Sunday, November 3, 2013

Nutritional Supplements

This post was originally posted in February 2013 but I've read several recent articles that shed additional light on the topic so clearly that I felt an encore was necessary with specific links to the articles.  The original post was one of the most widely read on my blog so perhaps a re-post is in order anyhow.  I've added the links at the bottom of this article and embedded them in the text as well.


Here is my original post:

I recognize how frightening cancer can be for a lot of patients.    One day you are cruising along in life taking care of business, the next day you are confronted with a life threatening diagnosis.  For many patients, it is a journey with unfamiliar terms, clouded along the way by scary thoughts of chemotherapy, illness, and death.

For some patients, fully embracing the health care system and trusting that it will provide the best care possible is too much to swallow.   Suspicion may even be healthy.  Does my doctor know what is best for my case?  Has my doctor adequately explained why we are taking the steps we are taking?  Add in the cost of getting ill and the craziness of navigating a broken healthcare system and just about anyone could go nuts.

In a situation that feels so out of control, I can completely understand why patients may want to take control of some aspect of their care.  In many cases that can be educating themselves to engage in the decision making, in some cases it may be traveling to see a “specialist.”  One of the more common manifestations I encounter is the use supplements.  I think self-treatment through use of supplements can often provide an aura of control that really appeals to quite a few patients or their loved ones.

Maybe it is because I practice in the Northwest where complementary alternative care competes with “western medicine” in the minds of many, but it comes up as a discussion point with the majority of patients I take care of.  I suspect quite a few patients never even tell me what they are taking.  Patients often bring the topic up somewhat sheepishly – as though they know they are doing something a “western” doctor would never endorse.

So let’s talk about what we know and what we don’t know and I will share my opinion.  I recognize this is a “near-religious” topic for many so I have no doubt I will offend a number of readers.  My apologies in advance – my intent is not to offend but to try to make sense of a topic that a lot of patients want to know more about.

Let’s start with the admission that EVERYTHING that we encounter is a “drug.”  Every so often, some uber-athlete dies in a marathon from drinking too much water.  Yes – water can be fatal!  If you sweat too much, lose a lot of sodium, and replace your fluids without the salt, you can have seizures and die.  Oxygen is clearly important, but give too much to a person with emphysema and their brain forgets to breath.  We are complex biologic organisms and things need balance.  Introduce ANY variable and the body has to adapt.  For MOST things we encounter day to day the body is up to the task – but start mixing lots of variables and sometimes you get unexpected results.

Another misconception is that if you are taking a “natural” product, it is somehow less likely to be harmful.  Interestingly several important chemotherapies came straight out of nature. Taxol was isolated from the bark of the Pacific Yew tree, adriamycin was discovered from soil samples near an Italian castle, and vincristine comes from the Madagascar periwinkle plant.  I’m not sure how that fits the idea that “natural” products are somehow safer than chemotherapy – in some cases they ARE chemotherapy.  While you may be tempted to conclude that naturopathic clinicians are therefore onto something, I would also point out that these compounds were then subjected to many years of intensive, focused research and clinical development that refined and re-refined the precursor compounds into validated effective therapies.  When you take one of these drugs, you know what you are getting.

There is also a near mystical belief that if it comes out of a culture that has practiced medicine for thousands of years it is likely to either be extra effective or maybe very safe.  Try telling that to thousands of Taiwanese who developed bladder canceror renal failure from Aristrlochia.  Before I sound too negative though, I should point out a favorable example too.  There is a rare form of very dangerous leukemia called “Acute Promyelocytic Leukemia.”  Perhaps the single most effective drug ever identified for this condition is actually arsenic.  Yes, arsenic has literally saved the lives of thousands of people.  It is approved for this use by the FDA – and guess where it was discovered…. traditional Chinese medicine.

So if we can agree that everything can be a drug, the lines between “natural” and “synthetic” are more blurry than we would like, and “traditional medicine” has its highs and lows I think most readers would agree that we are best off if we can really sort out fact from fantasy.

