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The controversy over whether people should be supplementing with vitamin D or not, and whether there are health benefits or harms from vitamin D supplementation is heating up. While observational studies have found health benefits with higher vitamin D blood levels, the beneficial results have generally not held up (or mixed findings) when people were randomly assigned to groups (randomized clinical trials). Most agree that blood levels of under 20 ng per mL is too low, but an issue is what is a desirable blood level? Should healthy people routinely supplement?

Having higher blood levels of vitamin D from sunshine appears to be good (it's the sunshine vitamin, after all). It's the taking of a vitamin D supplement that is now controversial and being debated. By the way, if one decides to take a vitamin D supplement, then the D3 form is desirable (rather than D2).

It was pointed out that a number of negative health effects can occur in those taking more than 4000 IU daily of vitamin D. For example, it may cause toxic effects such as renal impairment, hypercalcemia, or vascular calcification. In  2014, 3% of all U.S. adults and 6.6% of adults older than 60 years reported taking a vitamin D supplement of 4,000 or more IU per day. [See all vitamin D posts - most discuss observational studies finding benefits.]

The following are articles from Medscape (the medical site) and American Family Physician discussing recent research that is not finding health benefits with vitamin D supplementation, or mixed findings (e.g. one review found it may be protective in lowering death from any reason or from cancer; also reduce the number of upper respiratory infections)Therefore, some medical groups suggest that vitamin D screening is an unnecessary test, a waste of money,  and shouldn't be routinely done in healthy individuals. Note that many, many trials are going on right now to try to settle the vitamin D supplement issue (whether there are health benefits or not). ...continue reading "Mixed Findings In Vitamin D Supplement Studies"

Vitamin D supplements are incredibly popular, but whether vitamin D supplements should be taken during pregnancy and at what dose is still debated, and studies have had conflicting results. Now a review by Canadian researchers of 43 studies of vitamin D supplementation during pregnancy found that there is "insufficient evidence to guide recommendations during pregnancy". They said that overall the studies were small or of low quality -  and the "available data did not provide evidence of benefit" from vitamin D supplementation during pregnancy.

They found that vitamin D supplementation slightly increased the mean (average) birth weight by 2 ounces (58.33 g), reduced the risk of small for gestational age births, and reduced the risk of the child wheezing at age 3. There was no effect on preterm birth, and there was a lack of evidence of benefits of prenatal vitamin D supplementation for maternal health conditions (e.g. gestational diabetes) during pregnancy.

Currently recommendations regarding vitamin D supplementation vary widely among medical and professional organizations, and WHO (World Health Organization) currently recommends against routine prenatal vitamin D supplementation. Luckily there are a number of studies going on right now on this issue that may help answer this question - how much vitamin D, if any, should be taken during pregnancy? From Medical Xpress:

Insufficient evidence to guide recommendations on vitamin D in pregnancy

There is currently insufficient evidence to guide recommendations on the use of vitamin D supplements in pregnancy, conclude researchers in The BMJ today. A team led by Dr Daniel Roth at The Hospital for Sick Children in Toronto, say some of the most critical questions about the effectiveness of taking vitamin D supplements during pregnancy "will probably remain unanswered in the foreseeable future."

Vitamin D helps maintain calcium levels in the body to keep bones, teeth and muscles healthy. Numerous studies suggest that taking vitamin D supplements may also help protect against heart disease, cancer, respiratory infections and asthma - as well as conditions related to pregnancy, such as preeclampsia and gestational diabetes. But results are conflicting and recommendations vary widely among medical and professional organisations.

So Dr Roth and his team set out to assess the current and future state of the evidence on vitamin D supplements during pregnancy. They analysed results from 43 randomised controlled trials involving 8,406 women, to estimate the effects of taking vitamin D supplements during pregnancy on 11 maternal and 27 child outcomes.... The results show that taking supplements during pregnancy increased vitamin D levels in both the mother's bloodstream and umbilical cord blood, but the researchers did not consistently find that higher doses of vitamin D led to healthier women and babies.

