Yesterday, I set out to write about the latest findings of a government-funded research study that concluded that in older women, several commonly used dietary vitamin and mineral supplements may do more harm than good; even, in some cases, causing a small increase in the risk of death.

Death?  Really?  From Vitamin B6 and multivitamins?

There must be more to this than was being reported, so I decided to go to the source, The Archives of Internal Medicine, where the findings were published,  and read the study myself.   Here’s what I learned.

First: The Facts

Researchers assessed the use of 15 vitamin and mineral supplements (including multivitamins, Vitamins B6, C and D, folic acid, magnesium, Iron and Calcium) in relation to total mortality in nearly 39,000 women in the Iowa Women’s Health Study. The participants were just under 62 years of age when they began the study in 1986.  Supplement use, which was self-reported via a health questionnaire three times over 19 years, was widespread among these women and increased over the years.

In yesterday’s news reports about this study, we learned that the researchers found a small increase in the risk of death among older women who took dietary supplements compared with those who didn’t.  However, what wasn’t reported in many news accounts was the fact that the women in the study who took supplements tended to be healthier, more physically active and had lower rates of diabetes and high blood pressure, with a lower BMI and waist-to-hip ratio than women who didn’t. Their diets were healthier too.  Nevertheless, the women who took an iron supplement or multi-vitamin showed an increased risk for early death. Those who self-reported that they took Vitamin B complex, Calcium and Vitamins C, D, E had significantly lower risk of death compared with non use.

Over the 19 year period that these 39,000 women’s histories were tracked, about 16,000 – or 40 percent – died. Yet, the research did not explore whether supplements contributed to their deaths.  That’s because they didn’t know why the women were taking the supplements in the first place.

Conclusions 

So, can we conclude that vitamin and mineral supplements are a waste of money and even harmful. Does this study prove that the “try it, it can’t hurt,” attitude is old thinking?

The study’s first author, a researcher in nutrition at the University of Minnesota’s School of Public Health said, “this paper contributes to the growing amount of studies showing no benefits for supplement use in the prevention of chronic diseases. Millions of Americans take these, but there just don’t appear to be a lot of benefits.”

Bonnie Jortberg, a registered dietitian and senior instructor at the University of Colorado School of Medicine in Denver, said the research “bolstered arguments against using supplements other than in cases of known nutritional deficiency.”

Dr. David Heber, director of the UCLA Center for Human Nutrition, speaking to the  L.A. Times said, “I wouldn’t recommend anyone change what they’re doing based on this study. It’s very hard to conclude cause and effect.”

The Alliance for Natural Health, a non-profit organization self-described as “committed to protecting access to integrative medicine,” called this study “junk science.”  “To say the data is “unreliable” would be a generous description,” they wrote on their website yesterday. “In the study, all of the relative risks were so low as to be statistically insigificant. This kind of “data” has no place in a valid scientific study.”

IMHO, the findings of this study didn’t convince me that I should stop taking supplements. On the contrary, I feel better knowing that at least two of them, Vitamin D and Calcium, won’t likely be the cause of my death. Magnesium, which was among the 15 supplements assessed,  has helped reduce the frequency of leg cramps that wake me up at night.  So with a clear benefit for me, why should I stop taking this?

As with all studies, it makes you think about our own behaviors.  With so much money being spent on supplements — $11.8 Billion just last year, according to the Nutrition Business Journal –  maybe we should heed the advice of those scientists and medical professionals who say we should get all the nutrients we need from food whenever possible and only use supplements to correct diagnosed deficiencies.

What’s your take on this? Do you plan to cut back on the number of supplements you’re taking?

Related stories you might be interested in:

Use of Vitamins, Supplements Up
Vitamin Studies Spell Confusion for Patients 

So why are the new dosing recommendations so conservative if the benefits of vitamin D have proven to be so substantial?  The IOM said they based their recommendations on the levels needed to maintain strong bones alone since they did not believe that there was enough evidence to prove that low levels of vitamin D causes diseases. As they wrote in the recommendations: “Past cases such as hormone replacement therapy…remind us that some therapies that seemed to show promise for treating or preventing  health problem ultimately did not work out and even caused harm. That is why it is appropriate to approach emerging evidence about an intervention cautiously, but with an open mind.”

