My ongoing experiment with the Everyman polyphasic sleep schedule

I have a running diary going of my experiment getting more time using the Everyman polyphasic sleep schedule up on my “personal” blog. Maybe with the extra time I will be able to start more regularly posting content here.

In terms of the content of this blog, my diary most definitely represents purely anecdotal evidence. However I may write a couple of articles that are more similar to the other articles contained here.

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Sweet Misery Fact Check – Part 2

In the first part (read here) of my “fact check” on the Sweet Misery documentary, I mainly covered the claims that it leads to neurological disorders or is otherwise inherently unsafe. In this second part, the focus turns to the process of aspartame approval. The research for this turned out to be interesting, especially as occasionally the claims in the documentary would have a small nugget of truth buried in them. Sometimes they may even be wholly true, but still essentially meaningless. It is quite clear that aspartame does not lead to brain tumors. So claims that there were mismanaged studies that could have demonstrated this in the 70s are pointless, as we now know that aspartame does not cause cancer.

In this part I will generally only cover claims for which I can find some sort of documentation one way or another. Frequently the speakers in the documentary will say that they spoke to so-and-so at the FDA or Searle, or were shown some document, but no evidence is provided nor is there necessarily a way of disproving the statement. There are also claims about behind the scenes shady dealings of Donald Rumsfeld and other leaders of Searle and the FDA. But I have to consider it speculation and hearsay without some any evidence to back them up.

There is an HTML version available athttp://tinyurl.com/sweetfact2

A PDF version is available at:https://whatdoesthesciencesay.files.wordpress.com/2012/08/sweetmiseryfactcheckpart2.pdf

Claim: The “Bressler Report” found a 115-week DKP rat study to be fatally flawed

Around minute 27 of the documentary, Russell Blaylock discusses a 115 week DKP (diketopiperazine) rat study that the FDA had concerns with due to some inaccuracies in the collection and reporting of data. He mentions that the “Bressler Report” — the results of an investigation lead by Chicago division of the then-Bureau of Foods investigator Jerome Bressler — found that the DKP (and other) study was “horribly done research” and that there were tons of discrepancies. Assuming that the linked document on wnho.net is in fact the real Bressler report[1], then these are accurate statements. However, as best I can tell reading the actual report, Bressler never indicates that the discrepancies change these actual conclusions in a drastic way (Bressler 1977 [2]).

Page 68 has the summary of the some of the lesions and masses that were considered significant that were inconsistent with the submitted FDA study. It indicates that “for the most part” the pathology reports are “in agreement” with those of Searle. The report does find that the incidence of uterine polyps in the medium dose was 15% rather than 12%. This makes them potentially dose-related to the levels of DKP in the diet (which would seem to indicate that the rats did in fact consume the DKP and not avoid it). In the report summary, the “throwing out” of the tumors isn’t noted as significant.

On the face of it, it seems strange that when Bressler went to Searle to investigate the raw data, virtually none of the people who performed the study were available or had left Searle. Dr. K.S. Rao, the head of the study, had left and refused to be interviewed. While this seems fishy, it may be also be perfectly normal. Bressler was doing his investigation three years after the study had been submitted to the FDA (1974), with the study actually starting in 1971. There is a good chance that people were brought on from universities as interns, and that researchers were simply contractors there for the single study.

Claim: Rao / Waisman monkey study was covered up

Around minute 30, former FDA Investigator Arthur Evangelista begins discussing the “covered up” monkey study performed by K.S. Rao and Harry Waisman. He mentions that it had methodological issues. What he doesn’t mention is that Waisman died partly through the study, which led to it being terminated early. In other words, the study was never finished and yet Searle submitted what it had. Nonetheless, even based on the partial results, the FDA still opted to use it as the basis for the labelling for Phenylketonurics found on anything containing aspartame (much to the dismay of the Quaker company which pointed out that other protein-based components of its cereals contained much more phenylalanine than the aspartame had, making the warning confusing) due to the exhibition of seizure activity in medium and “high” dose groups. Note that even the “low” dose group was 32 times the estimated maximal intake (GAO [3]). A later similar study did not exhibit the same seizure activity as it spread out the food intake over a more normal period (rather than one massive spike at once… which the monkeys often didn’t finish) (Reynolds[4]). So, if anything, the criticised (by all) Rao/Waisman study found more problems with aspartame (specifically, the phenylalanine content) than actually appear to exist.

Evangelista also mentions that “1 or 2” died (it was one, and the cause was unknown). There were no seizures in the low dose group, which corresponds to about 32x the estimated maximal intake of aspartame. The seizures occurred in the medium and high dose (100 and 120 times maximal daily intake) and the authors note that this can be induced with the equivalent amount of phenylalanine by itself (so this is a known effect of phenylalanine, nothing special for aspartame here) (RAO p.11 [5],[6]). Another key point is that the low dose group never has the seizure, so there was apparently no “build up” of seizure-inducing chemicals (a favorite canard of the anti-aspartame folks).

Claim: Ralph Walton’s review of peer-reviewed aspartame studies show 97 non-industry independent studies find aspartame to be dangerous

In minute 32, Walton refers to his “independent review” of the peer-reviewed aspartame studies, finding that the positive ones were Searle-funded and the “independent” ones turned out against aspartame. I have covered this one before, as have others[7]. Virtually none of the studies he cites as “independent” are even studies, and certainly not peer-reviewed. Additionally, very few of them even directly address aspartame. For example, he will point to studies showing that large amounts of methanol can be bad. We know this. And this has has very little to do with aspartame. The couple that could be considered to directly address aspartame with negative consequences haven’t been reproduced or are of low methodological quality.

Specifically, it seems that only five of the mentioned studies could be considered to be peer-reviewed and directly relatable to aspartame:

  1. Camfield PR, Camfield CS, Dooley JM, et. al., Aspartame Exacerbates EEG Spike Wave Discharge in Children With Generalized Absence Epilepsy: A Double-Blind Controlled Study. Neurology 1992;42:1000-1003.
  2. Mahalik MP and Gautieri RF, Reflex Responsiveness of CF-1 Mouse Neonates Following Maternal Aspartame Exposure. Research Communications in Psychology, Psychiatry & Behavior 1984;9(4):385-403
  3. Pinto JM, Mahea TJ, Administration of Aspartame Potentiates Pentylenetetrazole and Fluorothyl-Induced Seizures in Mice. Neuropharmacology 1988;27(1):51-55.
  4. Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X, Fernandez-Lopez JA, Alemany M, Formaldehyde Derived From Dietary Aspartame Binds to Tissue Components In Vivo. Life Sciences 1998;63(5);337-349.
  5. Van Den Eeden SK, Koepsell TD, Langstreth WT Jr, et a., Aspartame Ingestion and Headaches: A randomized Crossover Trial. Neurology 1994;44(10):1787-93.

The Camfield study (as mentioned in the title) only applies to children with a specific form of epilepsy. As noted in an American Academy of Pediatrics articlereviewing “inactive ingredients” in various pharmaceuticals, they simply recommend that children who have untreated epilepsy avoid aspartame in large doses (AAP 1997 [8]). A later study by Rowan and Shaywitz was unable to reproduce seizure activity in a controlled study of 16 adults and 2 children.

The Mahalik study was unable to be reproduced following the same methods by McAnulty et al (McAnulty 1989 [9]). The primary difference in their methods is that Mahalik et al did not use concurrent controls, but rather used historical controls. Note that McAnulty appears to have been employed by the NutraSweet company.

