Tag Archives: scam

Homeopathy – The Placebo Effect

 

I’ve wanted to write about homeopathy for a long time. As you have probably already guessed if you frequent this website, I am somewhat of a sceptic. Questioning the truth and validity of things is in my nature. My training as a neuroscientist has only increased my disdain for pseudoscience and alternative medicine who’s growing popularity in this age of true science and discovery is nothing but woeful.

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‘Homeopathy is a pseudoscience – a belief that is incorrectly presented as scientific’

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Homeopathy, as we know it, was created by a man named Samuel Hahnemann in 1796 with the release of his book ‘Organon of Medicine’. Anything about homeopathy that you can find today is based on teachings from this book. This is where it all begin. The 6th edition of the book opens with this quote…

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‘The Organon may in time be widely recognized as one of the most important books in the entire history of medicine, because it introduces in the long story of man’s struggle against disease a successful system of medicinal therapy that contrasts radically with everything previously taught and practised.’

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Grammatical errors aside, I can assure you, that this will NOT be the case. One day homeopathy, as well as all unproven alternative medicine will fade into myth and memory as long as people continue to question it!

Homeopathy is aimed at a niche market split into two halves. One represents the naive buyers of homeopathic remedies which commonly have no active ingredient and are usually inert substances or water. These are normal people with no scientific training who have fallen for a scam or are trying something new based on a recommendation. The second half are the ignorant, ill-informed and vocal supporters of homeopathy many of whom are distrustful of empirically proven effective medicines and will stop at nothing to label anyone who speaks out against homeopathy as a brainwashed shill of the big pharmaceutical companies (we will meet some of those later).

We must do our best to question dubious pseudoscientific practices. Luckily the government is in agreement…

The United Kingdom’s House of Commons Science and Technology Committee has concluded that homeopathy is ineffective, and recommended against the practice receiving any further funding.

Read on to find out about the core beliefs of homeopathy, what the science says about the practise, and what happens when you question the hard-core believers.

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The core beliefs of homeopathy: pure magic

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The concept of homeopathy raises a number of issues before we even look at the science. The fact that homeopathic solutions are SO diluted that no active agent still persists is just one major issue that faces the homeopathic community. Others include notions of things like ‘water memory’ which state that water takes on the molecular form of any substance it comes into contact with. This is so preposterous that I just don’t know where to begin. Proponents of homeopathy are often very anti-pharmaceutical industry. If water really mimicked drugs do you think big pharmaceutical companies would spent literally billions of dollars developing drugs? No. I don’t think so.

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So what are the core principles of homeopathy? I’ve taken this mainly from www.hpathy.com as they have a good amount of detail about the different principles…

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The Law of Similia – ‘Like cures like’ :  the choice of the medicine is fundamentally based on the principle that the medicine must have the capability of producing similar symptoms of the disease to be cured in healthy persons. So backwards I don’t know where to begin. Based on this idea, in order to cure cancer a medicine must cause cancer -related symptoms in an healthy individual…makes…sense…

Law of Simplex – Only give one ‘homeopathic medicine’ at a time. This makes sense if we are testing the efficacy of a compound but many diseases require complex treatments requiring multiple drugs at once. 

Law of Minimum – Give the lowest possible dose of the medicine so that it doesn’t interfere with the vital source. This is based on the idea that small doses stimulate, medium doses paralyze and large doses kill. Dosing is VERY important in real medicine however homeopathic ‘treatments’ are often so dilute that they have no active ingredient left. Dosing is therefore entirely irrelevant. The less said about the ‘vital source’ the better. A large enough dose of pretty much anything can kill a person but that isn’t the issue. The issue is the idea that ‘infinitesimal’ doses are the most curative. Medicines usually work by targeting some sort of cellular receptor and changing a variety of signalling systems. If there is no drug (due to massive dilutions) these systems aren’t affected! 

Doctrine of Drug Proving – Recordings of drug proving give the only reliable knowledge of medicines which is very essential to cure disease homeopathicaly – drugs must be proved on animals as the symptoms of the drug and the disease are indistinguishable. We then must test on humans as mental symptoms are not seen with animals. At first glance this seems like actual planned drug testing first on animals and then scaled up to humans. Although some homeopaths do this their reasons are entirely backwards. According to Point 1 above that ‘like cures like’, effective medicines produce the same symptoms in healthy people as the diseased people experience – this is almost never the case. Taking Irritable Bowel Syndrome as an example; anti-motility medicines are often prescribed as they slow gut motility and  help relieve diarrhoea. Based on homeopathic teachings if I (a healthy person) were to take anti-motility medications, I would then suffer from diarrhoea. It just doesn’t hold up on any front.

 Theory of Chronic Disease – Chronic diseases are caused by chronic miasms. The miasms are Psora, Syphilis and Sycosis. Psora is the mother of all diseases and at least 7/8th of all the chronic maladies. You won’t see the words Psora or Miasm in the medical literature as they are only recognised by homeopaths. Lots of real research in the last few decades has shown that low-grade and often sub-clinical inflammation is a driver behind many different diseases ranging from diabetes to obesity and many chronic diseases inbetween. This was assessed through hundreds of well-designed studies. So it is true that lots of chronic diseases can have the same or similar underlying causes. However, The concepts of the miasms were invented by one man based on the observation that people had recurrence of symptoms when diseased. 

Theory of Vital Force – The human organism is a triune entity consisting of body, mind, and spirit. This spirit which is responsible for different manifestations of life was termed by Dr. Hahnemann as ‘Vital Force’. In the healthy condition, it is the vital force which maintains normal functions and sensations of the organism. The idea behind this is kind of on the right track. The body is a finely tuned machine constantly aiming to maintain balance and homoeostasis in multiple physiological symptoms. The theory of vital source believes that a misalignment of the triune entity leads to damage to the vital force which manifests as disease. You can sort of see where this idea sprang from – someone contracts a bacterial infection, the immune system kicks in to action, individual shows signs of disease as a result. To a homeopath the major points are Vital Source is compromised (somehow), disease manifests. 

Doctrine of Drug Dynamisation – Homeopathic dynamisation is a process by which the medicinal properties which are latent in natural substances while in their crude state, become awakened and developed into activity to an incredible degree. According to Dr. Stuart Close, “Homeopathic potentisation is a mathematico-mechanical process for the reduction, according to scale, of crude, inert or poisonous medicinal substances to a state of physical solubility, physiological assimilability and therapeutic activity and harmless, for use  as homeopathic healing remedies.” The quote is essentially a load of drivel, using big words to carry authority without really saying much. Dynamisation is achieved either using trituration (dilution of a potent drug powder with an inert diluent powder) or Succussion the action or process of shaking). According to homeopaths using these processes turns poisonous substances into ones of healing, increases the ‘dynamism’ of the medcine which is more important than quantity, medically inert crude subtances are transformed int powerful healing substances. Its this major point here that the medical community has so many issues with as it goes against the basics of chemistry and known biology and has never been shown to happen in any controlled study. Turning a poison into a powerful and true healing factor by shaking it or diluting it isn’t real!

