As this week ends, so does the “Homeopathy Awareness Week”.
As a professional scientist and pharmacologist by training and skeptical thinker, I have to say that the tenets of homeopathy are puzzling me.
Recently, the Swiss government applied laws to allow reimbursement of homeopathic products following a popular referendum. What does it tell? It tells that in the mind of public opinion homeopathy appears as a safe, efficient and natural alternative to conventional medicines. But does homeopathy is indeed supported by its claim or do we have indeed some marketing ploys in action that are just working as a smoke screen?
In this post, we will revisit the homeopathy and of course why science refutes most of the claims of homeopathy.
1) What is homeopathy?
The term homeopathy (from the Greek homeos = same,equal and pathos = suffering) was coined by Samuel Hahnemann (1755-1843), a German physician from Meissen, Saxony.
In Hahnemann’s mind, diseases could be treated by treating the patients with natural extract known to induce similar effects than the disease when administered in high doses, an analogy of “battling fire with fire”.
The tenet of homeopathy is defined by extracting compounds from a natural source, either from animal, plant or mineral product into a solution called “tincta mater”. This tincta mater undergo a series of dilutions and agitations steps that are believed to increase the potency of the remedy. The dilution are referred as “Cs”, with a 1/100 dilution step between each Cs. At 1C, the tinctura mater is diluted at 1/100, at 2C is has a dilution factor of 1:10’000 (100*100=10’000) and so until you achieve the desired dilution. Some preparation harbor a 12C (in other means 1 molecule of active ingredient surrounded by 10e12 molecules of water or one trillion molecules of water) or higher. “Oscillococcinum (R)”, a homeopathic product obtained from liver duck extract by Boiron laboratories, boast a 200C dilution or 10e200 dilution factor.
2) The mass-action laws of pharmacology and the concept of ligand-receptor
In pharmacology and modern medicine, the tenet of all medication is resumed by the “ligand-receptor” dogma. Ligand (from the Latin “ligare”: that bound, attach, unify) is a chemical compound that can bind to a receptor. Such ligand can be as small as an elemental atom as small as a proton (H+) and as big as a macromolecule made of thousands of atoms, that can be a protein, a sugar, a lipid or a nucleic acid.
A ligand and receptor interaction occurs following established physical and chemicals laws called action-mass laws that dictates how atoms and molecules can interact together. In practice, we can refer it as the “key and keylock” analogy:
L + R <=> LR
Such interactions follow a dynamic pattern in which the ligand and receptor can bind and separate equally, forming an equilibrium. Such equilibrium is dictated by different parameters including physical (temperature, pressure….) and chemical (Van der Waals interactions, hydrophobic, ionic interactions, hydrogen bonds, reagents concentrations…..) parameters that will dictate the amount of interactions ongoing. Indeed the association and dissociation are defined by two constants: ka and kd by the following equations:
ka= [LR]/([L]+[R]) and kd=([L]+[R]/[LR]).
In practice, kd is the most often parameter used for defining a drug interaction with its drug target. It is named as the dissociation parameter and usually is referred as the affinity for a ligand to its receptor. The lower this kd value is, the higher the ligand has affinity to its receptor. This dictates another tenet of pharmacology: the selectivity of a ligand to its receptor. A ligand will bind to one or several receptors at a defined concentration but can develop an affinity to other receptors when the concentration of the ligand increase. Such non-desired interactions are the same ones that are involved in medications side and averse effects.
As we mentioned, concentrations are key to a drug biological activity. These concentrations by convention are expressed as molar concentration (M or moles/L). A molar concentration is the amount of moles of a defined molecules dissolved in one liter of water or body fluid (usually we will discuss about drug plasma concentration).
A mole of a chemical is defined as the amount of a chemical atom or molecule that equals to the Avogadro Number N. N is to the number of carbon atoms contained in 12g (the mass element of carbon) of pure carbon. By convention this number referred as N is equal to 6.022 x 10e23 atoms/mol. Thus one mole of carbon contains 6.022 x 10e23 carbons, one mole of eggs will contain 6.022 x 10e23 eggs.
As we have discussed, concentration are referred as a molar concentration. In 1M (or 1 mole/L), we have one mole of a chemical dissolved in 1L (liter) of water. 1L of water weights 1000 grams. As the molecular weight of water (H2O) is 18 grams/mole, we can calculated that the amount of moles of water molecules in 1L is 1000/18=55 moles.
As 1 mole of water contains 6.022 x 10e23 molecules of water, 1L of water contains about 335 x 10e23 molecules of water per liter.
