Response to Annals Hysteria

Aside from the recent Times article that once again spread a message of fear and misinformation, three articles were published in the Annals of Internal Medicine that were accompanied by an editorial verging on hysteria that proclaimed in stentorious tones: DON’T TAKE THEM!

Is that a justifiable conclusion? Well, when you look at the studies undertaken, I don’t believe the answer is that clearcut.  However, there also may be evidence here that clarifies who may and may not benefit from a simple micronutrient supplement.  At the end of the article are links to other analyses that rebut the claims made.

Let’s take a little closer look at each of these three negative studies. First, one relatively large study, using a low dose combination of often synthetic vitamin constituents (Centrum Silver) among older individuals (1). Using these modest doses, the upshot of the study, which was otherwise well-controlled and randomized, found no benefit of the use of the supplement in offsetting or mitigating cognitive decline over about 10-14 years. This was part of the large physician’s study and the study was limited by the potential that the doses may have been too low for an otherwise well-nourished population. Is this generalizable to older individuals who are well-nourished?

Perhaps so and taking a Centrum is therefore quite probably a waste of money if maintaining cognitive function is the goal. However, this is the same study that had previously reported that even this simple intervention modestly reduced the risk of cancer. Is that a useful endpoint? And indeed, the authors note that the study may need to be up to 20 years or longer to adequately detect any significant differences.

The third study was a meta-analysis or review of the literature that has pre-specified criteria for the selection of studies to be reviewed and then applies stastical analytic techniques to combine the results into a conclusion (3). They sought to assess the use of multivitamins in the primary prevention of cancer or cardiovascular disease. (Drug studies indeed more commonly look at the use of a drug in preventing a second heart attack, for example: secondary prevention.) Having done these, I know there is a certain degree of judgment in what gets selected and the method used for analysis. In this case, the authors note that the primary limitations are as they note is 1) they only assessed four RCTs and one cohort study that used radically different multivitamin/mineral formulas; one of these was a study that used a multi with only 5 ingredients another only 3 vitamins; 2) these were ONLY among otherwise healthy adults (not secondary prevention studies). The PHS-II study, discussed above, and another the SU.VI.MAX study were the two largest studies. So what can we conclude from this? That the extant data do not robustly support the use of a multi for these indications? Possibly, though they also note that the large PHS-II study that found a benefit for reducing cancer risk also detected a benefit for fatal myocardial infarction (adjusted hazard ratio, 0.61 [95% CI, 0.38 to 0.995]; P < 0.048). It may again be that these interventions are not up to the rather daunting task of achieving the endpoint of primary prevention—such studies probably need to be larger and a lot longer to come up with definitive conclusions.

They also reviewed single and paired studies. They noted that calcium alone is ineffective overall and possibly dangerous as a single supplement, but you throw in vitamin D, and gosh–lower mortality, though just barely (unadjusted RR 0.94, 95%? CI 0.87,1.01). It begins to beggar the imagination however to think these extremely disparate trials can be combined in any meaningful way when the populations, interventions and even primary outcomes were so significantly different.

The third study, however, did assess the effects of chelation therapy, with or without a multivitamin/mineral combination as secondary prevention for a heart attack (myocardial infarction) (3). It was a relatively short study with a median follow-up of 31 months in the vitamin group. The article notes that there was a huge dropout rate. Of the 853 in the vitamin arm and the 855 in the placebo arm, 584 and 547 were lost to follow up, respectively but the analysis was done “intent-to-treat” and all were included in the final analysis. Further, the study was not powered to see a difference with the few that were finally enrolled and completed the study—i.e., the initial proposal was to enroll 2,372 patients. And there was a small difference: while the primary and secondary outcomes did not achieve statistical significance, one can see in the Kaplan-Meier curves that there is a lower rate of events in the multi arm compared to the control by about 11% and that appears to improve as the study progresses: had it lasted longer or been better powered, might this trend have improved over time? We don’t know. The effect is relatively modest but the study wasn’t powered to detect this difference.

It seems to me that the latter study reflects reality and should calm the anxieties about people using supplements expressed by the editors (4). The upshot: Most people don’t want to take vitamins as suggested by the Lamas study. If THAT conclusion is generalizable, they have little to fear—but is that wise public policy?

The other important fact to note was that all the studies showed no evidence of adverse events. For the most part, side effects of the use of supplements are exceedingly rare and generally arise with the use of single agents (e.g., vitamin E or beta-carotene alone). Probably not the wisest way to use interventions designed to work in a biological way or in a system that is severely oxidatively stressed.

I would suggest several caveats. First, this is irrelevant to people living with HIV. Even a fairly simple formula can have a significant impact in slowing disease progression and reducing mortality (modestly) with the use of a multivitamin/mineral. The results of our meta-analysis will, we hope, be published soon. (This of course does NOT mean they are a replacement for antiretroviral therapy! Absolutely not.)

