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Response to Annals of Internal Medicine editorial "Enough is Enough"

The Annals of Internal Medicine published an editorial on December 17, 2013 titled Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements.

Issue #1: The media. It’s all about ratings, not about the truth.

The worst part of this editorial is the media reporting of it! What a disservice the media has done to the general public with reports like:

Why doesn’t the media report on the number of deaths caused by prescription drugs (10’s of thousands per year!) and the fact that no drug prevents the occurrence of chronic disease or the death from it. Even CNN’s own Dr. Sanjay Gupta wrote, Gupta: Let's end the prescription drug death epidemic. Where was the press coverage? Of course, these are “accidental deaths. Hah! This will be the topic of a future post.

Issue #2: “Three articles in this issue address the role of vitamin and mineral supplements for preventing the occurrence or progression of chronic diseases.”

The authors cherry picked three studies and make them out to be representative of the entire field of nutrition and disease prevention. This is not even close to being the case.

  1. As a group, the study participants of all three studies were not representative of the U.S. population at large.

  2. Oral High-Dose Multivitamins and Minerals After Myocardial Infarction: A Randomized Trial. This study included Patients at least 50 years of age having had an acute myocardial infarction more than 6 weeks prior to enrollment.

  3. Long-Term Multivitamin Supplementation and Cognitive Function in Men: A Randomized Trial. This study used 5947 male physicians aged 65 years or older.

  4. Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force . This study states, “Limitations: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years.”

  5. The three studies presented looked at use of vitamins after myocardial infarction, long term use related to cognitive function in men, and primary prevention of cardiovascular disease and cancer. Specifically only cardiovascular disease, cancer, age-related eye disease, and cognitive decline were examined. Certainly not a comprehensive list.

  6. The three studies looked at only certain nutrients and one of the studies used one of the most poorly absorbed multi-vitamins manufactured (Centrum).

  7. None of these studies used objective scientific measurement of nutrient levels of the participants.

Issue #3: “With respect to multivitamins, the studies published in this issue and previous trials indicate no substantial health benefit.”

  1. Health was not studied in these studies! What an absurd statement! The field of medicine has no “health” standards. Tracy Kolenchuk, in her wonderful response, states, “Every so called 'health measurement' relies on measuring illness, not healthiness.”

  2. Oral High-Dose Multivitamins and Minerals After Myocardial Infarction: A Randomized Trial In his response published in the Huffington Post, Dr. Alan Gaby states that this study “found that supplementing with large doses of vitamins and minerals after a heart attack reduced the recurrence rate of cardiovascular events (such as heart attack, stroke, or heart surgery) by 11 percent, compared with a placebo. (2) However, because this reduction was not statistically significant, the editorial concluded (incorrectly) that the treatment was ineffective. The failure to demonstrate that an effect is statistically significant is not the same as demonstrating the absence of an effect. The correct conclusion is that the nutritional supplement reduced the number of cardiovascular events by 11 percent, but because this reduction was not statistically significant, we are less than 95 percent certain that the effect was real (as opposed to being due to chance).” (Source)

  3. Long-Term Multivitamin Supplementation and Cognitive Function in Men: A Randomized Trial. Dr. Gaby goes on to say, “The second study in the Annals found that daily use of a low-potency multivitamin (Centrum Silver) for an average of 8.5 years had no effect on cognitive function in elderly men participating in the large Physicians' Health Study II. (3) However, two other recent double-blind trials (which were not mentioned in the editorial) found positive effects of vitamins. In one of those studies, daily supplementation with 400 mcg of folic acid and 100 mcg of vitamin B12 significantly improved cognitive function in elderly men. (4) The other study showed that daily supplementation with 800 mcg of folic acid, 500 mcg of vitamin B12, and 20 mg of vitamin B6 slowed the rate of brain atrophy in elderly individuals suffering from mild cognitive impairment. (5) There are two potentially important differences between these positive studies and the negative study cited in the editorial. One difference is that the amount of vitamin B12 in Centrum Silver (25 mcg) is much lower than the amount used in the positive studies (100 and 500 mcg, respectively). Loss of cognitive function is a well-known effect of vitamin B12 deficiency. Although all of the study supplements provided more than the Recommended Dietary Allowance for vitamin B12 (2.4 mcg per day), recent research has shown that many elderly people need unusually large amounts of this vitamin (500 mcg per day or more in some cases) to achieve optimal vitamin B12 nutritional status. (6) The other difference is that several aluminum-containing artificial coloring agents are present in Centrum Silver (FD&C Blue 2 Aluminum Lake, FD&C Red 40 Aluminum Lake, and FD&C Yellow 6 Aluminum Lake), and these chemicals have the potential to adversely affect cognitive function. Artificial coloring agents are known to have negative effects on the behavior of children, (7) although these chemicals have not been well studied in adults. Moreover, there is evidence that long-term aluminum exposure can contribute to the development of Alzheimer's disease.(8) The ineffectiveness of a low-potency supplement that contains extraneous and potentially harmful additives does not negate the beneficial effects of higher-potency supplements reported in other trials.” (Source)

