by Ian Wishart
Facing media questions about why this trial showed promise where the Women’s Health Initiative study showed no benefits from vitamin D, Zurich University’s Dr Frank Ruschitzka told MedPage Today that the US WHI study (referred to earlier in this book) was “seriously underdosed” at 400IU a day, in comparison to 2000IU/day.
The American Journal of Cardiology has also recently published a major study of 10,899 patients enrolled in a University of Kansas cardiovascular programme between 2004 and 2009. It found that people with vitamin D above 30 ng/ml (75 nmol/L) reduced their mortality risk by 61% compared with people whose vitamin D levels were lower.[4]
In fact, people with low vitamin D were an incredible 164% more likely to die during the five year study period.
“Vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival,” wrote the study authors. “Vitamin D supplementation was significantly associated with better survival.”
The study did not just document vitamin D levels on enrolment (baseline levels), it also kept a record of where doctors decided to prescribe vitamin D as part of treatment. In total, 29.7% of the sample had good vitamin D levels, and 70.3% (7,665 patients) had low vitamin D. Of the 10,899 patients, a sub group of 2,423 who were vitamin D deficient at baseline were given supplements by their doctors each week. Some were given 1000IU a day, and others 50,000IU every fortnight, but the overall average across the subgroup was 2,254IU/day. These “deficient” patients given vitamin D supplements reduced their overall mortality risk – they still were 46% more likely to die than patients whose vitamin D levels had been high right from the start, but compare that with the “deficient” patients who were not given vitamin D supplements: their mortality risk increased by a massive 272%!
Vitamin D deficient heart patients were nearly three times more likely to die, and more than two and a quarter times more likely to develop diabetes mellitus, than patients whose vitamin D levels had been high from day one. They were nearly one and a half times more likely to develop high blood pressure.
Whilst this trial was not random or double-blind, because doctors made the choice to intervene and include high dose vitamin D as part of their cardiovascular treatment arsenal, it does clearly show three main sample groups: those who had high vitamin D to begin with; those who had deficient levels of vitamin D to begin with; and finally those who were deficient but whose doctors decided to treat with vitamin D, additional to their other heart medication.
Vitamin D expert Dr John Cannell once threw down a challenge to his medical colleagues:
“Should practitioners routinely screen and aggressively treat vitamin D deficiency in patients with serious or potentially fatal illnesses, or should such patients [be left to] combat their disease vitamin D deficient?”[5]
It looks like the University of Kansas answered that challenge, and in doing so proved his point.
In the final analysis, those with the highest vitamin D levels from day one had the best survival rates. Those who were deficient but later given supplements had the biggest improvement in their survival rates. Those who relied on traditional heart drugs without treating their vitamin D deficiency were overwhelmingly the most likely to die within five years.
The study sends another clear signal that getting the public’s vitamin D levels up is crucial, if people are to have the best chance of surviving major health scares. As you have seen so far in this book, people whose vitamin D levels are good before they are diagnosed with major disease are the real winners.
“Because vitamin D deficiency is widespread,” note the study authors, “strategies directed at population-based supplementation programmes could prove beneficial.”
Like the European team before them, the American researchers put previous “inconclusive” study results down to bad design of the studies: “It is possible that the lack of benefit in these studies resulted from sub-optimal levels of vitamin D supplementation…400 to 800IU…which might not be adequate to ensure optimal serum levels.”
A more “appropriate” daily dose for the public is “1000 to 2000IU”, they suggest.
“Our findings are consistent with [previous] studies, suggesting poorer patient outcomes for patients with vitamin D deficiency. In addition, our data further extended these findings by demonstrating better survival with vitamin D supplementation.
“The benefits of vitamin D supplementation on survival were significant for those patients with a documented deficiency. This benefit was independent of the concomitant use of other cardioprotective drugs such as aspirin or statins.”
The comment about statins raises another important finding. Another study has found statins play a huge role in boosting the power of vitamin D in the body, leading one researcher[6] to suggest there is a possibility “that some – or all – of the mortality reduction of statins may be mediated through increases in vitamin D levels.”
