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A nutritional approach to the treatment of HIV infection—same old woo?

I get all sorts of mail. I get mail from whining Scientologists, suffering patients, angry quacks—and I get lots of promotional material. I get letters from publishers wanting me to review books, letters from pseudo-bloggers wanting me to plug their advertiblog—really, just about anything you can imagine.

Most of the time I just hit “delete”; it’s obvious that they’ve never read my blog and they’re just casting a wide net for some link love. But a recent email from a PR firm piqued my interest: (it’s a long letter, and I won’t be offended if you simply reference it rather than read the whole thing now):

Hi Dr. Lipson,

My name is N. and I am reaching out to you on behalf of Dr. Jon Kaiser, an esteemed HIV/AIDS and nutrition specialist who specializes in supporting immune system function with nutrition.

I recently read your blog post titled “Will Congress Finally Reform Supplement Laws” and thought you might be interested in Dr. Jon Kaiser’s perspective on the role of nutritional supplementation in medicine.

Dr. Kaiser is well-known in the global AIDS/HIV community.  In the 1980′s, Kaiser pioneered the use of nutritional supplements in HIV/AIDS patients to help them build stronger immune systems; his research showed that conventional drug treatments were more effective if the patient’s immune system were strong.  Today, many AIDS and HIV patients around the world follow this treatment paradigm.

As a physician, Dr. Kaiser is well-known in the global AIDS/HIV community.  In the 1980′s, Kaiser pioneered the use of nutritional supplements in HIV/AIDS patients to help them build stronger immune systems; his research showed that conventional drug treatments were more effective if the patient’s immune system were strong.  Today, many AIDS and HIV patients around the world follow this treatment paradigm.  Building upon his success in HIV patients, Dr. Kaiser is applying the lessons learnt in HIV to patients with cancer, Chronic Fatigue Syndrome and other chronic diseases, general health and the elderly.

Dr. Kaiser is very passionate about advocating nutritional supplementation and views it integral to successful disease and general health management.   He would more than like to share and engage in a discussion about the supplements and the impact of the proposed reforms to supplement laws.

I’ve included more information on Dr. Kaiser and K-PAX and I have pasted links to a 2001 double-blind, placebo-controlled study funded by Bristol-Myers Squibb that demonstrated an increase in the number of CD4 lymphocytes in HIV-infected patients who were taking Dr. Kaiser’s natural immune support formula compared to patients taking a placebo (in addition to standard HIV medications). This formula has been refined over 15 years and is now in clinical trials with the goal of receiving FDA approval.  If successful, Dr. Kaiser will be one of the first nutritional suppliers to gain FDA approval for  the use of a nutritional supplement as an adjunctive therapy for disease management.

I’ve never heard of Kaiser, and the only K-PAX is know is home to Prot. So I looked it all up.

Before I assume anything about a doctor, I always check to make sure they’re really a doctor.  Jon Kaiser is an M.D. in northern California. He graduated from a real medical school where he apparently performed well.  According to the state medical board, his license is current and he has no official actions against him. He has reported to the state board that he is not board certified in any specialty, but claims non-boarded specialty status in internal medicine and infectious disease. He reported to the board and listed on his CV that he has one year of post-graduate training.  I’m not sure how one can claim to be an internist without specialty training, but he does.

To specialize in internal medicine requires three years post-graduate training, and to specialize in infectious diseases generally requires an additional 1-3 years of post-graduate training. It’s not unheard of for older HIV specialists to not have formal infectious disease training—many of them were internists who invented the field of HIV medicine out of necessity when the epidemic first appeared. But to practice internal medicine or infectious disease with only one year of post-graduate training (an internship probably) is very, very unusual.  My state currently requires completion of two years of post-graduate training in a certified program, although since two year programs are vanishingly rare, most licensed physicians will have at least three years.   In the old days, a doctor could finish an internship and hang up a shingle as a family doc.   But even back in the 80s, internal medicine had become far too complex to rely on just an internship.  Hell, my dad graduated from medical school in 1949 and even then internists were expected to compete a full residency program.

This doesn’t mean Kaiser isn’t a good doctor, but it raises the bar on any claims he makes.  If I know that someone is a boarded internist and infectious disease specialist, and is published in her fields of specialty, I’m likely to require a bit less as far as proving his or her credibility. Someone who completed a brief course of post-graduate training and declares themselves to be an expert will require a lot more to convince me of their expert status.

Most HIV specialists are infectious disease specialists first, and if they belong to a professional organization it is usually the IDSA or the HIVMA. His CV lists him as a member of the American Academy of HIV Medicine.  I’m not familiar with their work, but their website has some useful information. Included is a verification engine to see if a doctor is a member: Kaiser  is not listed on their verification site. He lists himself as being on multiple boards, so I’m assuming this is a glitch in the system.  He also lists himself as a founding member of the California Academy of HIV Medicine, an organization I cannot yet find on the web.  I asked his publicist about this and this was Dr. Kaiser’s response:

As a founding member of the American Academy of HIV Medicine, I was intimately involved in setting policy objectives for the organization in its early development phase beginning in 2000. I formed the Academy’s Reimbursement Committee in 2000, and was quoted in the attached AAHIVM newsletter (see middle column, paragraph #2). I have also been certified as an HIV Specialist by the organization on two separate occasions (see attached). It appears my membership to the national organization and California chapter inadvertently lapsed when I moved offices. This has been corrected and my membership is now currently active.

