Predictions of Evolution

PDF version: PredictionsofEvolution

I’m in the middle of an article on pesticides, so I thought I would revise some information I collected as part of a email debate. This is specifically around very specific predictions (of what scientists would discover) made by evolution that have been “fulfilled”. While technically not proof that evolution is true, they are strong evidence which increases the likelihood of it being a correct theory. It is only negative predictions that can really disprove a theory. And any honest theory should contain those negative predictions.


I want to add that the original pointers for most of these was found on other sites (especially here and here and here). Talk origins have tons more of these predictions, I just picked the ones I found particularly interesting and fleshed them out with additional explanations and sources.


Jaw to Ear Transition

In 1837, C.B. Reichert (who was a Creationist, but not much choice on those pre-Darwinian days), observed that when pig fetuses were growing, there was a point at which a portion of the jawbone detaches to become the tiny bones of the middle ear, which he found quite remarkable.  Once we had a theory of evolution, one of its early predictions was that there should exist a fossil between reptiles and mammals that essentially has two separate jaws, one of which was smaller and near the ear. When fossils of early cynodonts were found, specifically the Diarthrognathus (“two-jointed jaw”), this prediction was found to be true.  This is described better by Stephen Jay Gould in his book Eight little piggies: reflections in natural history.

Trilobite Precursors

Darwin predicted that precursors to trilobites should be found in pre-Cambrian fossils, honestly acknowleding that a lack of such would be bad for the theory (Darwin 1872 [1]) . Despite what a (presumably outdated) anti-Darwin site would like to believe, precursor fossils have been found, even in the scant fossils that exist pre-Cambrian (Gon 2009 [2]). The evidence is admittedly not 100% certain, but nothing can be.

Long-tongued Moth (1862-1903)

This is one of my absolute favorites. Darwin predicted in 1862, from observation of the Madagascar Star orchid, that there should exist a species of moth with a tongue a bit less than 30 cm (specifically “between 10 and 11 inches”) (Darwin 1862 [3]). At the time, one with a tongue that long had not been discovered. However, evolution predicts a battle between the orchid and moths in an “arms race” to get/deny nectar without proper “payment” (in the form of pollination in this case). In 1903, A hawk moth with a tongue around 300 mm was discovered, from the species known as Xanthopan morgani (the one pictured below only has a 7 inch tongue, but demonstrates the point I think) (Wikipedia 2010 [4])


Archaeopteryx Teeth (1872-1877)

When the first Archaeopteryx (a sort of intermediary between reptiles and birds) fossils  was found, the head was not in good shape and had no teeth. Then when Ichtyhornis and Hesperornis were found in 1872, they were determined to be seabirds, but they retained teeth (Huxley 1872 [5]). The early evolutionists of the time, specifically Henry Woodward of the British Museum, predicted that that the archaeopteryx should also have had teeth since reptiles had teeth, and birds descended from them. Woodward recognized the controversy of his proposal, putting words to it:

“But, it may be urged, ‘your proposition that the Archaeopteryx had teeth is a pure assumption. Show me some evidence of a fossil bird whose head and skeleton are in juxtaposition so as to leave no reasonable doubt of their unity’)”. (Woodward 1875 [6])

But if the Archeopteryx didn’t have teeth, that was a problem for evolution.

In 1877, more intact Archaeopteryx fossils were found… with teeth. It is now accepted (even among Creationists) that the Archaeopteryx had teeth. And Archeopteryx would have had teeth whether or not we thought it should. The point is, evolutionary theory virtually demanded that it, and the prediction held out.

Antarctica, and its fossils (1893-1982)

Believe it or not, we didn’t always knows Antarctica existed. In 1893, H.O. Forbes presented a paper at the Royal Geographic Society in which he discussed his findings in the Chatham Islands. He (and other naturalists) predicted that there should have existed a large sub-tropical southern continent:

Taking these fresh facts into consideration, he marshals all the data which he considers prove a strong case for the probability of the existence of a former southern continent, and he sketches on a map of the Southern Hemisphere what he believes was the configuration of Antarctica, as he has named that vanished continent. He believes that it followed nearly what is the 2,000-fathom line, and extended northward from a circumpolar area, by broad extensions, one to join an old New Zealand continental island (including the Antipodes, the Maquarries, New Zealand, the Chatham, Lord Howe, Norfolk, the Kermadec, and the Fiji Islands); another to East Australia with Tasmania; another to the Mascarene and surrounding islands (the Lemuria of Sclater); perhaps one to South Africa, and, lastly, one to South America. The form of this continent would not interfere with the opinions expressed by many authorities in the permanence of the great ocean basins. (Editors 1893 [7]).

