Recent trial results question supplementation benefits
By David Dunaief, M.D.
Vitamin D is one the most widely publicized and important supplements. We get vitamin D from the sun, food and supplements. With our days rapidly shortening here in the Northeast, let’s explore what we know about vitamin D supplementation.
There is no question that, if you have low levels of vitamin D, replacing it is important. Previous studies have shown that it may be effective in a wide swath of chronic diseases, both in prevention and as part of the treatment paradigm. However, many questions remain. As more data come in, their meaning for vitamin D becomes murkier. For instance, is the sun the best source of vitamin D?
At the 70th annual American Academy of Dermatology meeting, Dr. Richard Gallo, who was involved with the Institute of Medicine recommendations, spoke about how, in most geographic locations, sun exposure will not correct vitamin D deficiencies. Interestingly, he emphasized getting more vitamin D from nutrition. Dietary sources include cold-water fatty fish, such as salmon, sardines and tuna.
We know its importance for bone health, but as of yet, we only have encouraging — but not yet definitive — data for other diseases. These include cardiovascular and autoimmune diseases and cancer.
There is no consensus on the ideal blood level for vitamin D. For adults, the Institute of Medicine recommends more than 20 ng/dl, and The Endocrine Society recommends at least 30 ng/dl.
Cardiovascular mixed results
Several observational studies have shown benefits of vitamin D supplements with cardiovascular disease. For example, the Framingham Offspring Study showed that those patients with deficient levels were at increased risk of cardiovascular disease (1).
However, a small randomized controlled trial (RCT), the gold standard of studies, called the cardioprotective effects of vitamin D into question (2). This study of postmenopausal women, using biomarkers such as endothelial function, inflammation or vascular stiffness, showed no difference between vitamin D treatment and placebo. The authors concluded there is no reason to give vitamin D for prevention of cardiovascular disease.
The vitamin D dose given to the treatment group was 2,500 IUs. Thus, one couldn’t argue that this dose was too low. Some of the weaknesses of the study were a very short duration of four months, its size — 114 participants — and the fact that cardiovascular events or deaths were not used as study end points.
Long-awaited VITAL study results for cancer and cardiovascular events
Most trials relating to vitamin D are observational, which provides associations, but not links. However, results of the VITAL study, a large, five-year RCT looking at the effects of vitamin D and omega-3s on cardiovascular disease and cancer were just published this week (3). Study results were disappointing, finding that daily vitamin D3 supplementation at 2000 IUs did not reduce the incidence of cancers (prostate, breast or colorectal) or of major cardiovascular events.
In a meta-analysis of a group of eight studies, vitamin D with calcium reduced the mortality rate in the elderly, whereas vitamin D alone did not (5). The difference between the groups was statistically important, but clinically small: 9 percent reduction with vitamin D plus calcium and 7 percent with vitamin D alone.
One of the weaknesses of this analysis was that vitamin D in two of the studies was given in large amounts of 300,000 to 500,000 IUs once a year, rather than taken daily. This has different effects.
There is good news, but not great news, on the weight front. It appears that vitamin D plays a role in reducing the amount of weight gain in women 65 years and older whose blood levels are more than 30 ng/dl, compared to those below this level, in the Study of Osteoporotic Fractures (4).
This association held true at baseline and after 4.5 years of observation. If the women dropped below 30 ng/dl in this time period, they were more likely to gain more weight, and they gained less if they kept levels above the target. There were 4,659 participants in the study. Unfortunately, vitamin D did not show statistical significance with weight loss.
The U.S. Preventive Services Task Force recommends against giving “healthy” postmenopausal women vitamin D, calcium or the combination of vitamin D 400 IUs plus calcium 1,000 mg to prevent fractures, and it found inadequate evidence of fracture prevention at higher levels (6). The supplement combination does not seem to reduce fractures, but does increase the risk of kidney stones. There is also not enough data to recommend for or against vitamin D with or without calcium for cancer prevention. But as I mentioned previously, the recent VITAL study did not show any benefit for cancer prevention.
When to supplement?
It is important to supplement to optimal levels, especially since most of us living in the Northeast have insufficient to deficient levels. While vitamin D may not be a cure-all, it may play an integral role with many disorders. But it is also important not to raise the levels too high. The range that I tell my patients is between 30 and 55 ng/dl, depending on their circumstances — those who are healthy and those who have chronic diseases and what type of chronic diseases.
(1) Circulation. 2008 Jan 29;117(4):503-511. (2) PLoS One. 2012;7(5):e36617. (3) NEJM. 2018 published online Nov. 10, 2018. (4) J Women’s Health (Larchmt). 2012 Jun 25. (5) J Clin Endocrinol Metabol. online May 17, 2012. (6) JAMA. 2018;319(15):1592-1599.
Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.