Well, I guess that explains the discrepancy between his CV and the professional organization he claims membership and leadership experience in.  Unfortunately they didn’t find me a link to the CAAHIVM.  Perhaps they don’t have a website.

Anyway, I was curious about the publicist’s claim that Kaiser is a major player in the HIV community, so I did a PubMed search. It turned up three references.  I guess one can be a respected HIV clinician rather than a researcher, and that would certainly not show up in PubMed.  But that leads to another problem.

Kaiser bills himself as “combining the best of natural and standard therapies” for HIV disease.  I have no reason to doubt this, but since his approach is unorthodox and he isn’t an active researcher I’m not sure how he knows that his treatment is so good.  He does claim some pretty spectacular results:

Though long term stability in my patients has always been the rule, I can now definitely say that the progression of HIV disease in my practice is an extremely rare event. This experience, which has encompassed the care of over 500 HIV(+) patients during the past five years, allows me to make the following statements: Not one patient who has come to me during the past six years with a CD4 count of greater than 300 cells/mm3 has progressed to below that level. Not one patient who has come to me during the past six years with a CD4 count of greater than 50 cells/mm3 has become seriously ill or died from an HIV-related illness. This extraordinary level of good health and stability does not come without hard work. My patients follow an aggressive program of natural therapies to support their immune systems. They have also benefited tremendously from the new drugs, lab tests, and other recently released treatment options. What a difference a few years has made!

That seems pretty impressive to me, for a few reasons. In many circumstances, someone who has gathered this much favorable data would have published it.  Without seeing the data in a peer-reviewed journal, there’s no way to verify the validity of these claims, or the reason for them.  If the data are accurate, perhaps he attracts a very medically-adherent population.  At many of the HIV centers I’m familiar with, patients often have financial, social, and psychiatric barriers to care, and results aren’t so rosy.  So what’s this guy’s secret?  Does he have a really, really compliant set of patients, or is he doing something different, something not yet well-represented in the HIV literature?

According to him, the secret is his “comprehensive” approach:

I define a comprehensive approach as one which adds a program of aggressive natural therapies and emotional healing techniques to the standard medical treatment of an illness or condition. An aggressive natural therapies program includes a combination of diet therapy, vitamins, herbs, exercise, and stress reduction. Emotional healing encompasses a proactive program of psychological healing techniques that ideally includes a spiritually-oriented practice (prayer, meditation, yoga, etc.) combined with a significant level of social support.

That’s a bold statement.  He claims extraordinary results, and claims that a raft of disproved therapies are the answer. If, as he claims, this approach is especially beneficial to those who cannot tolerate proven therapy with anti-retroviral drugs, he really should be working off data, data that show that his approach is safe and effective.
And that brings us back to the original letter from his publicist.  In the letter, they claim that K-PAX (the supplement, not the planet) significantly increased CD4 counts compared to placebo in patients taking usual therapy.
Whether CD4 cell count is a useful measure in this setting is debatable.  Viral load is an important measure of HIV activity, and CD4 count varies from moment to moment.  Also, above a certain level, it’s not clear that CD4 cell count is a marker of clinical risk.  Important outcomes other than CD4 cell count and viral load include prevention of opportunistic infection.
In Kaiser’s study, published as a “rapid communication”, he measured many parameters in addition to CD4 count.  This was a very small study (40 patients) with a very brief follow up period (12 weeks).  In the results section, the author notes that there were differences in the characteristics between the test and control groups, and that these differences were not statistically significant:

(1) the micronutrient group had a lower CD4 count at baseline when compared with the placebo group (CD4: 357 ± 154 cells/μL vs. 467 ± 262 cells/μL, P = 0.13), (2) the participants in the micronutrient treatment group reported a greater number of months of neuropathy symptoms preceding enrollment than those in the control group (means: 21.4 months vs. 12.2 months, P = 0.14; medians: 14.2 months vs. 2.5 months), and (3) the micronutrient treatment group contained 3 patients with diabetes mellitus compared with zero in the placebo group (P = 0.09).

It is technically correct that most of these differences were not statistically significant, but, look at the results:

The mean absolute CD4 count increased significantly by an average of 65 cells in the micronutrient group versus a 6-cell decline in the placebo group at 12 weeks (P = 0.029)

CD4 counts vary quite a bit, and are an imperfect measure of disease activity and immune function.  As we can see from his groups, there was a very large range of CD4 counts in each group at the start.  An average change in CD4 count of 65 seems anemic at best. Kaiser is more optimistic:

This study demonstrates that a micronutrient supplement administered to HIV-infected patients taking stable HAART significantly enhances CD4 lymphocyte reconstitution. Our findings support the potential for a broad-spectrum micronutrient supplement to be used as adjuvant therapy in combination with HAART to provide patients with a more robust CD4 cell rebound after initiating antiretroviral treatment.