The Pinto study, like the Camfield one, relates to seizure activity, specifically around the phenylalanine content. As has been noted in other articles, aspartame is actually a relatively low source for phenylalanine and the results really only apply, potentially, to sufferers of PKU.

The Trocho study is about the formaldehyde/methanol concentrations. I discuss this in my first aspartame article . But in short, Tephyl et al notes that this study does not really apply to actual animals. Formaldehyde has never been demonstrated to build up on the body (and is a normal metabolic byproduct throughout the day from fruit juices), even when large direct doses of methanol are given to monkeys.

The Van Den Eeden study found that among people who self-report headaches after aspartame consumption, a subset of them actually seem to get more headaches when given aspartame versus placebo.

But if you follow the first link you can look at the studies he cites and decide for yourself. I’ve classified them by what type of study they are (peer-reviewed study, letter or case study) and whether they find aspartame to be “harmful”.

Claim: The Commissioner of the FDA (illegally) overruled the Board of Inquiry decision regarding aspartame approval

It is true that the Commissioner of the FDA did overrule the Board of Inquiry’s decision following the Task Force’s investigation. In his view, there was ample evidence of safety and no real evidence for brain cancer (which was their final fear). The concern of some of the board members was that there were not enough rats in the study to detect a 5% increase in chance of brain cancer. At the time that the GAO investigated the approval process, the National Toxicology Program’s standards were still only barely above what Searle had already done (in other words, even then in 1987 there was not a requirement to be certain of detecting 5% increase) (GAO p.55-59 [10]). In the documentary, James Turner claims that the Commissioner was violating law when he overturned the decision, but this does not appear to the the case. According to Title 21, the Public Board of Inquiry is a scientific not a legal body (CFR [11]).

Another interesting tidbit is that the documentary (around minute 55) says that it was a “clear conflict of interest” that Searle paid for an independent analysis (by UAREP, a consortium of nine universities) of the studies submitted to the FDA. In actuality, the FDA simply required them to foot the bill for the analysis. It was in no way sponsored by Searle (GAO pp.30-31).

The Missing Executive Order

I hesitate to say “and then things get weird”, considering what this article is reviewing. But then things get weird. About an hour into the video, Turner claims that the first action by Ronald Reagan upon coming into office in 1981 was to sign an Executive Order removing the ability of the FDA to stop the marketing of aspartame. No such Executive Order exists. Regan’s earliest one was signed on January 28th (Federal Register [12]). Naturally, Betty Martini claims the order was signed between the 20th and 26th and has been covered up. Why the entire government would choose to cover up just that one Executive Order is beyond me. Frankly, it is this exact type of thing that should make you question the entire documentary (assuming you weren’t already, as we have reached the end of the 2nd part of the series of articles). Absence of evidence is not evidence of anything.

Conclusions

While there is no doubt that pharmaceutical/chemical companies do everything in their power to get things certified, it does not appear that the evidence supports the notion of massive cover-ups of a deadly poison leading to improper approval.

The next, and hopefully final, part will discuss the story of a woman convicted of murdering her husband who has become a cause celebe for anti-aspartame crusaders who believe it was actually an aspartame overdose that led to his death (despite the fact that no such thing has ever been demonstrated to ever occur).


[1] I am a bit skeptical of the introductory portion which claims that the “worst 20%” were actually held back by the FDA and that portion has been restored in this version of it. As far as I can tell, the “missing” 20% is actually the portion of the review that covered two other aspartame studies, not the DKP study.

[2]Bressler, Jerome. 7 August 1977. Review of “115 Week Oral Tumorigenicity Study in the Rat, conducted with SC-19192 (diketopiperazine)”. Visited 16 July 2012. <http://www.dorway.com/bresslercomplete.pdf&gt;

[3]GAO (United States General Accounting Office). “Food And Drug Administration: Food Additive Approval Process Followed for Aspartame”. June 1987. GAO/HRD-87-46.

[4]Reynolds WA, Bauman AF, Stegink LD. “Developmental Assessment of Infant Macaques Receiving Dietary Aspartame of Phenylalanine” in “Aspartame: physiology and biochemistry” by Lewis D. Stegink. I believe that Stegink was associated with Searle in some capacity.

[5]Rao KS, McConnell RG, Waisman HA. “SC-18862: 52 Week Oral Toxicity Study in Infant Monkey”. October 1972. Note: Far as I can tell this was never published in a journal, so I have to assume that dorway.com has an accurate version of it

[6] Pedantic note. Throughout the internet and even in the documentary people refer to the Rao study as “SC-18862”. That is not the number of the study but rather the technical name (at the time) for aspartame. I would hazard a guess that it refers to “Searle Company”.

[7]aspartame.net “Aspartame Information replies to the New York Times”. 12 February 2006. Visited 15 July 2012. NOTE: aspartame.net is created by Ajinomoto North America, the makers of aspartame.

[8]‘“Inactive” Ingredients in Pharmaceutical Products: Update (Subject Review)’ PEDIATRICS Vol. 99 No. 2 February 1, 1997 pp. 268-278 (doi: 10.1542/peds.99.2.268)

[9]Absence of developmental effects in CF-1mice exposed to aspartamein utero. McAnulty PA, Colllier MJ. Life Science Research, Eye, Suffolk, England. The NutraSweet Company. Accepted 9 March 1989. Available online 27 September 2004. http://dx.doi.org/10.1016/0272-0590(89)90265-0

[10]GAO (United States General Accounting Office). “Food And Drug Administration: Food Additive Approval Process Followed for Aspartame”. June 1987. GAO/HRD-87-46. <http://www.gao.gov/assets/150/145477.pdf >

[11]CFR (Code of Federal Regulations) Title 21, Subpart B, S. 13.30. http://tinyurl.com/cfr21-13 (Visited August 26, 2011). I am not certain that at the time of aspartame approval the Board had more authority.

[12]National Archives. Federal Register:Executive Orders Disposition Tables. Ronald Regan – 1981”. http://www.archives.gov/federal-register/executive-orders/1981-reagan.html. Visited August 25, 2011.

Sweet Misery Fact Check – Part 1

There is an HTML version available at http://tinyurl.com/sweetfact1

A PDF version is available at: https://whatdoesthesciencesay.files.wordpress.com/2011/07/sweetmiseryfactcheckpart1.pdf

Introduction

I have covered aspartame twice before, but I thought to finally get it out of my system I would cover the documentary “Sweet Misery” which essentially contains all of the claims I have seen previously (and some of which I’ve covered) as well as the cast of characters which frequently pop up with this topic. In this way I can address the whole gamut of aspartame claims and be done with it.

For the most part, the movie amounts to 90 minutes of anecdotal evidence of aspartame causing all manner of harm. A few of the guests in the documentary at least have medical degrees, but their statements frequently contradict the best scientific evidence we have and are often backed only by books that they themselves have written.

As you read this, you will notice a trend in my thinking that I want to make clear now. As a non-scientist, I am only “qualified” to trust consensus scientific evidence. While it may turn out in the future that a series of high quality, reproducible, studies will emerge which demonstrate a link between aspartame and a number of neurological disorders, this has not occurred yet. A large body of anecdotes do not count as studies. Individual studies do not really even count as evidence against the large amount of existing studies. Odds are, individual studies (no matter what they find, for or against aspartame) are wrong in some way. It takes a volume of studies to create that proper body of evidence that leads to a consensus.

