Vitamin Supplements Associated With Increased Risk for Death.

[Argirios Argiriou]

October 10, 2011.

Medscape Medical News.

In women aged 55 to 69 years, several widely used dietary vitamin and mineral supplements, especially supplemental iron, may be associated with increased risk for death, according to new findings from the Iowa Women's Health Study.

Although many vitamin supplements did not appear to be associated with a higher risk for total mortality, several were, including multivitamins, vitamins B6, and folic acid, as well as minerals iron, magnesium, zinc, and copper.

Jaakko Mursu, PhD, from the Department of Health Sciences, Institute of Public Health and Clinical Nutrition at the University of Eastern Finland in Kuopio, Finland, and colleagues reported their findings in the October 10 issue of the Archives of Internal Medicine.

"Supplements are widely used, and further studies regarding their health effects are needed," Dr. Mursu and colleagues write. "Also, little is known about the long-term effects of multivitamin use and less commonly used supplements, such as iron and other minerals."

The current study sought to evaluate the link between supplement use and total mortality rate, using data from the Iowa Women's Health Study. A total of 38,772 older women were included in the analysis. Women were aged between 55 to 69 years, with an average of 61.6 years at the beginning of the study in 1986. Self-reported data on vitamin supplement use were collected in 1986, 1997, and 2004.

A total of 15,594 deaths were reported through December 31, 2008, representing about 40% of the initial participants. The use of multivitamins overall was associated with 2.4% increased absolute risk for death (hazard ratio, 1.06; 95% confidence interval, 1.02 - 1.10). Self-reported use of dietary supplements increased substantially between 1986 and 2004. In addition, supplement users had a higher educational level, were more physically active, and were more likely to use estrogen replacement therapy.

Vitamin B6, folic acid, iron, magnesium, and zinc were associated with about a 3% to 6% increased risk for death, whereas copper was associated with an 18.0% increased risk for total mortality when compared with corresponding nonuse.

In contrast, use of calcium was inversely related to risk for death (hazard ratio, 0.91; 95% confidence interval, 0.88 - 0.94; absolute risk reduction, 3.8%).

The researchers assessed the findings for iron and calcium in more detailed analyses conducted during shorter periods (10-year, 6-year, and 4-year follow-up) and found results similar to those for the analyses conducted during the entire time.

"In agreement with our hypothesis, most of the supplements studied were not associated with a reduced total mortality rate in older women," Dr. Mursu and colleagues conclude. "In contrast, we found that several commonly used dietary vitamin and mineral supplements, including multivitamins, vitamins B6, and folic acid, as well as minerals iron, magnesium, zinc, and copper, were associated with a higher risk of total mortality."

"Although we cannot rule out benefits of supplements, such as improved quality of life, our study raises a concern regarding their long-term safety," the authors add.

In a related editorial, Goran Bjelakovic, MD, DMSc, and Christian Gluud, MD, DMSc, from the Centre for Clinical Intervention Research, Cochrane Hepato-Biliary Group, Rigshospitalet, Copenhagen University Hospital, Denmark, note that the current study adds "to the growing evidence demonstrating that certain antioxidant supplements, such as vitamin E, vitamin A, and beta-carotene, can be harmful."

"We cannot recommend the use of vitamin and mineral supplements as a preventive measure, at least not in a well-nourished population," they add. "Those supplements do not replace or add to the benefits of eating fruits and vegetables and may cause unwanted health consequences."

This study was partially supported by the National Cancer Institute and the Academy of Finland, the Finnish Cultural Foundation, and the Fulbright program’s Research Grant for a Junior Scholar. One study author is an unpaid member of the Scientific Advisory Board of the California Walnut Commission. The other authors and editorialists have disclosed no relevant financial relationships.

Arch Intern Med. 2011;171:1625-1634.