I find the data from this pilot study entirely unconvincing.  His conclusions are hyperbolic and premature.  That’s not unusual, though.  Researchers sometimes get a bit excited about their work, and as an inexperienced author, perhaps he can be forgiven for a little unrestrained enthusiasm.
But it gets a bit more interesting that that.  In a letter to the editor, a careful reader noted something unusual. A patient showed him a brochure claiming that K-PAX could raise CD4 counts by 26%.  K-PAX, it seems, is the same product used in Kaiser’s study. The writer was concerned:

Most disturbingly, the first author on the paper, Jon D. Kaiser, MD, seems to be the same person mentioned in the brochure as the developer of K-Pax Vitamins.

[...]

Given the recent controversies at other medical journals about the failure of authors to disclose potential conflicts of interest, I am sure that this article would not have been published without disclosure (or at all) if the Editors had been aware of the conflicts of interest in this case.

There is a long, sordid history of conflicts of interest in published research.  Some drug companies have gone so far as to print their own faux-journals containing only favorable studies.  That is why most journals have strict disclosure rules for conflicts of interest. A study being sponsored by a drug manufacturer does not invalidate it, but failure to disclose this connection is unethical and problematic on many levels.
Kaiser was (correctly) allowed to respond:

After reporting the improved immune reconstitution of patients taking the micronutrients plus highly active antiretroviral therapy (HAART) to the Bristol-Myers Squibb team, I anticipated that they would show interest in pursuing the development of a therapy that had the potential to act as a safe and beneficial immune modulator.

On learning that they had no interest in pursuing the development of this compound, I chose to form a company, K-PAX, Inc., to keep the micronutrient supplement in production and make it available for sale while I worked to get the study results published.

I neglected to inform the Editors of this journal of this conflict of interest and any potential bias that existed during the paper’s submission and publication process. Nor did I inform the other authors on the paper of my financial interest in the company. They received no personal compensation for their efforts.

In other words, he is the guy who makes and sells K-PAX, and he owned up to failing to disclose this profound conflict of interest. I asked Kaiser through his publicist about this. His response was less conciliatory:

This research study was performed before there ever was a company or financial interest in a product (2001-2003). The data were analyzed by an independent Data Analysis Firm selected by Bristol-Myers Squibb in 2001. The JAIDS editorial board performed a thorough evaluation after Dr. Smith raised his concerns and found no evidence that either the data analysis or study conclusions were inaccurate.

I’m unimpressed by this response.
As I’ve said many times in this space, being wrong is not a moral failing—being deceptive is.  Many doctors who offer unproven therapies are genuine in their beliefs that they are doing good.  This doesn’t change the fact that promoting unproved treatments is a bad thing.  A doctor should know better than to use hyperbolic language to convince HIV patients that he somehow has the answer to their disease, an answer that no other specialist has.  Of course, most doctors have a lot more formal training that Dr. Kaiser, so perhaps he can be forgiven for his hyperbolic promotion of a single pilot study as a major breakthrough in HIV treatment.
Right?

Posted in: Herbs & Supplements, Nutrition, Science and Medicine

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36 thoughts on “A nutritional approach to the treatment of HIV infection—same old woo?

  1. Steve S says:

    Interesting. One critique. I am a Family Doc, I did 3 years of residency and teach at a residency program. After one of internship you can practice general practice, but you are not a family medicine doc. We also now have subspecialties, many overlap and are the same as internal medicine subspecialities, along with ob and sports medicine.

  2. Peter Lipson says:

    Yeah, folks who do a year of a rotating internship often call themselves GPs or “family docs” despite the fact that they are not really family docs. Calling oneself an internist and HIV specialist after one PGY year seems a bit…off…to me.

  3. cervantes says:

    In fact there are ongoing studies of the role of nutrition in HIV disease — large scale, well funded ones. One has recently been completed at my institution and I believe articles are coming out soon. So we will know more about this definitively — it’s not as though nobody ever thought of it before. It is the standard of practice in HIV care to counsel people to follow a healthful diet and maintain a good weight; people who are anorexic, due to medication side effects, or who have disease related wasting, are routinely given nutritional supplements (e.g., Ensure, Boost). This is normal practice already. I believe there have also been some trials in Africa, where sub-optimal nutrition is common, which have suggested that correcting vitamin deficiencies is helpful.

    So hold off on the wu (the usual spelling of the shamanistic practices of the mysterious East btw — I’m not sure why y’all have adopted woo). We’ll have more detailed and definitive info soon.

  4. Peter Lipson says:

    There are some studies in Africa, as you said. Kaiser also reports that his formula is currently undergoing more investigation for the purpose of gaining FDA approval.

  5. Steve S says:

    Agree Pete; Problem is a lot of people claim credit or credentials without adequate or even real training or expertise. Big problem even those with training and credentials go to the dark side. I know a number in the integrative medicine field or others that have real credentials, Family Medicine, Internal Medicine, Pediatrics etc. The problem seems to be that a lot claiming such claim to be a Nutritionist. We have a real medical allied field called Dietiticians. So woo tend to call themselves Nutritionists, not Dietiticians. On their part I think it is mostly just BS (Basic Speculation).

  6. I first heard of this in the mid-80s. The theory was that people were taking lots of drugs, and that the drugs would work best if the CYP pathways were in full working order, so B-complex vitamins were prescribed alongside the drugs to ensure that B-vitamins wouldn’t be a limiting factor.

