New Article on Vitamin D

[Cherie]

I had the opportunity yesterday to participate in an online discussion on the evidence available that Vitamin D impacts Multiple Sclerosis Disease progress. A link to the article published following that discussion can be found at this link:
Only registered and activated users can see links., Click Here To Register...

I tried to attach the article in both word and pdf format but it would not allow me to due to size. So I'll paste it if you cannot access the link.


Neurology

Friday Feedback: Vitamin D -- the MS Magic Bullet?
Published: Jan 24, 2014
By Elbert Chu

This week, Friday Feedback takes a second look at a reported correlation between vitamin D and slower disease progression in multiple sclerosis patients.
We reached out to a diverse group of physicians by email and asked them to respond to the following question:
On the strength of these observational data, how would you use these findings in the clinical management of your MS patients?

The participants this week:
Cherie C. Binns, RN, an independent multiple sclerosis-certified nurse based in Wakefield, R.I.
Marian L. Evatt, MD, MS, Department of Neurology, Emory University School of Medicine
Robert Fox, MD, an MS specialist in the Mellen Center for Multiple Sclerosis at the Cleveland Clinic
J. William Lindsey, MD, professor of neurology at the University of Texas Health Science Center at Houston (UTHealth) Medical School and a member of the Mischer Neuroscience Institute at Memorial Hermann-Texas Medical Center
Eva-Maria Maida, MD, professor and chair, department of neurology, Evangelical Hospital Vienna, Austria
Anthony T. Reder, MD, professor of neurology with a focus in multiple sclerosis, The Committees on Neurobiology and Immunology, University of Chicago Medicine
Study Adds to the Evidence

Marian L. Evatt, MD, MS: "This doesn't surprise me -- because of available data on MS and bone health, I've been trying to keep MS (and other neurology) patients >30 ng/mL for a while. So this study won't change what I do for MS patients. That said, I don't know how well these kinds of findings have gotten out to the general practice community, so this adds to the body of evidence to support general neurologists and primary care physicians paying attention to vitamin D levels in patients with newly diagnosed MS. Compared with many of my neurology colleagues, I am relatively aggressive about keeping 25OH vitamin D levels replete because there's plenty of evidence vitamin D interventions work for bone health and fall prevention (issues MS and other neurology patients commonly have)."

Eva-Maria Maida, MD: "I have been measuring the blood level of vitamin D in MS patients for several years. Nearly no one shows a normal level in Austria. I find this data very interesting. The methods of evaluating and looking for the correlation of vitamin D to MS progression, especially in the early stage of the disease, are convincing."

Robert Fox, MD: "There is a growing collection of data indicating that vitamin D deficiency is associated with poor outcomes in patients with MS. This study adds to that dataset and suggests that vitamin D supplementation may be beneficial in MS, even in patients already taking a standard MS therapy. Perhaps just as importantly, this study confirms previous observations that higher levels of vitamin D beyond normal levels do not confer further benefit. Vitamin D supplementation is not a "more is better" issue, but rather a "correct the deficiency" issue."

Cherie C. Binns, RN: "Many of the neurologists with whom I communicate are now trying to dose supplemental D3 to elevate serum levels to 80 or greater in their patients with MS. However, it's the People with Multiple Sclerosis (PWMS) who seem to be taking this far more seriously than their healthcare team and many admit to taking megadoses (100,000 IU or more weekly)."

J. William Lindsey, MD: "These observations agree with multiple previous studies reporting that low vitamin D levels are associated with more disease activity."

Anthony T. Reder, MD: "It is a correlation, but that is still important."

Case Closed?

Reder: "An alternative explanation for these findings could be healthy people play outside and have higher vitamin D from more sunshine. My recommendation to patients is take 4000 U per day in the winter, or take a winter vacation in a sunny place."

Binns: "Unfortunately, the FDA continues to maintain its low Recommended Daily Allowances (RDA) for D and there do not seem to be clear guidelines as to maximum dose of benefit or dose, when exceeded, that may be problematic. There is far too little information available as to signs of D toxicity or overdose. Please address this topic this year."

Evatt: "Presence and or worsening of several neurologic diseases have recently been associated with low vitamin D levels; the trouble is we don't know if the disease causes the low D or low D contributes to the disease/disease worsening. Evidence is strong that optimal bone health levels should be above 30, but we can't say whether it's better to get vitamin D levels higher ... e.g., above 40 or 60 or 70."