This same study, published one year ago, suggested taking multivitamins led to an 8% decline in cancer risk in men over age 50, while the risk of cataracts dropped by 9 percent, compared to placebo.

  1. Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force . Dr. Gaby states, “The third Annals study discussed in the editorial was a review of research examining whether vitamin and mineral supplements can prevent heart disease or cancer. (9) The editorial stated there is "no clear evidence" that taking a multivitamin can prevent cancer. However, the research review that was cited in the editorial actually found a statistically significant 7 percent reduction in cancer incidence in men, and no effect in women. While further research is needed to understand why the results differed between men and women, the findings certainly do not warrant the conclusion that the case is closed and to stop wasting money on supplements. With respect to heart disease prevention, the research review focused on two large studies that failed to find a beneficial effect. In one of those studies, Centrum Silver was given to men participating in the Physicians' Health Study II (mentioned above). In the other study, five nutrients were given (zinc, vitamin C, vitamin E, selenium, and beta-carotene). In both of these studies, zinc was not properly balanced with copper. Copper deficiency causes cardiovascular disease in experimental animals, and supplementing with large doses of zinc has been shown to induce copper deficiency in humans. It is possible that taking a moderate amount of zinc (15 to 20 mg per day, as used in these studies) for many years would also decrease copper status. Considering that the average copper content of various foods has declined substantially since around 1940,(10) a further decrease in copper status from long-term zinc supplementation could adversely affect the cardiovascular system. The study that included five nutrients gave 20 mg of zinc per day with no copper for 7.5 years. Centrum Silver does contain copper, but for approximately 70 percent of the 11-year study, the form of copper in the product was cupric oxide, (11) which cannot be absorbed by humans. (12)” (Source)

  1. Dr. Gaby concludes, “Multivitamin-mineral preparations have been shown in published research to have a wide range of benefits, including increasing energy and stress tolerance, improving pregnancy outcomes, decreasing infection rates, slowing bone loss, and improving cognitive function in schoolchildren. Some studies have also demonstrated protection against cardiovascular disease and cancer, although the evidence is conflicting. Furthermore, various individual nutrients or combinations of nutrients have been used successfully for the prevention and treatment of many other health conditions, including migraines, congestive heart failure, rheumatoid arthritis, kidney stones, diabetes, and depression. (13)” (Source)

  1. In a response to the Editorial by Balz Frei, Ph.D. of Oregon State University, Dr. Frei says,“… the largest and longest randomized controlled trial (RCT) of MVM supplements conducted to date, the Physicians’ Health Study II (PHS II), found a significant 8% reduction in total and epithelial cell cancer incidence in male physicians age 50 years and older, and a 12% reduction in total cancer incidence excluding prostate cancer (5). Furthermore, PHS II found a significant 9% lower risk of total cataract and a 13% lower risk of “any” nuclear sclerosis (nuclear cataract) (6). These findings of PHS II are consistent with those of several other RCTs (8,9), and are even more impressive given the fact that conventional RCT designs are strongly biased against showing any health benefits of essential nutrients (10,11).(Source)

  1. In another great response, Dr. Mark Lange states, “The authors of the editorial conclude that there was no clear evidence of a beneficial effect of supplements on cancer. This is in contradiction to the FDA approval of multiple qualified health claims for supplements, including selenium may reduce the risk of certain cancers including bladder cancer; antioxidant vitamins C and E may reduce the risk of stomach, bladder and colon cancer; and calcium supplements may reduce the risk of colon cancer.