    It didn’t sound woo-y at the time: it sounded fairly straightforward. I’m surprised that 25 years later, the usefulness of vitamin supplementation as an adjunct to drug therapy still hasn’t been either confirmed or discarded. It’s not as though it would be that difficult to evaluate.

  7. Steve S says:

    High dose vitamins and other nutrients have been tried in the past. The body only absorbs what it needs and you literally flush the rest down the drain. References: Principles of Evolutionary Medicine by Peter Gluckman, Alan Beedle and Mark Hanson. Also Evolution Rx by William Meller. Then look at their references.

  8. Wolfy says:

    Thank you for raising the importance of honest credentialing. Being shady about one’s training, or elevating one’s credentials, seems to be a common theme amongst those who practice woo. The practitioner who is dishonest regarding his/her educational background, may very well be dishonest in other areas.

  9. windriven says:

    “I’ve included more information on Dr. Kaiser and K-PAX..”

    K-Pax? Wasn’t that a Kevin Spacey movie whose protagonist may or may not have been an extraterrestrial?

  10. Skepacabra says:

    Are you sure this Jon Kaiser isn’t really Stephen Glass and the organization without a website isn’t Jukt Micronics?

    This reminds me of when I investigated Rashid Buttar’s claim that he was one of the Top 50 doctors in the United States.

  11. DREads says:

    It’s very sad to see yet another instance of vitamin/supplement peddlers preying on the desperation of sick people with “more money than sense” (to quote a British comedy sketch) and making a bundle in the process. The differences in CD4 counts between the treatment and placebo groups aren’t statistically significant and are likely the result of random variation. The lackluster results of the scant research on the supplement is probably the reason for Bristol-Meyers withdrawing its support for further research into its efficacy.

    It would be very disappointing if the FDA starts approving nutritional supplements for immune support without supportive data from rigorously conducted studies. Perhaps Dr. Kaiser does not expect to get FDA approval but markets the possibility of approval as a way of getting credulous HIV+ consumers to buy his product? This “FDA approval” nonsense could be part of his business strategy.

    As much as it stinks, it could be worse. Dr. Kaiser isn’t marketing his vitamins as a replacement for HAART therapy like the DNCB cranks did in the 1990s.

    The alt-med community commonly argues that it is in the interests of conventional medicine to squash any effective supplements for managing HIV disease because such supplements would eliminate a significant source of big pharma’s profit. This is a bogus argument because it ignores the fact that conventional medicine is made up of major players with different and complementary agendas and interests: insurance companies, physicians and hospitals, scientists, universities, and pharmaceutical companies (not an exhaustive list). A university medical professor’s main agenda isn’t a monetary one but rather to engage in scientifically rigorous research to understand disease and find effective methods for diagnosing, monitoring, and treating them. The goal of an infectious disease doctor is to treat their patients as effectively as possible. If the most effective treatment is also cost effective then this benefits a different player, insurance companies. If supplements were really shown to work, backed up with strong science, there would be a critical mass of non-big pharma players (including doctors) who would gladly endorse them. But the evidence just isn’t there.

    Monetary conspiracy theories are a cheap trick but it’s hard to make them convincing.

    Damian

  12. Steve S says:

    Correct. Also the CAM community like to bill their products as us against them or Big Pharma v us. IN reality most big pharma have seen the popularity and income potential of supplements, vitamins etc. And it is they who really manufactor the products the CAM people sell. Pharma likes it because there is no rigourous testing that has to go into conventional medicine. So that is another point of contraversory, contention, hypocracy or anything you like to call it.

  13. Fifi says:

    Unfortunately, nutrition and supplements is one area where science is still really only starting to understand what is going on. As usual, CAM finds rich soil to exploit in the gray areas where research is only starting to come to fruition or in the early stages. While I’m in no way endorsing CAM nutritional quackery – I find it very frustrating to see people being exploited by half truths and lies – we’ve got to be careful not to throw the baby out with the bathwater. Why? Because, ultimately, it ends up lending legitimacy to the quacks and makes SBM look ideological when medical research does uncover things like the role of vitamin D in the proper functioning of the immune system (recent research). Unfortunately clear nutritional information is hard to come by since there are so many players looking to profit from selling lies – from the food industry to CAM practitioners…and even some people who identify as being representative of SBM who have little knowledge of nutritional science but are purely reactionary regarding CAM. (I’m not suggesting that this blog post is an example of this, it’s just that nutrition and exercise are both areas where ideology seems to trump the actual science for both CAM and SBM advocates. I hope that the SBM blogging collective can find someone who is a specialist who can blog about the actual science being done so that there’s someone actually standing up for the science and public health.)

  14. rork says:

    “The differences in CD4 counts between the treatment and placebo groups aren’t statistically significant and are likely the result of random variation.” – DREads.

    I hate to thwart criticism of the unethical, but I think this statement is unfair. T-tests on the CD4 count differences (before – after) gave p=.029, and my reading is that the same test on percent change (same as taking logarithms) gave p=.01. I would have used that second test. (Perhaps I would plot the data, and also offer a Rank-sum test on the differences. Fancier models are possible, where I’d use the before values as covariates and estimate the regression coefficient, rather than assuming it was 1.0.)
    That’s not fantastic evidence, and I worry about data selection and patient selection, particularly from the conflicted, but it is some evidence. Either you are proposing to T-test the “after” means without considering the “before” values (and aren’t clear enough that you are testing a model that differs from the paper’s test), or you mean something by significant that you don’t make clear (I am hardly dogmatic about .05 or .01), or there’s some other trouble.
    Let’s keep the math clear.

