Vitamin-mineral supplement fails to reduce BP

Vitamin-mineral supplement fails to reduce BP

By Caroline Price

09 January 2008

J Hum Hypertens 2008; 121: 43-49

MedWire News: Study findings have failed to find any effect of consuming milk supplemented with additional potassium, calcium, magnesium, selenium, and vitamins C and E on blood pressure (BP).

The results "confirm the discrepancy between dietary intervention studies showing reasonable BP lowering effects and intervention studies with a combination of minerals or vitamins showing no effect," say the authors.

This highlights the need to explore potential BP lowering effects of vitamins and minerals consumed in "natural matrices" in the diet rather than as supplements, they add.

In a research letter to the Journal of Human Hypertension, P de Leeuw (University Hospital Maastricht, The Netherlands) and colleagues explain that dietary intervention studies have shown impressive reductions in BP, probably due in part to the mineral and vitamin components of such diets. Yet interventions with combinations of either minerals or vitamins have provided mixed results.

In the current study, the researchers tested the BP lowering effect of a combination of minerals and vitamins. They randomly assigned 124 adults with untreated mild hypertension to take a supplemented skimmed milk drink or a placebo drink daily for 8 weeks.

The milk was supplemented with 446 mg calcium, 100 mg magnesium, 40 µg selenium, 180 mg vitamin C, 30 mg vitamin E and tocopherol equivalents, and either 1500 mg (high-K) or 750 mg (low-K) potassium per serving.

At the end of the study, office systolic BP had decreased by 4.6, 4.5, and 5.1 mmHg from baseline in the low-K supplement, high-K supplement, and placebo groups, respectively. The differences in BP reduction among groups were nonsignificant.

Reductions in office diastolic BP, pulse pressure, 24-hour systolic BP, 24-hour diastolic BP, and heart rate over the 8 weeks did not differ among the three groups either.

The results "are in contrast with many studies addressing interventions with the individual components," the authors write. They note that the doses of the individual minerals and vitamins may have been too low, and that combinations of vitamins and minerals may counter the effects of the individual components.

Meanwhile, the contrast with findings of dietary interventions may reflect the reduction of components with negative effects by diet replacement, the increased presence of as-yet unidentified components in dietary interventions, or altered bioavailability of nutrients when provided in a dairy matrix.

"Future studies should focus on assessing the effect of subsets of combinations of minerals and vitamins in natural matrices to get a better understanding of the possible antagonistic action between some of these ingredients," de Leeuw and co-authors conclude.

Journal

Low Vitamin D Plus Hypertension May Worsen Cardiovascular Risks

Low Vitamin D Plus Hypertension May Worsen Cardiovascular Risks

BOSTON, Jan. 7 -- Moderate vitamin D deficiency nearly doubles the risk of myocardial infarction, stroke, and heart failure over a mean of 5.4 years in patients with high blood pressure, researchers here said.

The finding emerged from the Framingham Heart Study, which now includes the adult offspring of the study's original participants.

The researchers focused on those offspring who had participated in their sixth or seventh quadrennial exams from 1996 to 2001, Thomas J. Wang, M.D., of Massachusetts General Hospital, and colleagues reported online in Circulation: Journal of the American Heart Association. Participants with known cardiovascular or kidney disease at that time were excluded.

Compared with patients with higher vitamin D levels, the adjusted rate of first cardiovascular events was 1.62 times higher (95% CI: 1.11 to 2.36, P=0.01) in those with levels of 25-dihydroxyvitamin D below 15 ng/mL.

This effect was evident in participants with hypertension (hazard ratio: 2.13, 95% CI: 1.30 to 3.48) but not in those without hypertension (HR: 1.04, 95% CI: 0.55 to 1.96).

Up to half of middle-age and older adults in the U.S. have low levels of circulating vitamin D, Dr. Wang and colleagues said. However, they stopped short of calling for routine vitamin D testing or for supplementation in patients with known deficiencies.

"What hasn't been proven yet is that vitamin D deficiency actually causes increased risk of cardiovascular disease," Dr. Wang said. "This would require a large randomized trial to show whether correcting the vitamin D deficiency would result in a reduction in cardiovascular risk."

