Tuesday, May 22, 2012

The Supplement Controversy: Supporting Evidence

Supporting Evidence 

Journal of the American Dietetic Association, May 2012
More than half of US adults use dietary supplements. Some reports suggest that supplement users have higher vitamin intakes from foods than nonusers, but this observation has not been examined using nationally representative survey data.


The purpose of this analysis was to examine vitamin intakes from foods by supplement use and how dietary supplements contribute to meeting or exceeding the Dietary Reference Intakes for selected vitamins using data from the National Health and Nutrition Examination Survey among adults (aged 19 years or less) in 2003-2006 (n=8,860).


Among male users, mean intakes of folate and vitamins A, E, and K from food sources were significantly higher than among nonusers. Among women, mean intakes of folate and vitamins A, C, D, and E from foods were higher among users than nonusers. Total intakes (food and supplements) were higher for every vitamin we examined among users than the dietary vitamin intakes of nonusers. Supplement use helped lower the prevalence of intakes below the Estimated Average Requirement for every vitamin we examined, but for folic acid and vitamins A, B-6, and C, supplement use increased the likelihood of intakes above the Tolerable Upper Intake Level.


Supplement use was associated with higher mean intakes of some vitamins from foods among users than nonusers, but it was not associated with the prevalence of intakes less than the Estimated Average Requirement from foods. Those who do not use vitamin supplements had significantly higher prevalence of inadequate vitamin intakes; however, the use of supplements can contribute to excess intake for some vitamins.

Mutation Research: Fundamental and Molecular Mechanisms of Mutagenesis, May 2012): Vitamin and minerals influence genome integrity, and exposure/intake levels are associated with DNA damage prevention

Historically, the government has recommended daily amounts (RDAs) of vitamins and minerals based on the minimum amounts necessary to prevent deficiency diseases. Over the last couple of decades, however, researchers have seen that larger amounts of vitamins and minerals are necessary to prevent or reduce DNA damage which causes longer term health consequences. This editorial review suggests that improvements in assaying DNA damage provide a more accurate method of determining optimal amounts of vitamin and minerals in the body than that which has been available in the past. Because human populations vary in the way they absorb and metabolize vitamins and minerals, subpopulations should also be considered when establishing dietary guidelines.

Pro-vitamins such as lycopene, lutein, astaxanthin and zeaxanthin consistently protect genomes against DNA damage but vitamin A carotenoids can both protect DNA and cause damage possibly because they can function as oxidants.

Niacin is involved in the function of some enzymes necessary for DNA repair, but no human studies have been done to clearly determine optimal amounts. The authors state that some human population groups are well below the amounts suggested by animal studies, and supplementation in these cases may be beneficial.

Folate and B12 work together to maintain nuclear and mitochondrial genome stability. Low folate levels result in an increase of mistakes in copying DNA which leads to breaking of the strands and deletions in mitochondrial DNA (3). There is some evidence that low folate levels could reduce telomere length which in turn reduces the lifetime of the DNA. Since individuals vary in ability to absorb and metabolize these vitamins, the amount and type of folate and B12 recommended for supplementation must be determined for these subpopulations.

Choline is involved folate metabolism and deficiency impairs folate metabolism which in turn causes the same miscopying of DNA as previously mentioned. As with folate and B12, individuals vary in their ability to absorb and metabolize choline.

Vitamin D seems to play a role in protection against DNA damage and oxidation in animal studies but there are limited human studies to date.

Biotin plays a role in protection again DNA damage but because it is made in human intestines by bacteria, supplementation guidelines are difficult to establish. More studies are needed on the variations of gut flora in disease states and different population groups.

CoQ10 plays an important role in the electron transport chain in mitochondria and is a powerful antioxidant. Although animal studies have demonstrated the beneficial effects of supplementation on genome integrity, more dose-response studies in humans are necessary to establish optimal amounts necessary to prevent DNA damage.

Minerals necessary in small amounts are often toxic in larger amounts. Iron, selenium and zinc seem to cause chromosome breakage and other DNA destruction in high concentrations although they are protective at optimal, intermediate levels. The optimal levels of these minerals seem to vary with individual genotype and may also vary with age.