  15. Steve S says:

    The allied field of Dietetics already has a large research based data base. So a lot of it has been done. That does not mean that more cannot be learned through more research. Vitamin D does come into play with many things. However, saying that more needs to be done on other vitamins and we don’t know about them, is untrue. We do know a lot about other vitamins and so called vitamins and supplements. Of the 13 known vitamins, 6 can be taken in overdose. Over 50,000 people OD on vitamins/year in the US. 80% are usually children. 50 usually have serious illness and some even die. Anit-oxidants are pushed in this country. The Free radicals are used as signals in the body, so anti-oxidants may be harmful. But as I stated in an earlier post, they are strictly controlled by the body and taking more in by mouth makes more go out in the drain. The anti-oxidant theory, or hypothesis was first proposed by Denham Harman a free radical chemist for the oil industry in the 1950′s. That is where all the hype regarding free radicals and anti-oxidants started. Since then more research has shown that much of his idea is wrong. See Nick Lanes book Life Ascending for reference. In 2009 researches from the Womens Health Initiative, under the National Heart, Lung, and Blood Institute, finished a 15 year study that focused on strategies for preventing heart disease, various cancers etc. in postmenopausal women and found no evidence of any benefit from multivitamin use in any of the conditions examined. And interestingly, vitamins did nothing to lower the death rate. So we are not throwing out anything with the bath water, we are keeping the good stuff and just throwing out the dirty bath water.

  16. DavidCT says:

    Most supplements are eventually provided by Big Herb which is usually a wholly owned subsidiary of Big Pharma. Their products are natural so that means everything is just fine. These products do not require FDA approval if they carry the “Quack Miranda label”.

    The well known fact that people with deficiencies (African studies) do better with proper nutrition. This says nothing about the health prospects for the well nourished fighting serious disease. I recall Matthias Rath citing those kinds of studies to justify his multi-vitamine HIV treatments in South Africa. At least Dr.Kaiser does not suggest giving up on HAART.

  17. Fifi says:

    Steve S – “So we are not throwing out anything with the bath water, we are keeping the good stuff and just throwing out the dirty bath water.”

    The problem is that we’ve even seen some rather reactionary attitudes towards nutrition from an SBM blogger on this site…so they baby does get thrown out with the dirty CAM water at times by people who should know better. It’s why a SBM blogger who’s actually working in the field of nutrition would be such a massive asset and wonderful public resource to help people discern fact from fiction and science from pseudoscience.

    You’ll get no argument from me that the hype does nothing to help educate people or further actual knowledge about vitamins and nutrition in general. And this hype comes just as much from “conventional” industries as “alternative/CAM” ones…all the people interested in selling us their product (and this includes agricultural marketing boards). Throughout history, “magical” food has had its allure for people looking for magic bullets that bestow immortality, sexual virility, intelligence or beauty, and industry knows how to harness this and mix it up with a bit of pseudoscience to make money.

    For people living in places where they get adequate sunshine (and if they’re outdoors enough during the day), there’s no need for vitamin D supplementation. However, in a place like Canada it’s proving to be a very big public health issue (and there is increasing evidence that deficiencies in vitamin D may contribute to cancer rates, the first Canadian studies around vitamin D were focused on prostate cancer, if I remember correctly, and the first correlation that led to further research was between Canadians that took a yearly two week winter vacation in the sun).

    I also found the more recent research on anti-oxidants interesting. Generally speaking, mega-dosing or over-consumption of any one thing seem to be somewhat problematic. However, in the case of vitamin D it appears that we may well need a substantially higher dose than previously thought. We still have a lot to understand about nutrition, and not only individual vitamins and minerals but how they work together.

    The challenge for everyone, and this seems to include a lot of medical professionals who aren’t specialists or following the research, is discerning the science from the vast amounts of pseudoscience/marketing that we’re deluged with non-stop. My main point in brining up the baby/bathwater is about public perception and how to re-establish medicine as being the trusted source of information about nutrition.

  18. Steve S says:

    Fifi I would agree with you there. We can do a better job of publicising the science evidence to the lay public. I also agree that a lot of hype is out there, so trying to distinguish between valid and questionable claims is hard for lay public or even medical personal to do. Perception is truth as they say in politics. Unfortunately, in science that isn’t always so. As far as Vitamin D is concerned. Vitamin pills only contain one kind of vit D. We need 5 varieties, which we make from sunshine. We make about 10,000 IU of vit D after 30 min of sun exposure. The typical diet has only around 300 IU in the US. The USDA recommends 400 IU/day. So some recommend more sun. However, the dermatologists recommend against it for the reasons of skin cancer. So even within the medical scientific community there is disagreement on the best course. My own best guess it is probably some where in the middle. We need some sun to make all 5 varieties of vit D, but not constant sun exposure or tanning beds as we know that it the amount of exposure to UV over time that increase probability of skin cance. Another example Vit E. It has been promoted due to its so called anti-oxidant effects and as an aid to help slow down or prevent macular degeneration. There are some good studies now that it does no such thing, in fact there are some that show that show Vit E increase mortality 5% over placebo. From a report by Christian Gluud at the Center for Clinical Intervention Research at Copenhagen University Hospital. Yet more that 1/4 of americans take it. The only thing I know Vit E does is make rats fertile. In May 2009 in the Proceedings of the National Academy of Sciences published a report by researches in Germany and the US showing that antioxidant vitamins E and C actually reduce the benefits of exercise. Yet gurus like Andrew Weil and his ilk promote vitamins and supplements, especially their brand, which they are only too happy to sell you for a great price. I agree what we need is person of the caliber of Carl Sagan to promote and distribute facts about medical treatments, research etc.