The sad reality however is that we know VERY LITTLE about the interactions between supplements and chemotherapy.  This link references a good description of the problem.  I wish there was a more rigorous scientific effort to understand these things but it has always been too close to “fringe science” for grant driven academic researchers to risk taking their careers.  Once you start publishing about astragalus effects in lymphoma, research funding may start to dry up.  There have been several laudable exceptions such as curcumin, resveratrol, and green tea, but unfortunatley very few of these have made it far enough for human clinical testing. Things can look very compelling in laboratory experiments but until you do the human subject testing you really do not know much at all. 

So let’s consider some examples that might surprise you.

Grapefruit juice should seem harmless enough right?  Actually grapefruit is one of the worst things out there for just about anyone who takes drugs.  Grapefruit shuts off a set of liver enzymes that are responsible for clearing drugs out of the bloodstream.  I remember hearing about a colleague’s patient on a cholesterol lowering drug who decided to go on a grapefruit juice diet.  Unfortunately this resulted in toxic levels of the cholesterol drug.  The subsequent muscle tissue injury caused kidney failure.  It is so well recognized that when companies are developing drugs sometimes the FDA mandates that they study the interaction with grapefruit juice (another reason drug development sometimes takes so long).

Most of us would agree that smoking is bad – but did you know that the metabolic byproducts of tobacco can mess with the same liver enzymes as grapefruit juice but in the opposite direction?  Ironically (and sadly) this can rev up the metabolism of drugs such as erlotinib which we use to treat lung cancer.  There have been some publications suggesting that smokers taking erlotinib need much higher doses to get the same effect as lung cancer patients who have given up on smoking. 

Green tea is quite the rage these days.  There have actually been a number of good quality studies that have looked into its anti-cancer properties.  The “polyphenols” contained in green tea may indeed possess important anti-cancer properties – but just like water and oxygen, context is everything.  Green tea also contains ECGC.  Unfortunately a very important drug for treating myeloma called bortezomib (aka. Velcade) gets metabolically inactivated by green tea.  Not too long ago one of my myeloma patients on velcade having a suboptimal response to treatment informed me that she had been started on Green Tea by a local naturopathic practitioner.  While I don’t know if it was the green tea or just a bad case of myeloma you can imagine how we all felt.  Other green tea supplements have recently been linked to liver failure.  

Take st. john’s wart for depression?  You might be particularly depressed if it causes cataracts or gets you a horrific sunburn.  More freightening still is that it alters metabolism of quite a few different drugs.

The point of these examples is to highlight the dangerous interactions between things that we might not expect to interact.   If we agree that we know very little about the majority of supplements, the interactions that we DO know about give me reason to be VERY careful putting unknown drugs into the system.  I believe these examples should give us pause before launching into a twenty supplement regimen to “strengthen our immune system.”

I know one very reputable academic doc with a fantastic career who simply refuses to take care of patients if they engage in using supplements during chemotherapy.  While I don’t go that far, I do tell patients it introduces a level of uncertainty and risk that I cannot predict.  I often tell patients to try to avoid supplements during chemotherapy though I don’t so much mind them doing whatever they want when chemo is not in the mix.  On the other hand, if it seems like a patient is going to be doing a lot of supplements no matter what I say, I may not offer them participation in a clinical trial.  It isn’t fair to blame unpredictable side effects caused by a supplement / drug interaction on a research medication.  It could potentially slow down the development of a lifesaving drug.
By now, I've blurred the distinction on natural vs non-natural, traditional vs western, side effects, interactions, and so forth - but that is just the start of it!  In the nutritional supplement business there is comparatively little oversight.  Supplement manufacturers do not have to submit their processes to the same regulatory scrutiny as traditional drugs.  There can be big variations in dose between different manufacturers - as if we even knew what dose mattered in the first place.  Add in a pretty sophisticated science in pill manufacturing which influences how much drug even gets into your system and it is really impossible to know if you are even taking what you think you are taking.
With all that in mind, I ask my patients to avoid suplements during chemotherapy.  I don't get all upset if they ignore the recommendation - some people are going to look at the same information and make a different judgement.  I tell patients they are paying me for my opinion.  After eight years in the UC system, three at Harvard, and three at Stanford, hopefully it is worth the money.  They can disagree with me and choose a different path but it isn't one I would take for myself. 
There are a few things about the "supplement industry" that irritate me and one that makes me extremely mad.