Overall, vitamin D increased average birth weight by 58 g and reduced the risk of having a small baby, but more detailed analyses weakened the authors' confidence in these findings. There was a lack of evidence of benefits of vitamin D supplements for maternal health conditions related to pregnancy, no effect on other birth outcomes of public health importance, such as premature birth, and scant evidence on safety outcomes.  [Original study.]

Does vitamin D prevent cancer? There has been much debate over whether increasing levels of vitamin D (as measured in a person's blood) results in a lower incidence of cancer. Studies find a number of health problems linked to low levels of vitamin D (here, here, here), while studies looking at vitamin D and cancer have been "inconsistent" in their results. Some say yes - vitamin D is protective, while some say there is no effect from vitamin D supplements. Now a 4 year study (yes, yes - it's a very short length of time in which to study the onset of cancer) found no difference in the rate of cancer among two groups of postmenopausal women who received either: 2,000 IU per day of vitamin D3 and 1,500 mg per day of calcium OR an identical looking placebo. They looked for any kind of cancer occurring.

The Creighton University researchers found a difference among the women after 4 years, with the vitamin D plus calcium supplement group having fewer cancers (and a lower percentage of cancer) as compared to the placebo group, did not reach statistical significance. So you could say it was due to chance. But when the researchers looked at the number of cancers from year 2 to 4, then the difference was statistically significant - that vitamin D was protective. The researchers wonder if the cancers diagnosed in year 1 were already developing before the study started. Note: The 2,000 IU per day vitamin D3 supplements in this study are considered high doses - "high dose supplementation".

The researchers point out that the women who were given vitamin D3 and calcium supplements had a 30% lower risk of cancer, even though this difference in cancer incidence rates between the 2 groups did not quite reach statistical significance. But both groups started with a fairly high vitamin D level -  an average 25-hydroxyvitamin D (25[OH]D) levels of 32.8 ng/m (which is above the average US population level). And in the supplement group it was raised to 43.9 ng/mL. Note that some researchers view vitamin D levels of 33 ng/mL  (the baseline level in both groups) as already protective against cancer.

Also, even during the study the placebo group was allowed to take their own vitamin D and calcium supplements as long as it wasn't more than the recommended amounts (800 IU per day for vitamin D and 1500 mg per day for calcium) - which makes those individuals actually a low vitamin D supplementation group rather than no supplementation, which might hide any treatment effects and so make the results for the 2 groups look similar. What is needed is a much longer follow-up, larger groups of women, and both high and low dose vitamin D supplement groups. Some studies suggest that whether a low or high dose taken has an effect on cancer incidence.

I still think this study period was way too short - to me, 5 or more years would have been more convincing, and the groups too small. Also, it was unfortunate that they were also given calcium supplements or that there wasn't a just vitamin D group. Combining vitamin D with calcium supplements just muddies the results (in my opinion), and also because calcium supplements are linked to health problems such as cardiovascular disease. So in this study can't tell what the separate effects of calcium and vitamin D are. (Note that calcium rich foods, however, are beneficial to health.)

But a big positive of the study was that the women were randomly assigned to either the vitamin D plus calcium group or the placebo group, and no one - not the women or their doctors knew who got what until the end of the study (to eliminate bias it was "double-blind"). Note The supplements used were vitamin D3 and not D2. Vitamin D can also be easily obtained by exposure to sunlight in the summer months.

Excerpts from Creighton University release about the study in Science Daily: Does Vitamin D decrease risk of cancer?