 

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Well there you have it. That’s the major run down of the key principles of homeopathy. They tend to vary a little bit depending on the source. If you are interested in the original work that popularised homeopathy  in 1796 by Samuel Hahnemann, then you can find a PDF version of the 6th edition of this questionable book right here.

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What is the placebo effect?

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The placebo effect sometimes also called the placebo response is a truly remarkable medical phenomenon in which a fake treatment such as a ‘sugar pill’ can sometimes improve a patients condition simply because they expect it to. The whole core of this effect is that the patient BELIEVES what they are receiving is actual medicine, not just a fake pill or solution.

In the pharmaceutical industry, placebo treatments are commonly given alongside newly developed drugs. This is to determine whether new drugs have a therapeutic effect to a greater degree than we would see with a fake placebo drug – this helps determine the true medical benefits of a particular drug. Well-designed studies are described as ‘double-blind’. This means that neither the researcher giving the drugs or the participant taking the drugs known who is receiving the real medicine and who is receiving the placebo.  The information of who gets what drug (real or placebo) is usually held by another researcher who is not involved in the study or data analysis in any other way.

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If patients taking the real drug show significant improvement in comparison to the placebo group then this helps support the conclusion that the medicine is effective.

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The concept of positive thinking has been around for countless years – the idea that a positive outlook on situations can ultimately help said situations. The specific idea of the placebo response however is more recent and was popularised by a paper called ‘The Powerful Placebo‘ written by prominent anaesthesiologist Henry K Beecher back in 1955. This can be considered a type of meta-study in that he took a number of studies from the time which explored the placebo effect and then came to an overall conclusion based on the individual findings of these papers. In total he analysed 26 studies and found that, on average, 32% of patients respond to a placebo treatment. This has since been criticised for perhaps over-inflating the true numbers as he didn’t distinguish other factors from the placebo effect. He would later go on to write additional papers expanding on the idea of placebo-responders and non-responders. The general idea being that most people will simply not respond to a placebo treatment. Those who do however, show modest improvements in their conditions.

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It has been shown in the literature that placebos have real and measurable physiological effects…

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Athsma

Pain

Reduced anxiety

Reduction in depression symptoms

Irritable bowl syndrome

Parkinson’s disease

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Interestingly, the opposite can also occur. Placebos can actually cause negative or side effects. This is described as a nocebo effect.

These effects don’t have to be produced by a physical intervention such as a placebo drug but can also occur if someone is given a negative medical prognosis.

Although the placebo effect may seem like a good thing (especially for homeopaths as this is the only route by which homeopathy may be beneficial) it means much greater care is required when trialling new drugs. We have to control for the placebo effect. 

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The placebo effects is real but how or why does this happen?

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Proposed mechanisms

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Although the placebo effect produces real physiological responses- exactly why or how this happens is not full understood. There appear to be a number of process occurring simultaneously which may produce the observed effects.

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‘The placebo effect is part of the human potential to react positively to a healer. A patient’s distress may be relieved by something for which there is no medical basis. A familiar example is Band-Aid put on a child. It can make the child feel better by its soothing effect, though there is no medical reason it should make the child feel better’

-Medicine Net

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Expectancy and conditioning: 

The placebo effect is related to the expectations and perceptions of the patient. If they view the placebo as helpful then generally we see some kind of healing effect. Conversely, if the placebo is seen as harmful we will observe a detrimental effect – the nocebo effect. Expectation plays an additional role when we consider what the placebo looks like – bigger more colourful placebo pills often equate to a bigger health effect. Interestingly, it was thought the placebo was based on the notion that patients believe they are receiving medicine when in fact it is a ‘dud’ pill. Essentially a form of deception. However, it has been shown that even when people with Irritable Bowl Syndrome are told that they are receiving a placebo, we see a modest improvement in symptoms. Placebos can act similarly through classical conditioning, wherein a placebo and an actual stimulus are used simultaneously until the placebo is associated with the effect from the actual stimulus. This concept was famously explored by Pavlov with his dogs and bells.  So we know that the placebo effect is based on what people expect to happen…but what about the true phyiological effects produced when taking a placebo?

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Effects on physiology:

A number of studies have shown measurable changes in physiology as a result of placebo treatment. These changes likely underlie any reduction in symptoms in health benefits observed. The effects of placebo analgesia (pain relief) on higher brain circuits have been studies in depth primarily using MRI scanning to highlight areas of activation in the brain.

Placebo responses are linked with enhanced dopamine and opiod signalling in reward and motivated behaviour pathways. Additionally, nocebo responses were associated with deactivation of these same circuits and reduced dopamine and opiod release.

Moving away from pain-related treatment, placebos have other   measurable physiological effects. I mentioned earlier that placebo can have a positive effect on Parkinson’s disease – this is down to increased dopamine secretion (Parkinson’s is typically caused by a destruction of dopaminergic neurons). When looking at depression, placebo treatment appears to affect many of the same areas activated by common anti-depressants with most emphasis being on the prefrontal cortex. In another interesting study, coffee which contained ‘placebo-caffeine’ caused an increase in dopamine secretion. The concept of placebo ergogenic aids (performance enhancers) has been debated on and off by the sporting industry as to whether they should be allowed.

We know that the placebo effect is real and that is stems from our perception of drugs and what we expect them to achieve – we also know that symptom improvement can be due measurable physiological changes such as changes in hormone secretions. However, the broader question of exactly why our bodies show physiological alterations just because we think they should is still quite baffling.

Hopefully I’ve explained fairly clearly what the placebo effect is and how it can produce modest physiological effects in placebo-responders. The placebo effect also explains why wacky interventions like homeopathy can in fact alleviate symptoms in those who believe it will.

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Nothing about the concept of homeopathy is special – it is simply the placebo effect.

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What does the science say about homeopathy? The papers I will be consulting will be non-biased, peer-reviewed papers. Not poorly conducted ‘studies’ by practitioners of homeopathy. When performing your own research, if you can, aim for well respected journals, that publish peer-reviewed papers  with no-conflict of interest from the authors. If you want to be extra careful you can also search for the authors and check the quality of the papers they have published in the past.

