News Keeps Getting Worse for Vitamins

November 20, 2008, 12:45 pm 


The best efforts of the scientific community to prove the health benefits of vitamins keep falling short. 

Consumers don’t want to give up their vitamins. (Tony Cenicola/The New York Times)

This week, researchers reported the disappointing results from a large clinical trial of almost 15,000 male doctors taking vitamins E and C for a decade. The study showed no meaningful effect on cancer rates.

Another recent study found no benefit of vitamins E and C for heart disease.

In October, a major trial studying whether vitamin E and selenium could lower a man’s risk for prostate cancer ended amidst worries that the treatments may do more harm than good.

And recently, doctors at Memorial Sloan-Kettering Cancer Center in New York warned that vitamin C seems to protect not just healthy cells but cancer cells, too.

Everyone needs vitamins, which are critical for the body. But for most people, the micronutrients we get from foods usually are adequate to prevent vitamin deficiency, which is rare in the United States. That said, some extra vitamins have proven benefits, such as vitamin B12 supplements for the elderly and folic acid for women of child-bearing age. And calcium and vitamin D in women over 65 appear to protect bone health.

But many people gobble down large doses of vitamins believing that they boost the body’s ability to mop up damaging free radicals that lead to cancer and heart disease. In addition to the more recent research, several reports in recent years have challenged the notion that megadoses of vitamins are good for you.

A Johns Hopkins School of Medicine review of 19 vitamin E clinical trials of more than 135,000 people showed high doses of vitamin E (greater than 400 IUs) increased a person’s risk for dying during the study period by 4 percent. Taking vitamin E with other vitamins and minerals resulted in a 6 percent higher risk of dying. Another study of daily vitamin E showed vitamin E takers had a 13 percent higher risk for heart failure.

The Journal of Clinical Oncology published a study of 540 patients with head and neck cancer who were being treated with radiation therapy. Vitamin E reduced side effects, but cancer recurrence rates among the vitamin users were higher, although the increase didn’t reach statistical significance.

A 1994 Finland study of smokers taking 20 milligrams a day of beta carotene showed an 18 percent higher incidence of lung cancer among beta carotene users. In 1996, a study called Caret looked at beta carotene and vitamin A use among smokers and workers exposed to asbestos, but the study was stopped when the vitamin users showed a 28 percent higher risk for lung cancer and a 26 percent higher risk of dying from heart disease.

A 2002 Harvard study of more than 72,000 nurses showed that those who consumed high levels of vitamin A from foods, multivitamins and supplements had a 48 percent higher risk for hip fractures than nurses who had the lowest intake of vitamin A. 

The Cochrane Database of Systematic Reviews looked at vitamin C studies for treating colds. Among more than two dozen studies, there was no overall benefit for preventing colds, although the vitamin was linked with a 50 percent reduction in colds among people who engaged in extreme activities, such as marathon runners, skiers and soldiers, who were exposed to significant cold or physical stress. The data also suggested vitamin C use was linked with less severe and slightly shorter colds. 

In October 2004, Copenhagen researchers reviewed seven randomized trials of beta carotene, selenium and vitamins A, C and E (alone or in combination) in colon, esophageal, gastric, pancreatic and liver cancer. The antioxidant users had a 6 percent higher death rate than placebo users. 

Two studies presented to the American College of Cardiology in 2006 showed that vitamin B doesn’t prevent heart attacks, leading The New England Journal of Medicine to say that the consistency of the results “leads to the unequivocal conclusion” that the vitamins don’t help patients with established vascular disease.

The British Medical Journal looked at multivitamin use among elderly people for a year but found no difference in infection rates or visits to doctors.

Despite a lack of evidence that vitamins actually work, consumers appear largely unwilling to give them up. Many readers of the Well blog say the problem is not the vitamin but poorly designed studies that use the wrong type of vitamin, setting the vitamin up to fail. Industry groups such as the Council for Responsible Nutrition also say the research isn’t well designed to detect benefits in healthy vitamin users.

Lack of Exercise Explains Depression-Heart Link

November 26, 2008, 2:43 pm

By Tara Parker-Pope

For years cardiologists and mental health experts have known that depression raises risk for heart attack by 50 percent or more. 

But what hasn’t been clear is why depressed people have more heart problems. Does depression cause some biological change that increases risk? Does the inflammatory process that leads to heart disease also trigger depression? 

The answer may be far simpler. A new study suggests that people who are depressed are simply less likely to exercise, a finding that explains their dramatically higher risk for heart problems.