Since the integrity of each individual’s genome is sensitive to their vitamin and mineral status, dietary recommendations for intake of vitamins and minerals should be based on DNA damage prevention rather than only on avoidance of deficiency diseases. More human studies looking at the dose dependent effect of vitamin and mineral levels alone and in conjunction with each other on genome stability should be performed to establish more accurate supplementation recommendations. In addition, individual metabolic variations should be taken into account. 

BMJ confirms media's cozy relationship to Big Pharma
The relationship between doctors and drug company marketers is finally falling under increased scrutiny, but a new group is stepping in to take drug company money -- journalists and media organizations looking for easy funding. The Australian, a newspaper in Australia run by the Murdoch empire, has accepted an undisclosed amount of sponsorship money from the drug industry for a series of articles on health policy. The idea was first proposed at a meeting between advertising agents. Many are saying that such financial closeness between journalists and the companies they report on raises concerns. According to an article in the British Medical Journal: “... [W]hat we’re witnessing is a slow and subtle attempt to buy influence and goodwill within the media, which in general have become increasingly rigorous in their coverage of the unhealthy aspects of pharmaceutical marketing ... Spreading around cash, free travel, and sponsorship has an effect -- if it didn’t, the industry wouldn’t do it.”

Supplements increase mortality in older women?
A study just published in Archives of Internal Medicine called, "Dietary Supplements and Mortality Rate in Older Women: The Iowa Women's Health Study," states:

"Researchers assessed the use of vitamin and mineral supplements in relation to total mortality in 38 772 older women in the Iowa Women's Health Study; mean age was 61.6 years at baseline in 1986. Supplement use was self-reported in 1986, 1997, and 2004 questionnaires. Of the 15 594 deaths (only 40% of the sample size because they were unable to obtain the death records of many of the subjects) identified through the State Health Registry of Iowa, the a multivariable adjusted proportional hazards regression model, the use of multivitamins absolute risk, vitamin B6, folic acid, iron, magnesium, zinc, and copper were associated with increased risk of total mortality when compared with corresponding nonuse (the risk being the strongest with supplement iron).

Bonnie and Steve - not surprisingly, the media failed to mention how the supplements positively affected the subjects. We thought we would mention it. Here is a direct quote from the study:

"Compared with nonusers, supplement users had a LOWER prevalence of diabetes mellitus, high blood pressure, and smoking status; a lower BMI and waist to hip ratio; and were less likely to live on a farm. Supplement users had higher educational level, were more physically active, and were more likely to use estrogen replacement therapy. Also, supplement users were more likely to have lower intake of energy, total fat, and monounsaturated fatty acids, saturated fatty acids, and to have higher intakes of protein, carbohydrates, polyunsaturated fatty acids, alcohol, whole grain products, fruits, and vegetables."

So why was there no mention about supplemental benefit for many of these lifestyle factors? The lead researcher of the study has published negative, questionable research on supplements before, only to be proven wrong years later (i.e. beta carotene and vitamin A).

There were several factors in the supplement group that needed to be addressed: taking synthetic estrogen, not eating enough monounstaurated fat, eating too much polyunsaturated (inflammatory) fat, and eating too many carbs. All of these factors contribute to heart disease and cancer. It is fascinating to note that when researchers excluded supplement users who had CVD and diabetes, the supplements did not show any adverse affect on mortality. So, in essence, the supplement users were better off than the nonusers based upon the aforementioned lifestyle factors.

What does this say? That researchers can extrapolate data however they see fit, especially from a questionnaire-based study. For example, we can extrapolate from this study that if you looked solely at supplement users who were most likely to take synthetic estrogen, most likely to eat inflammatory fats and carbs, and who ate the least amount of monounsaturated fats, we guarantee that mortality risk would skyrocket. Even more egregious is that the researchers did not remove subjects who used synthetic estrogen, which has been linked to a greatly increased risk of CVD and cancer. This should be enough to discredit the study outright.

One other issue: we do not know what brands of supplements these subjects were on. If many of them were on brands such as Centrum, who knows. We do not consider those healthful supplements.

The media did get what it needed, however. Any time they can jump on a study discrediting supplements, they are all over it.
Local Doc dishes on supplements
Courtesy of Dr. Patrick Massey, contributor to the Daily Herald

Do vitamins increase the risk of death? According to one recent medical study, the conclusion may be yes. However, does the data really support the conclusions or are the results being exaggerated? In my opinion, the conclusions of the study are a real stretch based on the structure of the study itself.