I occasionally hear the assertion that there is some enormous conspiracy to keep a cure for cancer under wraps.   Sometimes the drive for supplements has a distinctly "conspiratorial" overlay.  If there is a huge conspiracy I must really be a dope because I am smack dab in the middle of it and I had no idea.

Two things that bother me about the "supplement industry" are the ridiculously false claims you occasionally see or the claims that have some truth at their basis but takes it far beyond what the data supports.  Yes glucose is an important nutrient for cancer cell survival but you cannot really get your sugar levels low enough to kill the cancer without having a serious brain injury at the same time.  Yes pH is important but the body very tightly regulates pH so try making yourself more acidic or alkaline and you are either wasting your time or risking serious injury.
What really makes me furious though is the occasional exploitation of really sick patients.  I have seen a number of patients exploited by the “alternative care industry” when they are at their most vulnerable time.   Not a week goes by where I am not asked about some form of alternative care and some cost huge amounts of money.  Many times thesetreatments are dressed up to look like real science.  Sometimes I have a hard time at first glance sorting out the real from the fake but if I take the time, I can usually tell them apart.  
But what about the desperate mother of a dying child whose treatment has failed at the hands of “Western Medicine?  I can’t blame her for grasping for hope – but what makes me furious are the charlatans out there ready to take her money knowing full well they are selling crap (see this amazing 60 minutes documentary for point of reference).   

There are MANY well-meaning alternative care providers out there who try their hardest to help their patients and sincerely believe their interventions will help.  I am not writing about them.   My advice: if they are both recommending and selling the product - and it costs a lot - ask them where else you can buy it - and how the other products compare to theirs.  If the answer is “nowhere” or “the others are not as good” I would be concerned.

One last thought.  The American diet is truly awful.  I was shocked when taking a human anatomy class in medical school how fat we all are.  Even people who look "average" often have inches of goey yellow fat padding huge areas of the body.  Our fast / quick food culture undoubtedly leaves our bodies wanting something different.  I like to eat organic when possible.  I've watched Food Inc and realized that corporate agriculture introduces things into my diet that I want to avoid.  For me, eating at McDonalds is truly an act of desperation.

The first time "chemotherapy" was tried in children with acute leukemia should serve as a grave warning though about trying to replace "missing nutrients."  Sydney Farber - the American "father" of chemotherapy was studying pernicious anemia and had found that some patients responded to folic acid - a common additive in multivitamins.  His first experiment involved giving children with acute leukemia large doses of folic acid.  Unfortunately, this was a "missing ingredient" for the cancer cells and they immediately started growing faster and the children died.  Sydney almost got ran out of Harvard for it, but after deciding what he really needed was an "anti-folate" he started work on methotrexate -  a drug that we still use today.  60 years later the Dana Farber cancer institute in Boston still gives tribute to his early discoveries.

I need to wrap this up. 

I think a lot of patients or their loved ones seek out supplements to try to make a bad situation better.  Sadly, I think it is possible to accept some myths about alternative care and get yourself into a worse situation.  For most alternative care providers, I don't question their intent - most are good people who want to help.  Cancer is an incredibly savvy enemy though and I  believe there are extremely few magic bullets out there to be discovered amongst the supplement aisle.  If you are going to do supplements, it is probably safest to do it when chemotherapy is not in the mix.  If you are in watch and wait or some remission, it is probably fine in most cases - just beware that you can hurt yourself with supplements and the claims are not regulatred by the FDA. 

That is my opinion.

Herbal Supplements Are Often Not What They Seem

Herb-Drug Interactions in Oncology

The Quackish Cult of Alternative Medicine

Common US Supplements linked to liver failure