Researchers, led by doctors from the Veterans Affairs Medical Center in San Francisco, recruited 1,017 participants with heart disease to track their health and lifestyle habits. As they expected, those patients who had symptoms of depression fared worse. About 10 percent of depressed heart patients had additional heart problems, during the study, compared with 6.7 percent of the other patients. After controlling for other illnesses and the severity of heart disease, the finding translates to a 31 percent higher risk of heart problems among the depressed people, according to the study published this week in the Journal of the American Medical Association.

But once the researchers factored in the effect of exercise, the difference in risk among depressed people disappeared. In the same study, patients who didn’t exercise, whether or not they were depressed, had a 44 percent higher risk of heart problems, after controlling for a variety of factors including medication adherence, smoking and other illnesses.

The findings are important because some earlier studies have suggested a link between antidepressant use and lower heart risk. The explanation may be that patients who take antidepressants start to feel better and take care of themselves, adopting healthy behaviors including exercise. In a study of nearly 2,500 heart-attack patients, published in the Journal of the American Medical Association in June 2003, behavioral therapy to treat depression didn’t change survival rates compared with patients who received regular care. But among about 20 percent of patients in the study who ended up on antidepressants, the risk of dying or suffering a second nonfatal heart attack was 42 percent lower. Another study, called Sadheart (which stands for Sertraline Antidepressant Heart Attack Randomized Trial) showed the death rate from heart-related problems was 20 percent lower among patients taking the drug, although the data weren’t statistically significant.

The research suggests that doctors treating patients for depression should also talk to them about their lifestyle habits, and encourage them to exercise. The findings, say the researchers, suggest that the heart problems associated with depression “could potentially be preventable.”

The evidence that health behaviors fully explain the link between depression and heart disease in this study is convincing, says Dr. Mary A. Whooley, professor of medicine, epidemiology and biostatistics at the University of California, San Francisco. However, she notes the study is limited to older men with stable coronary disease, and as a result, more study is needed of women and other patients with heart disease.

It remains an open question whether the study findings will change the way doctors counsel their patients. “The clinical practice question is a challenging one,” says Dr. Whooley. “It’s easy for us to tell patients to exercise, take their medicines, and refrain from smoking, but actually changing health behaviors is very difficult.”

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Scientists Find Clues to Aging in a Red Wine Ingredient’s Role in Activating a Protein

November 27, 2008

By NICHOLAS WADE

A new insight into the reason for aging has been gained by scientists trying to understand how resveratrol, a minor ingredient of red wine, improves the health and lifespan of laboratory mice. They believe that the integrity of chromosomes is compromised as people age, and that resveratrol works by activating a protein known as sirtuin that restores the chromosomes to health.

The finding, published online Wednesday in the journal Cell, is from a group led by David Sinclair of the Harvard Medical School. It is part of a growing effort by biologists to understand the sirtuins and other powerful agents that control the settings on the living cell’s metabolism, like its handling of fats and response to insulin. 

Researchers are just beginning to figure out how these agents work and how to manipulate them, hoping that they can develop drugs to enhance resistance to disease and to retard aging.

Sirtris, a company Dr. Sinclair helped found, has developed a number of chemicals that mimic resveratrol and are potentially more suitable as drugs since they activate sirtuin at much lower doses than resveratrol. This month, one of these chemicals was reported in the journal Cell Metabolism to protect mice on fatty diets from getting obese and to enhance their endurance in treadmills, just as resveratrol does.

Though the sirtuin field holds considerable promise, the dust has far from settled. Resveratrol is a powerful agent with many different effects, only some of which are exerted through sirtuin. So drugs that activate sirtuin may not be as splendid a tonic for people as resveratrol certainly seems to be for mice. 

The new finding concerns maintenance of the chromosomes, the giant molecules of DNA that make up the genome. 

Each cell has six feet of DNA packed into its nucleus, carrying the 20,000 or so genetic instructions needed to operate the human body. Each cell must provide instant access to the handful of these genes needed by its cell type, but also keep the rest firmly switched off to avoid chaos. 

Sirtuin’s normal role is to help gag all the genes that a cell needs to keep suppressed. It does so by keeping the chromatin, the stuff that wraps around the DNA, packed so tightly that the cell cannot get access to the underlying genes.

But sirtuin has another critical role, one that is triggered by emergencies like a break in both DNA strands of a chromosome. After a double strand break, sirtuin rushes to the site to help knit the two parts of the chromosome back together. But in this salvage operation, it leaves its post, and the genes it was repressing are liable to come back into action, causing mayhem. 

This, Dr. Sinclair and his colleagues suggest, may be a fundamental cause of aging in mice and probably people, too. 