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και

Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

[Loumakis]

  Βρηκα και παραθετω το αρθρο στο οποιο βασιζονται οσα γραφω σε αλλο Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδοςτου φορουμ για τη χρηση των συμπληρωματων ασβεστιου. Οι υπογραμμισεις μεσα στο αρθρο ειναι δικες μου.

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May 30, 2012 (Heidelberg, Germany [UPDATED])— Authors of another study suggesting that calcium supplements might increase the risk of MI say people who do need more calcium should first and foremost try to up dietary intake of this mineral [1]. Reporting their findings in the June 2012 issue of Heart, Dr Kuanrong Li (German Cancer Research Center, Heidelberg, Germany) and colleagues conclude that calcium supplements "should be taken with caution."

I wouldn't say calcium supplements are harmful, but I wouldn't say they are harmless.

Senior author, nutritionist Dr Sabine Rohrmann (University of Zurich, Switzerland), told heartwire : "I wouldn't say calcium supplements are harmful, but I wouldn't say they are harmless." And while she does not believe there should yet be a warning not to use such supplements, "because more work is needed," doctors should initially try to encourage anyone they feel is deficient in calcium to get what they need from their diet, she urges.

"My advice is that doctors should look carefully at the diet of their patients and try to make adjustments (recommend appropriate foods). If calcium intake is not high enough they should recommend a supplement that has a dose of a maximum of 500 mg. Even better would be a lower dose recommended to be taken twice a day."

And Dr Ian R Reid, who together with his colleague Dr Mark J Bolland (University of Auckland, New Zealand), has penned an accompanying editorial [2], agrees. "The general advice is that patients should not self-prescribe calcium supplements, but should aim to obtain their calcium requirement (700–1000 mg/day) from a balanced diet. This is reflected in the American Society of Bone and Mineral Research recommendations," he told heartwire .

"There are obviously commercial vested interests that resist this advice," Reid adds. "There are also some doctors who remain wedded to the use of calcium supplements, but I believe they need to consider the mounting evidence of adverse effects and balance this against the relatively scanty evidence for efficacy — the use of calcium supplements only appears to reduce fracture risk by about 10%. Thus, the balance of risk vs benefit is negative."

Large Boluses of Calcium Might Provide a "Spike," Driving Atherogenesis

Both Li et al and Reid and Bolland — who have both previously published research on this topic — say they believe the "spike" in calcium concentrations that occurs in the blood following supplementation with large boluses of calcium might be the culprit in the increased MI risk, possibly driving or accelerating atherogenesis.

We should return to seeing calcium as an important component of a balanced diet and not as a low-cost panacea to the universal problem of postmenopausal bone loss.

In contrast, dietary calcium is taken in small amounts spread throughout the day, usually together with fat and protein, so as a result it is absorbed slowly, causing little change in serum calcium levels, they point out.

"Calcium supplements have been widely embraced by doctors and the public, on the grounds that they are a natural and, therefore, safe way of preventing osteoporotic fractures," say Reid and Bolland.

"It is now becoming apparent that taking this micronutrient in one or two daily boluses is not natural, in that it does not reproduce the same metabolic effects as calcium in food. We should return to seeing calcium as an important component of a balanced diet and not as a low-cost panacea to the universal problem of postmenopausal bone loss," they add.

"Evidence Mounting" for a Cardiovascular Effect of Calcium Supplements

Li et al analyzed epidemiological data from one of two German cohorts, Heidelberg, participating in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). There were 23 980 participants aged 35 to 64 years, free of major cardiovascular events at recruitment. A self-administered food frequency questionnaire (FFQ) was used to assess consumption of 148 food items in the 12 months before the date of recruitment. And in a baseline interview and follow-up questionnaires, participants were asked if they had regularly taken vitamin/mineral supplements in the past four weeks.