So you may read this paper and find yourself thinking “he is just trusting scientists, he is just trusting the government, but they lie to us/are bought by industry/are biased”. I do not trust scientists, I trust science. And the current science shows no link between aspartame and all of these disorders. You should not trust me. And you certainly should not trust a few people in a documentary. But I firmly believe you should trust the large body of actual, peer-reviewed, studies that make of the evidence, especially in the form of reviews of multiple studies which can aggregate the results. I have no evidence of wide-spread corruption and fraud in the scientific community in this regard. Individual cases, sure. That’s why you go with the wide body of evidence.

If you are convinced that anything that comes from “mainstream” science is flawed, you may as well stop reading now.

Cast of Characters

The doctors and patients in the video are all people who are violently opposed to aspartame. The patients are not random people they found who had these issues, but are actively engaged in the idea that aspartame causes any number of issues.

The “Experts”

Russell Blaylock is a retired neurosurgeon who writes and speaks frequently about “excitotoxins” (which is not very prevalent in the scientific literature). He even manages to bring autism into the picture. He is also anti-fluoride.

Jim Bowen is a former medical doctor who appears to believe in all manner of other conspiracy theories, especially those related to the “Zionist Conspiracy”. You can easily find him searching for “Jim Bowen aspartame” on Google. He also wrote a pleasantly-titled article called “Aspartame Murders Infants”. He also appears as one of the sufferers in the video.

Arthur Evangelista is apparently a former FDA investigator (not sure how to confirm or deny this) who, ironically enough, runs a company that helps herbal supplement company “avert” oversight by the FDA. His PhD is in “Industrial and Occupational Safety”, not biochemistry, biology, chemistry, etc.

HJ Roberts appears to be/have been a doctor, but now writes books against apartame. One aspect, at least, where he seems to be “right” is in his criticism of taking vitamin E supplements in large doses. That criticism appears to be backed by real science. But otherwise his views do not appear to fit with mainstream consensus science.

Ralph Walton is psychiatrist who believes that aspartame leads to number of neurological disorders. I have covered [1]his supposed list of 97 “peer reviewed” articles against apartame previously (in short, while it is a list containing about 97 items… most are not peer-reviewed, about aspartame, or even against aspartame).

Many of the sufferers in the video have websites and and are in business related to anti-aspartame and “natural” industries. However I could not absolutely positively identify them (I would rather not link to sites that turn out not to be the same person) and so will leave that as an exercise for the reader. But as far as I could tell, these were not simply people they found off the street who were affected by aspartame, but rather fellow anti-aspartame crusaders.

The point is not to promote the genetic fallacy or perform an ad hominem attack, but rather to show that these are not necessarily “experts” who we should take at face value and that we should be extra sure to look into the evidence (or lack of) that they present for their claims. The claims must still stand or fall on their own grounds.

The Claims

Claim: Studies show a growing trend of multiple sclerosis, brain tumors, diabetes,etc in recent years linked to the introduction and usage of aspartame

Claim is made in first three minutes of video by the narrator, Russel Blaylock and HJ Roberts.

HJ Roberts says he noticed “conflicting” themes and that the rise was not due to lack of adequate scanning devices and that other cancers stayed the same while brain cancer incidence went up.

It’s not clear what studies are showing this trend (as the documentary doesn’t have a list of sources), but, at least for brain tumors, the incidence has bounced up and down and in fact started going up before aspartame was introduced, and went back down between 1990 and 2002.

Brain Tumors

According to the National Cancer Institute:

From 1990 to 2002, the overall age-adjusted incidence rates for brain cancer decreased slightly; from 7.0 cases to 6.4 cases for every 100,000 persons in the United States. The mortality rate from 1990 to 2002 also decreased slightly; from 4.9 deaths to 4.5 for every 100,000 persons in the United States.[2]

“Incidence” refers to the numbers of new cases.

NCI Continues, “However, aside from the small percentage of brain tumor cases that can be linked to exposure to high-dose ionizing radiation or to certain inherited genetic alterations, few specific risk factors have been convincingly linked to brain tumors.”

They do mention that they are looking at “sweeteners” (among many other things) as potential causes, but studies were initiated in 1994 and I think I can show that aspartame has been ruled out quite well.

The Olney Study

I suspect that their “source” for the information in the first place, as the documentary makes reference to it, is the infamous J.W. Olney (mentioned above) study brain tumor “study” which looked at brain tumor incidence. The study has been highly criticised for cherry-picking the data and its methodology.

The NCI addresses the study and mention the fact that brain tumor incidence rises (for the time in question for this documentary) started 8 years prior to the introduction of aspartame:

Questions regarding the safety of aspartame were renewed by a 1996 [the Olney study]  report suggesting that an increase in the number of people with brain tumors between 1975 and 1992 might be associated with the introduction and use of this sweetener in the United States. However, an analysis of then-current NCI statistics showed that the overall incidence of brain and central nervous system cancers began to rise in 1973, 8 years prior to the approval of aspartame, and continued to rise until 1985. Moreover, increases in overall brain cancer incidence occurred primarily in people age 70 and older, a group that was not exposed to the highest doses of aspartame since its introduction. These data do not establish a clear link between the consumption of aspartame and the development of brain tumors.  [3]

Additionally, from the French Food Safety (AFSSA) report on aspartame from 2002 (French 2011 [4]) (emphasis mine):

 In 1996, Olney et al. published an article.. the authors concluded that there was a significant increase in the frequency of brain tumours in the mid-1980s, that is to say the period following aspartame came onto the market.  The conclusions of this epidemiological  study have been criticised by a number of  scientists who questioned the methodology, the use of the data and their interpretation (Levy et al., 1996; Linet et al., 1999; Ross, 1998; Seife, 1999; Smith et al., 1998). One of the major criticism is that the authors  only took into account the frequency of brain tumours during a selected period (1975-1992). When all the epidemiological data are used (1973-1992) a different conclusion is reached, as the frequency of brain cancers began to increase in 1973 and stabilised from the mid-1980s (Levy  et al., 1996). Furthermore, Olney  et al. did not provide any quantitative or qualitative relationship between the exposure of the population to aspartame and the observed frequency of brain tumours.

Additionally, there was a case-control study that attempted to demonstrate any sort of link, and failed to do so (Gurney 1997). [5]

In short, except for the Olney statistical analysis, all actual studies of humans and the data demonstrate no link between brain cancer and aspartame usage.

Multiple Sclerosis

Even the National Multiple Sclerosis Society does not support the claim that aspartame has anything to do with it. On their “Old Theories That Have Been Disproved” page, they put aspartame in there with allergies and owning a dog as having no scientific evidence linking it with MS. (National [6])

Or if you’re not a fan of the National MS Society, how about the Multiple Sclerosis Foundation? On their page “Examining the Safety of Aspartame”, they call out the “Nancy Merkle” hoax which kick started a lot of this nonsense and state pragmatically [7]:

While nothing can be considered 100 percent safe, aspartame has undergone extensive testing. With the exception of a few very mild side effects, aspartame appears to be quite safe. Those individuals, who experience problems after consuming aspartame, should eliminate foods and beverages that contain this sweetener from their diet.

I think it would stretch credibility quite a bit to believe that both of these groups are somehow “in the pocket” of the NutraSweet company.

Diabetes

Jim Bowen makes the claim that Diabetes jumped 33% (not sure which years)

Since 1960 or so, diabetes incidence has grown by about 3% a year (Onkamo 1999 [8], Diabetes [9]).  So over any given 10 year period, it would grow ~30% from the start. So a very misleading statistic.

