Vitamin D seems to be making headlines this week (see Cancer survival disparities and vitamin D). The Orthomolecular Medicine News Service recently released "Government Gets it Wrong Again:
U.S. Recommendation for Vitamin D and Calcium Supplementation is Too Low". Read the full article below courtesy of OMNS.
Government Gets it Wrong Again:
U.S. Recommendation for Vitamin D and Calcium Supplementation is Too Low
by William B. Grant, Ph.D.
(OMNS June 14, 2012) The U.S. Preventive
Services Task Force (USPSTF) reviewed the evidence regarding vitamin D
and calcium supplementation for preventing cancer and osteoporotic
fractures in adults and concluded that there is insufficient evidence to
assess the balance of the benefits and harms of vitamin D with or
without calcium for the primary prevention of cancer [1]. This finding
is based on reviewing the evidence from two randomized controlled trials
(RCTs) of vitamin D plus calcium supplementation and two reviews of the
literature.
There are several problems with their
review and recommendation. First, they accepted the most critical
interpretations of the two RCTs, which essentially stated there was no
benefit. The first study [2] claimed that since cancer was not the
primary focus of the study, incidence may not have been correctly
analyzed. However, a careful comparison of the incidence rate for women
in the control group with incidence rates for women living in or near
Nebraska at that time and with that age distribution finds excellent
agreement with the expected rate. There is no indication that those who
took supplements were treated for medical conditions differently from
those who didn't take supplements.
In the second study [3], no
statistically significant correlation was found between vitamin D plus
calcium supplementation and cancer incidence rates for the entire group.
However, a reanalysis of the results of that study found [4]:
In
15,646 women (43%) who were not taking personal calcium or vitamin D
supplements at randomization, CaD significantly decreased the risk of
total, breast, and invasive breast cancers by 14-20% and
nonsignificantly reduced the risk of colorectal cancer by 17%. In women
taking personal calcium or vitamin D supplements, CaD did not alter
cancer risk (HR: 1.06-1.26).
This implies that those who were taking
supplements at the start of the study already had received the benefit,
so that additional calcium and vitamin D had less of an effect. In
addition, the USPSTF overlooked a recent paper in which men with
low-grade biopsy-verified prostate cancer were given 4000 IU/d vitamin
D3 for a year and had a 55% rate of tumor regression compared to 20% in
historical controls [5]. Apparently, an adequate dose of vitamin D can
greatly lower risk. For those who don't receive an adequate dose of
summer mid-day sun, supplements can make a big difference.
This brings us to the second major
point. The USPSTF treats vitamin D like a drug. Pharmaceutical drugs
must be tested in medical trials since they are, by definition,
artificial, and must be evaluated for efficacy and harm. Solar
ultraviolet-B (UVB) is the primary source of vitamin D for most people,
and has been an important contributor to optimal health since before man
walked on earth. It is not a drug, but is synthesized in the skin from
sunlight! Skin pigmentation has adapted to where people live, dark
enough to reduce risk of skin cancer, yet light enough to permit
adequate vitamin D production [6]. Thus, evidence from geographical and
observational studies should also be used to evaluate the role of
vitamin D in reducing risk of cancer.
The evidence from geographical studies
clearly shows that those living where solar UVB doses are higher have
lower cancer incidence and/or mortality rates. A recent review concluded
[7]:
This
review consistently found strong inverse correlations with solar UVB
for 15 types of cancer: bladder, breast, cervical, colon, endometrial,
esophageal, gastric, lung, ovarian, pancreatic, rectal, renal, and
vulvar cancer; and Hodgkin's and non-Hodgkin's lymphoma. Weaker evidence
exists for nine other types of cancer: brain, gallbladder, laryngeal,
oral/pharyngeal, prostate, and thyroid cancer; leukemia; melanoma; and
multiple myeloma.