Lindsey: "The outstanding remaining question is whether treatment to increase vitamin D levels will have a clinical benefit in MS. The results from a few small studies of vitamin D supplementation in MS are contradictory. At present, it is reasonable to measure vitamin D levels in MS patients, and give supplements to those with low vitamin D."

Fox: "Confirmation that vitamin D supplementation is indeed helpful in MS still awaits a formal clinical trial."

Friday Feedback is a feature that presents a sampling of opinions solicited by MedPage Today in response to a healthcare issue, clinical controversy, or new finding reported that week.

[agate]

I'm so glad you posted this, Cherie. In 2011 my vitamin D was 56.5, and so the doctor increased my daily supplement from 2,500 IU to 3,000 IU. Early in 2012 it was increased to 5,000 IU daily, and in October 2013 my vitamin D level was 73.1. I believe the doctor would like to see it at 80.

[Cherie]

The whole purpose of the interview that led to the writing of this article was to see which of the topics about MS were important to expand upon on MedPage today during 2014. So it looks like they took us seriously that Vitamin D lack of useful guidelines that are sanctioned by our Neurologists and the FDA...not just naturopathic physicians and some nutritionists...are Clearly needed and there should be more coming on suggested intake and optimal levels as well as side effects of toxicity or too much vitamin D sometime during the coming year.

[Virginia]

Thanks Cherie, glad they are coming out with more information regarding vitamin D. I have been taking it since 2001, but my level the past two times it was checked had gone down from in the 70s to in the 40s range. My Neurologist wants me to get it back up. I noticed you were the only one that mentioned D3. Everyone else just said vitamin D.

[Cherie]

Right after the article showed up online on MedPage Today, there were 8 comments logged and most were people who were argumentative with no science behind their arguments. What we are trying to do is eliminate that and win over the docs to help support us with nutritional supplementation and guidelines that make that supplementation safe. The people who argue just prolong the process and make it less seriously taken. Just like some people here. Trying to make a difference.

[Cherie]

A follow-up article was published today on the VITAL trial which is ongoing to test effect of D supplementation on those with low levels versus a placebo group that would not take more than 800IU daily. Here is the article:


Is There a Flaw in This Large Vitamin D Trial?
Published: Jan 31, 2014 | Updated: Feb 1, 2014

By Todd Neale, Senior Staff Writer, MedPage Today
save|AA

A 57-year-old woman had her vitamin D level checked by her primary care physician based on her mix of risk factors, and the level was found to be low. Her doctor prescribed a high-dose vitamin D supplement of 50,000 IU administered once a week.

Such a scenario is likely not uncommon, but this case is unique because the woman is a participant in the VITAL trial, which is designed to show whether supplementation with vitamin D (2,000 IU per day), fish oil (840 mg of marine omega-3 fatty acids per day), or both can prevent the development of cardiovascular disease and cancer in women 55 and older and men 50 and older. The trial's protocol asks participants to avoid taking out-of-study vitamin D supplements exceeding 800 IU per day.

The woman's low vitamin D level indicates that she likely was receiving the placebo vitamin D capsule, and by starting a high-dose supplement she essentially crossed over into another randomized treatment group. If that occurs frequently among the rest of the participants, it might harm the integrity of the trial and make it difficult to detect differences in outcomes between the groups.

But one of the co-principal investigators of the trial, JoAnn Manson, MD, DrPH, of Brigham and Women's Hospital in Boston, told MedPage Today that it doesn't appear to be a major problem.

She acknowledged that the use of out-of-study medications or supplements is "a very real concern" and a potential limitation in any randomized controlled trial, but said that looks at the data so far have shown that fewer than 5% of the VITAL participants have reported taking a high-dose supplement outside of the protocol, with only small differences between the study groups.

The study organizers' confidence that crossover will not represent a major flaw is bolstered by analyses of both baseline and follow-up blood levels of 25-hydroxyvitamin D. Levels have not changed in the placebo groups, whereas the expected substantial increases have occurred in the participants taking active vitamin D, which comes in the form of vitamin D3 (cholecalciferol).

How Common Is Vitamin D Measurement?