Claim Summary

Misleading and wrong. Brain tumor incidence did go up, but not from aspartame. And incidence actually dropped in subsequent years (while usage of apartame has probably gone up). Aspartame did not cause a rise in brain tumors or multiple sclerosis. Not only is there no evidence linking aspartame with brain tumors, but when anybody actually tries to find evidence for it, the studies demonstrate nothing. So this is not a case of there just not being enough/no testing. There is a wealth of testing which has led to negative evidence of a link between aspartame and these disorders.  So what opponents of aspartame mean when they say there hasn’t been “enough” testing is really that there hasn’t been enough that agrees with their view.

Claim: The components of aspartame break down into poisons and build up in the body over long periods of time to create toxic effects

Approximately minutes 4 to 7, with some later as well

Russell Blaylock – People say they take MSG, aspartame with no obvious effects. “Subtle toxic effects in those who don’t have obvious problems” Over long term will have disease.

… long term “Exposure to large amounts of the components of aspartame is toxicity”.

… “We know aspartame is a poison,it affects protein synthesis, and how the synapse operates in the brain. Affects DNA”

… “Sub-chronic level” … Slow build up of toxins. Disrupts endocrine system

“aspartame with carbohydrates, reduces availability of L-tryptophan, an precursor for seratonin”

… “methyl ester becomes free methyl alcohol.. a real poison”

… “made sense that aspartame would lower seizure threshold”

… “Poisonous effect of methyl alcohol and ester is well known”

Lorena: Drinking water.  “Searched for aspartame. Eyes lit up and started crying. I counted 79 of the 92 symptoms”

Methanol/Methyl Alcohol

I have a whole article essentially devoted to methanol/formaldehyde from aspartame that you can review, but I have looked a bit deeper for this current one[[10]]. While it is technically true that aspartame has methanol (and then formaldehyde) as one of its metabolic byproducts, it is also a bit of a red herring. Fruits break down into more methanol than numerous cans of soda. Meat contains much more phenylalanine than aspartame.

Kirchner found .8 mg/kg of fresh orange juice and 62 mg/kg stored and canned (Kirchner 1957 [11]). Assuming my math is right, this would equate to about 0.2mg in a fresh 8oz glass, and about 15mg stored. Compare this with a single 12oz can of soda, which has about 150mg (on the high end) of aspartame, 10% (15mg) of which metabolizes to methanol. Nobody seems to think the orange juice is going to kill you. On the low end of aspartame concentrations, juices and fruits are going to have much more. And anti-aspartame advocates are well of aware of this, and simply claim that there are “protective factors” in these fruits, juices and wines that make it not matter. This is special pleading. There is no evidence that methanol from aspartame in fact builds up.

The actual reason for the toxicity of methanol is from the build-up of formic acid/formate from high acute ingestion of methanol within a single exposure (good luck finding a study that finds evidence of long-term build up… they all refer to acute exposure). There is no evidence that it builds up indefinitely over years. In fact, the formic acid is able to leave the body faster than it is produced. Formaldehyde by itself appears to not contribute directly to the toxic effects of high doses of methanol (McMartin 1978 [12]).

Scientists have in fact looked at whether or not there might be build up of formic acid or methanol in the blood following ingestion of aspartame… and there simply is not.

Lewis Stegink performed a study finding no increased levels of formate after consumption if even “abuse” levels of aspartame (Stegink 1981 [13]). Stegink also has a larger review of the studies performed on the various components in aspartame, in which he discuses the results of that study and others which have looked into formic acid build-up:

blood and urine formate levels were determined in subjects administered the highest dose of aspartame (200 mg/kg body weight). No significant change in blood formate concentration was noted however, urinary formate excretion was increased significantly over preloading values in urine samples collected 0-4 h and 4-8 h after aspartame loading. Urinary formate excretion returned to preloading values in samples determined 8-24 h after loading. Because the rate of formate synthesis apparently did not exceed the rate of formate metabolism and excretion, blood formate levels were not detectably elevated. Thus, there appears to be little risk from aspartame’s methanol content at the doses studied (Stegink 1987 [14]).

In other words… the body easily gets rid of the byproducts via urination. When dri benking/eating products containing aspartame, you are not getting an acute dose of methanol that would cause harm. The normal metabolic processes of your body get rid of the methanol. If it didn’t, then you would have to avoid fruits and vegetables as well.

Phenylalanine

While people with the rare disorder phenylketonuria (PKU) should avoid products containing phenylalanine, diet soda and other “light” products are the least of their worries. A single can of soda is going to have ~150mg (0.150g) of aspartame. Let’s say 50% of that is phenylalanine, which would get you about 0.075g (75mg)  in a can of soda.

Using a tool available at http://www.bitelog.com/narrow-food-search.htm, you can calculate how much of a nutrient is contained in various food items.

An 8oz glass of milk contains 0.395g of phenylalanine.

An 8oz hamburger has 2.29g of phenylalanine.

1 medium banana has about .058g of phenylalanine.

So < 0.1g is well below many other foods that most people wouldn’t think twice about. Even if you drink 6 cans a day, you only get a little bit past the glass of milk but still nowhere near a hamburger.

Aspartic Acid

Aspartic acid is one of the “non-essential” amino acids, as our body is able to synthesize it on its own. In high doses, some would call it an “excitotoxin” but I can find little evidence of this being backed by scientific consensus. I have not seen too many specific claims against aspartic acid, so I don’t see any reason to talk too much about it.

Claim: There have been thousands of complaints to FDA about aspartame, more for neurological conditions

3:41 HJ Roberts – By 1988, “80% of complaints about food additives were for aspartame”. Where’s the evidence of this?

I covered this one a bit in my article entitle “Extraordinary Claims about Aspartame in the Huffington Post”. The fact of the matter is that there is no real evidence that the document shown in the documentary is legitimate. Even assuming it is, there are thousands of complaints about many additives submitted each year, but after investigation they are not reproducible. The list of 92 symptoms appears to come from yet another document by, not surprisingly, Betty Martini. As best I can tell, the scan of the document she (claims to have) received from the FDA is located on Scribd.  But, as I will discuss below, the FDA (and others) has looked into the various reports and found no real causation.

The FDA does in fact have an Adverse Event Reporting System (AERS), where you can go and report effects you believe you’ve had (and naturally people have reported aspartame). The FDA uses this to compile a list of “potential” dangers that consumers and health officials should be aware of (FDA 2010, Potential [15]). However, you won’t find Aspartame listed in that current set. Or for that matter on any of the warnings from 2008 to 2010.

I think it is useful to quote from the FDA here about what the AERS is and is not as it relates to causality (FDA AERS [16]):

AERS data do have limitations. First, there is no certainty that the reported event was actually due to the product. FDA does not require that a causal relationship between a product and event be proven, and reports do not always contain enough detail to properly evaluate an event. Further, FDA does not receive all adverse event reports that occur with a product. Many factors can influence whether or not an event will be reported, such as the time a product has been marketed and publicity about an event. Therefore, AERS cannot be used to calculate the incidence of an adverse event in the U.S. population.

If you would like to dive into the actual complaints available, there are data files you can download. If aspartame were such a danger, there should be at least a few references for aspartame, but I don’t find any. You will however find aspirin in there, which makes sense as it is a potent and effective drug [17].

This documentary (and list shown on screen) show various neurological disorders that aspartame apparently causes, but the majority of these are diseases and disorders for which the the medical community does not have a known cause or cure. So of course we cannot definitively say “aspartame did not cause this.” However, aspartame most definitely is not in the running by any established or credible research agency into any of these diseases.

Tollefson and Barnard did an analysis in 1992 of the 900 or so claims available at the time. They only looked into seizure related ones and found that the data “did not support the claim” of a linkage to seizures and aspartame consumption (Tollefson [18]).