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Homeopathy: what does the science say?

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Below, I’ve summarised the most prominent studies into the effects of homeopathic treatment on a variety of disorders and diseases.

 

 

http://www.whillyard.com/pseudo-science/homeopathy.html

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Before we go into studies a little bit about how homeopathy is currently regarded in the scientific community…

The fact that homeopathic preparations often lack even a single molecule of the original diluted substance has been the basis about the effects of preparations for decades.  The concept of ‘water memory‘ is now thrown about by modern proponents of homeopathy. The idea being that water has the innate ability to mimic the effects of whatever it is diluted with. This goes against our current understanding of matter has never been demonstrated to be true in any way. Quite obviously, basic pharmacological research has shown that stronger biological effects come from higher doses of active ingredient, not lower.

In true medical and scientific circles (i.e. not alternative medicine), homeopathy has never been taken seriously as a treatment for anything and is often considered a sham or pseudoscience. Those who support and promote homeopathy, rightly or wrongly, are often labelled quacks. Now the reasons for this are very straight forward –

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”There is no sound statistical evidence of therapeutic effect, which is consistent with the lack of any biologically plausible pharmacological agent or mechanism”

-From: Ernst E  ‘A systematic review of systematic reviews of homeopathy‘ Clin Pharmacol. 2002;54(6):577-82.

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Some practitioners of homeopathy put forward very advanced and abstract theoretical physics concepts in order to explain why homeopathy works. These concepts include quantum entanglement, quantum non-locality as well as chaos theory. The people putting these theories forward are not even close to being experts in these fields and often explain them incorrectly. They are also not supported by any actual experiments – its all just speculation and nonsensical explanations.

Aside from a lack of any solid evidence to support the efficacy of homeopathic treatments – the key ideas of homeopathy conflict with fundamental concepts of physics and chemistry.

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Looking at systematic reviews of the literature…

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‘No individual preparation has been unambiguously shown by research to be different from placebo’

Ernst 2002

‘Studies that were explicitly randomised and were double-blind as well as studies scoring above the cut-points yielded significantly less positive results than studies not meeting the criteria’

Linde K et al 1999 – explaining that as study design has become more fair, homeopathy shows even LESS efficacy than it has in the past

“The most reliable evidence  fails to demonstrate that homeopathic medicines have effects beyond placebo.”

Cochrane Systematic Reviews 2010

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Almost all modern meta-studies  show no effect of homeopathic treatment beyond what we would expect with a placebo effect. Those meta-studies which DO show a small effect also state that this outcome is likely due to weak trial design which leads to biased results. As study sign has improved – these positive outcomes are no longer observed.

A quick look at the dilutions involved just so you have an idea of what a ‘minute or infinitesimal amount really is. In homeopathy the most commonly used dilution is called 60X or 30C. This is a 10-60 dilution of the original agent. That might not sound crazy but let this put it into perspective…

At a concentration of 60X/30C…

‘Dilution advocated by Hahnemann for most purposes: on average, this would require giving two billion doses per second to six billion people for 4 billion years to deliver a single molecule of the original material to any patient.’

-Wikipedia: Homeopathic Dilutions

For all intents and purposes, this dilution isn’t even close to containing a fraction of a single therapeutic molecule of medicine. 

The science concerning the efficacy of homeopathy is conclusive and has been or a long time. Read on for what happened when I disagreed with the NHS funding homeopathic treatments…it’s mental.

 


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The ‘Facebook Fight’

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I usually try to avoid openly arguing with certain people. In this case I simply couldn’t help myself. I was scrawling through Sky News and noticed a small story at the bottom about NHS homeopathy funding.

I thought ‘surely that can’t be right’.

But it was right. Turns out, tax payers money does fund a small homeopathic budget. I found this pretty ridiculous. I think people should be able to spend their own money on pretty much anything, but taxpayers money? On something that has been repeatedly disproved? I decided to dig a little deeper.

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I came across the British Homeopathic Association Facebook page. I had a look around the page and saw that the (very few) members were up in arms about a story detailing that health chiefs were planning to cut homeopathic funding. At this point I couldn’t help but chime in. Oh dear. What a mistake that was. Delve into the madness below…

Admittedly my opening gambit was a bit full on, perhaps poorly worded in hind sight. However, the argument/conversation that followed was very interesting.

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Zoom in on this. It’s worth a read!

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Linda Holmes was very vocal throughout the exchange and a quick peak at her Facebook page reveals someone completely absorbed in conspiracy theories and pseudoscience.

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Lovethispic.com sounds like a legitimate research source…

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I’m not sure why but in my research it seems that pseudoscience believers are so often always conspiracy theory crackpots, yelling in various Facebook groups and forums that ‘Big Pharma’ is trying to keep us sick to make money and that cancer has been cured but there’s ‘no money in cures’.

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Take off the tin foil hat Linda! Aliens aren’t reading your thoughts

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It’s all mad and it’s terrifically difficult if not impossible to convince these people that maybe, just maybe, the world isn’t trying to murder them and coffee doesn’t cure Alzheimer’s.

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‘Drugs will always drugs’

-Linda

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Our friend Katie (final comment from the large exchange above) cherry picks one particular example of a (probably), self-resolving infection (no details of the use of actual medicine but if she was a real nurse then presumably this infant would also be on some kind of antibiotics) in a new born. She has then attributed this positive outcome to the use of homeopathic medicine i.e. water. As such, no amount of real scientific evidence or research AGAINST her belief will convince her that she is wrong.

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What homeopaths and almost all other practitioners of allopathic/alternative medicine rely upon is anecdotal evidence and personal testimony both of which spit in the face of the scientific method. Quackwatch points this out rather well:

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‘Imagine if the FDA or pharmaceutical companies, like GSK, decided that large scale drug trials where too expensive and ‘pointless’ and relied on the experiences of a few patients when interviewed about a particular new drug.’

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Katie has used an ‘n’ of 1 in her observation. An ‘n’ number in a study, put simply, is an experimental unit. If you are testing the efficacy of a compound on 20 mice then that experiment has an n number of 20. We conduct a power analysis before an experiment to determine how many n number we need in order to detect a difference between experimental groups when a real difference actually exists. This is important as it limits the ‘over-use’ of precious animals and also means you don’t under-power your experiment and potentially waste your time and the lives of your animals. Katie has an n of 1 which is useless in all situations I can think of. Again, it’s anecdotal and personal experience.

