 IU (n=55), weekly oral doses of 4200 IU (n=54), or monthly oral doses of 18,000 IU (n=57).
After 4 months, the 600 IU daily dose increased mean serum 25(OH)D levels the most, by 18.9 ng/mL; the 4200 IU weekly dose increased levels by 16.3 ng/mL, and the 18,000 IU monthly dose increased levels the least, by 11 ng/mL (P<.01 between groups). Serum 25(OH)D levels in the placebo group didn’t change. The average patient age of 84 years and high dropout rate (18.3% died or withdrew) limit this study.3
Oral D3 may be the best bet
The best route and form of vitamin D may be oral D3. A prospective intervention study randomized 32 female nursing home patients (66-97 years of age) to 4 treatment arms: oral D3, intramuscular (IM) D3, oral D2, or IM D2 (8 women per arm).4 Oral D3 in a dose of 300,000 IU increased 25(OH)D levels more effectively than the same dose of IM D3, oral D2, or IM D2.
All subjects had serum 25(OH)D levels below 32 ng/mL at baseline. One month after a single 300,000 IU dose, serum 25(OH)D levels increased by 47.8±7.3 ng/mL in the oral D3 group. Comparable differences (baseline to 1 month after treatment) in serum 25(OH)D levels for the other 3 arms were 15.9±11.3 ng/mL for IM D3; 17.3±4.7 ng/mL for oral D2; and 5±4.4 ng/mL for IM D2; P<.001 comparing 30-day serum 25(OH)D levels in the oral D3 group with the other 3 groups.4
Recommendations
The Institute of Medicine (IOM’s) 2011 report on dietary requirements for calcium and vitamin D doesn’t address the ideal treatment of deficiency, but it states that adequate levels of serum 25(OH)D are 20 ng/mL—not 30 ng/mL. The IOM advises that the upper limit of safe vitamin D intake is 4000 IU per day for people 9 years and older, and is lower for infants and young children.5
An online textbook recommends treating vitamin D deficiency (serum 25[OH]D levels below 20 ng/mL) with 50,000 IUs of vitamin D2 or D3 orally once a week for 6 to 8 weeks, followed by a maintenance dose (such as 800 to 1000 IUs of vitamin D3 daily). The same textbook recommends treating nutritional insufficiency (serum 25[OH]D levels between 20 and 30 ng/mL) with 800 to 1000 units of vitamin D3 daily. The authors recommend vitamin D3 over vitamin D2 for supplementation.6
SEVERAL VITAMIN D REPLACEMENT REGIMENS ARE EFFECTIVE. Cumulative dosing may be more important than frequency of dosing (strength of recommendation [SOR]: C, inconsistent results from randomized controlled trials [RCTs] of disease-oriented outcomes).
Vitamin D3 (cholecalciferol) may increase serum 25-hydroxy vitamin D (25[OH]D) concentrations more effectively than vitamin D2 (ergocalciferol) (SOR: C, a single RCT of disease-oriented outcomes).
Evidence summary
The total cumulative dose of vitamin D may be more significant than frequency of dosing. An RCT evaluated 38 postmenopausal women (median age 61.5 years) randomized into 3 groups (placebo or daily oral vitamin D2 in either 5000 or 10,000 IU doses).1 Only 1 patient had a baseline serum 25(OH)D level greater than 34 ng/mL. After 3 months, 8% of the placebo group, 50% of the 5000 IU daily group, and 75% of the 10,000 IU daily group had levels greater than 34 ng/mL. The cumulative D2 doses were 0, 450,000, and 900,000 IU, respectively. The number needed to treat (NNT), compared with placebo, was 3 (95% confidence interval [CI], 1-15) for the 5000 IU daily group and 2 (95% CI, 1-3) for the 10,000 IU daily group.
In another RCT that evaluated 48 women (average age 81±8 years) with hip fracture, the same cumulative dose of vitamin D3 (1500 IU orally per day, 10,500 IU per week, or 45,000 IU per month) approximately doubled serum 25(OH)D levels over the 2-month study period. After a cumulative dose of 90,000 IU, serum 25(OH)D levels rose from 15.7 ng/mL at baseline to 33.2, 29.2, and 37.1 ng/mL, respectively, for the daily, weekly, and monthly dose groups. These levels didn’t differ significantly from each other.2
But frequent dosing also shows effects
On the other hand, an RCT of 338 nursing home patients concluded that dosing frequency makes a difference. Patients (78% female; mean age 84±6.2 years) were randomized to 4 treatment arms: placebo (n=172), daily oral doses of vitamin D3 of 600 IU (n=55), weekly oral doses of 4200 IU (n=54), or monthly oral doses of 18,000 IU (n=57).
