Natural Health Expo(sed)?

Driving around Hamilton the past few weeks I couldn’t help but notice the signs sprinkled around the city for the “Natural Health Expo” which is to take place here this week end. As I perused the website for this event yesterday I was disturbed by the large number of anti-scientific “treatments” that will be showcased. Like my co-blogger Grant who has already posted on this, I was troubled by the amount of misinformation that will be leveled directly at consumers.

As I was pondering how to answer the bewildering array of AltMed that will be promoted I checked my email and found a great little article just published in Chiropractic & Osteopathy (made available through the open access publisher BioMed Central).

The paper, “Why do ineffective treatments seem helpful? A brief review” written by Steve E Hartman, looks at how practitioners and patients can fool themselves into thinking that ineffective medical interventions actually work. An excellent example of Evidence Based Medicine 101, Steve covers the cognitive biases that hinder our ability to draw logical conclusions in the medical sphere such as the Post Hoc, Ergo Propter Hoc logical fallacy, confirmation bias and cognitive dissonance. Also covered are explanations of how it can seem that a treatment has been directly responsible for improvement in a patient’s condition when it may not  have been.

The paper touches on disease natural history, which simply refers to how a particular malady might be expected to progress without treatment. Self limiting diseases such as colds, headaches and fatigue can be expected to get better on their own . If a patient is taking a treatment at the time, the treatment (rather than their own immune system) might erroneously be given the credit.

This combined with the overlapping arenas of the placebo effect and regression to the mean can be a powerful confounding factor when treatments are not being considered in light of scientifically controlled settings. The placebo effect is referred to frequently in common culture but regression to the mean is a less well known entity for the layman. Steven does a good job of explaining the concept, essentially people experience a variety of different intensities in their symptoms. Also they will tend to seek medical help when the symptoms become severe, knowing that the severity of the symptoms will tend to cluster about a mean value it is likely that whether treatment is sought or not the patient’s condition will tend to get better.

Thus the patient will feel relief and attribute that relief to what ever modality they are using at the time. Practitioners are not immune to these effects either and will in their practice see time and again that patients are getting better after their pet therapy is applied. In which case they will feel justified in proclaiming it works in the absence of confirming studies (or even in the face of disconfirming evidence).

The one aspect that I felt was missing from the paper, although it may have been obliquely implied, is the role of prior plausibility in evaluating treatments. Many modalities that will be on offer at the Natural Health expo are not only unusual they fly in the face of currently understood science. Scientific plausibility is our compass, without it we can become lost in the wilderness of fanciful ideas without any method of discerning the way forward. This concept is what separates Science Based Medicine from simply Evidence Based Medicine. The former takes the plausibility of a treatment into account when deciding the threshold of evidence needed before it can be considered effective. The later only measures outcomes and so is less able to distinguish true effects from chance outcomes.

Consider the following scenario: I claim to be able to influence the outcomes of coin tosses by virtue of what I had for breakfast on a particular day. If I have eggs then tails with predominate, lettuce produces more heads. Now without considering the plausibility of the setup we could run a trial, perform statistical analysis and find that my predictions are correct. But given that there is no good reason to suspect that my diet can influence a coin toss the positive is more likely to be because of chance than because of a real effect. In this case then a higher standard of evidence would need to be achieved than if I had said I could alter the probabilities be sticking a piece of gum to one side.

All-in-all though this a very nice paper and my complaint is a small one, given the probable readership of the journal the inclusion of plausibility may even have alienated those that might otherwise have been receptive to the other points presented. I recommend reading it for yourself, it is a very easy and informative read.

Gardasil Post-licensure Study

Last month the Post-licensure safety study for Gardasil (the HPV vaccine) was released. The study focused on the reports of adverse events as reported to the VAERS database by the manufacturer, doctors and patients or caregivers. Much has been made by detractors of the vaccine about the serious alleged side effects that have struck young women given the course of injections. These allegations have been supported by referring to the VAERS database itself so if they are valid they should be upheld by this study.