A more overarching review was done by the CDC, and also found no reason to suspect a “widespread public health hazard” (but cautioned that were a small number that could be attributable to aspartame)  (Bradstock 1986 [19]).

Claim Summary

There is always a chance that a small number of people have side effects from aspartame. Like any chemical, it can react to the body. But when apparent claims are looked into broadly, they come to nothing. And in the case of these specific symptoms, they are generic ones that we all go through for random reasons and rarely have obvious causes (itching, headaches, etc). So, if you feel weird after consuming aspartame stop consuming it. But millions of us consume it without ill effects. Both sides are anecdotal evidence, not science. The science shows that there is no effect across a broad spectrum.

Claim: People who stop consuming aspartame have their symptoms go away, and re-intake causes symptoms to come back

Approximately minutes 9 to 25, with some gaps. Claim is made by Joan (Goodman), Ed Johnson, HJ Roberts,Jim Bowen, Lorena Murray

“When I got off of NutraSweet, the symptoms stopped” … “My doctors will not say it is aspartame in the official records, but say it to the side” … “She didn’t have lupus or MS.. her husband made her stop drinking the diet drinks and the symptoms went away” … “I put the diet drink down, Friday the 19th… within 24 hours” … “When aspartame removed, the symptoms go away. That’s what you call strong circumstantial evidence”

HJ Roberts: “after they re-challenge themselves with aspartame, the symptoms come back, sometimes within minutes. That’s more than anecodotal. “That’s reproducing the problem. Many of these ‘aspartame reacters’ have testing themselves multiple times”.

Jim Bowen says with his patients when they go off aspartame it goes away. Says he developed therapeutic outlooks working with experts on environmental toxicology.

Not “more than” anecdotal

First of all, these various claims are not “more than” anecdotal. They fit absolutely into the very definition of anecdotal. Having a lot of (supposed) people making a claim does not suddenly carry the weight of actual science. The claim must be tested.

Definitions of ‘anecdote’/’anecdotally’:

  • From dictionary.com: “non-scientific observations or studies, which do not provide proof but may assist research efforts
  • From oxforddictionaries.com: “(of an account) not necessarily true or reliable, because based on personal accounts rather than facts or research”

In other words, it stops being an anecdote when the claims are tested with an actual controlled study. For the case of multiple sclerosis, it does not appear that there is enough scientific plausibility to even warrant a study. As noted at the beginning, the various national MS foundations/groups absolutely do not support this claim. In the case of migraines controlled studies find no link (and sometimes a negative link!) [[20],[21]]. For brain tumors, no link. Seizures, very little link (except those with PKU). So, sure, start with anecdotes. But when the science shows no link, accept it and move on. Of course still follow the advice that applies for all food and drugs: If you get ill effects from using it, stop using it.

Relapsing-Remitting Multiple Sclerosis

The most common form of MS — 85% of people are initially diagnosed with this, versus 15% of the progressive form — is what is known as relapsing-remitting MS where the sufferer has occasional relapses, sometimes coming on suddenly over a period of days or even hours. This is followed by long periods, months and often years, of remission with complete recovery. RRMS affects women at a 2:1 ratio to men and it usually occurs in the 20s and 30s. After approximately 10 years, but even up to 30 years, later it will usually progress to Secondary-Progressive MS in which there is less remission. [[22]]

There is no way to know whether or not the people in the video actually had MS, or if they had the “popular” RRMS early form. But based on the fact that there is simply no scientific evidence of a link between aspartame and MS along with the assumption that those appearing in the video are telling the truth, the way that RRMS shows itself is at least a potential explanation for the apparent ability to make the symptoms “disappear” and reappear very quickly… as this is exactly what RRMS does. Couple that with the belief that aspartame is the “only” thing that changed, and you have a recipe for strong correlation without causation. Depending on the person, RRMS can slowly cause permanent degeneration of function and ability, which seemed evident in some of those in the video.

Also, interestingly, incidence of multiple sclerosis appears to increase as you get further from the equator (though this trend has apparently gotten weaker) and the female to male ratio is actually growing.  I would definitely be very surprised if intake of aspartame also follows a distance-from-equator gradient. [[23]]

Conclusion

This article covered the first 30 minutes of the Sweet Misery documentary by Cori Brackett. This part looked at the initial claims that there has been a rising trend in various neurological disorders caused by the toxic byproducts of aspartame. I believe I have demonstrated that these claims are not backed by the scientific evidence. Not only does the scientific consensus not support claims that brain cancer and multiple sclerosis is related to aspartame intake, but the national public and private foundations for these ailments do not support the notion. Additionally, the individual parts of aspartame are contained in much larger quantities in foods that would be considered “harmless” such as fruit and meat.

If you feel weird after consuming aspartame stop consuming it. But millions of us consume it without ill effects. Both sides are anecdotal evidence, not science. The science shows that there is no effect across a broad spectrum.

I plan on doing two more additional articles to cover the full 90 minute movie so that I can be done with aspartame once and for all.


[1] DeWald, Joshua. “Aspartame and Formaldehyde: What does the science say?”. June 13, 2010.

[2] NCI. “National Cancer Institute Brain Tumor Study in Adults: Fact Sheet”. http://www.cancer.gov/cancertopics/factsheet/Risk/brain-tumor-study.Visited April 26, 2011

[3] NCI. “Artificial Sweeteners and Cancer”. http://www.cancer.gov/cancertopics/factsheet/Risk/artificial-sweeteners. Visited April 26, 2011

[4] French Food Safety Agency. “Assessment report: Opinion on a possible link between the exposition to aspartame and the incidence of brain tumors in humans”. May 7, 2002. http://www.food.gov.uk/multimedia/pdfs/afssaeng.pdf

[5] Gurney JG, Pogoda JM. J Natl Cancer Inst. Aspartame consumption in relation to childhood brain tumor risk: results from a case-control study. 1997 Jul 16;89(14):1072-4

[6] National Multiple Sclerosis Society. “Old Theories That Have Been Disproved”. http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/what-causes-ms/disproved-theories/index.aspx. Visited April 26, 2011

[7] Multiple Sclerosis Foundation. “Examining the Safety of Aspartame”. http://www.msfacts.org/article-details.aspx?articleID=40. Visited April 26, 2011

[8] Onkamo P. “Worldwide Incidence of Type 1 Diabetes–the analysis of the data on published trends”. Diabetologia. 1999 Dec. 42(12).

[9] Diabetes and the Environment. “Type 1 Diabetes Incidence: Historical Trends”. Author includes source references http://www.diabetesandenvironment.org/home/incidence/historical

[10] DeWald, Joshua. What does the Science Say? (blog). “Aspartame and Formaldehyde (Or not…)”. http://wp.me/pH6F5-S

[11] Kirchner JG, Miller JM. Volatile water-soluble and oil constituents of Valencia orange juice. J Agric Food Chem 1957;5:283-91.

[12] McMartin, KE. “Lack of a role for formaldehyde in methanol poisoning in the monkey”. Biochemical Pharmacology. Volume 28, Issue 5. 1 March 1979. pp645-649

[13] Stegink LD, Brummel MC, McMartin K.. Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame. Journal of Toxicology and Environmental Health 7: 281- 290. 1981.