Viewing the article, you can see that it was not just about a single bird, but actually a wide variety of species whose distribution only made sense in light of there being this continent. At this time Antarctica had been spotted, but was seen as just being ice shelves. Additionally, at this time scientists were just starting work on the idea of prior large connected continents that broke up over millions of years. In any case, Antarctica was obviously finally discovered.

One of his examples was “Marsupials – Nototherium, Diprotodon, Thylacoleo, Thylacinus in Australia ; Prothylacinus, Amphiproviverra in Patagonia.There were obviously not going to be live marsupials extent in the current Antarctica, but it stood to reason that there should be fossils from the Mesozoic era.

These were found in 1982, with Polydolops. It was a 9-foot marsupial (Woodburne 1984 [8])

No doubt you can find papers for all the other fossils that were predicted to exist.

Flying Insects with Hemocyanin (2003)

The theory of evolution held for a long time that flying insects evolved from gilled crustaceans (Burmester 1996 [9]). Those crustaceans use a protein known as hemocyanin to circulate oxygen. Evolutionary theory would hold that there should be still be remnants of that in some flying insects, but none had been found. In 2003, scientists discovered a type of stonefly (generally considered to be some of the most “primitive” of insects, which makes sense) which still had functional versions of that protein (Hagner-Holler 2004 [10]). This is discussed more fully in an article by James H. Marden where he talks about the evolution of flight in aquatic insects (Marsden 2008 [11]).

Ancestral whale with teeth and baleen (-2008)

Currently there are two types of whales: those that have teeth, and those that have baleen to filter their food. None exist currently that have both. On the assumption that all whales must have descended from a common ancestor, it was predicted that there must have existed a whale that had both teeth and baleen at the point in time when the two diverged. Even today, baleen whales start with tooth buds that disappear (evidence that the toothed whale was first).  Well,  in 2008 this transitional form was found to have existed  24-28 million years ago, when baleen whales where splitting from toothed whales (Coyne 2010 [12]).

“Junk” DNA fingerprinting

“Junk” DNA can actually be used to predict (coming from a retrovirus) whether two seemingly-unrelated animals shared a common ancestor. Or, to put it another way. When we know that two species are related, we can predict whether or not they will share certain sequences of “junk” DNA. For example, There is a particular sequence found in hippos, whales  and cows but not in humans, mice, kangaroo, elephants or horses. This would lead to conclusion that there was a common ancestor that split off and shared by hippos , whales and cows (which is true). And based on this theory, they should be able to find this  same set of “junk” DNA in deer, but not in monkeys. Incidentally, finding this particular “junk” DNA in monkeys would actually be a point against evolution, since the retro-virus that caused it came after the ancestor to primates. (Lindsay 2010 [13])

As another example, both guinea pigs and humans have a specific defect in the gene that encodes for Vitamin C processing, meaning that anything from guinea pigs up to humans should have that mutation (the math works out that that genetic divergence would have occurred approximately 20 million years ago) (Nishikimi 1988 [14]). If this exact same “typo” (of the same letters) were found outside of the primate line from guinea pigs to humans, that would be a problem for evolution.


As I said at the beginning, strictly speaking none of these predictions actually prove evolution to be correct. But the fact that they were able to be made, and found true, might leave you pondering how that could be if it weren’t true. Outside of evolution, there is no reason for many of them to be true, and certainly no reason to predict ahead of time for them to be true. Creationism is unable to make any predictions of this sort. Compare these with the predictions that Creationism/Intelligent Design attempts to make.

[1]Darwin, Charles. “The origin of species by natural selection”. Odhams Press Limited. 6th ed. 1872. pp338

[2]Gon III, S.M. “Origins of Trilobites”. Updated Jan 22, 2009. Accessed Nov 10, 2010. <;

[3]Darwin, Charles. “On the various contrivances by which British and foreign orchids are fertilised by insects”. Harvard University. 365 pages. pp. 198

[4]Wikipedia contributors. “Xanthopan morgani.” Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 9 Nov. 2010. Web. 11 Nov. 2010.

[5]Huxley, TH. “Prof. Huxley’s lectures on the evidence as to the origin of existing vertebrate animals”. Nature. Volume 13. 1876. p.515

[6]Woodward, H. “Birds with teeth”. The Popular Science Review. 14(57). 1875. 337-350.