Of the 12,424 reports that VAERS received in the 2.5 year period following implementation of the vaccine, 772 (6.2%) were classified as “serious”, the total number of vaccine doses distributed in this period was 23 million. The category of “serious” was defined according to the FDA regulatory definition of an adverse event that “is life threatening; results in death, permanent disability, congenital anomaly, hospitalization, or prolonged hospitalization; or necessitates medical or surgical intervention to preclude one of these outcomes”.

It must be noted at this point that the VAERS database cannot determine causality, the events reported merely have to occur after vaccination takes place. Therefore anything that happens to a patient in this time frame that someone thinks might be related to the vaccine may be entered. I point this out only to remind that while we may be looking at vaccine safety life does go on, accidents happen and co-incidences occur. The point of a study such as this is to determine if these events are occuring at a frequency higher than what we would expect in the normal population. In other words, is there really a correlation between these events and the vaccine or is is simply a statistical fluke.

The study looked into each type of adverse report in detail and attempted to answer the above question, does the rate of reporting exceed that which would be expected in the general population? In almost all cases the answer appears to be “No”, the exceptions to this were reports of syncope (fainting) and venous thromboembolic events (blood clots), this finding will certainly be followed up in future studies. Curiously one of he more prominent adverse effects that has been concerning many on both sides of the debate, Guillain-Barre´ Syndrome was not found to occur more than expected.

Guillain-Barre´ Syndrome is an auto-immune condition that can be brought on by vaccines but also by normal infections. The syndrome is caused when the immune system is stimulated by an antigen but then starts to target the body’s own nervous system, it usually exhibits as an ascending paralysis noted by weakness in the legs that spreads to the upper limbs and the face along with complete loss of deep tendon reflexes. As vaccines are made to induce an immune reaction the link between vaccines and the syndrome is biologically plausible and not controversial in the medical community.

The study concludes favourably but cautiously, as scientific studies are wont to do:

Vaccination with qHPV has the potential to decrease the global morbidity and
mortality of HPV-associated diseases, including cervical cancer. After hepatitis B vaccine, which can prevent liver cancer, qHPV is only the second vaccine licensed with an indication to prevent cancer. The postlicensure safety profile presented here is broadly consistent with safety data from prelicensure trials. Because VAERS data must be interpreted cautiously and cannot generally be used to infer causal associations between vaccines and AEFIs, postlicensure monitoring will continue, and identified signals may be
evaluated using epidemiologic observational studies.

The full study can be found here, a summary of the study here and a comprehensive discussion of the study here.

Cancer is Depressing

I don’t think the observation that cancer contributes to depression would win any awards for profundity, it’s likely such news would put a crimp in anyone’s day. Indeed, the very fact that the news of cancer itself can influence our emotions  makes it difficult to examine the contributing factors toward depression in those suffering from cancer. Our ability to foresee our own possible demise and react emotionally to it confounds attempts to tease out the strands of cause and effect. Approximately 10% of cancer sufferers are diagnosed with clinical depression and up-to two thirds experience some sort of mood disorder.

In order to separate out the effect of conscious knowledge of the disease from the psychological symptoms researchers have to turn to rats. How do you tell if a rat is depressed? To find out the scientists monitored the rat’s Twitter and Facebook pages for negative statements, no actually the rats are subjected to a swimming test, the longer the rats floated in the water without trying to escape the more depressed the animal is. The researchers found that rats with cancer showed signs of depression but not other behaviours normally associated with sickness, implying the rats were not simply feeling unwell.

Analysis of the rats tumours, blood and brain showed an increase in specific cytokines that have been linked to behavioural changes. In other words the presence of the tumour triggers changes in the brain that influence behaviour. This means that depression could be considered another symptom of cancer and not merely a by-product of knowledge of the cancer. This could have implications for how we treat depression in cancer patients and help them deal with the side-effects, simply knowing that being depressed is not something under their own control might itself be helpful.