In pharmacology, a drug with a good affinity for its receptor is usually in the nM range. As 1nM= 10e-9M/L, the number of drug molecules in one liter of water will be 6.022 x 10e14 atoms per 335 x 10e23 molecules of water. If we make a ratio of this number, we would have less than 0.02 particle per billion (ppb) or 20 particles per trillion (ppt).
If we go back to numbers advanced by homeopathy preparation, a 12C preparation already is below our nM range, as this dilution translates into 1 ppt that is already twenty times below the standard level. I dont even mention oscillococcinum that has 200C dilution, you can do the math. But you can see that there is already an issue with the homeopathic dilution. Either compounds in homeopathy are super-selective and hit affinities in the order of the picoM range (10-12M) or we deal with virtually an absence of molecules in the solution.
3. Drug concentration, dose and pharmacokinetics
In practice, we have to consider a concentration as dose, expressed usually as mg/kg and refer to the plasma concentration (mg/L) as a circulating concentration to define the drug biological activity.
To give a practical example, we will discuss the case of acetaminophen (Tylenol (R)), an OTC painkiller that everyone can buy in any pharmacy. Acetaminophen common dose is 50mg/kg. For a adult weighing 70kgs, thats brings us about 1000mg dose.
To ease the understanding, we assume we inject the acetaminophen using the oral route. The average plasma concentration at maximal absorption is about 18 ug/mL (or 18mg/L) following the oral absorption of 1000mg at once (http://www.rxlist.com/tylenol-drug/clinical-pharmacology.htm).
To be effective, a drug has to achieve a concentration higher than the minimum efficacy concentration (MEC) but also stay below the minimum toxicity concentration (MTC), as concentrations above this level are known to induce side effects and even toxic effects.
Now if we go back to our active concentration, we need to have 18mg (=0.018g) of acetaminophen per liter of plasma. Acetaminophen has a molecular weight of 151 g/mol. The molar concentration of acetaminophen is therefore equal to 0.018/151 = 0.000119 mol/L plasma or 1.19 x 10-4 mol/L plasma. Therefore, we need about 7 x 10e19 molecules per liter of plasma to achieve a therapeutical activity. If we approximate plasma to water, we have to have about 2 particles per million (ppm) to achieve an activity. Yet homeopathic products rely on an extract of a natural product. Because of the DHSE Act, homeopathic products are not falling within the Food and Drug Administration accountability and therefore the manufacturer have no need to provide any information sheet on the composition of their product, as well as any data related to their pharmacokinetic profile. If we assume, a 12C preparation (that titrates 1ppt) and a 1 ounce fluid (30mL) administered to an healthy adult (5L of blood) , with 100% bioavailability, we will have a dilution of 166 times of the active compound. We are now discussing about a compound that can exert its activity to a concentration of 0.006 ppt. We are discussing here a compound that carry its activity with one million lesser concentration that a common painkiller. I am not even discussing about the duck liver extract that makes homeopathic claim the most ridiculous ever. Conventional Medicine = 2 – Homeopathic Medicine = 0.
- Clinical efficacy and placebo effect:
A tenet of modern and science-based medicine is the assessment of clinical efficacy of a compound. This is usually run through clinical trials, in which a drug candidate is tested in a small number of patients volunteering to participate (Phase II) and further extended to different locations with a higher number of patients enrolled (Phase III).
A common experimental setup for clinical trial is the “double-blind/placebo-controlled” study in which patients are divided into two groups: a treated group that receive the drug candidate prepared in a pill or solution, a placebo group that receive the same pill or solution except devoid of the drug candidate.
Neither the patient nor the doctor knows which group they have been assigned to until the end of the study period. By comparing the results between the two groups with the use of statistical analysis, clinical researchers can determine if a drug showed an activity.
If the treatment showed a therapeutical effect that was significantly different from the placebo, it is considered effective and further continue in the R&D pipeline until the FDA approval and its entrance in the market. If not, it is dismissed and its R&D is tossed.
Because homeopathy is considered natural, it does not have to follow the same pipeline than conventional medicine. However, because there are some proponents of homeopathy as a viable alternative medicine, there are some clinical studies that have been achieved. In the case of oscillococcinum, the outcome is fairly terrible. In a recent meta-analysis (http://www.ncbi.nlm.nih.gov/pubmed/23235586) done on six independent studies (two aimed as prophylactic treatment and four as ability to treat flu-like symptoms), patients treated with oscillococcinum failed to show a significant improvement compared to placebo-treated groups. At best alternative medicine treatments (including acupuncture, chiropractic or hypnosis) failed to show a robust response in patient versus placebo in various meta-analysis investigating conditions such as nocturnal enuresis (http://www.ncbi.nlm.nih.gov/pubmed/22161390), postpartum hemorrhage (http://www.ncbi.nlm.nih.gov/pubmed/24277681), irritable bowel syndrome (http://www.ncbi.nlm.nih.gov/pubmed/24222383) or psychiatric disorders (http://www.ncbi.nlm.nih.gov/pubmed/21733480). If homeopathy was effective as conventional medicine, it would be used to treat conditions that are qualified as serious or life-threatening. Yet, it failed because it is simply not working.