Second, these are SUPPLEMENTS – diet and access to clean water need to be the first consideration and far too many people have limited access to these basics while millions of others are forced to consume what is available on the market, which is often poor quality, processed, loaded with chemicals, preservatives, antibiotics, hormones and potentially dangerously genetically modified.

And finally, supplements are NOT drugs in key ways. They are supporting the body’s ability to fight disease while retaining an optimal level of health, especially when we are discussing the use of vitamins and minerals (as opposed to botanicals). Whether the optimal dosages have been determined, whether the findings are generalizable to everyone, whether there are groups, like people with HIV, for whom they are demonstrably beneficial—these are questions hardly answered to the point of declaring no one should ever use them as these editors have done.

Links:

Harvard rebuts the Annals of Internal Drugs.

http://www.hsph.harvard.edu/nutritionsource/multivitamin/

Linus Pauling Institute of Oregon State University.

http://lpi.oregonstate.edu/news/enoughisenough-response.html

Michael Mooney’s overview:

http://www.michaelmooney.net/Erroneous_Annals_Of_Internal_Medicine_Study_Says_Vitamins_Don%27t_Work.html

Industry’s Council for Responsible Nutrition:

http://www.nutraceuticalsworld.com/contents/view_blog/2013-12-18/enough-is-enough/?email_uid=dee72d271a/list_id=396c189146/

Michael Murray, ND:

http://doctormurray.com/?utm_source=WOW+-+Editorial+in+Medical+Journal+Promotes+Propaganda+Against+Multiple+Vitamin+&utm_campaign=CCmailing6-12-13&utm_medium=email

References:

1. Grodstein F, O’Brien J, Kang JH, et al. Long-Term Multivitamin Supplementation and Cognitive Function in Men: The Physicians’ Health Study II. Annals of Internal Medicine. 2013;159(12) :806-814-814. doi: 10.7326/0003-4819-159-12-201312170-00006.

2. Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. 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. Ann Intern Med. Nov 12 2013;159(12):824-834-834. doi: 10.7326/0003-4819-159-12-201312170-00729.

3. Lamas GA, Boineau R, Goertz C, et al. Oral High-Dose Multivitamins and Minerals After Myocardial Infarction. Annals of Internal Medicine. 2013;159(12):797-805-805. doi: 10.7326/0003-4819-159-12-201312170-00004.

4. Guallar E, et al. Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements. Ann Intern Med. 2013;159(12): 850. Retrieved 19 Dec 2013 from http://annals.org/article.aspx?articleid=1789253

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Lutein may improve vision

It is always encouraging to have evidence-based medicine to help determine the value of any intervention, drug or supplement. A recent double-blind, randomized and controlled study showed some benefit for visual acuity when participants were assigned to 20 mg of lutein.

Lutein supplementation improves visual performance in Chinese drivers: 1-year randomized, double-blind, placebo-controlled study.

Source

Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao-tong University, Shanghai, P.R. China.

Abstract

OBJECTIVES:

Although it is known that the carotenoid lutein can affect visual performance, we still have much to learn about its effect in occupational populations, like drivers. The aim of this study was to examine the effect of lutein supplementation on visual function in healthy drivers with long-term light exposure.

METHODS:

The study was a randomized, double-blind, placebo-controlled, 1-y intervention study. It included 120 normal participants (drivers). The active (A) group consumed 20 mg of lutein daily. Participants were assessed at baseline, 1, 3, 6, and 12 mo (V0, V1, V2, V3, and V4, respectively). Assessment included visual acuity, serum lutein concentrations, macular pigment optical density (MPOD), and visual performance. At the onset and at the end of the intervention, dietary intakes of lutein and visual-related quality of life were measured.

RESULTS:

There was a trend (in the active group) toward an increase in best spectacle-corrected visual acuity measured, but there were no significant differences. Serum lutein and central MPOD in the active group increased significantly, whereas no change was observed in the placebo group. We observed significant increases in contrast and glare sensitivity, especially in the mesopic condition. There were significant improvements in the score of the National Eye Institute 25-Item Visual Functioning Questionnaire driving subscale in the active group.

CONCLUSIONS:

Daily supplementation with 20 mg of lutein increases MPOD levels. Lutein may benefit driving at night and other spatial discrimination tasks carried out under low illumination.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID: 23360692

Neuropathy pain and HIV: supplement recommendations

You may have read reports in late February 2012 about the FDA’s skeptic ism about a patch called Qutenza, which had been tested for relief of neuropathy pain in people with HIV. Following a meeting to review the evidence, an FDA panel concluded that Qutenza, whose active ingredient is a synthetic form of capsaicin (the compound that makes chili peppers hot) was not effective for HIV-related neuropathy pain.