[14] Stegink, LD. “The aspartame story: a model for the clinical testing of a food additive”. Am J Clinical Nutrition. July 1987. Vol 46:1. p207

[15] US Food and Drug Administration. “Potential Signals of Serious Risks/New Safety Information Identified by the Adverse Event Reporting System (AERS) between January – March 2010”. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm216272.htm. Visited 7/12/2010

[16] US Food And Drug Administration. “Adverse Event Reporting System (AERS).” http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm082196.htm. Visited 7/9/2010

[17] US Food And Drug Administration. “The Adverse Event Reporting System (AERS): Latest Quarterly Data Files”. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm082193.htm. Visited 7/9/2010

[18] Tollefson L, Barnard RJ. An analysis of FDA passive surveillance reports of seizures associated with consumption of aspartame. J Am Diet Assoc. 1992 May;92(5):598-601.

[19] Bradstock MK, Serdula MK, Marks JS, Barnard RJ, Crane NT, Remington PL, Trowbridge FL. Evaluation of reactions to food additives: the aspartame experience. Am J Clin Nutr. 1986 Mar;43(3):464-9. PubMed PMID: 3953484.

[20] Schiffman, Susan S., et al., 1987. “Aspartame and Susceptibility to Headache,” The New England Journal of Medicine, Volume 317, No. 19, page 1181-1185.

[21] Garriga MM, Berkebile C, Metcalfe DD. A combined single-blind, double-blind,placebo-controlled study to determine the reproducibility of hypersensitivity reactions to aspartame. J Allergy Clin Immunol. 1991 Apr;87(4):821-7.

[22] National MS Society. “How Relapsing-Remitting MS (RRMS) Differs from Progressive Courses of MS”. Visited May 10, 2011. http://www.nationalmssociety.org/about-multiple-sclerosis/relapsing-ms/relapsing-remitting-ms-rrms/how-rrms-differs-from-progressive-courses-of-ms/index.aspx

[23] Alonso A, Hernan M. “Temporal trends in the incidence of multiple sclerosis”. Neurology. July 2008. Vol 71, No 2.

Homeopathy

A printable PDF can be found here, as well as an HTML version.

In speaking with friends, it has become clear that there is some confusion as to what homeopathy actually is. Frequently the answer I get is that it is basically the same as an herbal remedy. The reality is quite different — a homeopathic preparation is nothing more than a sugar pill or water. A homeopathic preparation could begin life as an herbal remedy (or pretty much anything), but the end product is generally nowhere near since it has been prepared according to the the Law of Similars (“like cures like”) and Law of Minimum Doses (dilution) first proposed by Christian Hahnemann in the 1700s. So what may begin life as a tincture of arsenic (to cure arsenic poisoning), caffeine (to cure insomnia) ends life as nothing more than water or sugar. I thought it would be interesting to give an overview of just what homeopathy is, what it is claimed to be, and what it is claimed to fix. I think you will agree at the end that the operation of homeopathy is completely implausible, and the scientific evidence for its efficacy is lacking.

While it actually pleases me that most people have never heard of homeopathy (because this means they are not intentionally taking it regularly),  my concern is in unknowingly coming across it at a drug store and, naturally, coming to the conclusion that this box or bottle of stuff actually, you know, works. That is what you assume that pharmacies sell: actual functional drugs. I recently was in a popular chain drug store and came across some of these preparations. If that were not bad enough, each of them had a store brand version, with the label “pharmacist recommended”! Much to my wife’s dismay, I could not resist the urge to take it to the counter and ask if, in fact, they would recommend it. I was pleased to hear “It pretty much just tastes like sugar, I don’t think it works”, which is not quite a ringing endorsement. I was somewhat saddened that he said he had actually tried it, but perhaps that is just due diligence.

Just what is homeopathy?

The Law of Minimum Doses

One of the core tenants of homeopathy is that of the Law of Minimal Doses, or Law of Infinitesimals. The US government, under the auspices of the National Institutes of Health, actually has what is known as the National Center for Complementary and Alternative Medicine. Rather than being meant to put alternative medicines in their proper place, it actually somewhat sponsors it and gives it credibility. Putting aside the obvious problem with that, let’s quote from its page on homeopathy (NCCAM 2009 [1]):

“The principle of dilutions (or “law of minimum dose”) states that the lower the dose of the medication, the greater its effectiveness. In homeopathy, substances are diluted in a stepwise fashion and shaken vigorously between each dilution. This process, referred to as “potentization,” is believed to transmit some form of information or energy from the original substance to the final diluted remedy. Most homeopathic remedies are so dilute that no molecules of the healing substance remain; however, in homeopathy, it is believed that the substance has left its imprint or “essence,” which stimulates the body to heal itself (this theory is called the “memory of water”).”

Thankfully they later point out that if this were true, it violates all known laws of physics. As cool as that would be, homeopathy has not remotely been demonstrated in a way that would make us rethink physics or chemistry.

Law of Similars

Let’s get our next description from another site, in case you think I am just printing government propaganda (though perhaps I did, if you define propaganda as something designed to convince us as true something that is not… such as alternative medicine). From the National Center of Homeopathy (note: not a government entity, which you can tell because they are selling stuff) (NCH 2006 [2]):

“The homeopathic doctor chooses the proper remedy by following a special rule of nature called the Law of Similars. This law states “like cures like,” or that a medicine can cure a sick person if it can cause similar sickness in a healthy person. For instance, if you peel an onion, your eyes burn, itch and water. You might also have a runny nose and begin to sneeze. If you had similar symptoms during a cold or allergy attack, such as a runny nose, watery eyes and sneezing, a homeopathic micro-dose of the remedy Allium cepa (red onion) would help your body heal itself. The word “homeopathic” is derived from the Greek words homeos meaning “similar” and pathos meaning “disease” or “suffering.” Thus, homeopathy means “to treat with a remedy that produces an effect similar to the disease or suffering.”

In summary, you start with a small amount of some substance which would normally cause the symptoms of some illness or disease (or in some cases, the disease itself). You dilute it down such that nothing remains (shaking in between) and through some sort of law of nature, you now have a substance which will cure the disease/illness that would have originally been caused (or symptomatic of). And the more dilute, the stronger its effects.

Isn’t that how vaccines work?

The previous description may superficially sound like the way that vaccines operate, but it is not at all. The original ingredients of homeopathic preparations are chosen based on “provings” in which the substance causes effects similar to that which is being treated. They are not necessarily the cause in the first place. Vaccines actually operate by triggering the production of anti-bodies when the body encounters either contains the actual virus (live attenuated), dead viruses, or simply proteins found on the casing of viruses. When a full-strength version of the virus in question enters the body, the immune system is already prepared for it (CDC 2009 [3]).

I guess you could compare it to when dogs will be given a shirt (or other item of clothing) which contents the scent of some item or person they need to locate. The next time they detect that same scent, they have most likely found the original source.

So vaccines are doubly so unlike homeopathic remedies, because homeopathic remedies are meant to cure what ails you right now. Vaccines simply prepare you to fight the illness later.

And also, vaccines actually do something.

Livers and Hearts, oh my!

Let’s take what we learned and see how it’s used in the real–I hesitate to use that word–world. There is a flu remedy available on the market called Oscillococcinum (“Oscillo” for short). I first came across it at my local grocery store, but it is prominently displayed at checkstands at “natural” food stores (Whole Foods and the like). It is also one of the few homeopathic preparations available at Wal-Mart. So this is not something would have to really hunt for, it is readily available. If you stumbled on it at the store, there is a decent chance that you would purchase it on the assumption that it is real medicine.

The listed “active” ingredient for Oscillo is “Anas barbariae hepatis et cordis extractum 200CK HPUS” (Boiron 2010 [4]). The “HPUS” means that it is listed in the “Homeopathic Pharmacopeia of the United States”, which the FDA amazingly allows to be used by homoeopathic preparations to list themselves as FDA approved (The Oscillo site actually improperly links to the actual regulations).

