The Annals of Internal Medicine published two important reviews this month. In the first review, Dr. Anastassios Pittas and colleagues from Tufts University reviewed 106 articles and combined the 32 quality studies, a meta-analysis, looking at "cardiometabolic" outcomes such as diabetes, hypertension, and cardiovascular disease. Their conclusion: "Lower vitamin D status seems to be associated with increased risk for hypertension and cardiovascular disease, but we do not yet know whether vitamin D supplements will affect clinical outcomes." Read on. Pittas AG, et al. Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med. 2010 Mar 2;152(5):307–14.
The second Annals of Internal Medicine review, by Dr. Lu Wang and colleagues at Harvard, looked at studies of vitamin D supplementation and found two randomized placebo-controlled trials to combine. Dozens of different types of studies have looked at vitamin D and cardiovascular outcomes. The latitude studies are clear, the closer you live to the equator, the less cardiovascular disease. The dietary studies are mixed, because vitamin D is not contained in the diet, at least not in significant amounts. The epidemiological studies are clear. Wang L, Manson JE, Song Y, Sesso HD. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med. 2010 Mar 2;152(5):315–23.
Dr. Wang concluded, "To date, evidence from prospective observational studies and randomized controlled trials suggests that vitamin D supplementation at moderate to high doses may have beneficial effects on reducing the risk for cardiovascular disease."
About the same time that the two above meta-analyses were published, Dr. Brent Muhlestein, director of cardiovascular research at the Intermountain Medical Center Heart Institute in Murray, Utah, presented a paper at this year's American College of Cardiology's annual scientific session in Atlanta.
170% greater risk of heart attack with lowest vitamin D levels
The Utah group studied 31,000 patients over one year and found those with the lowest vitamin D levels had a 170% greater risk of heart attacks than those with the highest levels. Those with the lowest vitamin D levels also had an 80% greater risk of death, a 54% higher risk of diabetes, a 40% higher risk of coronary artery disease, a 72% higher risk of kidney failure and a 26% higher risk of depression. Mittelstaedt M. Vitamin D may slash risk of heart-disease risk. Globe and Mail. 2010.03.15.
In order to prove that it was the vitamin D, and not a confounder (confusing fact), Dr. Muhlestein took 9,400 patients and gave them vitamin D, finding a 30% reduced risk of death. He did not think it was ethical to withhold vitamin D in a placebo control group, in order to do a randomized controlled trial.
This Utah study is unique in that these remarkable results were obtained in only one year—not the usual ten years—so the initial 25(OH)D blood test probably represented an accurate picture of vitamin D health. Dr. Muhlestein is not waiting for further studies, saying, "My recommendation to all my patients, and certainly I did it for myself, is to get your vitamin D checked and if you're very low or even a little bit low, start taking supplementation and then get it rechecked."
My recommendation is if you have cardiovascular disease—and even if you don't—take at least 5,000 IU of vitamin D3 (cholecalciferol) per day and be sure to have your blood tested periodically for 25-hydroxyvitamin D. (You may not need any vitamin D in the summer.) Since you already have a fatal disease, and cardiovascular disease is a fatal disease, maintain your 25(OH)D levels in the high normal range, 70–100 ng/mL (175–250 nmol/L), not the mid-normal range, 50–70 ng/mL (125–175 nmol/L), you want if you are healthy.
Remember to obtain a copy of your 25-hydroxyvitamin D 25(OH)D blood test report to guarantee your doctor ordered the correct test. Too many doctors are still ordering the wrong test, a 1,25-dihydroxyvitamin D, thinking they are checking for vitamin D deficiency, when they are doing nothing but falsely reassuring you and wasting your money. Get an actual copy of your lab report and be sure it says 25-hydroxyvitamin D or 25(OH)D.
Also, remember that vitamin D needs numerous co-factors to work in the body. The ones you have to worry about are magnesium, zinc, boron and vitamin K because many people are deficient in these four nutrients. You can get these by simply eating a handful of seeds and nuts every day, while being careful to eat green leafy vegetables once a day.