Did heart patients with high vitamin D survive longer because the vitamin made the statins more effective?
A stunning new twist in this emerged in 2009. A group of Turkish researchers studying the effects of statins at a hospital in Ankara were stunned at an unexpected side-effect of their study. A group of mostly Muslim women were taking part in an eight week trial of rosuvastatin therapy. When their blood was tested, the 25(OH)D levels had risen from an average of 14 ng/ml to 36.3 ng/ml over the eight weeks. These people were not on vitamin D supplements, it was winter, and most of them wore full garb. The kind of vitamin D increase they enjoyed is not normally seen without massive vitamin D supplementation or lots of summer sun.
Staggered, the researchers organised a second, randomized controlled trial of a similar population sample at the same hospital, in the same months of a different year. They threw in a different statin, fluvastatin, in order to see whether the effect was common or specific to the rosuvastatin.
At the end of eight weeks, the rosuvastatin group had, again, increased their blood serum vitamin D from 11.8 ng/ml to 35.2 ng/ml. There was no significant rise in the fluvastatin group.
“We propose that some statins may be increasing the absorption of vitamin D by stimulating the expressions of cholesterol transporters,” wrote the study authors in 2012. “This effect, which was shown with atorvastatin, can be studied with rosuvastatin, and may open up a horizon to explain the link between statins and vitamin D.”[7]
From that study, it certainly appears that some statins are using vitamin D to weave magic in the body.
One way that vitamin D doesn’t appear to affect the heart is through influence on the arteries. A University of Wisconsin team speculated that the vitamin reduced arterial “stiffness”, and gave 114 women a cookie each day. Half the sample had biscuits laced with 2500IU of vitamin D, and the other half just ordinary biscuits. After four months, they found no impact on arterial stiffness or blood pressure.[8]
That’s not always the way the cookie crumbles, however. A Danish study of 112 patients – half given 3000IU of vitamin D and half a placebo – found that over 20 weeks in winter, systolic and diastolic blood pressure measurements lowered significantly, by 7 and 2 points respectively.[9]
To put that in perspective for the ordinary reader, the newspaper headlines summed it up: “As good as drugs”.
“The reduction in systolic blood pressure was quite significant – this is what powerful drugs do in trials,” noted Glasgow University’s Professor Anna Dominiczak, the vice-president of the European Hypertension Society. “This is an initial study, so it needs to be confirmed, but it is potentially interesting as part of an overall strategy for managing hypertension in patients with low levels of vitamin D.”[10]
The Koreans, meanwhile, have had more success linking arterial health with vitamin D in elderly patients. They didn’t use cookies, so technically it wasn’t a trial. They did however measure the arterial wall thickness of 1000 men and women over the age of 65 and selected randomly for a cohort study.
They found those wi
th the lowest vitamin D levels (below 15 ng/ml) were three times more likely to have significant coronary artery stenosis than people with vitamin D levels higher than 30 ng/ml.[11]
Congestive heart disease, heart attacks and blood pressure are not the only areas where the sunshine vitamin is showing promise. It’s being hailed as protective against fatal strokes as well.
A study of nearly 8,000 Americans found whites were more than twice as likely to suffer a fatal stroke if they have low vitamin D levels, defined in the study as less than 15 ng/ml, compared to a benchmark level of 31 ng/ml. Interestingly, the same effect was not found in African-Americans, even though they have proportionately more fatal strokes than Americans of European ancestry.
“Vitamin D deficiency was associated with an increased risk of stroke death in whites but not in blacks. Although blacks had a higher rate of fatal stroke compared with whites, the low 25(OH)D levels in blacks were unrelated to stroke incidence. Therefore 25(OH)D levels did not explain this excess risk.”[12]
In Hawaii, the complete medical records of 8,000 Japanese-American men who’d visited the doctor in the mid 1960s as part of the Honolulu Heart Programme were examined to see how they’d fared over time. After ruling out those with pre-existing stroke conditions, the sample of just under 7,400 was studied for health outcomes up to and including the 1999 year – a 34 year timespan for those who’d first been enrolled in the study in 1965.[13]
Of the 7,385 men, 960 went on to suffer strokes later in life. Based on the detailed dietary analysis provided during regular check-ups as part of the Heart Programme, researchers were able to calculate dietary intake of vitamin D.