Because there is nothing in these “drugs”, the FDA does not require any expiration notices to be placed on them (water and sugar do not “go bad” when properly sealed). Also since there is nothing to them, homeopathic preparations are exempt from the “identity and strength” testing that real drugs must go through to, you know, make sure they actually have what they say they have (FDA 1995 [5]). That would be literally impossible to test with a homeopathic preparation (yet, somehow, your body can detect it?).

The Google translation of this string of Latin is “Duck with barbarism and of the liver and the heart”. Yum. Barbaric duck. But it is actually the Muscovy Duck, also known as the “Barbary Duck”. So, yes, it is made of ground up duck liver and heart. Why duck? Well, because of that “law of similars” mentioned above. Duck seems to have been chosen due to its carrier susceptibility to (avian) flu, which it can then transmit to others.

As much as I would be happy for someone to have an excuse not to take this, the next section will demonstrate that you are more likely to encounter non-vegetable matter in a glass of bottled or tap water than you would in this particular remedy.

Potentization

Recall that the “active” ingredient was “Anas barbariae hepatis et cordis extractum 200CK HPUS”. The interesting part is the “200CK”. This means that it is a “200 centesimal” dilution. A 1C dilution would be 1 part in 100. The sort of minimum historic dilution is “3C”, or 1 part in 1,000,000 (that penny is now just one part of $10,000), which can be written as 1 in 10^5 (Little  2001 [6]). Essentially, each “C” is an additional 1 in 100 dilution, whereby 1 part of the original solution (say, 1 drop) is placed into 100 times that (100 drops). Oscillo says it using a 200C dilution. The K of “CK” means it uses the Korsakovian method, which just means that instead of taking a drop from the mixture and putting it into another container, the same container is reused by pouring out “99%” of it, and just leaving the 1% (1 drop). Boiron has even patented their version of it (Boiron 1985 [7]).

I have no idea what the molecular weight of duck liver might be, so I am going to assume that it is close to that of sugar (342g/mol). Why sugar? Because a dose of Oscillococcinum (and most other preparations) is just granules of sugar that the “active” ingredient is placed onto. Plus, you will see that it does not actually matter one way or another.

Let’s assume also that we are starting with 100 grams of the water that we are mixing with, such that we have a single gram of our “active” ingredient. There are about are about 45 atoms per molecule of sugar, and 342.3 grams per mol, and so if you work out the math, about 8×1022 atoms per gram (the great part about homeopathy though is that it really doesn’t matter if we’re off by multiple orders of magnitude here).

Let the mixing begin.

Dilution

Atoms remaining

Notes

1C

8×1020

2C

8×1018

9C

80,000

We have spread that initial 1 gram over 10^18 grams of water. In perspective, one estimate of the number of grains of sand on Earth’s beaches is 7.5×1018 (McAllister [8])

10C

800 atoms

12C

8 atoms[9]

Spread out over 10^24 grams of water. This is more water than is estimated to exist in all of the oceans in the world.

14C

Nothing

Spread over 10^28 grams of water. One estimate for the amount of matter in all the Earth is only 1027 (Weisenberger [10]).

44C

Nothing

Spread over 10^88 grams of water. There is estimated to be only on the order of 10^86 atoms of matter (so much less grams) in the entire universe.

And now you can also see that assuming that the ground up liver and hearts is about the same molecular weight as sugar, we have pretty much none of it left after only 12 dilutions. Clearly any more mixing will, in this specific case, remove every trace of the original substance. Even if it were 100 times more dense, or 1000, a couple more rounds would get rid of it.

So around 12 or 13 C, if you started with a single drop of the “anas barbariae”, you would need all the water in all the oceans on earth to have a single drop left of the original solution. Keep in mind that you are getting a small part of the final dilution mixed with a sugar pill (hence the “no side effects”)

At less than 50C (only 25% complete toward the 200CK goal), we have effectively diluted the original ingredient so much that to to be sure of reconstituting it, we would need the entire universe (in practice, it is all on the Earth, but this is how the math works out).

And let me restate the “selling” point of all this: The dilution is supposed to make it more powerful!

It should be clear to you that there is absolutely no plausible way for this process to impart any sort of healing ability on the “active” ingredient. Assuming that the original “Law of Similars” had any actual effect, the ingredient it is now so effectively mixed in with anything else that has ever touched that water, that its effects would have long ago been drowned out. Or, to paraphrase how someone else put it, you are as likely to be consuming fish feces as you are active ingredient (duck liver in this case).

What does the science say?

Technically, some homeopathic remedies, including Oscillococcinum, are “approved” by the FDA. But this is only through what is essentially a loophole regulation that allows homeopathic preparations to be marketed in accordance with historical homeopathic “provings”. This is no way means that it “works” in the same way that aspirin works. The most ironic part of the existence of Oscillo is that traditionally homeopathic preparations are completely “individualized” by the “doctor” to treat the very specific illness of their patient. When all of the clinical trials fail, they argue it is because you cannot use a “one size fits all” preparation. And yet, Oscillo is a “one size fits all” treatment.

But getting to the actual question. Even on Boiron’s own site, they say that the average decrease in symptoms versus placebo was 6 hours (this is just the middle of the 95% CI). That seems to me clearly no better than a placebo (given that the range of placebo effects can vary so widely). And yet, they see this as beneficial (and worth the $14/box that I saw at the local pharmacy).

Systematic Reviews

Taken as a whole, it should come as no surprise at this point that homeopathy works no better than a sugar pill (which it also is). This means that its effects can vary widely, and in specific cases it can appear to “work”. And this only applies to illnesses that will go away on their own after less than a week, and that are hard to gauge objectively (headaches, cold, aches and pains). This is exactly the same set of illnesses for which the placebo effect applies. Homeopathic trials tend to be of low methodological quality which directly correlates with its findings of a “positive” effect.

The Creighton University School of Medicine hosts a page listing the various studies and reviews that have been done on homeopathic preparations.

Perhaps the most “famous” review is that of Shang et al which concluded (Shang 2005 [11]):

Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.

Cucherat et al had similar findings (Cucherat 2000 [12]):

However, sensitivity analysis showed that the P value tended towards a non-significant value (P=0.08) as trials were excluded in a stepwise manner based on their level of quality. Conclusions : There is some evidence that homeopathic treatments are more effective than placebo; however, the strength of this evidence is low because of the low methodological quality of the trials. Studies of high methodological quality were more likely to be negative than the lower quality studies. Further high quality studies are needed to confirm these results.

 

I’d also recommend Edzard Ernst’s review of reviews. He also discusses Oscilloococcinum.

Virtually all homeopathic studies end with the disclaimer that we need “more high quality trials”. The fact is that the high quality trials show no effects. Homeopathy has been studied since the early 1900s, it seems safe to say that we are not going to suddenly come across “high quality” studies showing actual effect. And that is because it does not work. It cannot work.

Specific reviews of Oscillococcinum

There have only been 2 studies of Oscillo of high enough quality to be able to derive data for. These served as the basis for the only Cochrane systematic (though I’d hesitate to use that term here) review done by Vickers and Smith. Boiron actually links to the review (I suspect it is because the trial found that Oscillo could reduce symptoms vs placebo between 1 and 12 hour before), despite the conclusion (Vickers 2006 [13]):

Though promising, the data were not strong enough to make a general recommendation to use Oscillococcinum for first-line treatment of influenza and influenza-like syndromes. Further research is warranted but the required sample sizes are large. Current evidence does not support a preventative effect of Oscillococcinum-like homeopathic medicines in influenza and influenza-like syndromes.