After 4 months, the 600 IU daily dose increased mean serum 25(OH)D levels the most, by 18.9 ng/mL; the 4200 IU weekly dose increased levels by 16.3 ng/mL, and the 18,000 IU monthly dose increased levels the least, by 11 ng/mL (P<.01 between groups). Serum 25(OH)D levels in the placebo group didn’t change. The average patient age of 84 years and high dropout rate (18.3% died or withdrew) limit this study.3
Oral D3 may be the best bet
The best route and form of vitamin D may be oral D3. A prospective intervention study randomized 32 female nursing home patients (66-97 years of age) to 4 treatment arms: oral D3, intramuscular (IM) D3, oral D2, or IM D2 (8 women per arm).4 Oral D3 in a dose of 300,000 IU increased 25(OH)D levels more effectively than the same dose of IM D3, oral D2, or IM D2.
All subjects had serum 25(OH)D levels below 32 ng/mL at baseline. One month after a single 300,000 IU dose, serum 25(OH)D levels increased by 47.8±7.3 ng/mL in the oral D3 group. Comparable differences (baseline to 1 month after treatment) in serum 25(OH)D levels for the other 3 arms were 15.9±11.3 ng/mL for IM D3; 17.3±4.7 ng/mL for oral D2; and 5±4.4 ng/mL for IM D2; P<.001 comparing 30-day serum 25(OH)D levels in the oral D3 group with the other 3 groups.4
Recommendations
The Institute of Medicine (IOM’s) 2011 report on dietary requirements for calcium and vitamin D doesn’t address the ideal treatment of deficiency, but it states that adequate levels of serum 25(OH)D are 20 ng/mL—not 30 ng/mL. The IOM advises that the upper limit of safe vitamin D intake is 4000 IU per day for people 9 years and older, and is lower for infants and young children.5
An online textbook recommends treating vitamin D deficiency (serum 25[OH]D levels below 20 ng/mL) with 50,000 IUs of vitamin D2 or D3 orally once a week for 6 to 8 weeks, followed by a maintenance dose (such as 800 to 1000 IUs of vitamin D3 daily). The same textbook recommends treating nutritional insufficiency (serum 25[OH]D levels between 20 and 30 ng/mL) with 800 to 1000 units of vitamin D3 daily. The authors recommend vitamin D3 over vitamin D2 for supplementation.6
1. Mastaglia S, Mautalen C, Parisi M, et al. Vitamin D2 dose required to rapidly increase 25(OH)D levels in osteoporotic women. Eur J Clin Nutr. 2006;60:681-687.
2. Ish-Shalom S, Segal E, Salganik T, et al. Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients. J Clin Endocrinol Metab. 2008;93:3430-3435.
3. Chel V, Wijnhoven H, Smit J, et al. Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. Osteoporosis Int. 2008;19:663-671.
4. Romagnoli E, Lascia M, Cipriani C. Short- and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93:3015-3020.
5. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53-58.
6. Dawson-Hughes B. Treatment of vitamin D-deficient states. UpToDate [online database], version 18.3. Waltham, Mass: UpToDate; June 2010.
1. Mastaglia S, Mautalen C, Parisi M, et al. Vitamin D2 dose required to rapidly increase 25(OH)D levels in osteoporotic women. Eur J Clin Nutr. 2006;60:681-687.
2. Ish-Shalom S, Segal E, Salganik T, et al. Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients. J Clin Endocrinol Metab. 2008;93:3430-3435.
3. Chel V, Wijnhoven H, Smit J, et al. Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. Osteoporosis Int. 2008;19:663-671.
4. Romagnoli E, Lascia M, Cipriani C. Short- and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93:3015-3020.
5. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53-58.
6. Dawson-Hughes B. Treatment of vitamin D-deficient states. UpToDate [online database], version 18.3. Waltham, Mass: UpToDate; June 2010.
Evidence-based answers from the Family Physicians Inquiries Network