Man Flu, the Disappointing Reality

Man Flu, scourge of modern Manly life. Struck down by this dreaded disease men are reduced to a shadow of their former glory, unable to maintain the meager level of household responsibility they usually get away with or even care for their own well being. Reduced to mewling invalids, men afflicted with Man Flu have little recourse beyond bed rest and watching daytime television while a significant other tends to their every need. After being ridiculed by wives and girlfriends for decades science has come to the rescue and vindicated us, the Man Flu exists!*
*The preceding is a work of fiction and any resemblance to real people or events is coincidental.
Despite what the media would have us believe recent advances in scientific research has not in fact established that Man Flu is a real phenomena beyond simply showing our inability to deal with sickness effectively. The real science behind the hype, as usual, is much more modest in it’s scope and consequences.

So what was actually studied? The research was carried out by McGill University in Canada and looked at the effects of a certain protein, caspase-12. The study involved investigating how the activity of this protein affects immune response against Listeria monocytogenes bacteria, a microbe that can cause serious food poisoning, in mice. Part of the study also investigated the effect of gender on the activity of the protien and whether any difference was mediated by the hormone oestrogen. To do this researchers infected mice with the bacteria and looked at spleen and liver bacteria levels in male and female mice with and without the gene for the protein and male mice with the gene and being treated with estrogen. 

The interesting thing is that this gene did have a different effect on how sick the mice got depending on the presence or absence of estrogen. Those male mice with the gene were more susceptible to the infection than females or males recieving hormone treatment, but the gene is inactive in most humans. Only about 20% of native Africans have a working version of the gene, so this research has virtually no applicability to general differences in flu severity between men and women. I guess Man Flu remains a myth, for now.

Folic Acid Fortification, a extra tidbit

It seems topical to discuss folic acid fortification as it has recently been in the news and by the end of the year it will be a legal requirement that breads contain approximately 135µg of folate per 100g. I will actually not wade into the debate directly, fortuitously a study was published mid last month on one of the potential benefits of folate supplementation. The study looked at the effect of supplementation on the number of very preterm births and found that it had a protective effect.

First a little background might be in order, Folic acid is one of the B vitamins and is important in cellular metabolism. As a vitamin it is a nutrient that we must obtain through our diet. Food stuffs such as leafy vegetables and liver (mmm, liver) are good sources of folate however it is still a part of our diet that tends to be lacking. Because of this many western countries now mandate fortification of grain products with the vitamin. This is because of the important role it also plays in pregnancy and in particular the prevention of Neural Tube Defects, notably Spina bifida.

The study looking at folate supplementation and preterm births found that the important factor seemed to be duration of supplementation prior to pregnancy rather than the dosage of supplementation. In particular durations of greater than 12 months seemed to be most beneficial. However as the study was undertaken in the US the supplementation was taking place in conjunction with an existing fortification of bread products, this implies that the fortification alone was not sufficient to prevent all preterm births and that women that are planning pregnancies should continue to supplement with folate even after fortification is introduced.

In addition the folate supplementation was self reported by the women in the study at enrolment and after pregnancy had begun rather than being proscribed prior to attempts to conceive. This seems to mean that we must rely on the memory of the women to be accurate regarding the duration of supplementation. Despite this limitation there still seems to be a good correlation between supplementation and reduction in preterm births. Bottom line appears to be that supplementation in addition to fortification is a good idea for the childbearing among us.

Herbal Medicines

It certainly seems that in recent years herbal style medicines have grown more popular and more widely available. I’m certainly not going to espouse the view that these medicines are a waste of time, that they do nothing or that they have no plausibility. However neither do I think that simply because they are seen as “natural” (whatever that means) that they are necessarily superior to drugs produced by pharmaceutical companies. The problem with herbal/natural remedies isn’t that there isn’t a plausible mechanism of action, (as in Homeopathy for instance) but that there is usually not enough good quality data to support their use for a particular indication. In addition, while drugs developed for the pharmaceutical industry must pass stringent safety and efficacy tests those that are labeled herbal supplements often get a free pass. So not only may there not be evidence that they work but no evidence that they are not harmful.

There also seems to be a disturbing corollary to promoting remedies despite lack of evidence and that is the continued use in the face of dis-confirming evidence. Recently good studies have been published refuting claims for benefits to taking either Ginkgo Biloba extract for cognitive function or Echinacea for colds. Though I expect this information to have zero impact on sales even if the results of the studies gain wide distribution.