The gene-gagging role of sirtuin was discovered in the 1980s by biologists studying yeast, a standard laboratory organism. Dr. Sinclair and Leonard Guarente of the Massachusetts Institute of Technology found in 1997 that sirtuin could also repair a certain kind of genomic damage in yeast, and in doing so extended the yeast cell’s lifespan. But this particular kind of damage does not occur in mammalian cells, raising the puzzle of why extra sirtuin should be good for them.

Dr. Sinclair’s new report, if verified, resolves this problem by showing that sirtuin has retained its genomic repair role in higher organisms but that the repair is focused on a different kind of genomic damage — that of breaks in a chromosome.

These experiments “elegantly demonstrate” that sirtuin works in much the same way in mammals as in yeast, Dr. Jan Vijg of the Albert Einstein College of Medicine wrote in a commentary in Cell. The question now is whether sirtuin is a pro-longevity factor in mammals, he said in an e-mail message. 

Ronald Evans, a biologist at the Salk Institute, said the new report was provocative but did not prove the case that the relocation of sirtuin was a cause of aging. Tests with mice genetically engineered to lack the sirtuin gene could show if the mice suffered from premature aging, as Dr. Sinclair’s idea would predict.

Dr. Sinclair said he agreed that the case for sirtuin’s role in aging had not been proved. “We are careful not to say this is the cause of aging, but based on everything we know it’s not a bad hypothesis,” he said. 

It would be nice to test aging in mice that lack the sirtuin gene, as Dr. Evans proposed, but they die too young, Dr. Sinclair said.

Dr. Sinclair has been taking large daily doses of resveratrol since he and others discovered five years ago that it activated sirtuin. “I’m still taking it, and I feel great,” he said, “but it’s too early to say if I’m young for my age.” 

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Study Suggests Some Cancers May Go Away

November 25, 2008
 
By GINA KOLATA

Cancer researchers have known for years that it was possible in rare cases for some cancers to go away on their own. There were occasional instances of melanomas and kidney cancers that just vanished. And neuroblastoma, a very rare childhood tumor, can go away without treatment.

But these were mostly seen as oddities — an unusual pediatric cancer that might not bear on common cancers of adults, a smattering of case reports of spontaneous cures. And since almost every cancer that is detected is treated, it seemed impossible even to ask what would happen if cancers were left alone.

Now, though, researchers say they have found a situation in Norway that has let them ask that question about breast cancer. And their new study, to be published Tuesday in The Archives of Internal Medicine, suggests that even invasive cancers may sometimes go away without treatment and in larger numbers than anyone ever believed.

At the moment, the finding has no practical applications because no one knows whether a detected cancer will disappear or continue to spread or kill. 

And some experts remain unconvinced. 

“Their simplification of a complicated issue is both overreaching and alarming,” said Robert A. Smith, director of breast cancer screening at the American Cancer Society.

But others, including Robert M. Kaplan, the chairman of the department of health services at the School of Public Health at the University of California, Los Angeles, are persuaded by the analysis. The implications are potentially enormous, Dr. Kaplan said. 

If the results are replicated, he said, it could eventually be possible for some women to opt for so-called watchful waiting, monitoring a tumor in their breast to see whether it grows. “People have never thought that way about breast cancer,” he added.

Dr. Kaplan and his colleague, Dr. Franz Porzsolt, an oncologist at the University of Ulm, said in an editorial that accompanied the study, “If the spontaneous remission hypothesis is credible, it should cause a major re-evaluation in the approach to breast cancer research and treatment.”

The study was conducted by Dr. H. Gilbert Welch, a researcher at the VA Outcomes Group in White River Junction, Vt., and Dartmouth Medical School; Dr. Per-Henrik Zahl of the Norwegian Institute of Public Health; and Dr. Jan Maehlen of Ulleval University Hospital in Oslo. It compared two groups of women ages 50 to 64 in two consecutive six-year periods. 

One group of 109,784 women was followed from 1992 to 1997. Mammography screening in Norway was initiated in 1996. In 1996 and 1997, all were offered mammograms, and nearly every woman accepted.

The second group of 119,472 women was followed from 1996 to 2001. All were offered regular mammograms, and nearly all accepted. 

It might be expected that the two groups would have roughly the same number of breast cancers, either detected at the end or found along the way. Instead, the researchers report, the women who had regular routine screenings had 22 percent more cancers. For every 100,000 women who were screened regularly, 1,909 were diagnosed with invasive breast cancer over six years, compared with 1,564 women who did not have regular screening.

