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

More supplement hysteria

Here we go again. Sanity seems once again to have fled the playing field. Some “scientists” have declared supplements are all worthless at best or dangerous at worst. This is as ridiculous as those who would say all “drugs” are worthless or dangerous.

First, we have an article published on 12/22/13 in the New York Times. (Note: link embedding seems to be broken on WordPress: http://www.nytimes.com/2013/12/22/us/spike-in-harm-to-liver-is-tied-to-dietary-aids.html?emc=eta1 ).  Once again, an article that purports to be informative distorts knowledge in pernicious ways. Let’s unpack it a bit.

The article notes that some people have reported liver damage due to supplements. Here they conflate the effects of supplements themselves with the notion that some supplement manufacturers are crooks who spike their products with drugs. And then they trot out the usual lie that the FDA is helpless because of the Dietary Supplement Health Education Act (DSHEA). Eventually, they note that the FDA DOES indeed have the power to go after companies that have a corrupt product; it’s just they only recently started to actually do this work, in a very limited way. Why? Because they don’t have the budget (thank you, horrible Congress) to do their job of assuring that dietary supplements AND drugs AND food are pure and contain what the label says.

More critically, they go on to the topic of the potential of some supplements to harm the liver. Here, there IS truth–though a bit of context may help. The specific example they go after is the potential for the catechins found in green tea to be hepatotoxic (liver damaging). Indeed, this can happen but is extremely rare; some cases of presumptive damage by green tea was again due to a contaminant by the herb, germander. (Other cases of young people using it to get “cut” in bodybuilding one may expect liver toxic steroid use or supplements again so adulterated.) However, some few cases have been reported and consumers using Green Tea supplements should be on the alert for liver trouble. We have amended our entry on Green Tea to reflect this. But overall, the benefits of green tea supplements or drinking green tea outweigh this potential risk.

The case of the young man facing a liver transplant is indeed horrible. What remains unclear is whether this was directly due to the supplement or whether there was a contaminant in the supplement. Such an anecdote of harm, however, is no more valid than an anecdote of benefit.

We need a robustly funded FDA to assure that products are what they say they are.

Coming up–a review of the Annals of Internal Medicine–bits of truth lost in more hysteria.

The MAC-Pack: a unique multivitamin – antioxidant package for people with HIV

The New York Buyers’ Club continues to stock its multivitamin-antioxidant combination package, the MAC-Pack. At half the price of K-PAX, the MAC-Pack provides a similar package of multivitamin supplementation (with emphasis on the crucial B vitamins), together with acetylcarnitine (especially important, we believe, if you are dealing with neuropathy) and the antioxidant combo, alpha lipoic acid plus NAC (N-acetylcysteine).

A 2006 research study found an increase in CD4 count among HIV+ individuals using this type of multivitamin-antioxidant combination. Dr Jon Kaiser, the study’s author, subsequently developed K-PAX, which has been included on various Medicaid and ADAP formularies, but is often just too expensive for those who must buy it out of pocket.

For more details, see the NYBC entry:

MAC-Pack

NYBC’s ThiolNAC – Antioxidant Supplement

ThiolNAC at NYBC

NYBC’s specially manufactured antioxidant supplement, ThiolNAC, is again in stock at the nonprofit co-op. Below is the product description for this combination supplement, which is available only through NYBC, and which provides a key part of NYBC’s MAC-Pack, our LOW COST alternative to K-PAX:

ThiolNAC (NYBC) Each bottle, 90 tablets, sustained release formula. Each tablet contains 500 mg of NAC and 134 mg of alpha lipoic acid. As part of the MAC Pack, three per day provide the equivalent dose as used in the original neuropathy study published in the journal AIDS: 1500 mg of NAC and 402 mg of alpha lipoic. This is an excellent formula for those suffering from liver inflammation. It is also extremely convenient for many PWHIVs who take both NAC and Lipoic Acid since this 2-in-1 combination eliminates some pills while providing the same, generally accepted dosages. Suggested use is 2-3 tablets daily with meal or as directed. Reduce dose if headaches occur.

Note: This version of NYBC’s ThiolNAC intentionally decreases the alpha lipoic acid amounts per tablet from our original formula’s 200mg/tab to the present formula’s 134mg/tab. This change brings us precisely in line with the dosage studied in Jon Kaiser’s study, and also responds to a concern raised by our colleague Lark Lands regarding higher dose alpha lipoic and hypothyroidism.

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!

Quercetin: New Study Suggests Its Potential for Hepatitis C Treatment

Quercetin has been available as a dietary supplement for decades. This plant-derived compound can be found in various foods, such as onions, apples, red wine, grapefruit juice, orange juice, pomegranate juice, as well as white, green and black teas. It is an antioxidant and has been shown to inhibit the oxidation of LDL cholesterol (the so-called “bad cholesterol”)–thus checking one of the primary processes implicated in the development of cardiovascular disease. It has also been investigated as a support for respiratory function.

But what excited us recently were reports about the potential of Quercetin to thwart the hepatitis C virus, and so perhaps provide a new, less toxic way of combating this debilitating disease that affects an estimated 270 to 320 million people worldwide. While there are currently approved treatments for hepatitis C (ribavirin and interferon), they can have significant side effects, and are not always effective. The recent Quercetin research, published in 2010, finds that this plant-derived compound may inhibit hepatitis C replication in a novel way, targeting cellular proteins rather than viral proteins. Clinical trials with Quercetin are now planned, and will focus especially on a type of hepatitis C that is least susceptible to successful treatment by the current medications. We will certainly stay tuned for more news on this topic!

NOTE: NYBC stocks Quercetin 500mg/100 and Quercetin 500mg/200

Reference:

Samuel W. French, et al. The heat shock protein inhibitor Quercetin attenuates hepatitis C virus production. Hepatology, Volume 50 Issue 6, Pages 1756 – 1764.

Antioxidant Optimizer: broad spectrum antioxidant formula

NYBC now stocks Antioxidant Optimizer from Jarrow Formulas, a broad spectrum antioxidant supplement that provides a blend of water and fat soluble antioxidants ( meaning they are widely absorbed in the body), including:

Lutein and lycopene, which protect the eyes, cardiovascular system, breast, cervical, and other tissues and organs;

and

Green tea extract, olive fruit extract, grape seed extract, and milk thistle, which support liver health and cardiovascular system health.

For more details, see the NYBC entry:

Antioxidant Optimizer

Yes, you’ll also notice that NYBC’s nonprofit co-op price for this product is very reasonable!