Men with the lowest dietary intake of vitamin D were found to have had a 27% increased risk of ischemic stroke.
For women, the story might be even better.
The Harvard School of Public Health has recently published the findings of a meta-analysis of current research, where results from similar studies are pooled and examined to provide a larger dataset. Based on the comparison of 464 women who had experienced ischemic stroke, and a similar control group who hadn’t, researchers found women with the highest levels of vitamin D reduced their risk of ischemic stroke by 49%.[14]
Further drilling down into a group of datasets, the Harvard team found women in the highest vitamin D group enjoyed up to 59% reduction in stroke risk. “Maintaining adequate vitamin D status may lower the risk of stroke in women,” the study concluded.
In the long run, given that it’s usually either heart disease or cancer that takes you in the end, the studies on longevity tell the biggest story.
When data from the blood samples of 3,400 Americans was analysed in the Third National Health And Nutrition Examination Survey (NHANES III), researchers found those with the lowest vitamin D levels were three times more likely to die of heart disease, and two and a half times more likely to die of any cause.[15] That’s not a measure of absolute mortality, of course, because clearly we all die eventually, but cancer and heart disease are taking people early so if you can put it off for a while you reap the rewards.
More significantly from a community point of view, less disease means lower healthcare costs, and more productive time per capita.
A recently released study by the University of Washington further shatters the myth that there’s no proof of a link between low vitamin D and tragedy. The research team wanted to find out how much vitamin D needed to be circulating in the blood to lower risk of serious events, and to do that they tested blood samples of 1,621 Caucasian adults.[16]
The samples had been in storage since the Cardiovascular Health Study of the early 1990s, and one of the great things about blood banks is that researchers can go back decades now in some cases and test samples. This particular test cohort had been aged 65 and over when their blood was first stored.
Having obtained their 25(OH)D blood serum readings, the research team then pulled out the medical files for each patient to discover what had happened to them. More to the point, they wanted to know how soon after the blood test the patient had suffered a “major event”.
Of the 1,621 tested, within the next 11 years just over a thousand had indeed experienced an “event”. The files revealed 335 developed cancer. A hundred and thirty-seven fractured a hip, 186 had heart attacks. Three hundred and sixty had died.
Study leader Ian de Boer told journalists that the likelihood of these “events” rose the lower the patient’s vitamin D level was. There were strong seasonal signals, reflecting the low vitamin D generation during winter and spring, and the high vitamin D levels of summer and autumn.
Significantly, the danger point was when blood serum levels of vitamin D fell below 20 ng/ml (50 nmol/L), which is lower than the 30 ng/ml threshold most vitamin D experts now recognise.
What’s important to remember is that nearly every vitamin D study has identified a sliding scale where the benefits become more pronounced the closer the patient gets to 40 or 50 ng/ml (100 to 125 nmol/L). But sliding scales mean a trend can be identified early, at 20 ng/ml for example, whilst allowing that benefits would likely be greater and the trend even stronger if blood levels were even higher. Statistical probability curves allow for the fact that while some people will start seeing benefits at lower levels, a greater number will join that trend further up the scale.
One of the things to emerge from ongoing research, however, is that simply popping a vitamin D pill will not necessarily bring results. Case in point: a study of 107,811 people in the US found those with vitamin D levels higher than 30 ng/ml had a “statistically significant” lower risk with their lipid levels [fats in the blood]. This much we know. Researchers then wondered whether giving vitamin deficient patients a D supplement to improve their vitamin D blood levels would have a flow on effect and improve their lipids.
They tried. It didn’t.
A sub-sample of 8,592 patients were given supplements, which did indeed raise their 25(OH)D serum levels, but which did not have any major impact over the 26 week study on LDL cholesterol or triglycerides. There was a small impact on HDL cholesterol for these patients.