Earlier research had suggested links between lower vitamin D levels and other factors related to heart disease, such as coronary artery calcification and blood pressure.

Dr. Wang and colleagues wanted to know whether vitamin D levels in the Framingham offspring from the 1996-2001 exams were correlated with the rate of first cardiovascular events occurring later. In addition to MI, ischemic stroke, and heart failure, these events included angina, coronary insufficiency episodes, transient ischemic attacks, and claudication.

The researchers also adjusted for such factors as age, gender, smoking and diabetes status, weight, and cholesterol levels in their statistical analyses. Mean follow-up after the exams was 5.4 years.

Patients with very low vitamin D levels -- less than 10 ng/mL -- along with hypertension were at substantially greater risk of cardiovascular events.

Dr. Wang and colleagues found a hazard ratio of 3.19 (95% CI: 1.70 to 5.99), adjusted for age and gender, for these individuals relative to hypertensive participants with vitamin D levels of 15 ng/mL or greater. When also adjusted for clinical parameters including C-reactive protein levels, the hazard ratio for these participants was 2.43 (95% CI: 1.23 to 4.80).

The study did not investigate potential mechanisms. However, Dr. Wang and colleagues pointed to other research indicating that vitamin D deficiency and hypertension independently affect vascular remodeling and cardiac hypertrophy.

Vitamin D deficiency may also directly promote development of hypertension, they suggested.
As a result, they wrote, "hypertension could magnify the adverse effects of vitamin D deficiency on the cardiovascular system."

Dr. Wang and colleagues could not rule out the possibility that vitamin D deficiency is not causative. "Unmeasured characteristics associated with vitamin D deficiency … could account for the increased cardiovascular risk," they acknowledged.

They pointed out that "an alternate explanation for the present findings is that vitamin D deficiency is a marker of chronic nonspecific illness rather than a direct contributor to disease pathogenesis."

They also noted that all the participants in their study were Caucasian, indicating that the results may not apply to non-whites who have a higher prevalence of vitamin D deficiency.
Dr. Wang said that until future studies confirm a causal link between vitamin D deficiency and cardiovascular risk, patients -- especially the elderly, who are at particular risk for low vitamin D levels -- should simply ensure their diets satisfy the recommended daily allowance of vitamin D.

Do Diet, Folic Acid, and Vitamins Matter?

Title

Do Diet, Folic Acid, and Vitamins Matter?: What Did We Learn From The Women's Health Initiative, The Women's Health Study, The Women's Antioxidant and Folic Acid Cardiovascular Study, and Other Clinical Trials?[Review]

Author
Wenger, Nanette K. MD

Institution
From the Department of Medicine, Division of Cardiology, Emory University School of Medicine; the Division of Cardiology, Grady Memorial Hospital; and the Emory Heart and Vascular Center, Atlanta, Georgia.

Source
Cardiology in Review. 15(6):288-290, November/December 2007.

Abstract
Data from recent randomized clinical trials have contributed substantially to our understanding of appropriate interventions for coronary heart disease in women. Addressed in this monograph are issues of diet, folic acid, and antioxidant vitamins. Importantly, these randomized clinical trials have helped to clarify conflicting information from observational data, and to aid clinicians and their women patients in making appropriate choices of coronary and cardiovascular preventive therapy.

The 2007 update to the AHA women's prevention guidelines concludes that antioxidant vitamin supplements (eg, vitamins C, E, and beta carotene) should not be used for the primary or secondary prevention of CVD, a class III recommendation.

Antioxidants Don’t Lower Heart Risk

Antioxidants Don’t Lower Heart Risk

Study Examines Vitamins C, E, Beta-Carotene for Preventing Heart Attack, Stroke

By Salynn Boyles WebMD Medical News


Aug. 13, 2007 -- Vitamins C, E, and beta-carotene are not effective for preventing heart attacks, strokes, or related deaths, according to one of the longest studies ever to examine the cardiovascular impact of antioxidant supplements.


The study included more than 8,000 women at high risk for cardiovascular disease who took the vitamin supplements, either alone or in combination, for close to a decade.