After an average follow-up time of 11 years, 354 MIs, 260 strokes, and 267 cardiovascular deaths were documented. There was no association between calcium-supplement use and stroke or CV mortality. But users of any supplements containing calcium had a significantly increased risk of MI compared with nonusers of supplements (HR 1.86; 95% CI 1.17–2.96) after multivariate adjustment. This effect was even more pronounced in those who used calcium supplements only, as opposed to combination supplements containing calcium (HR 2.39; 95% CI 1.12–5.12).

While Rohrmann admits the number of events was small, just 20 MIs out of 851 users of any supplement and just seven MIs among the 256 people who took only calcium supplements, compared with 256 MIs among 15 959 nonusers of supplements, she says the findings are still valid "because they are statistically significant."

Also, she says the new results add to those from several other observational studies and meta-analyses over the past few years that have hinted at a link between calcium supplementation and increased risk of MI.

Reid and Bolland agree in their editorial that this is another piece of the puzzle. "Thus, the evidence is steadily mounting for a real cardiovascular effect from the use of calcium supplements, raising the question as to whether this is large enough to abrogate the beneficial effects on fractures."

That doesn't mean that calcium isn't important, but I would urge people to use dietary sources as an alternative to supplements.

Li et al also found that total dietary intake of calcium was somewhat protective against MI, although they did not observe a linear association, as has previously been reported. Compared with those in the lowest quartile of dietary and dairy calcium intake, those in the third quartile had around a 30% reduced risk of MI (HR of 0.69 and 0.68), which was significant. But while those in the highest quartile also had a lower risk of MI than those in the lowest quartile, this difference was not significant, said Rohrmann.

"I'm not an osteoporosis expert," she says, "but people under 50 years of age require about 1000 mg of calcium a day and those over 50 around 1200 mg. And what we do know from the literature is that much more than this doesn't add much [benefit]. Also, there are much more effective things to recommend [for osteoporosis prevention] than calcium, such as exercise and vitamin D. That doesn't mean that calcium isn't important, but I would urge people to use dietary sources as an alternative to supplements. For those who don't tolerate milk products well, broccoli, cabbage, and kale are rich sources of calcium, and there are mineral waters and orange juices available that are fortified with lower doses of calcium than supplements."

Press Coverage "Okay" on the Whole, Says Researcher

Li et al's paper and the accompanying editorial generated much press coverage around the world last week, with a search as of today detailing 199 articles on the topic.

Many went with the headline of calcium supplements almost doubling the risk of heart attack. However, many of these reports clarified in the text that such supplementation should be viewed with caution, rather than going so far as to suggest use should be abandoned. Other news headlines were more circumspect, including the New York Times, which used the headline "Taking calcium may pose heart risks [3].

Some publications were ambiguous in their coverage; the UK Daily Telegraph [4] ran a story entitled, "No need to panic over new calcium heart attack research," which linked to a video interview with Natasha Stewart, a British Heart Foundation (BHF) senior cardiac nurse. She advised those who have been prescribed calcium supplements by their doctor to continue to take them but to consult their physician with any queries. "Don't be worried about what these results say; we need more research," she noted. However, an article on the same study that also ran online on that website [5] yelled, "Calcium pills 'double heart attack risk,' " as did the headline on the story that ran on the front page of the print version of that newspaper. More responsible reports tried to tell both sides of the story [6], aiming to tease out important messages for readers.

On the whole, Rohrmann told heartwire , the press coverage was "okay. We expected that physicians treating osteoporosis patients would be hesitant about our results. As a nutritionist, I would always recommend that people should try to get their nutrients from diet. And I believe that too many rely on supplements to make up for an unbalanced diet. However, for patients, it is important to clarify the situation with their physician."

Reid concurs, advising patients: "If your doctor has prescribed calcium supplements for you, then you should discuss the matter with your doctor before changing your use of supplements. However, if you have started yourself on calcium supplements, then it is likely that these are doing more harm than good, and it would be sensible to discontinue them. However, discussing this with your doctor is also a sensible course to follow."