This study, published in the Archives of Internal Medicine, is not a double blind, placebo controlled, prospective study. It is part of a larger study and concluded that elderly women who took vitamins had a slightly increased risk of death compared with those who did not. In contrast, this study also suggested that calcium, as a supplement, was associated with a 3.8 percent reduced risk of death.

The data was part of the very large Iowa Women’s Health Study consisting of 41,836 postmenopausal women, ages 55 to 69 who filled out questionnaires in 1987, 1997 and 2004. The questionnaires covered many aspects of health including vitamin use. Although these studies are essential because they provide a large amount of data, correlation does not prove causation. This means that self-reported data is notoriously unreliable, and since there are no controls, the results are far from conclusive. These types of studies are usually the foundation for further, well-designed and controlled studies.

There are a number of factors that can affect the skew, the statistics and the conclusions. It may be possible that those women who have more illnesses and are at a greater risk of death simply use more. Medication use also is important. Even safe over-the-counter pain medications can increase the risk (small but real) of serious hospitalization and death. In addition, physical activity, diet and habits like smoking and alcohol abuse all can affect the outcome.

Among health care professionals, whether vitamins are helpful, harmful or a waste of money is very controversial. However there are, literally, thousands of well-designed, prospective studies worldwide demonstrating the benefits of vitamins for heart disease, diabetes, high blood pressure, pain, Alzheimer’s disease, etc. It is important that accurate information is available to the general public and health care community.
Fortunately, there are now a number of credible resources for accurate information about vitamin use. One of these sources is the Natural Health Research Institute (I hold an unpaid position on the scientific advisory board). The institute is described as “an independent, nonprofit organization that supports science-based research on natural health and wellness.” Its goal is to inform people about the benefits of good food, supplements (if needed) and healthy lifestyles.

The institute is having its sixth annual scientific symposium in Schaumburg on Friday, Oct. 28. The symposium is open to the public and the speakers are internationally recognized experts in the area of vitamins and health. The topic is “Measuring the efficacy, safety and cost savings of dietary supplements.”

• Patrick B. Massey, M.D., Ph.D is medical director for complementary and alternative medicine for the Alexian Brothers Hospital Network.

Supplement Safety Versus Drug Safety 
As posted on fda.gov:
Why Learn about Adverse Drug Reactions (ADR)?
Institute of Medicine, National Academy Press, 2000
Lazarou J et al. JAMA 1998;279(15):1200–1205
Gurwitz JH et al. Am J Med 2000;109(2):87–94

Over 2 MILLION serious ADRs yearly
100,000 DEATHS yearly
ADRs 4th leading cause of death ahead of pulmonary disease, diabetes, AIDS, pneumonia, accidents and automobile deaths
Ambulatory patients ADR rate—unknown
Nursing home patients ADR rate— 350,000 yearly 


Based on the figures presented by the FDA, at least30 million people have suffered serious injury or death as a result of taking FDA-approved drugs just since 1998 when the first cited study was published. If you go back several more decades, it is clear that potentially hundreds of millions of people have been directly harmed.

Results from Adverse Event Reporting (AER) System
The Food & Drug Administration AER system ensures that dietary supplement and prescription drug manufacturers report significant adverse events related to their products. 
The figures from 2008 were recently published.
1,080 from supplements (over half the US population, 154 million, take supplements)
526,527 from prescription drugs. For every adverse event from supplements, there are 488 adverse events from prescription drugs.