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I could provide these people with multiple large scale studies (lots of n) showing the fallacy of homeopathic medicine but they wouldn’t read them and even if they did, it would still be denied. No one likes being proven wrong, including me, but sometimes you have to take a step back and really look at the evidence, or lack thereof, that support your claims.

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This sort of thinking spills over into all aspects of these peoples lives. One commentator on this post has a Facebook page almost entirely dedicated to quackery. Highlights in included:

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‘Big pharma has a cure for cancer but won’t release it’

‘The FBI created HIV’

‘Peanut butter cures Alzheimer’s’

‘Green tea cures cancer and pharma doesn’t want you to know’

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I’ve written extensively about the myths surrounding green tea before.

Looking at Alzheimer’s, even just a small amount of research on the topic of peanut butter and Alzheimer’s would show this is not true. Do these people not realise that if their claims were true then what they preach would be common place? We are seeing an increase in Alzheimer’s in this country due to an ageing population. I work alongside an Alzheimer’s research group in fact. If peanut butter really did cure the disease do you think members of that research lab would be working long hours on in vitro release study’s and in vivo models desperately trying to combat it?  No.

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Harsh but fair.

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But what about when homeopathy appears to work?

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We know that modern, well-controlled and designed studies show that overall, homeopathy is no better than a placebo. Then how do we explain all these anecdotes or personal testimonies from homeopaths about them witnessing healing miracles?

Quite simply. Science offers a number of explanations as to how homeopathy may cure diseases or alleviate symptoms despite having no true medical efficacy…

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  • The placebo effect –  expectations for the homeopathic preparations may cause the effect.
  • Therapeutic effect of the consultation – this falls under the umbrella of the placebo effect. The care and reassurance a patient experiences when talking to a caregiver can have a positive effect on the patient’s health.  Studies have shown this effect to be real.
  • Unassisted natural healing – many diseases are disorders are self resolving. ‘Homeopathic’ healing is wrongly attributed to the natural healing process over time.
  • Unrecognised treatments – changes in diet, exercise habits and lifestyle choices can have massive positive impacts on health but may not be recognised as the cause of healing at the time.
  • Regression towards the mean – lots of diseases are described as ‘cyclical’ with patients going through good and bad periods. As people are more likely to seek treatment when feeling the worst, the odds are that from that point they will start to feel better due to this cycle even without medical intervention. Mistakenly attributing healing to a homeopathic remedy during the ‘bad’ phase of the cycle is probably fairly common.
  • Medical intervention – patients may also receive standard medical care at the same time as homeopathic treatment with real medicine being responsible for health improvements.

In reality, healing effects are probably due to a combination of these occurring at once. All the anecdotes and stories you hear from homeopaths will be down to one or more of these reasons. These are actually very straight forward ideas but few people stop to consider them – especially those with no interest or knowledge in real biology or health sciences

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What to make of all this?

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Research into the placebo effect is still ongoing. As of now, the effect is known to be real but the exact mechanisms by which it works are still under investigation. In individual cases were homeopathy ‘works’, the benefit is due to the placebo effect. I have no problem with this. People genuinely recovering from mild illnesses can only be a positive thing. However I DO have a problem with the mentality of hard believers of homeopathy who will often claim their ‘water’ is more effective than modern medicine.

This is not only false but also potentially dangerous – you should NEV ER seek out alternative treatments instead of evidence based, proven medicines. 

Another area of contention are companies and individuals, who, knowing homeopathy is hocus pocus, market and sell expensive potions to willing and naive homeopathy practitioners. I just wish that in this day and age we were beyond this medieval mind set.

Modern medicine is EVIDENCE BASED. Homeopathy is not.

While homeopathy may provide beneficial effects for mild disorders (through the placebo effect) it will not in any way cure serious or life threatening diseases and it is unfair and untrue to claim that it will.

My advice?

By all means, take homeopathic remedies to combat things like anxiety if you must (try not to spend too much, it is water after all), but never EVER choose homeopathy over evidence based modern medicine for anything remotely serious.

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Thanks for reading!

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-ScienceGuy

Reach me in the comments below or at ed@scienceguysupplements.com

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References

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References can now be found linked directly in the text rather than listed in this section. Delving deeper into the research has never been easier!

If you are looking to do a bit of your own research, on any topic, PubMed and Google Scholar both have a huge literature collection.

The Green Tea Facade

Green tea has been consumed, mainly by Asian nations (having originated in China) for hundreds and hundreds of years. Over the course of history numerous and powerful heath effects have been attributed to frequent consumption of green tea.

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In the modern day, green tea and green tea based products are major staples of health food and fitness shops with much emphasis placed on it’s ‘fat melting’ properties.

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Green tea has also been linked to other extraordinary benefits…

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  • A cure for various cancers
  • Decreases risk of cardiovascular disease
  • Improves glycemic control
  • Reduces ‘bad’ cholesterol
  • A general reduction in risk of death
  • Reduces inflammation
  • Powerful weight loss aid

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These are all extraordinary claims which of course require extraordinary evidence. Luckily a fair amount of research has looked more closely at these proposed benefits…

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Is green tea beneficial to health: What does the science say?

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I’ve gone through the major ‘health benefits’ of green tea and addressed them below. Where possible I’ve used meta-studies to support my arguments. These are large scale reviews of all the available data on the topic and can provide stronger evidence than individual studies alone.

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Cancer: There are a few studies which make suggestive links between consumption of green tea and reduced risk of certain types of cancer in specific populations. A small decrease in esophageal cancer rates amongst the Chinese and slightly lower rates of oral cancers in Asian populations. (1, 2). However it is impossible to control for all variables in these sort of population studies and although overall cancer rates were very slightly lower in green tea drinkers, there are also many many other differences in lifestyle habits that could lead to this outcome.  When all current data is taken together, there is no firm, conclusive evidence that green tea consumption prevents or treats cancer  (3,4).

Search for 'green tea and cancer' and this is one of the first image results. Most of this is wrong. Pseudoscience like this is why I started this website in the first place. Red writing was added by me not some lunatic arguing with himself in an info graphic.
Search for ‘green tea and cancer’ and this is one of the first image results. Most of this is wrong. Pseudoscience like this is why I started this website in the first place. Red writing was added by me not some lunatic arguing with himself in an info graphic.

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Cardiovascular disease: A recent meta-study which compiled a large amount of data on this subject concluded that daily intake of green tea was associated with  a roughly 5% chance reduced risk of death from cardiovascular diseases (this includes things like heart attacks and stroke) (5). A well respected Cochrane review also compiled data from numerous randomised trials a few years previously and reported a small reduction in blood pressure associated with  tea consumption (6). In fitting with these findings, a number of other studies have suggested green tea consumption may also be associated with a reduced risk of stroke (7).