  19. Angora Rabbit says:

    As a nutritional scientist at a major research university and a reader of SBM for the past several months (thank you, Skeptical Inquirer for promoting it), I’ve been largely disappointed, with a few excellent exceptions, at the magnitude of misunderstanding in the SBM community regarding nutrition research. Vitamin A (my expertise) was discovered almost 100 yrs ago, and there is an enormous and outstanding literature since then on what nutrients and micronutrients can – and cannot – do. There are some on this list who dismiss anything “nutritional” as woo, and that is simply not true. This blanket attitude undermines what SBM ought to be about and is a disservice to those who chose nutrition research and training as a profession. Nutritionist does not equate with woo, but because nutritionist is not a legal definition, there are some woo-meisters who like to pretend they are us.

    Regarding K-PAX, it’s pretty much a standard micronutrient supplement plus a few extras handling methyl metabolism. What the individual doesn’t store, as Steve S correctly says, turns into expensive pee (as I tell my students).

    But, could extra micronutrients benefit those with HIV? There are some suggestions it might. How might it do so? One route might be in changing micronutrient metabolism per se. HIV is associated with muscle wasting because of associated fevers and infections, which elevate basal metabolic rate at the expense of protein, and increase the utilization of antioxidant minerals such as iron, copper and zinc (antioxidant because they are utilized in anti-oxidant defensive enzymes such as SOD). So sure, their nutrient requirements could be increased.

    A second nutritional problem in HIV is the virus’s effects on oral and gut structure and function; the antiviral drugs also can cause gut damage (inhibitors of RNApol can also interfere with DNApol). The ulcers and poor gut mucosa make it hard for the individual to eat, and when they do eat, it makes it hard for nutrients to be adequately absorbed. So this will increase their nutrient requirement. For this reason, many HIV clinics have a dietitian who works with the patients. You can find studies on this topic in a simple PubMed search (HIV x nutrition support gives 923 references).

    In fact, here’s a nice review:
    Colecraft E. Proc Nutr Soc. 2008 Feb;67(1):109-13.
    HIV/AIDS: nutritional implications and impact on human development. PMID: 18234139

    An interesting post, but disappointing that there wasn’t a real discussion of what is in K-PAX and whether there might be real science underlying the possible claim. This is not to say that Kaiser is right or wrong (and I’m generally suspicious of anyone who publishes on proprietary claims without disclosure – an especially if they claim a proprietary nutrient mixture). But the level of discourse on K-PAX itself could have been more rigorous.

    Regrading Fifi’s excellent comment that: “how to re-establish medicine as being the trusted source of information about nutrition.” A good first step would be to make nutrition a requirement for medical students instead of an optional course, as the current situation at many institutions, including my own. Very sad.

  20. Harriet Hall says:

    Fifi said “The challenge for everyone, and this seems to include a lot of medical professionals who aren’t specialists or following the research, is discerning the science from the vast amounts of pseudoscience/marketing that we’re deluged with non-stop.”

    It’s not so hard to tell the science from the pseudoscience and hype. I think the bigger problem is that the science is not sufficient. Decisions about nutrition are necessarily based on inadequate data. Some people are willing to change their habits believing that current speculations may pan out in the future, while others are less willing to make changes because they know that most speculations don’t pan out.

  21. Peter Lipson says:

    Angorra, the point is not that the KPAX claims are implausible—they aren’t implausible prima facie. The point is the hyperbolic claims based on a single pilot study with a significant COI.

    The claims of micronutrients supps in HIV disease are plausible but not overwhelmingly interesting given the enormous benefit of HAART. Still, it’s worth studying, and it’s being studied, but there’s not hurry.

  22. But if HAART works better when the liver has all the coenzymes it needs to process all the drugs, why place them in opposition?

    Again, this is the theory that I heard back in the 80s. It had nothing to do with pharmaceutical effects of magic vitamins, and everything to do with a very pragmatic wish to ensure that nutritional status did not interfere with medication AND that the nutritional stress represented by the medication did not affect the individual’s health.

    If HAART regimes do not require coenzymes, then of course this theory is baseless.

  23. Fifi says:

    Dr Hall, while some of us may not have a hard time telling the hype and pseudoscience from the real science being done around nutrition, it’s pretty clear that the general public, people who promote pseudoscience that genuinely believe they’re promoting science, and some medical professionals and even some advocates of SBM have a hard time discerning what is true and what is marketing/hype. There are a lot of hyped up messages that are heavily marketed to the public from a wide variety of sources (with a big emphasis on magical foods) and very few reliable SBM resources that don’t just fall into reactionary anti-CAM stances without really looking at the science. (To be clear, I’m in no way defending the product being discussed in this blog, I’m simply promoting that the SBM blogs find someone qualified to actually deal with the woo so that science can reclaim nutrition from the food and supplement industries.)