Observational studies based on serum
25-hydroxyvitamin D [25(OH)D] at or before the time of cancer diagnosis
are also useful. Case-control studies, in which serum 25(OH)D
concentrations are determined at time of diagnosis have found the
strongest inverse correlations between serum 25(OH)D concentration and
cancer incidence rates. Based on five such studies for breast cancer
including the most recent one from Mexico [6], those with 155 nmol/l (62
ng/ml) had a 70% lower incidence of breast cancer than women with 25
nmol/l (10 ng/ml) [Grant, submitted].
Nested case-control studies from cohort
studies are also useful but are more difficult to interpret since they
generally report a single serum 25(OH)D concentration at the time of
enrollment, then follow people for up to 28 years. During the follow-up
time, serum 25(OH)D concentrations typically vary, thereby reducing the
observed effect [8].
As to the oft-repeated refrain that
findings from geographical and observational studies need to be verified
through RCTs, good luck. It is very difficult to conduct RCTs for
vitamin D properly for a number of reasons. For one, there are several
sources of vitamin D, so it is difficult to isolate the effects of the
supplement [4]. For another, there are large individual variations in
serum 25(OH)D concentration for a given oral intake [9]. Also, it is
important to use available information to estimate the serum
25(OH)D-health outcome relation. And it's important to enroll people
with serum 25(OH)D concentrations in a range where additional vitamin D
from supplements will have a measureable effect on health outcome.
Further, it's important to measure serum 25(OH)D concentrations at least
every year or two during the study [10]. The Women's Health Initiative
RCT study [3] didn't follow these guidelines and, as a result, hardly
found any positive results.
Based on the best information available
to date from geographical and observational studies and RCTs, serum
25(OH)D concentrations should be above 100 nmol/l (40 ng/ml) for optimum
health. To achieve this concentration could take 1000-5000 IU/d. It is
also recommended that serum 25(OH)D concentrations be measured before
starting a vitamin D supplementation program, then again after
supplementing for a few months.
Disclosure:
The author receives funding from the UV
Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the
Vitamin D Council (San Luis Obispo, CA), the Vitamin D Society
(Canada), and the Sunlight Research Forum (Veldhoven).
References:
2.Lappe JM, Travers-Gustafson D, Davies
KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces
cancer risk: results of a randomized trial. Am J Clin Nutr.
2007;85:1586-91.
3. Wactawski-Wende J, Kotchen JM,
Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ, et al. Calcium plus
vitamin D supplementation and the risk of colorectal cancer. N Engl J
Med 2006;354:684-96.
4. Bolland MJ, Grey A, Gamble GD, Reid
IR. Calcium and vitamin D supplements and health outcomes: a reanalysis
of the Women's Health Initiative (WHI) limited-access data set. Am J
Clin Nutr. 2011;94:1144-9.
5. Marshall DE, Savage SJ, Garrett-Mayer
E, Keane TE, Hollis BW, Host RL, et al. Vitamin D3 supplementation at
4000 international units per day for one year results in a decrease of
positive cores at repeat biopsy in subjects with low-risk prostate
cancer under active surveillance. J Clin Endocrinol Metab. April 16,
2012 jc.2012-1451 epub.
6. Grant WB. Ecological studies of the UVB-vitamin D-cancer hypothesis; review. Anticancer Res. 2012;32:223-36.
7. Fedirko V, Torres-Mej¡a G,
Ortega-Olvera C, Biessy C, Angeles-Llerenas A, Lazcano-Ponce E, et al.
Serum 25-hydroxyvitamin D and risk of breast cancer: results of a large
population-based case-control study in Mexican women. Cancer Causes
Control. 2012;23:1149-62.
8. Grant WB. Effect of interval between
serum draw and follow-up period on relative risk of cancer incidence
with respect to 25-hydroxyvitamin D level; implications for
meta-analyses and setting vitamin D guidelines, Dermatoendocrinol.
2011;3:3:199-204.
9. Garland CF, French CB, Baggerly LL,
Heaney RP. Vitamin D supplement doses and serum 25-hydroxyvitamin D in
the range associated with cancer prevention. Anticancer Res
2011;31:617-22.
10. Lappe JM, Heaney RP. Why randomized
controlled trials of calcium and vitamin D sometimes fail.
Dermatoendocrin. 2012;4(2) epub
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