The study, funded by the National Institutes of Health, is a randomized clinical trial of the effects of vitamin D supplementation on all types of cancer combined. The four-year study included 2,303 healthy postmenopausal women 55 years and older from 31 counties in Nebraska. Participants were randomly assigned to take either 2000 international units (IU) of vitamin D3 and 1500 mg. of calcium or identical placebos daily for 4 years. The vitamin D3 dose was about three times the US government's Recommended Dietary Allowance (RDA) of 600 IU for adults through age 70, and 800 IU for those 71 and older. Women who were given vitamin D3 and calcium supplements had 30% lower risk of cancer. This difference in cancer incidence rates between groups did not quite reach statistical significance. However, in further analyses, blood levels of vitamin D, specifically 25-hydroxyvitamin D (25(OH)D), were significantly lower in women who developed cancer during the study than in those who remained healthy.

Since so many people are taking Vitamin D supplements because of its supposed health benefits, the question becomes - how much is too much? For those desiring to take vitamin D supplements, what is a good maintenance dosage to take daily? That question has not been answered from the studies I've seen other than 1000 units per day is safe. However, sunlight is the best and safest source of vitamin D (even though that makes dermatologists nuts because of their concern with sunlight leading to skin cancer).From Science Daily:

Vitamin D toxicity rare in people who take supplements, researchers report

Over the last decade, numerous studies have shown that many Americans have low vitamin D levels and as a result, vitamin D supplement use has climbed in recent years. Vitamin D has been shown to boost bone health and it may play a role in preventing diabetes, cancer, cardiovascular disease and other illnesses. In light of the increased use of vitamin D supplements, Mayo Clinic researchers set out to learn more about the health of those with high vitamin D levels. They found that toxic levels are actually rare.

A vitamin D level greater than 50 nanograms per milliliter is considered high. Vitamin D levels are determined by a blood test called a serum 25-hydroxyvitamin D blood test. A normal level is 20-50 ng/mL, and deficiency is considered anything less than 20 ng/mL, according the Institute of Medicine (IOM).

The researchers analyzed data collected between 2002 and 2011 from patients in the Rochester Epidemiology Project...Of 20,308 measurements, 8 percent of the people who had their vitamin D measured had levels greater than 50 ng/mL, and less than 1 percent had levels over 100 ng/mL.

"We found that even in those with high levels of vitamin D over 50 ng/mL, there was not an increased risk of hypercalcemia, or elevated serum calcium, with increasing levels of vitamin D," says study co-author Thomas D. Thacher, M.D., a family medicine expert at Mayo Clinic. Hypercalcemia, or high blood calcium, can occur when there are very high levels of vitamin D in the blood. Too much calcium in the blood can cause weakness, lead to kidney stones, and interfere with the heart and brain, and even be life threatening.

The Mayo researchers also found that women over age 65 were at the highest risk of having vitamin D levels above 50 ng/mL. The result was not surprising because that's a group that often takes vitamin D supplements, Dr. Thacher says. Another notable outcome: The occurrence of high vitamin D levels over 50 ng/mL increased during the 10-year period of the study, from nine per 100,000 people at the start of the study up to 233 per 100,000 by the end.

Only one case over the 10-year study period was identified as true acute vitamin D toxicity; the person's vitamin D level was 364 ng/mL. The individual had been taking 50,000 international units (IU) of vitamin D supplements every day for more than three months, as well as calcium supplements. The IOM-recommended upper limit of vitamin D supplementation for people with low or deficient levels is 4,000 IU a day. 

Some natural sources of vitamin D include oily fish such as mackerel and salmon, fortified milk, and sunlight.

Big question: will vitamin D supplementation prevent cognitive decline? And what should be a daily supplement dose for adults? An earlier post cited a Medscape article suggesting that taking 1000 IU of vitamin D3 daily would be a good daily level of supplementation. From Medscape:

Vitamin D Deficiency Predicts Cognitive Decline

A new study supports a link between low levels of vitamin D and increased risk for cognitive decline, prompting calls for clinical trials to test whether vitamin D supplementation may delay or prevent dementia. In a group of cognitively intact older adults, serum 25-hydroxyvitamin D (25OHD) levels below 75 nmol/L at the outset predicted cognitive decline over roughly the next 4 years, independent of other factors.