  24. Fifi says:

    Dr Hall – And I agree that there’s a lot of speculation that goes on by both science and pseudoscience sources that then gets promoted as fact by various industries. This is yet one more reason to have a qualified SBM blogger to sort through fact, speculation and pure fiction so that people can gain a better understanding of nutrition and basic biology vis a vis nutrition.

  25. Fifi says:

    Another interesting area that it would be great to have a qualified SBM blogger to comment on is how specific vitamins or supplements interact with certain medications or treatments. (Though this may be more of a pharmacologist’s area of expertize.)

  26. Lawrence C. says:

    Angora Rabbit,

    Thank you very much for your comments. It is clear to me you do know of what you speak as this is a familiar topic for me. I especially appreciate your mentioning the problems of malabsorption and how it relates to nutrient intake. In the case of those with HIV, sometimes one must eat much more to get even a little and regularly taking a multivitamin supplement of some kind is recommended by many HIV specialists. (Whether or not the specific K-Pax formulation is as special as its marketing claims is another question!)

    You also note that the “level of discourse” on this could have been “more rigorous” and suggest that it was partly due to the optional nature of nutritional education in medical schools. I think this is a well-deserved criticism and often accounts for the reflexive dismissal by so many medical doctors of anything having to do with nutrition. It’s not that they dismiss things based on evidence but too often based on a lack of knowledge. Indeed, there is a great deal of evidence as you note from a simple PubMed search but in the hectic world of medical school and residency, unless such things are required, there simply isn’t time for optional work. This is a situation that should change as regards nutrition education.

  27. Angora Rabbit says:

    Dr. Lipson, I totally agree with you. N=1 doeth not a clinical conclusion make. And the COI is another strike.

    I also agree that the drugs are doing remarkably well for patient outcomes. Nutritional support cannot be a substitute for the drug regimens.

    Apologies for missing the thrust of your post. One pursues the rabbit of personal interest! :)

    A discussion of why something like K-PAX might gain traction with the public could be a potentially useful exercise for the readers. I find these supplement claims often claim a spark of truth that becomes fanned into an all-out conflagration. Being able to recognize the spark and where that spark vanishes into smoke can be helpful for critical thinking about nutrition claims.

  28. DREads says:

    rork: Sorry for not being clearer. The differences in CD4 counts between the treatment and placebo groups pre-treatment was shown by the authors not to be statistically significant (P=0.13) as well as other factors (neuropathy and diabetes). Demonstrating a lack of statistical significance in these cases is a good thing as we want there to be as few differences as possible between the treatment and placebo group before the experiment.

    I do not have access to the data they used. I tried downloading the paper but unfortunately, the journal website is down. I would prefer to have the data for all subjects but the only statistics I have are the ones quoted in the original blog post.

    There are two random variables that come to mind to evaluate the effect of a treatment: a subject’s CD4 count (X) or the difference in CD4 count of a subject pre-treatment vs. post-treatment (Y=X_after-X_before). One possibility is to take the mean of each group with respect to either one or both of these random variables then apply a statistical test. I am not a statistician (I work in machine learning, which studies algorithms for estimating predictors from data) but it is my lay opinion that a good study should show an effect for both variables.

    Before performing tests to see whether the effect (after – before) is statistically significant, note the standard deviations (s_XT and s_XP) are pretty large, pre-treatment. I do not know the SD of total CD4 count post-treatment (variable X) nor do I have the SD of the differences (variable Y). Thus, I can only speculate that differences between two groups post-treatment wrt random variable X would not be statistically significant since the increase of 65 cells would bring the means of the two groups closer, and then their error bars would overlap considerably (not good). The error of any decision rule is going to be at least as high the Bayes Risk (or Bayes Error if you are using a 0/1 loss function), which gets larger the more two distributions overlap. If the Bayes Risk is high, then one can’t say much at all. Without the numbers, one can consider this rushing to an unfair judgement. I am sorry for this. It is my opinion that a more satisfying experiment would show statistical significance for both variables, X and Y. I can’t immediately do this for X without knowing more information but my hunch is that there would be considerable overlap between the two groups post-treatment.

    With small sample sizes and high variance, one must be especially careful about how to measure an effect and how to make a judgement on efficacy. There is always a potential for bias towards finding the right analyses that are consistent with one’s hypothesis.

  29. rork says:

    DREads:
    I’m not trying to dispute that it would be nice to have both tests be significant, but I would have only tested the differences (after log-transform), which they did.

    I might note about the conclusion of the paper and perhaps folks here can grudgingly concur: If I would have been testing a compound against mice with tumors (I would have done about the same test) and gotten p=.01 and that size of an effect, the docs (and I) would have written approximately the same conclusions, and we would have been a wee bit excited. For them, the effect size was 25% on average = the difference in % change. It’s not a case of small-p-thanks-to-massive-N, but effect being tiny, as in cases like “Females have higher IQ”.