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Blood glucose control: Data here is a little bit messy. Green tea lowered fasting blood glucose in one trial but data generated on fasting insulin levels as well as glycated hemoglobin levels (used to determine longer term average blood glucose) was inconsistent (8,9). Both these references are large scale meta-studies so we can be fairly certain that green tea consumption has no real impact on glycemic control.

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Cholesterol: In this area green tea does appear to have some small but clear benefits. Another Cochrane review (can’t get enough) of longer term trials over 3 months in duration, concluded that green tea consumption lowers total blood cholesterol concentrations in the blood including LDL (low density lipoprotein) cholesterol sometimes called ‘bad cholesterol’ (10).

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LDL - Bad HDL - Goof
LDL – Bad
HDL – Good

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General risk of death: Two separate meta-studies concluded that frequent consumption of green tea resulted in a small reduction in the percentage chance of death from any cause (11,12).

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Inflammation: Green tea consumption is not associated with a significantly lower concentration of c-reactive protein in the blood. C-reactive protein is an acute phase protein from the liver that increases in response to macrophage and T cell activation so is used as a marker of inflammation (13).

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Green tea and pills containing concentrated green tea extract (catechins being the most important component) are  a multi-million dollar market. Although there is some suggestive evidence of small health benefits (see above), green tea is most commonly sold as a weight loss aid.

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But does it actually help with weight loss?

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Green tea is not a weight loss aid

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If you can convince people that your product will help them lose weight then you will make a guaranteed profit. The population is getting fatter and more than ever, people are desperate for a quick fix for weight problems.

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As you’ve guessed – there is no magic pill or easy fix for weight loss. It requires a maintained change to your eating and exercise habits.

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Ridiculous
Ridiculous

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Green tea is described on lots of product labelling as a ‘metabolic booster’ or ‘fat burner’. The main molecule that is often reported to be the ‘fat burner’ is a catechin called  epigallocatechin gallate (EGCG) . So what sort of conclusions are drawn from study’s looking at the ‘fat burning’ properties of green tea?

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Important point to bare in mind: Your average cup of green tea contains about 50-60 mg of EGCG

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One study from 2009 looked directly at the effects of green tea on body composition, measuring things like intra-abdominal fat, waist circumference and total body fat in control subjects and subjects receiving a varying amount of EGCG and caffeine. The group receiving the highest daily dose of EGCG and caffeine saw a clear reduction in all three measurements (14).

.Sounds great right?

.Well not really.

.This group was receiving 900 mg of EGCG a day as well as 200 mg of caffeine on top.

That’s the equivalent of about 18 cups of green tea and 5 cups of coffee...

Neither of which can be described as ‘healthy’ in the long term.

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Another study, published in 2008 approached from a different angle and looked at if green tea could enhance exercise-induced weight loss.

These participants were receiving over 600 mg of EGCG a day. The paper describes a ‘trend towards greater fat mass  loss in the catechin group’  which is another way of saying there was no statistically detectable difference between the groups. (15).

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What about claims that green tea ‘boost or increases metabolism’?

Short answer: It doesn’t.

A number of studies have shown that green tea consumption has no effect at all on the basal metabolic rate of healthy participants (16, 17). Importantly, these studies were measuring basal or resting metabolism . People peddling ‘fat burning’ green tea supplements want you to believe that green tea will simply burn away the extra calories all while you sit on the sofa. Impossible!

A more recent Cochrane meta-study, taking data from 18 separate studies and involving close to 2000 participants concluded that green tea does lead to small weight loss in obese people. However this is described as ‘non-significant and unlikely to be clinically important’. Additionally, green tea has no effect on weight loss maintenance (18).

All strong evidence that Green Tea or Green Tea Extract products are close to useless when it comes to weight loss. 

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Take home message

 

So what have we learned about green tea…

Commonly advertised attributes and the truth side by side:

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  • A cure for various cancers : No
  • Decreases risk of cardiovascular disease: Small reduction 
  • Improves glycemic control: Currently inconclusive
  • Reduces ‘bad’ cholesterol: Small but clear reduction 
  • A general reduction in risk of death: Potentially true but could be explained by many other variables
  • Reduces inflammation: No
  • Powerful weight loss aid: No

 

Although there is some evidence that green tea consumption can have health benefits such as a reduced risk of death from cardiovascular disease and a reduction in cholesterol, relying on supplements for this benefit isn’t necessary. Reducing your intake of trans fats and exercising more will provide you with these benefits plus many more.

In terms of the fat burning potential of green tea, it simply doesn’t exist. 

If you enjoy green tea then by all means enjoy a hot brew every now and then. However if you are forcing yourself to drink green tea for the advertised benefits  or paying through the nose for green tea extract pills then it’s not worth your time or money.

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Thanks for reading,

ScienceGuy

 

 

 

 

References

 

I recommend using Google Scholar for quick access to these studies.

1) Zheng JS, Yang J, Fu YQ, Huang T, Huang YJ, Li D (January 2013). “Effects of green tea, black tea, and coffee consumption on the risk of esophageal cancer: a systematic review and meta-analysis of observational studies”. Nutr Cancer (Systematic Review and Meta-Analysis). 65 (1): 1–16.

2) Wang W, Yang Y, Zhang W, Wu W (April 2014). “Association of tea consumption and the risk of oral cancer: a meta-analysis”. Oral Oncol (Meta-Analysis). 50 (4): 276–81.

3)  Boehm K, Borrelli F, Ernst E, et al. (2009). “Green tea (Camellia sinensis) for the prevention of cancer”. Cochrane Database Syst Rev (Systematic review) (3): CD005004

4) Johnson R, Bryant S, Huntley AL (December 2012). “Green tea and green tea catechin extracts: an overview of the clinical evidence”. Maturitas (Review). 73 (4): 280–7.

5) Tang J, Zheng JS, Fang L, Jin Y, Cai W, Li D (July 2015). “Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis of eighteen prospective cohort studies”. Br J Nutr (Meta-analysis). 114: 1–11.

6) Zhang C, Qin YY, Wei X, Yu FF, Zhou YH, He J (February 2015). “Tea consumption and risk of cardiovascular outcomes and total mortality: a systematic review and meta-analysis of prospective observational studies”. Eur J Epidemiology(Systematic Review and Meta-Analysis). 30 (2): 103–13.