Some of the leading Vitamin D researchers expressed their disagreement with the IOM’s recommendations on the website of Grassroots Health, an organization of leading vitamin D scientists that educate healthcare practitioners and consumers about the importance of vitamin D.  They have stated that 40-75 percent of the world’s population is vitamin D deficient. Its founder and director,  Carole Baggerly, wrote that the IOM panel “set aside many studies that did not fit their narrow definition of evidence.”

Cedric F. Garland, MD, a professor of the University of California San Diego School of Medicine, said that “pending testing, the minimum intake for all men, women and children one year and older should be 2,000 IU/day and the upper limit should be 8,000 IU/day.  Moreover, adults should be tested every two years, preferably in March.

Dr. Carlos Camargo, an epidemiologist and Associate Professor of Medicine at Harvard Medical School says that public health problems like vitamin D deficiency shouldn’t be solved with a one-size fits all approach. Rather, people should get their blood level of 25(OH)D tested and tailor the vitamin D dose and frequency for their needs.  ”Vitamin D is a hormone and just like any other hormone, good health requries a level that is not too low but also not to high. This optimal level may differ for different people…but my guess is the optimal level for most people is a 25(OH)D level around 40ng/ml.”

So where does that leave us? As with hormone therapy, there is a lot of research that the public can read first-hand. And there is also a simple blood test to determine if you are vitamin D deficient. Based on those results and armed with information, you will be in a better position to discuss your options with your physician and take a vitamin D supplement in a dose that is right for you.

The website of GrassrootsHealth is a good place to start your research. It offers an enormous amount of information and video presentations by leading vitamin D researchers and scientists.  You can also order a home test kit on their website or through the Canary Club.

While waiting for my physician, I saw a new wall display containing a collection of ten brochures on a wide range of health topics, including menopause. Branded as “Healthy Advice,” it acknowledged “the generous sponsors who support this educational program.” I was already skeptical but curious.  I picked up the booklet on Menopause and turned to the back page to confirm who I thought the sponsor would be. Pfizer. Yes! I knew it.  They are the makers of the hormone therapy replacement drug, Prempro, which contains estrogens from horse urine and Progestin, a synthetic form of Progesterone.  Inside, under “latest findings,” the authors caution us against using soy to ease menopause symptoms because “the benefits are still questionable.”  They also caution us against trying a vitamin, supplement or other natural product to help with symptoms since “some of these may make things worse.” The brochure also advises patients on hormone therapy to “take the smallest dose that works for you for the shortest amount of time. This helps lessen the risks.”

Those hormone replacement therapy risks, barely alluded to in the sponsored brochure, were explained in greater detail today in front-page news stories about the results of an 8-year follow-up study of nearly 13,000 women who participated in the federally financed Women’s Health Initiative (WHI). That study was halted in 2002, three years ahead of schedule, when researchers saw that the hormones were causing an increased risk of breast cancer, strokes and blood clots in the lungs.  This is the first report from the WHI that includes death rates from breast cancer related to hormone use.

Researchers concluded that Prempro, already linked to higher breast cancer and heart disease rates, was tied to increase mortality from tumors. In other words, women who took hormones after menopause and developed breast cancer were more likely to die from the disease than breast cancer patients who had never taken hormones. The study’s lead researcher, Dr. Rowan T. Chlebowski, an oncologist who treats breast cancer patients at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, pointed out that today’s assumption that women can safely take hormones for four or five years for menopause symptoms, like hot flashes and night sweats, is no longer valid.  As quoted in the New York Times today, he added, “I don’t think you can say that now. I know some people have to take it because they can’t function, but the message now is that you really should try to stop after a year or two.” He told the reporter, Denise Grady, that it is not known whether there is any length of time for which these hormones can be taken without increasing breast cancer risk.

In an editorial accompanying an article about the study’s results in The Journal of the American Medical Association, Dr. Peter Bach, a physician at Memorial Sloan Kettering Cancer Center in New York wrote; “If you care about preventing this disease and keeping women from suffering and dying from it, then it’s hard to look at these drugs and not have serious concerns about them being used, even for what are intended to be relatively short periods of time.”