Manson pointed out that routine screening of vitamin D levels is not recommended on a population basis. When the Institute of Medicine (IOM) released its updated recommendations for the daily allowances of vitamin D and calcium in 2010 -- with Manson serving on the panel -- it cast doubt on many of the health benefits attributed to vitamin D and on the need for routine measurement of vitamin D levels.

Other organizations have also failed to endorse routine screening, according to Wanda Filer, MD, MBA, a practicing family physician in York, Pa., and a member of the board of directors of the American Academy of Family Physicians.

That lack of firm guidance on the need for measurement of vitamin D levels has resulted in variability in everyday practice, Filer told MedPage Today, noting that she doesn't typically measure them and doesn't know of any colleagues who do.

"So what we're seeing at this point is more individualized decisions based on a patient's particular risk and preferences," she said. "I would guess that it's all over the board because we don't have evidence-based guidelines yet that are clear on what we should be doing."

Even if VITAL participants have their vitamin D levels checked, however, it's likely that only a small subset will have deficiencies that require high-dose supplements, Manson said.

One reason is that people with certain characteristics tied to vitamin D deficiency -- including osteoporosis, fracture, other bone health issues, or malabsorption conditions -- probably weren't included in the study if they were already taking a high-dose supplement, she said.

Another reason is that the trial participants are allowed to eat whatever foods they want and to take out-of-study vitamin D supplements up to 800 IU per day, as recommended by the IOM.

So having blood levels of vitamin D tested "wouldn't necessarily reveal to the participants whether they're in the placebo group or active treatment group," Manson said. "It is true that if their blood is tested and it turns out that they're deficient that it's more likely they're in the placebo group than the active treatment group, but it does not appear to be happening often."

Addressing the Concern

Besides allowing participants to supplement on their own up to the recommended 800 IU a day, Manson said she and the other study organizers have mitigated concerns about high-dose supplementation mainly through education.

At the start of the study, participants were given information about the uncertainty over the benefits of vitamin D supplementation and the need for a large clinical trial to provide more definitive answers. The need for further study to prove or disprove the purported benefits of vitamin D supplementation is also reinforced through regular newsletters and reminders when the participants fill out their questionnaires.

"We keep them really well informed about what the research is showing and that these questions are still unanswered -- still inconclusive -- and that the VITAL trial is still critically important to answering these clinical and public health questions," Manson said.

And, she pointed out, "We have extremely dedicated participants. They understand the importance of the trial, and they really want to help to make the trial as valid and informative as possible."

Why Is VITAL Important?

Authors of a meta-analysis published earlier this month concluded that, as a whole, the evidence does not support a benefit for vitamin D supplementation in protecting against a range of health outcomes, including cardiovascular disease and cancer. They also concluded that large ongoing trials are unlikely to change that.

But Manson disagreed, saying that VITAL could very well shift the weight of the evidence. "By no means is the question already answered and this issue settled."

She said most of the studies included in the meta-analysis studied low-dose vitamin D supplementation, many tested nondaily dosing, which could have limitations in terms of physiological response, and most were designed to look at effects on bone health, with secondary outcomes that included cancer and cardiovascular disease.

Manson said the dose tested in vital -- 2,000 IU per day -- should balance efficacy and safety and should result in blood levels that have been linked to reductions in cancer and cardiovascular disease without increasing the risks of hypercalcemia.

Also, although the trial -- which includes about 26,000 participants -- is designed to address effects on cancer and cardiovascular disease, it also includes ancillary studies looking at several other outcomes, including diabetes, cognitive function, depression, and infection rates.

Another unique aspect of the VITAL trial, according to Manson, is the inclusion of more than 5,000 black participants; other trials have not had that degree of racial/ethnic diversity.

"We believe very strongly that VITAL will answer many important questions, that it remains highly relevant, and that the results could sway the meta-analysis findings," she said.

The final results are expected early in 2017.

From the American Heart Association:

Omega-3 Fatty Acids and Cardiac Arrhythmias: Prior Studies and Recommendations for Future Research

[agate]

The study has 20,000 participants, according to its Webpage:

Only registered and activated users can see links., Click Here To Register...

[Cherie]

Sometimes I wonder if we will ever get any solid guidance on this. There is even stuff out there that is written indicating that some people normally have low D levels that cannot be brought up with supplementation. Oy....