7)  Khalesi S, Sun J, Buys N, Jamshidi A, Nikbakht-Nasrabadi E, Khosravi-Boroujeni H (September 2014). “Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials”. Eur J Nutr (Systematic Review and Meta-Analysis). 53 (6): 1299–1311

8) Liu K, Zhou R, Wang B, Chen K, Shi LY, Zhu JD, Mi MT (August 2013). “Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials”. Am J Clin Nutr (Meta-Analysis). 98 (2): 340–8.

9) Zheng XX, Xu YL, Li SH, Hui R, Wu YJ, Huang XH (April 2013). “Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials”. Am J Clin Nutr (Meta-Analysis). 97 (4): 750–62.

10)  Zheng XX, Xu YL, Li SH, Liu XX, Hui R, Huang XH (August 2011). “Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials”. Am J Clin Nutr (Meta-Analysis). 94 (2): 601–10.

11)  Tang J, Zheng JS, Fang L, Jin Y, Cai W, Li D (July 2015). “Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis of eighteen prospective cohort studies”. Br J Nutr (Meta-analysis). 114: 1–11.

12) Zhang C, Qin YY, Wei X, Yu FF, Zhou YH, He J (February 2015). “Tea consumption and risk of cardiovascular outcomes and total mortality: a systematic review and meta-analysis of prospective observational studies“. Eur J Epidemiology(Systematic Review and Meta-Analysis). 30 (2): 103–13

13)  Serban C, Sahebkar A, Antal D, Ursoniu S, Banach M (September 2015). “Effects of supplementation with green tea catechins on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials”. Nutrition (Systematic review & meta-analysis). 31 (9): 1061–71.

14) Wang et al  (August 2009). ”Effects of catechin enriched green tea on body composition” Obesity 18 (4):773-9

15) Maki et al (December 2008) ”Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults” Journal of Nutrition  139(2):264-70.

16) Lonac et al (August 2010) ”Influence of short-term consumption of caffine-free EGCG supplement on resting metabolism and the thermic effect of feeding”.  Obesity  19(2):298-304.

17) Gregersen et al (May 2009) ”Effect of moderation intakes of different tea catechins and caffeine on acute measures of energy metabolism under sedentary conditions”Journal of Nutrition 102(8):1187-94.

18)  Jurgens et al (December 2012) ”Green tea for weight loss and weight maintenance in overweight or obese adults”.  Cochrane Library 

The Multivitamin Hoax

I was flicking through good old Facebook, the book of face, the other day when I came across an advert for yet another multivitamin product under the name of VITL. Presumably a play on the word vital…as in, you vitally need this supplement to be healthy. Or do you?

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Multivitamin supplements and other products that fall into that sort of category such as anti-oxidant pills are consumed in huge quantities in the UK and US. Many people swear by them and start their day swallowing down a random amount of varied vitamins. Vitamins are good right? They are important in loads of physiological processes so surely more of them is better?

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Looks enticing but 35.99 a month is a bit steep....
Looks enticing but 35.99 a month is a bit steep….

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In reality the science suggests two things rather clearly if you are an average person:

  • All your vitamin needs are met by your diet if its fairly balanced
  • Taking too much of a particular vitamin can have serious repercussions to your health

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I don’t wish to target VITL directly as many companies are peddling their vitamin wares. It’s not the product itself I have an issue with but the target market. It makes medical sense to supplement a vitamin that you are clinically deficient in but trying to sell expensive vitamins to people who don’t need them is a complete waste of the customers money and in some cases potentially harmful to their health.

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What is a ‘vitamin’ 

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 A vitamin can be defined as such :

‘A vitamin is an organic compound and a vital nutrient that an organism requires in limited amounts’ (the key phrase here is ‘in limited amounts’)

Technically speaking, ‘vitamin’ refers to a chemical compound that an organism requires but cannot synthesise by itself in sufficient quantities. The vitamin must therefore largely be obtained from dietary sources.

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Vitamins are classed based on their biological and chemical activity, not on their structure. Therefore a number of vitamin-like compounds (vitamers) may be grouped together under one umbrella vitamin name. For example ‘Vitamin B’ includes a large number of ‘vitamers’ each with their own B number and additional name. Vitamin B9 for example is Folic Acid. Not all vitamers are in the biologically active state but can be converted into this form in the body.

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Thirteen vitamins are currently recognised: Vitamins A, B (8 vitamers), C, D, E and K

 


Physiological Roles

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Vitamins play a varied and diverse role in the body and have widely different functions.

I’ve made a table to summarise this section in brief as it’s fairly in depth!

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vitamin-table-1

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The large group of vitamin B type-compounds  act as co-enzymes (and precursors) in metabolic processes. Co-enzymes are non protein compounds that are required by the protein enzyme to catalyse specific reactions in a cell (1). They therefore perform an extremely important role in the minute by minute function of cells. Acting as co-enzymes is their most recognised functional role but there are many others (2). Large amounts of research effort has been put into uncovering the therapeutic potential of the B vitamin family of compounds. Many do have true therapeutic value but only in the treatment of serve disorders. B9 for example, also known as folic acid, has been shown to reduce the rate of neural tube defects (NTDs) in infants and as a result can be found fortified into many different foods in a hope to reduce the incidence of NTDs in the population (3). There is also some evidence that folic acid supplementation may confer a small reduction in the risk of stroke and cardiovascular disease if taken over a long period of time (4)

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Vitamin D possesses hormone-like functions and act as regulators of mineral metabolism and plays a part in the control of tissue growth and differentiation (5). A chronic lack of vitamin D famously leads to ‘rickets’, a disorder of bone growth and structure. Sunlight (certain wavelengths) modify Vitamin D into its active form which is why at least some exposure to the sun is important. Foods are often fortified with vitamin D in countries that receive lower levels of sunlight (less hours and or/less intensity) but can be found naturally in oily fish and eggs (6).

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Vitamin C acts as both an enzymatic co-factor and also  functions as  an anti-oxidants to protect agasint oxidative stress. The vitamin is a co-factor in a number of important enzymatic reactions, a few of which are related to the synthesis of collagen,  a key structural protein. A lack of vitamin C can impact collagen production leading to scurvy. 

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Yaaaaargh. Eat an orange.
Yaaaaargh. Eat an orange.

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Vitamin C is a well studied vitamin and makes common appearances in health food shops and websites as a sort of ‘cure-all’ especially targeting things like the common cold and other respiratory pathologies (that website link claims you can cure pretty much any disease). However vitamin C supplementation studies have shown conflicting results. A number of studies suggest that vitamin C supplementation may reduce the duration of common colds (7) but it doesn’t seem to prevent colds in the first place (8). The potential protective effects of vitamin C supplements regarding cardiovascular health and lung cancer has also been explored in depth but overall studies suggest no detectable protective effect (9,10,11). Two of these references are systematic reviews and analyse the data from multiple studies. One of which is a Cochrane review who are known to be very thorough in their approach.