There are other explanations, but researchers say that they are less likely than the conclusion that the tumors disappeared.

The most likely explanation, Dr. Welch said, is that “there are some women who had cancer at one point and who later don’t have that cancer.” 

The finding does not mean that mammograms caused breast cancer. Nor does it bear on whether women should continue to have mammograms, since so little is known about the progress of most cancers.

Mammograms save lives, Dr. Smith said. Even though they can have a downside — most notably the risk that a woman might have a biopsy to check on an abnormality that turns out not to be cancer — “the balance of benefits and harms is still considerably in favor of screening for breast cancer,” he said.

But Dr. Suzanne W. Fletcher, an emerita professor of ambulatory care and prevention at Harvard Medical School, said that it was also important for women and doctors to understand the entire picture of cancer screening. The new finding, she said, was “part of the picture.” 

“The issue is the unintended consequences that can come with our screening,” Dr. Fletcher said, meaning biopsies for lumps that were not cancers or, it now appears, sometimes treating a cancer that might not have needed treatment. “In general we tend to underplay them.” 

Dr. Welch said the cancers in question had broken through the milk ducts, where most breast cancers begin, and invaded the breast. Such cancers are not microscopic, often are palpable, and are bigger and look more ominous than those confined to milk ducts, so-called ductal carcinoma in situ, or DCIS, Dr. Welch said. Doctors surgically remove invasive cancers and, depending on the circumstances, may also treat women with radiation, chemotherapy or both.

The study’s design was not perfect, but researchers say the ideal study is not feasible. It would entail screening women, randomly assigning them to have their screen-detected cancers treated or not, and following them to see how many untreated cancers went away on their own.

But, they said, they were astonished by the results.

“I think everybody is surprised by this finding,” Dr. Kaplan said. He and Dr. Porzsolt spent a weekend reading and re-reading the paper.

“Our initial reaction was, ‘This is pretty weird,’ ” Dr. Kaplan said. “But the more we looked at it, the more we were persuaded.”

Dr. Barnett Kramer, director of the Office of Disease Prevention at the National Institutes of Health, had a similar reaction. “People who are familiar with the broad range of behaviors of a variety of cancers know spontaneous regression is possible,” he said. “But what is shocking is that it can occur so frequently.”

Although the researchers cannot completely rule out other explanations, Dr. Kramer said, “they do a good job of showing they are not highly likely.” 

A leading alternative explanation for the results is that the women having regular scans used hormone therapy for menopause and the other women did not. But the researchers calculated that hormone use could account for no more than 3 percent of the effect. 

Maybe mammography was more sensitive in the second six-year period, able to pick up more tumors. But, the authors report, mammography’s sensitivity did not appear to have changed. 

Or perhaps the screened women had a higher cancer risk to begin with. But, the investigators say, the groups were remarkably similar in their risk factors. 

Dr. Smith, however, said the study was flawed and the interpretation incorrect. Among other things, he said, one round of screening in the first group of women would never find all the cancers that regular screening had found in the second group. The reason, he said, is that mammography is not perfect, and cancers that are missed on one round of screening will be detected on another.

But Dr. Welch said that he and his colleagues considered that possibility, too. And, he said, their analysis found subsequent mammograms could not make up the difference.

Dr. Kaplan is already thinking of how to replicate the result. One possibility, he said, is to do the same sort of study in Mexico, where mammography screening is now being introduced.

Donald A. Berry, chairman of the department of biostatistics at M. D. Anderson Cancer Center in Houston, said the study increased his worries about screenings that find cancers earlier and earlier. Unless there is some understanding of the natural history of the cancers that are found — which are dangerous and which are not — the result can easily be more treatment of cancers that would not cause harm if left untreated, he said. 

“There may be some benefit to very early detection, but the costs will be huge — and I don’t mean monetary costs,” Dr. Berry said. “It’s possible that we all have cells that are cancerous and that grow a bit before being dumped by the body. ‘Hell bent for leather’ early detection research will lead to finding some of them. What will be the consequence? Prophylactic removal of organs in the masses? It’s really scary.”

But Dr. Laura Esserman, professor of surgery and radiology at the University of California, San Francisco, sees a real opportunity to figure out why some cancers go away.

“I am a breast cancer surgeon; I run a breast cancer program,” she said. “I treat women every day, and I promise you it’s a problem. Every time you tell a person they have cancer, their whole life runs before their eyes.

“What if I could say, ‘It’s not a real cancer, it will go away, don’t worry about it,’ ” she added. “That’s such a different message. Imagine how you would feel.”

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