At least one professor is having none of this. Dr. Lenore Buckley of Virginia Commonwealth University thinks vitamin D may do cardiovascular harm, even at low doses. She also thinks vitamin D supplementation should be racial, with Whites getting more than Blacks. Whites enough to obtain blood levels of 20–30 ng/mL (50–75 nmol/L), and Blacks enough to obtain levels of only 15 ng/mL (37.5 nmol/L). Jancin B. Skepticism Mounts on Need for Vitamin D Supplementation. Family Practice News Volume 40, Issue 3, Pages 1–2 (15 February 2010).
Dr. Buckley quotes two papers only. One—on calcium supplementation alone—was a randomized controlled trial while the second paper on vitamin D levels was cross-sectional, meaning it was a picture in time.
In the first paper, Dr. Mark Bolland and colleagues of the University of Auckland gave 1,000 mg of calcium citrate over five years to 700 women in the treatment group who were already getting 800 mg/day of calcium in their diet and compared the treatment group to placebo controls who were getting 800 mg/day of calcium from their diet alone. So the study compared 1800 mg/day to 800 mg/day. Bolland MJ, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008 Feb 2;336(7638):262–6.
They found 1800 mg/day of calcium may well do harm, with apparent increased rates of cardiovascular disease. However, they excluded anyone with frank vitamin D deficiency, exactly the patients who may benefit the most from extra calcium. (The extra calcium may decrease renal metabolic clearance of the little vitamin D such patients have.) The real problem came when they tried to verify the reported cardiovascular events with the national database in New Zealand; their findings were then of marginal significance (P=.05).
The authors noted that previous studies of total calcium intake (both diet and supplements), such as the Boston Nurses Study or the Iowa Women's Health Study have both found that women with the highest total calcium intake had either the lowest death rates or the lowest cardiovascular disease. That said, it seems it is better to get your calcium from your diet and not from a pill, always a good rule.
This is a good time to say that vitamin D sufficient adults need about 1,000 mg of calcium a day from all sources, including diet and supplements and even that recommendation is based largely on studying vitamin D deficient people. In my opinion, no vitamin D sufficient person should be taking 1,000 mg of calcium/day in supplements, unless they get zero from their diet, pretty difficult to do. Dietary Supplement Fact Sheet: Calcium. National Institutes of Health.
No one knows how much calcium supplements vitamin D sufficient older people need to take, but it is undoubtedly less than the 1200 mg/day the NIH recommends, as someone with a 25(OH)D level of 32 ng/mL (80 nmol/L) absorbs a lot more calcium than does someone with a level of 10 ng/mL (25 nmol/L). If you want an answer to the question of vitamin D/calcium interactions, the person to ask is Professor Robert Heaney and I know where you can ask him. Dr. Heaney is speaking to an all-day Grassroots Health seminar on vitamin D in San Diego on Friday, April 9, 2010. His talk is "Interactions: vitamin D, calcium and safety." Please tell me what he says.
Getting back to Dr. Lenore Buckley of Virginia Commonwealth University, she based her racial recommendations (Blacks should be given less, not more, than Whites) entirely on a single cross-sectional study by Dr. Barry Freedman and colleagues at Wake Forest University (In the spirit of full disclosure, Wake Forest University is my old nemesis as I am a UNC grad). Freedman BI, et al. Vitamin d, adiposity, and calcified atherosclerotic plaque in african-americans. J Clin Endocrinol Metab. 2010 Mar;95(3):1076–83.
Dr. Freedman and his Wake forest colleagues measured vitamin D levels and plaque (the build-up in your arteries) on 340 diabetic, obese (BMI 35) African Americans and found higher vitamin D levels were associated with more plaque build up in the arteries.
I feel sorry for Dr. Freedman at Wake Forest but not for Dr. Buckley, the physician who decided that one Wake Forest study was enough to keep her Black patients vitamin D deficient. Dr. Buckley, in considering only one vitamin D study, has decided to treat her African American patients different then her White patients. She apparently gave no consideration to the thousands of vitamin D studies in other diseases, and no consideration to the other calcification and plaque study, this one a much larger and better-controlled (prospective cohort controlled study), published 8 months ago. de Boer IH, et al. 25-hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. J Am Soc Nephrol. 2009 Aug;20(8):1805–12.