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Vitamin E has a number of roles including acting as a fat-soluble anti-oxidant. The vitamin essentially mops up free radicals preventing oxidation stress and tissue damage. This vitamin has also been the subject of a study looking at protective effects against major cardiovascular events in middle aged men but supplementation does not increase protection (12) Surprisingly one report suggested vitamin E supplementation might even increase the risk of lung cancer for already at-risk individuals.(13)

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Vitamin K is required for the complete synthesis of a number of important proteins involved in blood coagulation (various coagulation factors) , vascular biology and bone metabolism (14). In somewhat of a developing theme, vitamin K supplementation was explored as a means to prevent or reduce the incidence of cardiovascular disease. This makes sense as vitamin K deficiency is associated with the stiffening of arteries (15). Despite this, there is no good evidence that vitamin K supplementation will stop cardiac events occurring in the first place (16). The science also refutes fairy common claims that vitamin K supplements can slow cancerous tumour growth (17).

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Overall, studies which look at standard supplementation (rather than the effects of over-supplementation) have produced few promising results. Unless you are deficient in a particular vitamin then supplementation has no detectable benefit to your health. The only possible exception to this is vitamin C supplementation in regards to common cold duration. Additionally, vitamin C supplementation may help in the prevention of common colds when individuals are exercising rigorously in cold environments (18, 19). This seems like a super specific scenario but if you plan on skiing naked for a prolonged period of time than maybe pop a vitamin C tab or two (but not three…that’s just getting silly)

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*Tactical dong strap*

 


Daily multivitamins are potentially harmful

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I’m going to take aim at Berocca here as an example. Berocca is an effervescing tablet that you plop into a glass of water and it releases all it’s tasty, healthy vitamins and minerals (we know the truth berocca you scum bag!). Now, unlike VITL, who I assume have done their research on vitamin absorption, the people behind Berocca have added a ludicrously large % of your RDA (Recommended Daily Allowance) for many of the vitamins. I mean, 1071% of your recommended daily allowance of B1! That is mental for a number of reasons.

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A quick excerpt from the brilliant website quackwatch.org about RDAs:

”The RDAs have been published by the National Research Council approximately every five years since 1943. They are defined as “the levels of intake of essential nutrients that, on the basis of scientific knowledge, are judged by the Food and Nutrition Board to be adequate to meet the known nutrient needs of practically all healthy persons.” Neither the RDAs nor the Daily Values listed on food labels are “minimums” or “requirements.” They are deliberately set higher than most people need. The reason quacks say that the RDAs are too low is obvious: if you believe you need more than can be obtained from food, you are more likely to buy supplements”

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The doses in VITL stay within recommended limits
The doses in VITL stay within recommended limits

 

1000 % of your RDA is 900 % too much!

Firstly I have already shown you that for the average healthy person, supplementing with any vitamin doesn’t provide protection against diseases or make you ‘healthier’ in general. 

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Secondly, vitamins are only required in limited quantity. The phrase ‘more is better’ is almost always wrong when applied to biology. Any additional vitamins taken in are excreted as waste so those doses are needlessly high.

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Finally, those super high percentages may hide a sinister detail. Not only are excess vitamins pointless they have also been linked to increased risk of a variety of diseases. Over-dosing on some of the vitamins can also induce a specific set of symptoms depending on the vitamin as summarised below.

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picture

Major studies looking into the effects of long term vitamin supplementation have produced surprising but solid data.

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General Mutlivitamin Tablets: Two large meta-studies, headed by the same researchers, that had access to data from hundreds of thousands of people (more likely to show a true effect) found that individuals taking daily multivitamins had an INCREASED RISK OF MORTALITY in comparison to people who don’t (20,21). Mortality of course covers death from all causes so those people taking multivitamins daily have an increased risk of dying in general. That’s pretty bleak. Other studies have looked at certain vitamins in particular and their effects on the incidence rates of specific diseases. The situation is no less bleak unfortunately…

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Vitamin A: As the table further up the article shows, vitamin A can be found in green leafy veg, oranges and milk to name just a few sources. Carrots are also a great source. You only need to eat half a carrot to obtain you recommended daily allowance. Now these studies are specific to smokers but beta-carotene (form of vitamin A) was explored for it’s therapeutic value in lung cancer development. Shockingly those smokers on beta carotene supplements saw a 28% increased incidence of lung cancer (which is already comparatively high in smokers), a huge increase! So unexpected was this result that the trial was terminated ahead of schedule. (22, 23)

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The horror!
The horror!

 

Vitamin E: A large number of studies have been conducted concerning Vitamin E supplementation and, like vitamin A, the results are rather disturbing. A study trying to determine if vitamin E could be used to reduce cancer and cardiovascular disease uncovered an increased risk of heart failure in patients taking ‘excessive amounts’ of vitamin E (this why those crazy high % RDAs in some products are dangerous!). These patients all had existing vascular disease or diabetes mellitus (24). Perhaps excessive vitamin E exacerbates circulatory problems that surface with both vascular disease and chronic diabetes.

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Another study produced a similar finding to the Vitamin A meta-studies in that vitamin E supplementation correlated with increased mortality (25). This was a large study involving over 100,000 individuals. The conclusion says it all:

”High-dosage (> or =400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided.”

Of relevance to men, a more recent 2011 study with 35,000 participants  showed that vitamin E supplementation significantly increased the risk of prostate cancer (26)

Ultimately, the science refutes the phrase ‘you can’t have too much of a good thing’. Multivitamins and specific vitamin supplements have been linked with an increased risk of death in general, prostate cancer in men, skin cancer in women and  heart failure in those already at risk.

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Admittedly, these trials expose participants to vitamin levels far above their recommended allowance but that shows us how potentially dangerous it is for companies to make products (for daily consumption) with 5 or 10 times the recommended levels. 

 


Summary: Do you need daily multivitamin supplements?

 

For the average person, the simple answer is a resounding no. All your vitamin needs are met by your diet.

In fact, it should be an aggressive  ‘no’ because you may in fact actually be damaging your health. If you do still wish to take daily vitamins then for the love of god at least check the % RDA on the back and stay away from those products that provide 1000% of your RDA in one daily serving.

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”2000 percent of my RDA? F*ck that sh*t!”