During this time no evidence emerged of a benefit for antioxidant supplementation.


The findings are consistent with other major studies showing antioxidants and other nutritional supplements to be ineffective for the prevention of heart disease and strokes, cardiovascular nutrition expert Alice Lichtenstein, DSc, tells WebMD.


Some of these studies even found specific supplements to be harmful, although the latest study did not.


“Right now we are all being very cautious about dietary supplements,” says Lichtenstein, who directs the cardiovascular nutrition lab at Boston’s Tufts University. “These supplements don’t seem to have clear advantages in people who aren’t deficient, and there is a concern that overdoing them may have adverse consequences.”


Antioxidants and the Heart


Oxidative damage at the cellular level is thought to play an important role in heart and vascular disease by promoting inflammation. The thinking has been that antioxidants like vitamin C, E, and beta-carotene could protect against cardiovascular disease by reducing oxidative stress.


Researcher Nancy R. Cook, ScD, and colleagues from Harvard Medical School and Brigham and Women’s Hospital in Boston tested the theory in their study, published in the latest issue of the journal Archives of Internal Medicine.


A total of 8,171 women were recruited who had had either a heart attack or stroke or who had at least three cardiac risk factors such as having high cholesterol, diabetes, or high blood pressure, being a current smoker, and being obese.


The average age of the women at recruitment was 60, and they were followed for an average of 9.4 years.


During this time, the women took either vitamin C, vitamin E, beta-carotene, a combination of the antioxidants, or placebo. There were 274 heart attacks, 298 strokes, 889 bypass surgeries or angioplasties, and 395 deaths due to cardiovascular causes.


None of the vitamins, either alone or in combination, were found to significantly impact any of these cardiovascular outcomes.


Women who took vitamins C and E did have slightly fewer strokes, but it was not clear if the association was real or a function of the study design.


“Overall we found no benefit on the primary combined end point for any of the antioxidant agents tested, alone or in combination. We also found no evidence for harm,” Cook and colleagues wrote in the Aug. 13/27 issue of the Archives of Internal Medicine.


“While additional research into combinations of agents, particularly for stroke, may be of interest, widespread use of these individual agents for cardiovascular protection does not appear warranted.”


Healthy Diet Lowers Risk


While the intervention studies examining antioxidant supplements for protection against heart attacks and strokes have proven disappointing, study after study has also shown that eating a nutrient-rich diet can lower risk, says Lichtenstein, who is a spokeswoman for the American Heart Association.


“Isolating individual components of a healthy diet hasn’t worked, but it does appear that a diet that includes plenty of fruits, vegetables, and whole grains is protective,” she says.


Study co-author JoAnn Manson, MD, who is chief of preventive medicine at Brigham and Women’s Hospital, agrees.


“This research underscores the importance of focusing on proven methods for preventing cardiovascular disease, including physical activity, healthy diet, controlling high blood pressure and high cholesterol, maintaining healthy weight, and avoiding tobacco,” she says in a news release.



SOURCES:

Cook, N.R. Archives of Internal Medicine, Aug. 13/27, 2007; vol 167: pp 1610-1618. Nancy R. Cook, ScD, associate biostatistician, Brigham and Women’s Hospital; associate professor of medicine, Harvard Medical School, Boston. Alice Lichtenstein, DSc, senior scientist and director, Cardiovascular Nutrition Lab, Tufts University, Boston; spokeswoman, American Heart Association. JoAnn Manson, MD, chief, preventive medicine, Brigham and Women’s Hospital, Boston

Antioxidant vitamins increase mortality

Qual o impacto que um trabalho como esse poderá trazer à prática médica brasileira?

Antioxidant vitamins increase mortality

http://www.theheart.org/article/773375.do

Copenhagen, Denmark - The largest analysis of data on antioxidant vitamins ever conducted has shown that beta-carotene, vitamin A, and vitamin E probably increase mortality [1]. Two other antioxidant substances—vitamin C and selenium—had no effect on mortality.