“The seemingly conflicting findings of the cross-sectional analysis and longitudinal analysis suggest that while vitamin D deficiency is associated with an unfavorable lipid profile, correcting a deficiency through therapeutic vitamin D supplementation may have limited value in improving lipids,” study leader Manish Ponda told journalists.[17]
In this case, he suspects, the vitamin D, rather than causing improved lipid profiles, may simply reflect better lipid profiles in those patients.
For participants in one recent study, however, vitamin D has been good news. Three thousand patients with heart failure were measured against a 47,000 control group. Those with the highest vitamin D levels, in both the sample and the controls, had the lowest risk of dying. And on the subject of popping pills, heart failure patients taking pills reduced their future mortality risk by 32%.[18]
That’s got to be worth something to someone, somewhere.
[1]http://www.cdc.gov/heartdisease/facts.htm
[2] “Vitamin D levels predict all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome: the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study,” Thomas et al, Diabetes Care. 2012 May;35(5):1158-64. Epub 2012 Mar 7.
[3] “Vitamin D may help in HF,” MedPage Today, 22 May 2012
[4] “Vitamin D deficiency and supplementation and relation to cardiovascular health,” Vacek et al, American Journal of Cardiology, 2012; 109:359-363, http://www.trackyourplaque.com/userdata/3038/file/Vitamin%20D%20and%20CVD%20-%20AJC%20Feb%202012.pdf
[5]http://0101.nccdn.net/1_5/3a0/1e8/00e/Cannell-Vitamin-D-study.pdf
[6] “Use of vitamin D in clinical practice,” Cannell & Hollis, Alternative Medicine Review, March 2008, Vol 13(1), http://0101.nccdn.net/1_5/3a0/1e8/00e/Cannell-Vitamin-D-study.pdf
[7] “Statins and vitamin D: a hot topic that will be discussed for a long time,” Yav
uz & Ertugrul, Dermato-Endocrinology, Vol 4, Issue 1, Jan/Feb/Mar 2012
[8] “A Prospective Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Cardiovascular Disease Risk,” Gepner et al, PLoS One, 7(5): e36617. doi:10.1371/journal.pone.0036617
[9] “Vitamin D Supplementation During Winter Months Reduces Central Blood Pressure In Patients With Hypertension,” Larsen et al, 22nd European Meeting on Hypertension and Cardiovascular Protection. April 201
[10] “Vitamin D supplements ‘as good as drugs’ at reducing BP,” ZeeNews India, 26 April 2012
[11] “Vitamin D inadequacy is associated with significant coronary artery stenosis in a community based elderly cohort etc,” Lim et al, Journal of Endocrinology & Metabolism, January 1, 2012, Vol. 97(1):169-178
[12] “25-Hydroxyvitamin D deficiency is associated with fatal stroke among whites but not blacks: The NHANES-III linked mortality files,” Michos et al, Nutrition, Volume 28, Issue 4, April 2012, Pages 367–371
[13] “Low Dietary Vitamin D Predicts 34-Year Incident Stroke,” Kojima et al, Stroke, first published online before print, May 2012, doi: 10.1161/STROKEAHA.112.651752
[14] “25-Hydroxyvitamin D Levels and the Risk of Stroke: A Prospective Study and Meta-analysis,” Qi Sun et al, Stroke, Published online before print March 22, 2012, doi: 10.1161/STROKEAHA.111.636910
[15] “Prospective Study of Serum 25-Hydroxyvitamin D Level, Cardiovascular Disease Mortality, and All-Cause Mortality in Older U.S. Adults,” Adit A. Ginde MD, MPH,Robert Scragg MBBS, PhD, Robert S. Schwartz MD, Carlos A. Camargo Jr. MD, DrPH, Journal of the American Geriatrics Society, Volume 57, Issue 9, pages 1595–1603, September 2009, http://onlinelibrary.wiley.com/doi/10.1111/j.1532-5415.2009.02359.x/full
[16] “Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: a cohort study,” de Boer et al, Annals of Internal Medicine, 2012 May 1;156(9):627-34