Why You Should Not Stop Taking Vitamins
Do vitamins kill people?
How many people have died from taking vitamins?
Should you stop your vitamins? By Dr. Mark Hyman
It depends. To be exact, it depends on the quality of the science, and the very nature of scientific research. It is very hard to know things exactly through science. The waste bin of science is full of fallen heroes like Premarin, Vioxx and Avandia (which alone was responsible for 47,000 excess cardiac deaths since it was introduced in 1999).
That brings us to the latest apparent casualty, vitamins. The recent media hype around vitamins is a classic case of drawing the wrong conclusions from good science.
Remember how doctors thought that hormone replacement therapy was the best thing since sliced bread and recommended it to every single post-menopausal woman? These recommendations were predicated on studies that found a correlation between using hormones and reduced risk of heart attacks. But correlation does not prove cause and effect. It wasn't until we had controlled experiments like the Women's Health Initiative that we learned Premarin (hormone replacement therapy) was killing women, not saving them.
A new study "proving" that vitamins kill people is hitting front pages and news broadcasts across the country. This study does not prove anything.
This latest study from the Archives of Internal Medicine of 38,772 women found that "several commonly used dietary vitamin and mineral supplements may be associated with increased total mortality". The greatest risk was from taking iron after menopause (which no doctor would ever recommend in a non-menstruating human without anemia).
The word "may" is critical here, because science is squirrelly. You only get the answers to the questions you ask. And in this case, they asked if there was an association between taking vitamins and death in older woman. This type of study is called an observational study or epidemiological study. It is designed to look for or "observe" correlations. Studies like these look for clues that should then lead to further research. They are not designed to be used to guide clinical medicine or public health recommendations. All doctors and scientists know that this type of study does not prove cause and effect.
Why Scientists are Confused
At a recent medical conference, one of most respected scientists of this generation, Bruce Ames, made a joke. He said that epidemiologists (people who do population-based observational studies) have a difficult time with their job and are easily confused. Dr. Ames joked that in Miami epidemiologists found everybody seems to be born Hispanic but dies Jewish. Why? Because if you looked at population data in the absence of the total history and culture of Florida during a given time, this would be the conclusion you would draw. This joke brings home the point that correlation does not equal causation.
Aside from the fact that it flies in the face of an overwhelming body of research that proves Americans are nutrient deficient as a whole, and that nutritional supplements can have significant impact in disease prevention and health promotion, the recent study on vitamins is flawed in similar ways.
How Vitamins Save Money and Save Lives
Overwhelming basic science and experimental data support the use of nutritional supplements for the prevention of disease and the support of optimal health. The Lewin Group estimated a $24 billion savings over five years if a few basic nutritional supplements were used in the elderly. Extensive literature reviews in the Journal of the American Medical Association and the New England Journal of Medicine also support this view. Interventional trials have proven benefit over and over again.
The concept that nutritional supplements "could be harmful" to women flies in the face of all reasonable facts from both intervention trials and outcome studies published over the past 40 years. Recent trials published within the last two years indicate that modest nutritional supplementation in middle age women found their telomeres didn't shorten. Keeping your teleomeres (the little end caps on your DNA) long is the hallmark of longevity and reduced risk of disease.
A plethora of experimental controlled studies -- which are the gold standard for proving cause and effect -- over the last few years found positive outcomes in many diseases. These include the use of calcium and vitamin D in women with bone loss; folic acid in people with cervical dysplasia (pre-cancerous lesions); iron for anemics, B-complex vitamins to improve cognitive function, zinc; vitamin C, E, and carotenoids to lower the risk of macular degeneration, and folate and vitamin B12 to treat depression. This is but a handful of examples. There are many more.
Why Most Vitamin Studies are Flawed
There is another important thing to understand about clinical trials that review the utility of vitamins in the treatment of disease. The studies that show harm are often designed like drugs studies. For example, a study may use a high dose of vitamin E and see what happens. This is actually a prescient example also explored in recent media. Studies recently found that high doses of vitamin E and selenium didn't prevent prostate cancer and may increase risk. What this study didn't explore properly was the true biochemical nature of vitamin E and selenium. These nutrients work as antioxidants by donating an electron to protect or repair a damaged molecule or DNA. Once this has happened the molecules become oxidants that can cause more damage if not supported by the complex family of antioxidants used in the human body. It's sort of like passing a hot potato. If you don't keep passing it you will get burned. This study simply failed to take this into account.