Remedies that consist of preparations made from the raw plant also suffer from inherent variation between plants, both between individual plants and in the same individual over time. So even if there is an efficacious active ingredient the dose would not be controlled. If herbal remedies have an effect on the body then they are drugs, by definition, they should be treated as such. In other words they should be evaluated for safety and effectiveness, considered when taking other medications for potential interactions and dispensed by those who are trained to appreciate the risks/benefits and science based medicine.

Resources

http://www.theness.com/neurologicablog/?p=424

http://www.sciencebasedmedicine.org/?p=293

DiabeCell® – Curing diseases one trademark at a time

You may have heard lately about a trial to be conducted in New Zealand concerning the transplantation of Porcine (pig) cells into humans. The cells to be implanted are pig pancreatic cells, these are the cells that produce insulin and the ones that don’t work in people with Type I Diabetes. First a little back ground on Diabetes, there are two main types imaginatively named Type I and Type II, each is the result of an inability of the body to regulate glucose levels using insulin. In Type I diabetes this is caused by the immune system malfunctioning and attacking the body’s own cells, specifically those that produce insulin. This means that insulin has to be introduced to the body through another means, for many years this has been through manual injections by the sufferer. But this is not the only way, if we can somehow replace the patient’s insulin producing pancreatic cells then the need for injections could be reduced or eliminated altogether allowing those with this form of Diabetes to take as much notice of their insulin needs as you do.

This is where a company called Living Cell Technologies (LCT) comes in, LCT is a New Zealand conceived international biotechnology company that researches xenotransplantation to treat disease. This week a new trial to be conducted out of Middlemore hospital was approved. The trial will consist of inserting a gel capsule containing pig pancreatic cells into the abdomen of the patient. The gel acts to shield the transplanted cells from the patient’s immune system, otherwise procedures such as this, like organ transplants from humans, would need to be accompanied with immunosupressing drugs. These drugs stop the body attacking the transplanted tissue but also reduce the patient’s ability to fight off otherwise normal infections.  The transplanted cells should then act like the patients own pancreas and produce insulin in response to increased blood glucose levels.

The trial is small and will have only 8 participants trialling two different “Doses” of cells, if this proves to be successful then a larger trial will be planned to assess wider effectiveness of the treatment prior to making it available to the Type I diabetes population at large. The treatment has been dubbed DiabeCell® by LCT, catchy, sounds like a high tech battery. I think work like this is very exiting, it makes me hopeful that the diseases the human body is prone to will, one by one, become a thing of the past. How cool is that?

Resources

http://en.wikipedia.org/wiki/Type_I_diabetes

http://www.lctglobal.com

http://www.lctglobal.com/downloads/cms_latest_news/2008-10-21-LCT-Receives-Ministers-approval-for-NZ-trial.pdf

http://www.nhc.health.govt.nz/moh.nsf/indexcm/nhc-news-consultationapplicationlivingcelltechnologies

http://www.scoop.co.nz/stories/PA0810/S00465.htm

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The Clean Plague

Arguably the most significant medical advance in history, in terms of lives saved, isn’t vaccines, or any particular treatment but simple hygiene. The recognition that unsanitary conditions lead to disease, the discovery that germs cause illness, and it’s corollary, that destroying germs prevents/cures illness. As a society we have become so conscious of cleanliness and sterile conditions that we buy antibacterial soaps by the gallon, demand antibiotics of our doctors and carefully regulate our children’s environments to remove any possible source of infection (ok not all of us but more than you might think). In the process are we compromising our overall health?

The “Hygiene hypothesis” has been put forward to explain apparent increases in the incidence of allergic diseases such as hay fever, eczema and asthma since industrialisation and in more developed countries. It essentially states that our immune system tuned to expect a certain immunological load from the environment in the form of infectious agents, symbiotic flora and parasites. If this load is decreased significantly through the use of antibiotics and cleaning agents then the immune system can cause problems such as over reacting to benign environmental stimuli (hay fever) or attack the body’s own tissues (autoimmune diseases such as Type 1 Diabetes). This hypothesis was given a boost in support this week with the publication of a study in mice that found exposure to common human intestinal bacteria provided a protective effect against developing Type 1 Diabetes.