The meta-analysis of 68 randomized trials with a total of 232 606 participants, published in the February 28, 2007 issue of the Journal of the American Medical Association, was conducted by a group led by Dr Goran Bjelakovic (Copenhagen University Hospital, Denmark).

Coauthor Dr Christian Gluud (Copenhagen University Hospital) commented to heartwire: "This is the most comprehensive collection of data on antioxidant vitamins ever conducted, and we have shown that on the whole these agents have no benefit. Indeed, vitamin A, vitamin E, and beta-carotene are associated with an increase in mortality at the doses studied. Vitamin A and beta-carotene seem to have a dose-related effect, with mortality increasing as doses increase, whereas vitamin E does not appear to have a dose-related effect, with all doses associated with increased mortality."

Jury still out on vitamin C and selenium

Gluud added that the jury is still out on vitamin C and selenium. "Vitamin C does not appear to be detrimental, but it is not beneficial either, and all the trials of selenium together suggest a small benefit, but when only the well-conducted trials are included, there appears to be neither benefit nor harm.

"Our data show that antioxidant vitamins should not be taken in an effort to prevent illness. People should instead eat a balanced diet and take regular exercise," he said.

In the paper, the authors note that many people are taking antioxidant supplements in the belief that they improve health and prevent diseases. Many primary- or secondary-prevention trials of antioxidant supplements have been conducted to investigate the prevention of several diseases—mainly cardiovascular disease and cancer—but results have generally not been positive, with some trials showing increases in mortality.

To find out more, they conducted the current systematic review to analyze the effects of antioxidant supplements on all-cause mortality of adults included in primary- and secondary-prevention trials. They included all primary- and secondary-prevention published trials in adults randomized to receive beta-carotene, vitamin A, vitamin C, vitamin E, or selenium vs placebo or no intervention.

Results showed that when all trials of antioxidant supplements were pooled together, there was no significant effect on mortality, but when the 47 trials said to have a low risk of bias (in a total of 180 938 participants) were analyzed alone, the antioxidant supplements as a whole significantly increased mortality, and beta-carotene, vitamin A, and vitamin E were all associated with increased mortality when given alone or in combination. Vitamin C and selenium had no significant effect on mortality.

The researchers note that more than two thirds of the included trials fell into the category of those with a low risk of bias, which they say highlights the validity of their results. "Antioxidant supplements not only seem to be one of the most researched topics in the world, they also seem to be one of the most adequately researched clinical questions," they say.

They point out that a large number of unpublished trials on supplements may exist, but as unpublished trials are more likely to have been either neutral or negative than to have shown beneficial effects, this suggests their estimate of a 5% increase in mortality is likely to be conservative.

Substantial public-health consequences

Noting that 10% to 20% of the adult population (80 million-160 million people) in North America and Europe may consume these supplements, Bjelakovic et al say the public-health consequences may be substantial.

Speculating on possible mechanisms, they point out that although oxidative stress has a hypothesized role in the pathogenesis of many chronic diseases, it may be the consequence of pathological conditions, and that eliminating free radicals may interfere with some essential defensive mechanisms.

In an interview with heartwire, Gluud also suggested that the antioxidant vitamins could actually also have pro-oxidant effects. "We don't know exactly how they are doing harm, but rather than preventing cardiovascular disease and cancer, they actually seem to be accelerating these conditions."

Lessons learned

He said these observations were "a huge disappointment" but added that at least it has been discovered. "We must see the positives in this. The question has been thoroughly addressed and we now know the answer—these agents are harmful. The companies selling these antioxidant vitamins have been able to dodge the issue for a long time, saying that any negative data have not been comprehensive. They cannot do this any longer. There are lessons to be learned here— for example, the importance of conducting trials with these agents and publishing the results."

Gluud added that food supplements should be regulated in the same way as medical products. "The governments of the world now have the responsibility to inform people of these results. They have been too slow in the past in requesting that health supplements be properly evaluated before allowing these products to be added to foods. People have been buying these supplements and foods advertised as having these supplements added under the impression that they are good for them, when in actual fact they are harmful. Any potential health supplements should not be allowed to be added to foods unless they have been shown to be beneficial or at least proven not to be harmful."