Dr. Ian de Boer and colleagues at the University of Washington studied 1370 patients for three years finding coronary calcifications are indeed associated with vitamin D deficiency, concluding that "each 10-ng/ml lower 25(OH)D concentrations was associated with a 23% increased risk" for developing calcification. And, in direct contradiction to the Wake forest study, Dr. de Boer found the 201 vitamin D deficient Black patients were more likely, not less likely, to develop such plaque than the Whites were.
Getting back to the Wake Forest study, why did their group get such different results than the researchers at the University of Washington? When I looked at Figure 1 in the Wake Forest study, the 25(OH)D measurements were all over the place, including about 30 Black patients with 25(OH)D levels greater than 40 ng/mL (100 nmol/L) and one with a level of 90 ng/mL (225 nmol/L). The way the Wake Forest study was designed, a few bogusly elevated 25(OH)D levels will invalidate all their results.
One only has to look at the Wake Forest group's methods section. Unlike the Washington study, which used the gold standard to measure vitamin D (DiaSorin RIA), Wake Forest decided to send their samples out to, you guessed it, Quest Diagnostics.
For new readers, this newsletter was the first to report Quest's 25(OH)D results were suspicious, in a July 2008 newsletter. The New York Times picked up on the story six months later. Pollack A. Quest Acknowledges Errors in Vitamin D Tests. The New York Times. 2009.01.07
Since the New York Times story, Robert Michel, editor of the Dark Report had 24 Aliquot samples (small amounts of the same blood drawn at the same time) sent to labs all over the country for a vitamin D test. Quest's results varied from 36 ng/mL (90 nmol/L) to 66 ng/mL (165 nmol/L), on the same blood sample. The good news was the methods used by LabCorp all clustered around 44 ng/mL (110 nmol/L).
After the New York Times story, Quest assured me they have fixed their test. But I don't know how Quest can run a million 25(OH)D tests every year on complicated mass spec machines that require meticulous sample preparation and highly trained operators, while requests for additional tests mount next to the operators. (In the spirit of full disclosure, I used to be a paid consultant for DiaSorin but have decided not to exercise my contract.)
Quest Diagnostics says they have fixed their diagnostic vitamin D testing. If they haven't, look at the consequences. Researchers at Wake Forest relied on Quest and Dr. Buckley relied on Wake Forest and is now treating her Black patients different than her White patients, keeping her Black patients vitamin D deficient. Some of Dr. Buckley's Black patients will die from vitamin D deficiency.
The first thing Wake Forest needs to do is take the same frozen samples they sent to Quest Diagnostics and send them to LabCorp, which uses a reliable DiaSorin testing method. I predict many of Wake forest's high 25(OH)D levels are, in reality, much lower, invalidating their findings.
You can help. Email Dr. Freedman and ask him to retest his samples using a DiaSorin method (email@example.com.)
Second, call around and find out which lab in your area uses Quest. At the same time, find out which lab in your area uses LabCorp or call Life Extension Foundation at 1-800-544-4440 (Life Extension uses LabCorp). Then have your 25(OH)D drawn on the same day. This will cost you, in total, several hundred dollars. (If you can't afford it, the Vitamin D Council will pay $100.000 of your total costs, once you send me copies of both Quest's and LabCorp's reports and your receipts.)
We need about 30 duplicate blood samples. We need copies of both Quest's and LabCorp's actual 25(OH)D lab reports, drawn on the same day. I will publish the findings in this newsletter, no matter what they show. The lives of thousands of African Americans may be at stake.
And yes, I have thought about what vitamin D could do for health care, and yes, I have thought about what it could do for health care costs, and yes, I have thought about what it could do to lower the accelerated death rate among Blacks, and yes, I have written newsletters about it, and yes, I have contacted the Obama administration and no, no one has answered my pleas.
John Jacob Cannell MD