It seems that you can have too much of a good thing, as in everything else optimal cleanliness is a matter of degree. Obviously I’m not advocating a return to the bad old days where raw sewage flowed in the street and we drew drinking water downstream from dead animals but we also don’t need to live in antiseptic bubbles. One of my favourite advertising campaigns is Persil’s “Dirt is Good” promotion for exactly this reason, I don’t even mind that they’re trying to sell me something on the back of it. 

Resources

http://en.wikipedia.org/wiki/Antibacterial_soap

http://en.wikipedia.org/wiki/Hygiene_hypothesis

http://www.medicalnewstoday.com/articles/122337.php

http://www.persil.com/DirtIsGood.aspx

http://www.theness.com/neurologicablog/?p=383

Ginkgo Biloba

Ginkgo Biloba, used for thousands of years in TCM for improving memory and cognition. This beneficial herb if taken will boost your ability to retain and recall facts, dates and appointments. It’s better than a calendar and cheaper than a PDA. It’s the brain enhancing drug we’ve all been waiting for, at least it would be if there was any evidence it actually did any of these things. The first documented use of this plant therapeutically is in 1436, to treat skin and head sores as well as, wait for it… freckles. Lucy Liu take note, keep away from Ginkgo. Anyway, it wasn’t until 1990, when a Nobel Laureate mentioned it in his Nobel Lecture on chemical synthesis, that interest in the plant really took off.

Studies had shown that ginkgo was effective at increasing blood flow, dementia researchers then speculated that increased blood flow to the brain caused by the active ingredient  might help counter memory loss. From this humble beginning the million dollar industry of promoting the herb as mind boosting wonder drug was born. Despite no credible evidence for it’s efficacy in improving the cognitive abilities of those not already suffering from dementia millions of people take this drug every day in the hopes of warding off that inevitable consequence of living and growing older, forgetfulness.

Now, I’m a forgetful guy, just ask my wife. And putting aside the lack of evidence and the the inherent irony of people concerned about forgetting things remembering to take a pill every day, I understand how tempting it is to want to believe that our every character flaw can be cured with the swallow of a tablet. Hey if there was a pill for charm, I’d be taking it no matter how dubious the research, ok, maybe not but I’d really want to. As with anything else the decision to take these things is up to the individual, but always be ready to change your mind about it if new information comes in. Also if a supplement has any biological activity at all, make no mistake, it is a drug and your doctor should be consulted if you have and medical condition or are on other medication.

Resources

http://www.slate.com/id/2165042/

http://www.theness.com/neurologicablog/index.php?p=202

http://www.eurekalert.org/pub_releases/2008-02/aaon-dgb022208.php

http://www.ncbi.nlm.nih.gov/pubmed/17443523?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1

http://www.stevenfoster.com/education/monograph/ginkgo.html

Animal Testing

Medical advances over the last two hundred years have, along with increased abundance of food, allowed us to both increase our life expectancy and the quality of that life. While the single most significant impact on disease was probably the widespread recognition of the value of hygiene, another extraordinarily useful tool in our arsenal has been animal testing. Today the usefulness of animal models for disease is as great as it ever was in the past but there is growing opposition to research that involves our non-human friends. Protest groups are not new, at least as far back as the 1890’s groups were being formed that rallied against animal testing.

The benefits we have reaped as a civilization from this research include: knowledge of vitamin deficiencies, treatments of heart disease, diabetes, whooping cough, arthritis, tuberculosis, pneumonia, spinal meningitis, typhoid fever, cancer, depression, leprosy, ulcers, development of antibiotics, surgical techniques, gene therapy, vaccines, anesthesia and antibodies for disease treatment, to name just a few. Although this research has provided valuable knowledge and saved countless lives those who oppose it are doing so with increasing forcefulness. Acts against researchers include threats via phone and email, vandalism of personal property and intimidation as well as the distribution of their children’s names, age’s and where they go to school.

