Double-dose vitamin D lowers cancer risk in women over 55
Many factors affect vitamin D levels (TABLE).9 Foods that contain vitamin D3 include fortified milk (100 IU per cup) and oily fish, including salmon, tuna, sardines, mackerel, and herring (200–300 IU per 3.5-oz serving). Sun exposure for 10 to 15 minutes (without sunscreen) at least twice a week to the face, arms, hands, or back is considered sufficient to provide adequate vitamin D during summer or in warm climates.
Many patients need supplements to reach the levels provided by 1000 IU daily, especially in colder climates. Most over-the-counter supplements containing vitamin D alone contain 400 to 1000 IU vitamin D3. Prescription vitamin D2 capsules contain 50,000 IU.9 Vitamin D is available as vitamin D2 and D3:
- Vitamin D2 is usually labeled vitamin D or calciferol. Vitamin D2 is only 30% as effective as vitamin D3 (doses should be adjusted accordingly).
- Vitamin D3 is labeled vitamin D3 or cholecalciferol.
TABLE
3 ways to get vitamin D: Food, sun, and supplements9
| SOURCE | AMOUNT | |
|---|---|---|
| Food | 1 cup of fortified milk | 100 IU vitamin D3 |
| One serving (3.5 oz) of oily fish (salmon, tuna, sardines, mackerel or herring) | 200 to 300 IU vitamin D | |
| Sun (ultraviolet B radiation) | Expose face, arms, hands, or back for 10 to 15 minutes (without sunscreen) at least twice a week during summer months or in warm climates | 3000 IU vitamin D3 per exposure |
| Supplements | Vitamin D3 | 1000 IU/day |
| Vitamin D2 | 50,000 IU every 2 to 4 weeks |
Study Summary: Cancer was a secondary outcome
This trial was well designed and executed, with impressive findings. The primary outcomes were related to skeletal status and calcium economy. Cancer incidence was one of the secondary outcomes.
This population-based study was randomized, double-blinded, and placebo-controlled, with concealed allocation. The researchers enrolled 1180 women older than 55 years of age, with no known cancer, and with adequate mental and physical health to allow an expected 4 years of participation in the trial. The trial was conducted in rural Nebraska. Eighty-six percent of the participants completed the study. Participants were randomly assigned to 3 groups:
- Placebo (calcium placebo plus vitamin D placebo, n=266)
- calcium-only (1400 mg calcium citrate or 1500 mg calcium carbonate plus vitamin D placebo, n=416)
- Calcium + D (1000 IU [25 mcg] vitamin D plus calcium [as above], n=403)
Every 6 months, adherence was assessed by bottle weight. Mean adherence (taking ≥80% of assigned doses) was 85.7% for vitamin D and 74.4% for calcium. Serum samples were analyzed for 25(OH)D at baseline and then yearly.1
Key results
Fifty women developed non-skin cancer during the study: 13 in the first year, and 37 during the second to fourth years. Excluding cancer diagnosed in the first year (it was assumed that these cancers were present, though undiagnosed, at entry), the relative risk reduction (RRR) for the calcium + D group was 0.232 (confidence interval [CI], 0.09–0.60; P<.005), and the RRR for the calcium-only group was 0.587 (95% CI, 0.29–1.21; P=.147) compared with the placebo group.
Number needed to treat (NNT) to prevent 1 case of cancer for the calcium + D group is 21, with an absolute risk reduction of 0.048, or approximately 5%.
Risk reduction. Using baseline 25(OH)D concentration as the predictor variable and cancer as the outcome variable in logistic regression, Lappe et al predicted a 35% reduced cancer risk for every 25 nmol/L (10 ng/mL) increase in serum 25(OH)D.1
What’s New? First RCT to show reduced cancer incidence
This is the first randomized-controlled clinical trial to show that vitamin D reduces cancer risk. (It is important to note that one prior randomized controlled trial10 found no impact on cancer incidence; however, that trial used a vitamin D3 dose of 400 IU, which is lower than the 1000 IU dose used by Lappe et al.)
Vitamin D curbs carcinogenic potential. The new findings build on prior basic research, which established the pathophysiologic process by which vitamin D may prevent cancer in humans. Vitamin D receptors are found not only in the small intestines, bones, and kidneys, but also in most other tissues, including skin, colon, prostate, breast, and brain. The interaction of 1,25(OH)2D with vitamin D receptors induces terminal differentiation and apoptosis and inhibits cellular growth, angiogenesis, and metastatic potential.10
Other studies suggest vitamin d plays a part. Previous population-based studies also suggested an association between vitamin D and reduced cancer incidence.
Lin et al, as part of the Women’s Health Study, found that higher intake of calcium and vitamin D was associated with a lower risk of breast cancer in premenopausal but not in postmenopausal women. The highest dosage quintile was >548 IU; therefore, many if not most women likely ingested an inadequate dose of vitamin D to reduce risk of cancer.11
The Health Professionals Follow-up Study, which followed a cohort of 47,800 men, from 1986 until 2000, found that low levels of vitamin D were associated with increased incidence of cancer and mortality.12
In the only other randomized controlled trial of vitamin D and cancer (also part of the Women’s Health Initiative), Wactawski-Wende et al found no difference in the risk of colorectal cancer between women taking calcium and vitamin D and women taking placebo, over an average of 7 years of follow-up. However, the vitamin D dose was only 400 IU daily, the dosage recommended for general health and bone health.13