Conventional medicine = 3 – Homeopathy medicine = 0.
- If homeopathy is not working, so where is the harm?
When faced with evidence of lack of efficacy, homeopathic proponents usually will come with this statement “where is the harm?”.
The harm is coming in two folds: a waste of taxpayers money on useless treatment and the cases of fatalities due to lack of proper treatments.
Homeopathic proponents boast the recent move of the Swiss government to include homeopathic treatment in the standard of care, claiming such decision was made on scientific basis (http://www.swissinfo.ch/eng/complementary-therapies_swiss-to-recognise-homeopathy-as-legitimate-medicine/42053830).
In reality, such decision is solely based on political decisions. Switzerland applies a form of direct democracy that can be overstretched if not wisely used. The common cliche is the popular vote still conducted in tiny villages in Switzerland by which the population vote by referendum on any decisions proposed by the town hall.
In Switzerland, you can force the referendum on the federal stage if you gather enough signature to support your proposition. Usually, you will need to gather 100’000 signatures to force the Federal Chancellery to set a referendum. Such initiative is laudable but also can reach some unexpected consequences, in particular as some populist political parties have been spearheading to advance some of their political agenda. Homeopathy proponents knew this tactic and were capable to bring to the referendum. Once in the referendum, any proposal that achieve a majority of yes will have to get enacted into law. This is what happened in Switzerland, in which the 2009 referendum ended up with a majority of “JA” and passed into law recently in the Swiss legal code.
To conclude this first point, the recent move in Switzerland was driven by political movements, not by science-based evidence. It shows that a high GDP and education index is not indicative of a science literacy index. If you can adopt political tactics, you can spread the most insane pseudoscience as fact within the average Joe, regardless of their socio-economic or educational background.
The second harm is driven by the recent stories of toddlers death in the news outlet due to parents neglectence to seek professional medical assistance for severe complications due to an infectious disease. Two recent cases made the news outlet: Ezekiel, that died from meningitis after parents refused to seek medical assistance and to rely on naturopathy to cure their son (http://news.nationalpost.com/full-comment/alheli-picazo-when-naturopathy-kills) and the Dleozier case that relied on homeopathy to treat a streptococcus sore throat (http://www.rocket-courier.com/node/141065#.VX111HD3aK0). Both died of infectious diseases that could have been avoided if properly treated with conventional medicine.
Not even mentioning the 400 other cases in which the recourse of homeopathy had lead to severe complications (http://whatstheharm.net/homeopathy.html).
Conventional Medicine = 4 – Homeopathy Medicine =0.
6. Concluding remarks:
Homeopathy medicine is perfect example of how irrational beliefs and lack of science literacy is allowing outdated and snake-oil quackery practice of medicine and pharmacy are maintained alive in the 21st century.
Do we still follow Galen’s four vital fluids to treat diseases? Do we still practice bleeding to adjust such fluids? Do we still ask barbers to perform surgery? Do we still ask the local shaman or sorcerer to prepare an herbal concoction? Of course not because as our knowledge has improved, we put these techniques in the archive of time because we understood these techniques did not work.
In less than 100 years, we have increased average life expectancy and population quality of life in a magnitude higher than 10’000 years of modern humankind (as I referred it considering modern humankind as set by the neolithic age). Yet, we maintain outdated practice of medicine and pharmacy that all fall either into the category of inefficient medicine or into quackery.
As science-based medicine have advantages, it also has issues that need to be addressed in particular the progressive distance in the patient-physician relationship or conflict of interests in certain clinical trials. These issues will be only solved when public authorities will understand that healthcare is not a business that should be build on the same standard of any other business: productivity and profit-driven goals.
In the other hand, the practice of homeopathy in the age made of personalized medicine and -omics based methods (proteomics, genomics, metabolomics) is not only based on irrational and pseudoscientific assumptions but also based on a certain form of medical dishonesty as healthcare professionals relying on homeopathic products consciously know that such products have no proven efficacy and will certainly not cure the patient and ultimately increase significantly the risks over benefits. An important axiom of Hippocatres oath is “do not harm”. Homeopathy has proven over and over that it is doing more harm than good.