The FDA’s finding on Qutenza reminds us again that neuropathy (generally, pain or tingling in the extremities) continues to be one of the most troublesome effects of HIV/AIDS and/or its treatment—and one of the most difficult to manage. According to a survey report in 2010, for example, more than one third of those on combination antiretroviral therapy for HIV do experience neuropathy, leading to lower quality of life and often disability. So, it may be worthwhile to repeat some of NYBC’s recommendations on this topic:

Peripheral neuropathy: “nukes” (nucleoside reverse transcriptase inhibitors) such mas ddI (Videx), and d4T (stavudine/ Zerit) – and Indinavir, T20, and even 3TC (Epivir)may all cause this feeling of pins and needles or numbness to toes and fingers. It can travel up the legs and become debilitating. HIV, diabetes, alcohol abuse, and vitamin deficiencies can all be causes of peripheral neuropathy. Supplements that are “good for your nerves” and that have the most robust data include acetylcarnitine (1-3 grams/ day, quite well studied for peripheral neuropathy) and alpha lipoic acid (200-600 mg/day). Other agents that can help are Vitamin B12, biotin, lecithin, magnesium, borage oil, evening primrose oil, choline and inositol.

See the NYBC website for more details about these supplements:
http://nybcsecure.org/

MS Sufferer Improves Dramatically

Here is a terrific YouTube post by Dr. Terry Wahls. She is a person living with secondary, progressive multiple sclerosis (MS). By 2008, she could not walk more than a short way with two canes. At this point, she began a journey into understanding how her disease progresses and ways in which diet and supplements can have an impact on that disease. Check out the video and see her remarkable results–one of the always remarkable and inspiring TED talks series!

How often to check vitamin levels?

MedPage Today, an online medical information service that addresses current health care findings, recently conducted a readers’ poll on the question of how often vitamin levels should be checked. Most of those responding to the poll agreed that factors such as processed foods, mineral-depleted soil, overcooked vegetables and daily stress have combined to create widespread deficiencies in some vitamins and minerals. The majority also agreed that vitamin levels should be checked yearly. Here are some of the comments:

We asked readers if and when patients should be assessed for vitamin deficiencies. Of the more than 2,200 votes, 69% said that patients’ vitamin levels should be assessed at least annually.

“I cannot remember how many patients have been rescued from dementia and psychosis by B12, especially when I have a geriatric focus,” said one doctor, who also touted vitamin D, calcium, fish oil, and thyroid testing. “Everybody deserves a look about once a year.”
[…]
“I have just been rescued from severely low vitamin D levels, and my daughter has been found to have low vitamin levels as well. I wish my doctors had been checking levels all along,” noted another MedPage Today reader.

And another expressed similar exasperation. “It was not until I was diagnosed with osteoporosis that I had a vitamin D 25-OH test, and found out that despite being outside every day, my level was insufficient. By then it was too late. I am very disappointed that my physician did not order this inexpensive test years ago. Now, I have asked for a B12 test as well.”

See details at http://www.medpagetoday.com/

Low Vitamin B12 Linked to Cognitive Decline

We’ve seen much information in recent years about the relationship between the B vitamins, especially B12, and cognitive function. But a new study fills in details about the mechanisms connecting low B12 levels and declining cognitive health. And one of the study’s authors has suggested that, while there is already a general recommendation for older adults to supplement with B12, there may be cause to advise middle age adults to do the same.

The mechanisms of cognitive decline associated with low levels of B12 include brain atrophy and cerebral infarcts (=blood flow blockage leading to tissue death). Other recent research has suggested that supplementing with B12 may slow brain atrophy as we age, so the current study linking low B12 levels to greater degrees of brain atrophy is not a big surprise.

The Institute of Medicine, an organization that establishes recommended daily allowances for vitamins, currently advises older adults to supplement with Vitamin B12, since seniors frequently are deficient in the vitamin due to declining ability to absorb nutrients. But according to one of the current study’s authors, it may make sense to screen adults for B12 deficiency even before they reach senior status, and address early signs of deficiency with supplementation.

NYBC stocks Vitamin B12 as in a highly absorbable form:

Methylcobabalmin

Also available is the B-complex:
B-right (Jarrow)

For more information about the B12 research on cognitive decline, see: http://www.medpagetoday.com/Neurology/GeneralNeurology/28740

Follow-up on folate and cancer risk

We’ve had a recent comment on our own post regarding the importance of B12 and folate supplementation for people with HIV. The comment expressed concern about some reports that folate may be associated with increased cancer risk. Here’s a reply to that comment:

We recommend this web page for a recent study of folate and REDUCED colorectal cancer risk:

http://www.michaelmooney.net/FolateReducesCancerWillet.html

The 2011 article cited, by a well-known nutrition scientist, finds folate from diet and folate from supplements both associated with reduced colorectal cancer incidence–when taken over a long period (we’re talking about 15-20-30 years). This fits with what is generally understood about the value of vegetables in reducing cancer risk. Not surprising to us is the other finding of the study: that short-term folate intake, around the time of the development of pre-cancers, is not going to help reduce cancer incidence! Indeed, many supplements do not necessarily produce pronounced short-term effects, but rather show health benefits over the long term.