    Missionary work: To not show all of the data for the main endpoint in a plot (log of before vs after), as well as coughing it up in a table (supplement is fine) is an abomination. I do not understand why it is tolerated. I often test 20K-50K assays per sample on arrays measuring mRNA and we MUST cough up the data for any good journal, but when folks have only a few assays per sample, they often fail to give up their data. When you review a paper, stipulate that this is not acceptable. That will help decrease fudging, and it can help science by permitting new uses of the same data – a common happening with bigger data.

  30. DREads says:

    rork: I agree with you that much more should be reported in studies. If a statistic (a mean, standard deviation) for a random variable is reported during one phase of an experiment but not in all phases, for one group but not another, the question arises whether the omissions were purposefully made to mislead the reader.

    In science, it is sometimes the case that we do not know what effects to expect to observe until an experiment is conducted and data is collected. Quite a number of random variables can be formulated and statistics can be computed to evaluate the effect of the independent variable on these different dependent variables. However, too much analysis from a small sample can be problematic because it can lead to overfitting. After applying several models and statistical tests to the data from the first experiment, some effects may be shown to be significant. Criteria is then established to conclude an effect but the final analysis cannot apply those same criteria to the same data used to derive the criteria. Either the experiment must be repeated or some of the data must be held out. The criteria is applied to this unused data to draw a final conclusion in the study. I would be delighted to see SBM go in this direction, if it hasn’t already.

    Experimental validation is particularly important when designing diagnostic tests. Take qualitative serologies for example. First, the serological assay is applied to a group of subjects, group A. Second, an estimation algorithm (pick your favorite paradigm like maximum likelihood, ERM, or SRM) is applied to the data in group A to estimate a prediction function, which employs an optimization algorithm to maximize the accuracy (empirical error or risk on A) of the prediction function applied to the data. A ROC curve is generated for different parameters given to the algorithm (such as regularization penalties). Optionally, a threshold can be chosen to decide positive or negative. However, these ROC curves cannot be used to draw any conclusions about the false positive rate vs. false negative rate when evaluating its predictive utility in the final analysis. The models (M1, M2, …, Mk) generated from group A must be applied to a held-out data set (group B) to evaluate predictive performance. However, if there is more than one model being compared and one wishes to choose the best among them M* (e.g. the model with the regularization parameter that leads to the most favorable accuracy, perhaps in terms of Area Under the ROC), one must apply M* to a third set, group C.

    One thing that disappoints me is that there are many fields in science where such statistical validation and use of statistical bootstrapping is lacking. I’d be curious if those familiar with the medical literature can speak to whether SBM medicine commonly employs such techniques.

  31. DREads says:

    I should also remark that one highly suspect practice that has concerned me for quite some time is repeating an experiment until a p-value is acceptably low enough then reporting the results only for that experiment. If one repeats an experiment enough, one can get eventually get lucky and arrive at a low p-value. No responsible, ethical scientist would ever do this deliberately but it could hypothetically happen in a large organization. Big companies have more resources and could hire several teams in different offices to perform the same or similar experiments for a particular drug. Teams who get favorable results are more likely to report their findings to upper management. Teams getting negative results are more likely to move onto something else rather than reporting the bad news up the chain. The overall pattern of repeating the same experiment across a large organization without monitoring consistency can happen without anyone’s knowledge. It also seems like it would be a hard thing to detect. Does anyone know if there’s been any serious studies that look into organizational controls for preventing this? Does this kind of thing happen in reputable pharmaceutical companies? I’d be curious to know.

  32. rork says:

    I don’t think this paper uses the data twice. Their model does not seem data instigated.
    Except:
    I now think their p=.01 test uses the straight after/before ratios, without logs, so I was wrong earlier, and I can now wonder if they have a few very high ratios which made it “better” to not take the logs. (Average ratios of .5 and 2.0 and you get 1.25, whereas averaging logs gives 0, the antilog of which is 1.0, not 1.25.) It’s utterly conventional to look at the log ratios.
    We can’t look into that since we don’t have the damn data – we do not even have a picture of the data. We can only see the summaries the authors permit us to see, and their choice may be crafty. Might be just ignorant instead though – can’t tell.

  33. Peter Lipson says:

    Dr. Kaiser has “responded” to the piece (or one iteration of it…i sort of posted this one all over the place). His response was, IMO, completely tangential to any of the criticisms, a long non sequitur.

    I responded back.

  34. squirrelelite says:

    On the subject of disease preventing or treating effects of supplements, some people might like to check out this new article from a major consumer research organization:

    http://www.consumerreports.org/health/healthy-living/diet-nutrition/vitamins-supplements/vitamins/overview/vitamins-ov.htm

  35. squirrelelite says:

    Another food supplement that may possibly have some use in limiting metastasis of cancer is modified citrus pectin.

    Here is an article I found at the American Cancer Society site:

    http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Modified_Citrus_Pectin.asp?sitearea=ETO

    Mike Adams seems to like it, so I’m not too hopeful, but does someone know anything more about it?

  36. MSGRANDONI says:

    I am a nutritionist and I always suspected that he was a quack.He extols the virtues of k-pax (because nutritionists can recommend it over things such as Juven)..He will give an hour lecture to dietitians on his ‘studies’ over dinner that he pays for (otherwise who would go?) then tells us that now we know more than the doctors about hiv. He is a creepy guy.

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