Back to my doctor’s examination room and the educational brochures from Healthy Advice, a company that offers drug makers a way to deliver patient education and brand messages in more than 21,000 primary care physicians’ exam rooms. They claim on their website that the brochures result in “a better-educated” and “more compliant” patient with an average new prescription lift of 10.24%.  So, the pharmaceutical companies are now able to leap-frog the traditional sales pitch to doctors and bring their messages directly into the examination room where doctors can be their ambassadors in creating awareness and demand for their products.  It’s a reminder that we should always investigate the source of the “advice” we are receiving, even if it is from our own physician’s office.

Of all the studies I’ve read about, this one hit home the most:  it wasn’t funded by a company trying to sell us something (which in my book makes it more credible) and it addressed the issue of belly fat, which, as a result of the natural redistribution of body fat during the menopause transition, puts mid-life w0men at risk for a number of diseases.  How do you know how much body fat is too much?  Measure your waistline.  If it’s more than 35 inches, you’ve got a problem.

To clarify, we’re talking about visceral or intra-abdominal fat that lies deep within the abdomen.  As explained  in the current Harvard Women’s Health Watch newsletter;

“when it comes to body fat, location counts. The fat lying deep within the abdomen is more perilous than the fat you can pinch with your fingers.  Visceral or intra-abdominal fat fills the spaces surrounding the liver intestines and other organs.  It’s also stored in the omentum, an apron-like flap of tissue that lies under the belly muscles and blankets the intestines. The omentum gets harder and thicker as it fills with fat.  Although visceral fat makes up only a small proportion of body fat, it’s a key player in a variety of health problems. That’s because researchers now believe that the fat cell is an endocrine organ, secreting hormones and other molecules that have far-reaching effects on other tissues …and researchers have identified a host of chemicals that link visceral fat to a surprisingly wide variety of diseases.”

Experts at Harvard Medical School say that visceral fat responds efficiently to diet and exercise, particularly aerobic activity and strength training, which can help to keep you lean by building muscle.  I highly recommend Joan Pagano’s book, Strength Training for Women, to help you get started on a program you can stick with.  Joan contributed a blogpost about “Strength Training, The New Star of Anti-Aging Strategies,” which is worth revisiting in light of this new research.  I also have written about other books that offer advice on diet and exercise that can help keep body fat from landing in the wrong place.

The FDA’s Center for Veterinary Medicine also has received two reports of dogs being exposed to Evamist and they cautioned that small dogs are at greater risk for estrogen sensitivity than larger ones.  One veterinarian I spoke with says that transference of topical hormones to pets is not as unusual as you think.  The Veterinary Information Network, a subscription web-based resource for veterinarians, compiled nearly twenty cases from around the nation of pets presenting with signs of estrogen excess, which according to a recently-published VIN article,  is manifested by labial enlargement in females and gynecomastia in males.  These symptoms go away when estrogen exposure to the pet is stopped.

The FDA statement includes helpful information for Evamist users.  If you want to report an adverse effect to Evamist, you can contact the FDA’s Medwatch program at 800-FDA-1088 or online on the Medwatch website .

Update (10/28/10) – See Tara Parker-Pope’s “Well” column in today’s New York Times for more on this topic:  ”When Hormone Creams Expose Others to Risks”

ABC News reported  earlier this week that the U.S. Food and Drug Administration has been aware of reports of spontaneous fractures, but did not inform the public or doctors who prescribe bisphosphonates of the possible side effect.  An FDA spokesman explained to ABC News that they didn’t think it was necessary at this time.  However, today, the FDA announced  that it will indeed investigate the possibility of a link between long-term use of osteoporosis drugs and thigh bone fractures though, “at this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures,” the statement said.

Bisphosphonates are vital for women who are at high risk for Osteoporosis. According to the National Osteoporosis Foundation, half of all women over the age of 50 will break a bone due to osteoporosis and more than 20 percent who break a hip die within one year.   “For most people taking bisphosphonate medicines, the benefits outweigh the risks of these unusual but serious conditions that appear to be associated with them,” the NOF said in a written statement on their website.   “These medicines play an important role in stopping bone loss and preventing broken bones.”

Though bisphosphonates  are commonly prescribed — some argue that they are overprescribed for women with marginal bone loss, or osteopinia-- you should carefully consider the need for taking osteoporosis medicine if your doctor thinks you’re a good candidate for drug therapy.  If you’ve had the bone mineral density test, obtain a copy of the report and go to this website for an explanation that will help you understand what the results mean. Then review the findings with your doctor and ask questions.