For this analysis, the researchers looked at data on 1927 community-dwelling elderly individuals (mean age, 73.9 years) participating in the Italian population-based cohort study, Progetto Veneto Anziani (Pro.V.A.).

Dr Toffanello and colleagues say studies are needed to evaluate whether vitamin D supplementation might help to delay the cognitive decline, especially in patients who already have cognitive impairment.

David J. Llewellyn, PhD, from the University of Exeter Medical School in the United Kingdom, who has studied vitamin D and cognitive function but wasn't involved in this study, agrees. He told Medscape Medical News that this new study "effectively replicates" a 2010 study by his group showing a link between low vitamin D levels and an increased risk for cognitive decline. He said the Pro.V.A . study results are also consistent with a study his group published just this year inNeurology. That study suggested older patients with vitamin D levels below 50 nmol/L have about a 122% increased risk for dementia compared with those with higher levels.

Two studies published in the British Medical Journal (BMJ) looked at Vitamin D. From NY Times:

Low Vitamin D Levels Linked to Disease in Two Big Studies

People with low vitamin D levels are more likely to die from cancer and heart disease and to suffer from other illnesses, scientists reported in two large studies published on Tuesday.

The new research suggests strongly that blood levels of vitamin D are a good barometer of overall health. But it does not resolve the question of whether low levels are a cause of disease or simply an indicator of behaviors that contribute to poor health, like a sedentary lifestyle, smoking and a diet heavy in processed and unhealthful foods.

Nicknamed the sunshine nutrient, vitamin D is produced in the body when the skin is exposed to sunlight. It can be obtained from a small assortment of foods, including fish, eggs, fortified dairy products and organ meats, and vegetables like mushrooms and kale. And blood levels of it can be lowered by smoking, obesity, and inflammation.

Vitamin D helps the body absorb calcium and is an important part of the immune system. Receptors for the vitamin and related enzymes are found throughout cells and tissues of the body, suggesting it may be vital to many physiological functions, said Dr. Oscar H. Franco, a professor of preventive medicine at Erasmus Medical Center in the Netherlands and an author of one of the new studies, which appeared in the journal BMJ.

The two studies were meta-analyses that included data on more than a million people. They included observational findings on the relationship between disease and blood levels of vitamin D. The researchers also reviewed evidence from randomized controlled trials — the gold standard in scientific research — that assessed whether taking vitamin D daily was beneficial.

Dr. Franco and his co-authors — a team of scientists at Harvard, Oxford and other universities — found persuasive evidence that vitamin D protects against major diseases. Adults with lower levels of the vitamin in their systems had a 35 percent increased risk of death from heart disease, 14 percent greater likelihood of death from cancer, and a greater mortality risk overall.

When the researchers looked at supplement use, they found no benefit to taking vitamin D2. But middle-aged and older adults who took another form, vitamin D3 — which is the type found in fish and dairy products and produced in response to sunlight — had an 11 percent reduction in mortality from all causes, compared to adults who did not. In the United States and Europe, it is estimated that more than two-thirds of the population is deficient in vitamin D. In their paper, Dr. Franco and his colleagues calculated that roughly 13 percent of all deaths in the United States, and 9 percent in Europe, could be attributed to low vitamin D levels.

In the second study, also published in BMJ, a team of researchers at Stanford and several universities in Europe presented a more nuanced view of vitamin D.

They concluded there was “suggestive evidence” that high vitamin D levels protect against diabetes, stroke, hypertension and a host of other illnesses. But they also said there was no “highly convincing” evidence that vitamin D pills affected any of the outcomes they examined.

Dr. Theodoratou was not alone in suggesting people hold off on taking vitamin D supplements for now. Even though Dr. Franco found them to be beneficial, he said that more research was needed to show what levels are best. Instead of taking pills, people could improve their vitamin D levels with an adequate diet and 30 minutes of sunlight twice a week, he said.