(Note:The review has actually been withdrawn because Cochrane policy requires reviews to be updated every two years, and not surprisingly new studies are not pouring in)

As Edzard Ernst (the first professor of complementary medicine in the UK) points out (Ernst 2002 [14]):

One homeopathic remedy (oscillococcinum) was found to be superior to placebo as a treatment and prevention of influenza but the effect size was small and therefore of debatable clinical relevance. Moreover, the volume of the evidence for oscillococcinum is small and therefore not fully conclusive

Not exactly a ringing endorsement. And as an average Joe, I would go for something that is actually effective. You have probably come to notice that the studies always find homeopathy to either be no better than a placebo or slightly better. Yet, the proponents discuss it as if it has a powerful effect, certainly much better than “conventional” medicine. My money is on the fact that the human body varies enough for placebo to be unpredictable, especially for a small number of sizes where false positives are very easy to come by. Even with a “statistically significant” p-value of 0.05, that means that 1 in 20 trials is going to have a false positive! And considering that most likely negative trials are rarely published, we have ourselves some explanation.

Even a 1989 study by Ferley et al which found a small positive effect added “Despite the use of terms such as ‘attributable fraction’ which have specific meaning in clinical epidemiology parlance, it would be unwise to claim that the  study has demonstrated a cause and effect relationship between the drug and the recoveries. (Ferley 1989 [15])

How do you recognize homeopathy?

Unfortunately, it can be difficult to actually recognize homeopathic products in drug stores as they will essentially disguise themselves as actual medication. But some key signs:

  1. FDA disclaimer of the form “These statements have not been evaluated by the FDA. This product is not intended to prevent or cure any illness”. Funny words for, you know, medicine. (Note: Oscillo actually does not have this warning, due to the loophole regulation allowing many homeopathic products through).
  2. “No side effects”. I’m sorry, but drugs have side effects. If a box can rightfully claim it has none, that means it has no actual active ingredient which can have any effect on your body.
  3. Weird latin phrases. Generally homeopathic active ingredients will be listed using their latin form (presumably to hide what it is?).
  4. The amount of sugar is the same as the amount of a serving. Where’re the drugs?
  5. Explicitly stated. Some will actually state “Homeopathic Medicine” on their box, as they are proud of it I guess. Though this can be misleading. Zicam is marketed as a homeopathic cold remedy, but its actual active ingredient is zinc gluconate (for at least hypothetically sound scientific reasons having to due with blocking the way the rhinovirus binds to nasal cells). Far from in fact being homeopathic in nature, the zinc is present in large enough amounts (in some of the products) that it seems to cause potentially permanent use loss of smell in its users (Lim 2009 [16]), forcing the FDA to recall the gel and swab versions in 2009. And in any case, the actual effectiveness of the zinc in Zicam is rather questionable (Caruso 2007 [17]).

Conclusion

Based on the lack of prior plausibility and completely inconsistent study results (but on the whole, quite consistent with the “placebo effect”, especially if you consider misuse of the p-value to demonstrate “statistical significance, whereby researchers will simply take the middle of their 95% CI and use it as the actual result (Atwood 2009 [18])), it seems clear to me that spending money on homeopathic remedies would be ill-advised if your intention is to actually get over the illness quicker than it would on its own. That is, assuming that your bar is higher than “slightly above placebo”. Also be careful of products which claim to be homeopathic in nature (such as Zicam) but in fact have a very real active ingredient with actual side effects.

And to those who might ask “but really, what’s the harm?”, I direct to the to wonderful (and scary) whatstheharm.net answer to this question. There you will find examples where the use and homeopathy (in conjunction with lack of use of “conventional” medicine) led to direct harm.

Further Information

In the UK (and possibly spreading to the US), there is something known as the 10:23 campaign (from the 1023 of Avogadro’s number for molecular weight) whereby large groups of people will simultaneously consume entire packages of homeopathic sleeping pills (or other remedies) in front of pharmacies to demonstrate the complete lack of effect.


[1]NCCAM. National Institutes of Health.“Homeopathy: An Introduction”. Published July 2009. Updated August 2009. Visited October 8, 2010. <http://nccam.nih.gov/health/homeopathy/&gt;

[2]NCH. National Center for Homeopathy. “What is Homeopathy?”. Published June 2006. Visited 8, October 2010. <http://www.homeopathic.org/content/what-is-homeopathy&gt;

[3]CDC. “How vaccines prevent disease”. Updated August 9, 2009. Access October 13, 2010. <http://www.cdc.gov/vaccines/vac-gen/howvpd.htm&gt;

[4]Boiron Information Center. Boiron, Inc. “Facts about Oscillooccinum”. Visited October 8, 2010. <http://www.oscillo.com/site/about-oscillo/facts.php&gt;

[5]Food and Drug Administration. “Conditions Under Which Homeopathic Drugs May Be Marketed”. Published May 1988. Updated Marh 1995. Visited October 8, 2010.<http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074360.htm&gt;

[6]Little, David. Homeopathic Academy of Natural Physicians.”The Centesimal and Lm potencies”. Published Winter 2001. Visited October 11, 2010. <http://www.hanp.net/general/article2&gt;

[7]Boiron, Jean. 1985. Method and apparatus for Korsakovian dilution. U.S. Patent 4,537,512, filed September 14, 1983, and issued August 27, 1985

[8]McAllister, Howard C. Montclair State College. “Grains of Sand on Earth’s Beaches”. Accessed October 11, 2010. <http://www.hawaii.edu/suremath/jsand.html&gt;

[9]In reality, we could not actually break it into its component atoms purely by mixing

[10]Weisenberger, Drew. Thomas Jefferson National Accelerator Facility – Office of Science Education. “How many atoms are there in the world?”. Visited October 11, 2010. <http://education.jlab.org/qa/mathatom_05.html&gt;

[11]Shang et al. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet. 2005 Aug 27-Sep 2;366(9487):726-32. PubMed PMID: 16125589.

[12]Cucherat, M. et al. Evidence of clinical efficacy of homeopathy: A meta-analysis of clinical trials. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. Volume 56, Number 1, 27-33

[13]Vickers AJ, Smith C. Homoeopathic Oscillococcinum for preventing and treating influenza and influenza-like syndromes. Cochrane Database Syst Rev. 2006 Jul 19;3:CD001957.

[14]Ernst, E. “A systematic review of systematic reviews of homeopathy”. Br J Clin Pharmacol. 2002 December; 54(6): 577–582.

[15]Ferley J.P., et al. A controlled evaluation of a homeopathic preparation in the treatment of influenza-like symptoms. Br J Clin Pharmacol. 1989;27:329-335

[16]Lim JH, Davis GE, Wang Z, Li V, Wu Y, et al. 2009 Zicam-Induced Damage to Mouse and Human Nasal Tissue. PLoS ONE 4(10): e7647.doi:10.1371/journal.pone.0007647

[17]Caruso, TJ, Prober CG, Gwaltney JM. “Treatment of naturally acquired common colds with zinc: a structured review”. Clin. Infect. Dis. Volume 45,Issue 5:569–74. doi:10.1086/520031.

[18]Atwood, K. “Acupuncture, the P-Value Fallacy, and Honesty”. Science Based Medicine. Published December 19, 2009. Accessed October 13, 2010. <http://www.sciencebasedmedicine.org/?p=2996&gt;

 

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Update: October 29, 2010 – Added link to whatstheharm.net.