The appeals court said “the evidence presented could allow a jury to find or infer that Wyeth was guilty of malicious conduct.”  According to the news report, Pfizer’s lawyers argued that the plaintiff received ample warning about the cancer risks tied to the company’s Prempro and Premarin drugs and chose to continue using them.

“Our results indicate that improved quality of life can be added to the list of exercise benefits and that these improvements are dose dependent and independent of weight loss, at least among people similar to this study’s sample,” Corby K. Martin, PhD, from Louisiana State University System, in Baton Rouge, and colleagues write.

The study was published in Archives of Internal Medicine, a bi-weekly, international peer-reviewed journal.

First, there’s skepticism among some physicians that there’s nothing new about Pristiq. It’s a modified version of Wyeth’s earlier anti-depressant drug, Effexor XR, whose patent expired last year.  “Every patient who takes Effexor produces Pristiq in their own body, at no additional charge,” said Dr. Daniel Carlat, a psychiatrist who wrote about Pristiq on his personal blog last year.

Second,  I wonder about the integrity of any research that is conducted and/or funded by the manufacturer.  In this case, a 26-week double-blind, placebo controlled study, which was “supported in part” by Wyeth Research, was led by David Archer, MD, a professor of obstetrics and gynecology at Eastern Virginia Medical School in Norfolk and four additional physician-researchers.  As described on the school’s website, Dr. Archer is past president and a former board member of the North American Menopause Society (NAMS), which is largely funded by Wyeth (and advocates the use of conjugated hormones made by Wyeth).  He is a consultant for Wyeth Research and has received grants and honoraria from the Wyeth Speakers Bureau. And by the way, the four other physicians who conducted the study are either consultants for, or employees of Wyeth Research.  One of them, Dr. Ginger D. Constantine co-authored an article praising Wyeth entitled “Wyeth: The Leader in Women’s Health – Yesterday, Today and Tomorrow” that appeared in a publication for the American Society for Reproductive Medicine (9/2004).

Dr. Archer also stated, a full year before the FDA approved Pristiq as a treatment for menopausal hot flashes, that “Pristiq is going to fill a needed void. For women who can’t take estrogens… it should be made available.”  Was he speaking as a researcher or promoter for Wyeth’s drug?

Another study that monitored 689 women on Pristiq or placebo over a 12 month period of time was led by Dr. Margery Gass, a professor of obstetrics and gynecology at the University of Cincinnati.  Dr. Gass has disclosed that she is a consultant and receives funding from Wyeth.

Oddly, the only study that concluded that Pristiq did not work much better than placebo and was inferior to a hot-flash-relieving drug not available in the U.S. was authored by a researcher who works for Wyeth, Dr. James Pickar.

So, what to make of all of this?  Know that Pristiq is NOT a new drug – it was approved for the treatment of depression one year ago.  While this class of drugs can correct the neurotransmitter imbalances that cause hot flashes and night sweats in some menopausal women, they can have side effects such as sexual dysfunction, sleep disorders, dry mouth, and nausea.

Also know that research studies tend to reach conclusions that the funders – in this case, Wyeth – are seeking.  From what I’ve been able to read on the web,  every physician-researcher involved with Pristiq has had ties to the company.  The FDA doesn’t seem to mind but if I were in charge of the health and welfare of this country’s population, I would insist on unbiased, third-party research.  Is there such a thing?

The short answer appears to be no, or at least not necessarily.  Though the study concluded there really is no reason to take a multivitamin if you have an adequate diet, the study’s authors acknowledge that the women participating in the study were not typical of the general public.  At least 80 percent finished high school, 40 percent had a college degree or higher, and overall, they had better health habits than the public at large.   So they concluded that multivitamin use “just doesn’t seem to make that much of a difference in this population,” explained Dr. Sylvia Wassertheil-Smoller, the principal investigator of the WHI study, at Albert Einstein College of Medicine.

So that still leaves me and others with the question – do we eat well enough that we can do without multivitamins?  In my opinion,  if a woman is dieting or exercising furiously to lose weight, or is too busy or stressed to prepare well-balanced meals, than she would likely benefit from a multivitamin supplement.

As the study’s authors noted, multivitamin use “confers no additional benefit but it also does no harm.” In other words, it can’t hurt.