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Whats important to remember is that although the evidence shows that vitamin supplements, in general, will not make you ‘healthier’ this is all assuming you have a fairly balanced life style and diet to begin with. If you are known to have a deficiency in a particular vitamin then supplementing may still be helpful as long as you stay within recommended daily intakes. Of course, listen to your doctor.

Finally, as an added note: I’ve written this article without touching on fitness or training at all. Not many studies focus on this topic and it would be a very short article if I did. The story is much the same as has been told above. Unless you have a legitimate reason to take vitamins, taking extra won’t effect your general health or really impact your training in any meaningful way. Vitamins are peddled all over fitness and body-building websites just like at health food equivalents but now you know that they are a TOTAL WASTE OF MONEY. 

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My only advice, and this applies to all supplements, is that actual food should always come first. That’s the whole idea of a supplement, to supplement what you are are (or are not) getting through your diet. Your money would be much better spent on frequent purchases of fruit and vegetables.

Any questions? Feel free to reach me at ed@scienceguysupplements.com

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Thanks for reading,

ScienceGuy

 


Text References 

I recommend using Google Scholar to quickly find these studies in full detail.

1) University of Bristol (2002). “Pantothenic Acid”. Retrieved 16 September 2012.

2) National Academy of Sciences. Institute of Medicine. Food and Nutrition Board, ed. (1998). “Chapter 6 – Niacin”. Dietary Reference Intakes for Tjiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Washington, D.C.: National Academy Press.

3) Bailey, Lynn B. (2009). Folate in Health and Disease, Second Edition. CRC Press. p. 198

4) Li Y, Huang T, Zheng Y, Muka T, Troup J, Hu FB (2016). “Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials”. J Am Heart Assoc. 5 (8)

5) Holick MF (March 2006). “High prevalence of vitamin D inadequacy and implications for health”. Mayo Clin. Proc. 81 (3): 353–73.

6) Holick, M.F. The Vitamin D Deficiency Pandemic: a Forgotten Hormone Important for Health. Health Reviews. 2010; 32: 267-283.

7) Douglas RM, Hemilä H, Chalker E, Treacy B (2007). Hemilä H, ed. “Vitamin C for preventing and treating the common cold”. Cochrane Database Syst Rev (3): CD00098

8) Heimer KA, Hart AM, Martin LG, Rubio-Wallace S (May 2009). “Examining the evidence for the use of vitamin C in the prophylaxis and treatment of the common cold”. J Am Acad Nurse Pract. 21 (5): 295–300

9) Fulan H, Changxing J, Baina WY, Wencui Z, Chunqing L, Fan W, Dandan L, Dianjun S, Tong W, Da P, Yashuang Z (October 2011). “Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression”. Cancer Causes Control. 22(10): 1383–96.

10) Ye Y, Li J, Yuan Z (2013). “Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials”. PLoS ONE. 8 (2): e56803.

11) Stratton J, Godwin M (June 2011). “The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis”. Fam Pract. 28 (3): 243–52.

12) Rimm E, Stamper M, et al.(May 1993). ”Vitamin E consumption and the risk of coronary heart disease in men” The New England Journal of Medicine . 328 (20) 1450-1456.

13) Heionen OP, Albanes D (April 1994). ”The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers” The New England Journal of Medicine. 330:1029-1035

14) “Vitamin K Overview”. University of Maryland Medical Center.

15) Maresz K (2015). “Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health”. Integrative Medicine (Encinitas, Calif.) (Review). 14 (1): 34–9.

16) Hartley L, Clar C, Ghannam O, Flowers N, Stranges S, Rees K (2015). “Vitamin K for the primary prevention of cardiovascular disease”. Cochrane Database Syst Rev (Systematic review). (9)

17) Ades TB, ed. (2009). “Vitamin K”. American Cancer Society Complete Guide to Complementary and Alternative Cancer Therapies (2nd ed.). American Cancer Society. pp. 558–563.

18) Douglas RM, Hemilä H (June 2005). “Vitamin C for Preventing and Treating the Common Cold”. PLoS Medicine. 2(6):

19) Hemilä H, Chalker E (January 2013). “Vitamin C for preventing and treating the common cold”. Cochrane Database of Systematic Reviews. 1

20) Bjelakovic G, Nikolova D, Simonetti RG, et al. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004 Oct 2-8;364(9441):1219-28.

21) Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007 Feb 28;297(8):842-57.

22) Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. Journal of the National Cancer Institute. 1996 Nov 6;88(21):1550-9.

23) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The New England Journal of Medicine. 1994 Apr 14;330(15):1029-35

24) Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005 Mar 16;293(11):1338-47.

25) Miller ER, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Annals of Internal Medicine. 2005 Jan 4;142(1):37-46.

25) Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011 Oct 12;306(14):1549-56.

Table References

1) Penniston KL, Tanumihardjo SA (2006). “The acute and chronic toxic effects of vitamin A”. The American Journal of Clinical Nutrition. 83 (2): 191–201.

2) “Thiamin, vitamin B1: MedlinePlus Supplements”. U.S. Department of Health and Human Services, National Institutes of Health.

3) Hardman, J.G.; et al., eds. (2001). Goodman and Gilman’s Pharmacological Basis of Therapeutics (10th ed.). p. 992.

4) Brunton, Laurence L.; Lazo, John S.; Parker, Keith, eds. (2005). Goodman & Gilman’s The Pharmacological Basis of Therapeutics(11th ed.). New York: McGraw-Hill.

5) Pantothenic acid, dexpanthenol: MedlinePlus Supplements”. MedlinePlus. Retrieved 5 October 2009.

6) Perry, T. A.; Weerasuriya, A.; Mouton, P. R.; Holloway, H. W.; Greig, N. H. (2004). “Pyridoxine-induced toxicity in rats: a stereological quantification of the sensory neuropathy”. Exp. Neurol. 190 (1): 133–144.

7) FAO; WHO (2002), “ch. 4, Folate and Folic Acid”, Human Vitamin and Mineral Requirements

8) The Dark Side Of Linus Pauling’s Legacy, Quackwatch

9) Masterjohn, C (2007). “Vitamin D toxicity redefined: vitamin K and the molecular mechanism”. Med Hypotheses. 68 (5): 1026–34. doi:10.1016/j.mehy.2006.09.051.

10) Gaby, Alan R. (2005). “Does vitamin E cause congestive heart failure? (Literature Review & Commentary)”. Townsend Letter for Doctors and Patients.

11) Rohde LE; de Assis MC; Rabelo ER (2007). “Dietary vitamin K intake and anticoagulation in elderly patients”. Curr Opin Clin Nutr Metab Care. 10 (1): 1–5.