Issue #4: Qualifiers and Contradictions abound!

  1. “Evidence is sufficient to advise against routine supplementation, and we should translate null and negative findings into action." Whose evidence is sufficient, the authors cherry-picked evidence? And as you have read above, the evidence is NOT sufficient.

  2. “The message is simple: Most supplements do not prevent chronic disease or death, their use is not justified, and they should be avoided.” It does not say ALL supplements, it says most supplements. So are there are some supplements that do prevent chronic disease or death? Which ones? Dr. Gaby explains this above.

  3. “With respect to multivitamins, the studies published in this issue and previous trials indicate no substantial health benefit.” We covered this one above too.

  4. “This message is especially true for the general population with no clear evidence of micronutrient deficiencies, who represent most supplement users in the United States and in other countries (9).” As mentioned above, none of the subjects of any of these studies ever had an objective measurement of these nutrients.

  5. An author of Long-Term Multivitamin Supplementation and Cognitive Function in Men: A Randomized Trial states, “Research gaps remain too, says John Michael Gaziano, a researcher at Brigham and Women’s Hospital and the VA Boston Healthcare System. He co-authored one of the new studies. “It drives me crazy that they say ‘enough is enough,’ when there’s only been one large study of (standard) multivitamins and it’s ours,” he says.” (Source)

Issue #5: Nutrient deficiency is proven in the U.S. population

  1. Dr. Mark Lange states, “The fact is that most people do not eat a healthy diet and instead consume excessive amounts of convenience food and/or highly processed foods depleted of nutrients. The soil of modern day mega farming has long ago been stripped of trace mineral content, resulting in less nutritious fruits and vegetables. A 2005 USDA report found that 93% of Americans have an inadequate intake of vitamin E, 56% have an inadequate intake of magnesium, 44% have an inadequate intake of vitamin A, 31% have an inadequate intake of vitamin C, 14% have an inadequate intake of vitamin B6, 12% have an inadequate intake of zinc, and 8% have an inadequate intake of folate.” (Source)

  1. Dr. Frei states, “While a well-balanced diet is the best way to get all of one’s essential nutrients, the reality is that Americans don’t get enough of them through diet alone. From the National Health and Nutrition Examination Survey (NHANES) we know that the large majority of the US population is not “well-nourished” and falls short of meeting many dietary intake recommendations by the Institute of Medicine’s Food and Nutrition Board (2). For example, more than 93% of US adults 19 years and older do not meet the Estimated Average Requirement (EAR) of vitamins D and E, 61% for magnesium, about 50% for vitamin A and calcium, and 43% for vitamin C (2). Other studies have shown that people who take a daily multivitamin/mineral (MVM) supplement with the Daily Value (DV) of most vitamins and minerals can fill most of these nutritional gaps safely and at very low cost (3,4)—a year's supply of a high-quality MVM can be purchased for less than a nickel a day, and daily MVM use has no adverse health effects (5,6).

  2. Dr. Frei concludes his response with, “Therefore, taking a daily MVM supplement will not only help fill the known nutritional gaps in the average American diet, thereby assuring normal biological function and metabolism and supporting good health, but may also have the added benefit of reducing cancer and cataract risk—which no existing pharmaceutical drug can do. To call “the case … closed” and label MVM supplements as useless, harmful or a waste of money is wrong and unscientific, and does not serve public health.”(Source)

In closing, so how do you know if you need supplementation, i.e. if your nutrients you are getting from your diet and/or supplements are being absorbed? Get measured! Click here to see how!

I could not agree more with Dr. Irvine Mason who writes, “I recommend to the patients that if they find a doctor who states that one receives all the vitamins out of the food that they eat, to find another doctor.” (Source)

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