[Loumakis]

  Αλλο ενα φρεσκο άρθρο στο ιδιο θεμα. Αν μάλιστα ακολουθησετε το link μεσα στο αρθρο, θα διαβασετε κι άλλη ερευνα που πραγματευεται το θεμα της αυξημενης καρδιαγγειακης νοσηροτητας απο χρηση συμπληρωματων ασβεστιου.

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Michael O’Riordan
Feb 04, 2013
 
BETHESDA, Maryland — The debate over the safety of calcium supplements has been muddied with the publication of a new analysis showing that a high intake of supplemental calcium increases the risk of cardiovascular disease (CVD) death in men but not in women [1]. Compared with individuals who took no calcium, men who consumed 1000 mg or more of supplemental calcium per day had a significant 20% increased risk of CVD death, a risk that was driven by a significant 19% increased risk of heart-disease death.

For women, however, there was no association between calcium intake and the risk of death.

"We found a significant interaction by sex," write Dr Qian Xiao (National Cancer Institute, Bethesda, MD) and colleagues in their paper, published online February 4, 2013 in JAMA: Internal Medicine. "Elevated CVD mortality with increasing supplemental calcium intake was observed only in men; however, we cannot rule out the possibility that supplemental calcium intake may be associated with cardiovascular mortality in women." The group calls the difference in risk between men and women "intriguing," adding that further studies are needed to determine whether such differential risks are real.

In an editorial [2], Dr Susanna Larsson (Karolinska Institute, Stockholm, Sweden) said the lack of association between calcium supplementation in women is "perplexing," especially given the results of a reanalysis of the WHI study conducted by Dr Mark Bolland (University of Auckland, New Zealand) and colleagues. In the original WHI analysis on the risks associated with calcium use, investigators found no adverse cardiovascular effects in women taking calcium and vitamin D when compared with those not taking the supplements. However, Bolland et al reexamined the WHI data because 54% of women were already taking calcium and vitamin D by personal choice at the start of the WHI study and were not told to stop if they were randomized to placebo. When the data were reanalyzed, the researchers observed a significant association between calcium intake, as well as vitamin D, with the risk of MI.

New Report From NIH Data

The latest report is taken from an analysis of the National Institutes of Health--AARP Diet and Health Study, a study that included 388 229 men and women 50 to 71 years of age from six US states. Individuals self-reported frequency of food intake and portion size during a one-year period and answered questions about the frequency in which they consumed multivitamins, calcium-containing antacids, or calcium supplements alone.

During a mean follow-up of 12 years, there were 7904 and 3874 CVD deaths in men and women, respectively. Dietary intake of calcium was initially associated with total CVD and heart-disease death in men and women, but the association was no longer significant after adjustment for CVD risk factors. Supplemental calcium intake (1000 mg/day vs no calcium supplementation), on the other hand, increased the risk of CVD death and heart-disease death by 20% and 19%, respectively, in men, but there was no association in women. In an analysis that looked only at those taking calcium supplements and not multivitamins, the risk of CVD death and heart-disease death was 24% and 37% higher in men who took 1000 mg/day of calcium compared with those who took no supplements. Again, no association was observed in women who took calcium supplements alone.

There is currently a debate surrounding the benefits and risks of supplemental calcium in men and women. In 2010, researchers published a meta-analysis in BMJ showing that Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος This increased risk was later confirmed in an analysis of the patients participating in the European Prospective Investigation into Cancer and Nutrition Study (EPIC).

In the editorial, Larsson concludes that the available evidence is suggestive of an adverse cardiovascular effect with excessive use of calcium supplements. Published as part of JAMA: Internal Medicine's series on "less is more" in medicine, the editorial states that more calcium, which is promoted because of its proposed benefits on bone health, does translate into health benefits. The best source of calcium, says Larsson, remains diet and the consumption of calcium-rich foods such as low-fat dairy, beans, and green leafy vegetables.