Nature doesn't work by giving you only one thing. We all agree that broccoli is good for you, but if that were all you ate you would die in short order. The same is true of vitamins. Nutrients are not drugs and they can't be studied as drugs. They are part of a biological system where all nutrients work as a team to support your biochemical processes.
Michael Jordon may have been the best basketball player in history, but he couldn't have won six NBA titles without a team.
Obesity is Linked to Malnutrition
The tragedy of media attention on poor studies like these is that they undermine possible solutions to some of the modern health epidemics we are facing today, and they point attention away from the real drivers of disease.
Take the case of obesity for example. Paradoxically Americans are becoming both more obese and more nutrient deficient at the same time. Obese children eating processed foods are nutrient depleted and increasingly get scurvy and rickets, diseases we thought were left behind in the 19th and 20th centuries.
After treating more than 15,000 patients and performing extensive nutritional testing on them, it is clear Americans suffer from widespread nutrient deficiencies including vitamin D, zinc, magnesium, folate and omega 3 fats. This is supported by the government's National Health and Nutrition Examination Survey (NHANES) data on our population. In fact 13 oercent of our population is vitamin C deficient.
Scurvy in Americans in 2011? Really? But if all you eat is processed food -- and many Americans do -- then you will be like the British sailors of the 17th century and get scurvy.
Unfortunately negative studies on vitamins get huge media attention, while the fact that over 100,000 Americans die and 2.2 million suffer serious adverse reactions from medication use in hospitals when used as prescribed is quietly ignored. Did you know that anti-inflammatories like aspirin and ibuprofen kill more people every year than AIDS or asthma or leukemia?
Flaws with the "Vitamins Kill You" Study
So what's the bottom line on this study on vitamins in older white women in Iowa?
After a careful reading of this new study a number of major flaws were identified.
1. Hormone replacement was not taken into consideration. Overall the women who took vitamins were a little healthier and probably more proactive about their health, which led them to use hormone replacement more often (based on recommendations in place when this study was done). 13.5 percent of vitamin users also used hormones, while 7.2 percent of non-vitamin users took hormones. Remember the Women's Health Initiative Study I mentioned above? It was a randomized controlled trial that found hormone therapy dramatically increases risk of heart attack, stroke, breast cancer and death. In this Iowa women's study on vitamins, the degree of the effect of harm noted from the vitamins was mostly insignificant for all vitamins except iron (see below) and calcium (which showed benefit contradicting many other studies). In fact, the rates of death in this study were lower than predicted for women using hormone therapy, so in fact the vitamins may have been protective but the benefit of vitamins was drowned out because of the harmful effects of hormones in the vitamin users.
2. Iron should not be given to older women. Older women should never take iron unless they have anemia. Iron is a known oxidant and excess iron causes oxidative stress and can lead to cardiovascular disease and more. This is no surprise, and should not make you stop taking a multivitamin. If you are an older woman, you simply need to look for one without iron. Most women's vitamins do not contain it anyway.
3. Patient background was ignored. In this observational study it was not known why people started supplements. Perhaps it was because of a decline in their health and thus they may have had a higher risk of death or disease that wasn't associated with the vitamins they were taking at all. If you had a heart attack or cancer and then started taking vitamins, of course you are more likely to die than people without heart attacks or cancer.
4. The population was not representative. The study looked only at older white women -- clearly not representative of the whole population. This makes it impossible to generalize the conclusions. Especially if you are an obese young African American male eating the average American diet.
5. Forms and quality of vitamins were not identified. There was no accounting for the quality or forms or dosages of the vitamins used. Taking vitamins that have biologically inactive or potentially toxic forms of nutrients may limit any benefit observed. For example synthetic folic acid can cause cancer, while natural folate is protective.
6. A realistic comparison between vitamins and other medications as cause of death was not made. 0ver 100,000 people die every year from properly prescribed medication in hospitals. These are not mistakes, but drugs taken as recommended. And that doesn't include out of hospital deaths. The CDC recently released a report that showed in 2009, the annual number of deaths (37,485) caused by improper/overprescribing and poor to non-existent monitoring of the use of tranquilizers, painkillers and stimulant drugs by American physicians now exceeds both the number of deaths from motor vehicle accidents (36,284) and firearms (31,228).

In short, this recent study confuses not clarifies, and it has only served up a dose of media frenzy and superficial analysis. It has left the consumer afraid, dazed, bewildered and reaching for their next prescription drug.

Please, be smart, don't stop taking your vitamins. Every American needs a good quality multivitamin, vitamin D and omega-3 fat supplement. It is part of getting a metabolic tune up and keeping your telomeres long!

Mark Hyman, MD

No comments: