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

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!

NYBC’s MAC-Pack on the “Ask The Experts” forum, thebody.com

We were glad to see a recent Q&A on the “Ask the Experts” forum of thebody.com, which is one of the leading online sources of information for people with HIV. The question concerned NYBC’s MAC-Pack, our low-cost, close equivalent to K-PAX, a multivitamin/antioxidant combination which has been shown in research to raise CD4 counts, and which is available thru some — but not all–formularies in some — but not all — states.

For more information, see NYBC’s entry

MAC-Pack
Here’s the exchange:

QUESTION: macpac
Jul 5, 2011
are you familiar with the co. NYBC and their MACPAC-combination multivitamin & antioxidant program sells for 65 dollars and they compare to KPAC for 1/2 the cost..don’t want to throw money away on useless vitamins or vitamins that are sub-par or not tested

ANSWER: Response from Mr. Vergel

Supplement quality is always an important issue. One available resource is http://www.consumerlab.com although they are a for-profit company. It would be preferable if there were a government agency that routinely tested supplements and published the results!
It will always be a bit of a crapshoot, but the good news is the majority of supplements tested by them either pass and those that do fail often do for relatively minor reasons (though some do spectacularly).
According to Jared Becker and George Carter from the New York Buyers Club, the brands used in NYBC’s MAC Pack come from companies as reputable as K-PAX and with longer histories. NYBC has assessed Jarrow, Douglas Labs and Montiff, the providers used to make the Mac Pack. A few years ago, NYBC sent Montiff’s acetylcarnitine for testing and it came back fine. NYBC also uses consumerlab’s reports to verify quality of our big suppliers like Jarrow and Douglas.

Nelson Vergel

Entry posted at: http://www.thebody.com/Forums/AIDS/Nutrition/Q216051.html?ic=700101

Nutrivir/No Sugar Added: for weight maintenance

NYBC stocks Nutrivir No Sugar Added, which is a very useful and easy-to-take supplement to maintain optimal weight, especially when dealing with chronic illness. It’s a combination of whey protein powder, antioxidants, vitamins and minerals that’s formulated by upstate New York biotech company BioNexus. NYBC has chosen to stock the No Sugar Added version because that option responds to the concerns of many who are cutting down on refined sugar in their diets.

Overall, NYBC members have found this product to be very useful for maintaining optimal weight and also just for its convenience in supplying antioxidant and multivitamin/mineral supplements in a single product that can be easily added to cold beverages, smoothies or yogurt. Note some of the additional active components of Nutrivir: digestive enzymes, vitamins A, C, E, beta carotene, lycopene, lutein, selenium, N-acetyl cysteine, alpha-lipoic acid, taurine and L-carnitine.

A fascinating website/graphic

Click on this link for a fascinating graphic that reviews literature on a wide array of supplements. The larger the bubble, the more searches. The higher up it is, the more robust the data (so far). When you click on a particular bubble, it opens up to a study on that particular compound.

Supplements for the Brain (and Nerves)

“For Your Peace of Mind…”

Recent research on supplements for memory, cognition and other neurological functions
You may remember (we hope you remember!) the Scarecrow’s petition to the Wizard of Oz for a brain. Be advised–we at NYBC do not stock new brains, so don’t come to us with that request.

However, we do follow the sometimes startling new research on supplements, brain function and related neurological issues. In this department, there’s special cause for concern for people with HIV. According to a Canadian study released in 2010, in a group of 1615 people receiving treatment for HIV during the decade 1998-2008, one fourth had neurological problems, including memory loss, cognitive impairment and peripheral neuropathy. Of course being worried about brain function–and neurological function in general–is not unique to people with HIV. As people age, they are more likely to experience memory loss or forms of dementia such as Alzheimer’s. And the nerve condition called peripheral neuropathy (pain, tingling in the feet and hands) is found not just in people with HIV, but also among the growing population with Type 2 diabetes.

Now, on to what we see as some of the most valuable recent findings about supplements and brain or neurological function:

B vitamins can be considered a foundation because they are needed in so many processes essential to the brain’s operation, from energy supply and healthy blood flow, to the formation of neurotransmitters (=chemical messengers of neurologic information from one cell to another). Furthermore, there is evidence that several groups of people, including those over 60 and those with HIV, have a greater risk for Vitamin B deficiencies. So supplementing with a B complex vitamin is a sensible start to cognitive health. More specifically, there is good research linking deficiency of vitamins B12 and B6 to mood disorders like depression—and depression earlier in life is associated with higher risk of dementia in later life. Last, there is also some evidence that B vitamins may reduce stroke risk in older people.

Omega-3 fatty acids (fish oil) support cognitive health in a variety of ways. In 2008, UCLA researchers reported on a lab study showing that the omega-3 fatty acid DHA, together with exercise, improved cognitive function. This caught our attention, because there is wide agreement that regular exercise strongly supports brain function as we age, and here the suggestion is that omega-3 fatty acids multiply that known benefit. A diet rich in omega-3 fatty acids/fish oil has also been linked to lower risk of depression—another plus. And still more: recent research found that omega-3 fatty acids block the development of retinopathy, a chief cause of blindness as we age. (The retina of the eye is actually part of the brain–it is full of nerve cells essential for vision.) All in all, the neurological benefits of omega-3 fatty acids seem both wide-ranging and quite convincing, so it’s high on our recommended list.

The amino acid acetylcarnitine has shown benefit for brain function in a number of studies with humans. In the last decade, acetylcarnitine has also been investigated for peripheral neuropathy in people with HIV. (Some recommend using it with evening primrose oil and Vitamin C.) A 2008 study found that acetylcarnitine influences a chemical process in the brain that triggers Alzheimer’s, so researchers are continuing to puzzle out how this supplement produces its neurological benefits.

Antioxidants. There’s much suggestive research about how antioxidants counter destructive oxidative processes in the brain, thus blocking memory loss and cognitive decline. For example, a 2003 report found that the antioxidant combination alpha lipoic acid and NAC reversed memory loss in aged laboratory mice. And there’s also been a lot of attention to the combination acetylcarnitine and alpha lipoic acid for memory impairment. Furthermore, other antioxidants such as curcumin are under study for their potential to fight the processes that lead to declining brain function.

Acetylcholine. The first neurotransmitter to be identified, acetylcholine is closely associated with memory, with lower levels linked to memory loss. NYBC currently stocks two combination supplements that support acetylcholine levels in the brain, while also providing other nutrients for neurological function: Neuro Optimizer (Jarrow), which includes acetylcholine enhancers, acetylcarnitine, and alpha lipoic acid; and Think Clearly (SuperNutrition), which includes B vitamins, as well as acetylcholine enhancers and a botanical traditionally used for cognitive support, ginkgo biloba.

Resveratrol. In the past decade, there has been intense scientific interest in this compound, most famously found in red wine. While some research ventures have hoped to find in resveratrol a life-extending supplement (a capacity demonstrated in animal studies), others have focused on its therapeutic value for conditions like diabetes or cognitive decline. For example, Cornell researchers reported in 2009 that resveratrol reduced the kind of plaque formation in animal brains that causes Alzheimer’s. And a year later another lab investigation, this one at Johns Hopkins, found that a moderate dose of the compound protected animal brains from stroke damage.

Ginkgo biloba, a botanical derived from Earth’s most ancient tree species, has been widely used for cognitive function. In the late 1990s, two reviews of dozens of ginkgo studies concluded that it could improve symptoms of dementia. However, a long-term trial of ginkgo published in the Journal of the American Medical Association in 2008 found that the supplement did not prevent development of dementia in a group of more than 3000 older people who had normal cognitive function at the start of the research. One possible conclusion: ginkgo may help symptoms of cognitive decline, but doesn’t address underlying causes.

NYBC’s RECOMMENDATIONS: A B complex supplement (like Jarrow’s B-right) and fish oil (like Jarrow’s Max DHA) are foundations for maintaining cognitive health, especially important for people with HIV or people over 60. There is some evidence for acetylcarnitine, alpha lipoic and acetylcholine supplementation for memory impairment and possibly for cognitive decline. Acetylcarnitine and other supplements can be used to address peripheral neuropathy. And stay tuned for emerging research on preserving brain function with compounds like resveratrol, NAC and curcumin.

Curcumin for strokes?

An article over at the BBC underscores a potential new use for curcumin, the substance derived from turmeric, in helping stroke patients. One thing would be nice is if they recognized the way it is used in Ayurvedic medicine. I.e., many formulas in traditions like Ayurveda (or Siddha) include honey, ghee or black pepper. These all can enhance the bioavailability of curcumin. Some may even help it to cross the blood-brain barrier. By contrast, it may merely need to reduce systemic inflammatory responses among cell types that do cross the BBB, thus reducing neuronal damage.