Without doubt the treatment of animals should be ethical and designed to minimize pain and discomfort at all times, but to declare such a valuable tool off limits is to cripple medical science. It is unfortunate that we can not yet use alternatives to animals but our knowledge of cellular responses and complex biological systems is still woefully incomplete and this is the reason we need them. Perhaps eventually all possible experiments could be done inside a virtual environment, but ironically, to get to that animal free future we must do even more research on those very same creatures.

Resources

http://newsroom.ucla.edu/portal/ucla/animal-generates-new-treatments-45057.aspx

http://www.njabr.org/programs/medical_milestones/

http://www.fbresearch.org/education/nobels.htm

http://en.wikipedia.org/wiki/History_of_animal_testing

Vitamin C

That cold season is upon us, is abundantly clear so I thought that it would be appropriate to look at the use of Vitamin C to stave off the dreaded common cold. It is a recognised fact that humans need this chemical in our diets to survive, or it wouldn’t be a Vitamin. It is also interesting to note that most mammals manufacture their own and while we have a copy of the gene for this it was deactivated millions of years ago and is a trait we share with the rest of the primates. But I digress.

The recommended daily allowance of Vit. C is 90mg for an adult male and a slightly lower 75mg for a female, about the amount in a glass of orange juice. I must say we have two bottles of Vitamin C tablets at home, each tablet contains 500mg of active ingredient and the instructions recommend taking 2-8 a day. Up to 4g of Vitamin C, that’s 45 times the amount you need. Such large amounts is called mega-dosing and is the suggested way to get the supposed added benefits of vitamin C, over and above keeping scurvy at bay I mean.

Most people have heard that taking the vitamin will help prevent colds but I’m afraid that the medical literature just does not back this up. At most the duration of a cold may be marginally reduced, by perhaps 10%. In addition to this the very act of taking these high doses can actually stimulate the kidneys to flush it from your body, so it seems that the money spent on buying the tablets is quite literally going down the toilet. I’ve occasionally been accused of pissing my money away but this is ridiculous.

Resources

http://www.quackwatch.org/01QuackeryRelatedTopics/DSH/colds.html

http://www.bmj.com/cgi/content/full/309/6956/719?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Vitamin+C&searchid=1&FIRSTINDEX=10&resourcetype=HWCIT

http://healthlink.mcw.edu/article/959704173.html

http://www.hortresearch.co.nz/index/news/503

Vaccines

Parents have a tough job. That’s a fact. However this job is made tougher by two things, 1. Fear for their children’s safety, 2. False information in the media. The first is completely natural and even necessary. The second unfortunately is also natural and is something that arises because of peoples fear.

Part of the reason is that when you are talking about someone’s child then any risk is too much. That is understood and absolutely forgivable, this leads to trouble though when that fear is misinformed and the public does not have the knowledge to decipher the facts for themselves. An inability to rationally weigh the risks also leads to making decisions that can be detrimental to health long term.

The trouble with the current concern over vaccines causing autism is that this is primarily a case of parents being overwhelmed by media coverage that is intended to produce ratings not provide accurate information. It is a recurring theme that the controversial stories are hyped and the factual follow ups are down played or overlooked altogether.

Multiple studies have shown that the putative link between the MMR vaccine and autism does not hold up, some of these are listed below. In addition the rise in autism diagnoses that anti-vaccination groups point to is widely regarded by the scientific community to be an artifact of the inclusion of a wider variety of disorders under the umbrella term of “Autism” in recent decades. Autism is defined by a certain constellation of symptoms being present and their severity. In recent years less severe examples of these symptoms have been added to the diagnosis of the autism spectrum. This allows for a greater number of diagnoses than in the past.

This is a very complex and emotional debate and I have only touched on it briefly here, I recommend reading up on the subject through the resources listed below.

Resources

http://www.cdc.gov/od/science/iso/mmr_autism.htm

http://www.theness.com/articles.asp?id=74

http://www.theness.com/neurologicablog/?p=37http://www.immunize.org/mmrautism/

http://www.immunize.org/catg.d/p2065.htm

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=26561

http://www.bmj.com/cgi/content/full/330/7483/112-d

http://www.bmj.com/cgi/content/full/324/7334/393