[7]Editors. “Antarctica: A Supposed Former Southern Continent”. Natural Science, vol. 3. July 1893. pp54-57 (summary of paper by H.O. Forbes)

[8]Woodburne MO, Zinsmeister WJ. “The First Land Mammal from Antarctica and Its Biogeographic Implications”. Journal of Paleontology. Vol. 58, No. 4 (Jul., 1984), pp. 913-948

[9]Burmester T, Scheller K. Common origin of arthropod tyrosinase, arthropod hemocyanin, insect hexamerin, and dipteran arylphorin receptor. J Mol Evol. 1996 Jun;42(6):713-28.

[10]Hagner-Holler S, Schoen A, Erker W, Marden JH, Rupprecht R, Decker H,

Burmester T. A respiratory hemocyanin from an insect. Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):871-4. Epub 2004 Jan 8.

[11]Marsden JH. “Evolution and Physiology of Flight in Aquatic Insects.” In: Aquatic Insects: challenges to populations. CABI 2008. pp230-248

[12]Coyne, JA. “Baleen whales: a lovely transitional form”.  Accessed 11/11/2010. <;

[13]Lindsay, D. “Different species with the same ‘Junk DNA’. Don Lindsay Archive. Updated 1/12/2001. Accessed 11/11/2010. <;

[14]Nishikimi M, Koshizaka T, Ozawa T, Yagi K. Occurrence in humans and guinea

pigs of the gene related to their missing enzyme L-gulono-gamma-lactone oxidase. Arch Biochem Biophys. 1988 Dec;267(2):842-6.



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.


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.


Atoms remaining








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])


800 atoms


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.



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



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]).


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) 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. <;

[2]NCH. National Center for Homeopathy. “What is Homeopathy?”. Published June 2006. Visited 8, October 2010. <;

[3]CDC. “How vaccines prevent disease”. Updated August 9, 2009. Access October 13, 2010. <;

[4]Boiron Information Center. Boiron, Inc. “Facts about Oscillooccinum”. Visited October 8, 2010. <;

[5]Food and Drug Administration. “Conditions Under Which Homeopathic Drugs May Be Marketed”. Published May 1988. Updated Marh 1995. Visited October 8, 2010.<;

[6]Little, David. Homeopathic Academy of Natural Physicians.”The Centesimal and Lm potencies”. Published Winter 2001. Visited October 11, 2010. <;

[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. <;

[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. <;

[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. <;


Please comment! 🙂

Update: October 29, 2010 – Added link to

Is Organic Food More Nutritious than Conventional?

A PDF version more suitable for printing can be found here

One reason that consumers feel that organic food is better than “conventional” and worth a premium price is that it is supposed to be more nutritious. What is meant by “more nutritious.”? What specific nutrients are being referred to? Are there nutrients that conventional food has more of, but that are considered harmful? When I looked into it, there appears to be no real scientific support for the claim that organic food is nutritionally superior to conventional, or even that different. In this entry I will look at what the latest science has to say on the matter. Pesticides are not discussed.

The article is broken up into two parts. The first goes over Vitamin C and Nitrates, which are the two items that come up most often when discussing the differences between organic and convention — organic claimed to be higher in Vitamin C and lower in nitrates and therefore better. The second part looks at the actual systematic reviews that have been done on this very question from the most recent in 2009 to an earlier one in 2000. There is also an appendix in which I thought it would be interesting to talk a bit about the most frequent studies referenced by the reviews (basically, what did the reviewers review).

Notes on a couple of nutrients

Vitamin C

While in general there seems to be no difference between organic and conventional, my reading is that there might be a slight trend toward some fruits and vegetables having a higher ascorbic acid (Vitamin C) content, however this conclusion is not supported by the most recent and, arguably, thorough review. Regardless, in the case of Vitamin C, the recommended daily intake is about about 75-90 mg for an adult. 1 cup of the orange slices has about 95mg [1](USDA DB 2010). I have seen some references put a single orange around 75mg. So if you have an orange and some peppers or tomatoes in a day, you will be well above the amount your body can hold in any case and will just release it in your urine. So it would not seem to matter much, even if organic produce does have a trend toward slightly higher Vitamin C.


Even in more recent studies, conventional produce tends to have a higher nitrate content (generally due to differences in fertilizers), which proponents of organic food consider to be a major win. It seems that they are holding on to pre-2000 notions on the safety of dietary nitrate content. In 1945 there were 2 cases of methemoglobinemia (“blue baby syndrome”) in small infants which they traced to very high concentrations of nitrate in rural well water. This led to limits on drinking water levels of 10 ppm [2](EPA 2009). Additionally, In the 1970s it was believed that dietary nitrate was a potential carcinogen, but this conclusion was not able to be supported by the science done since then.

Research starting around 1994 demonstrated that dietary nitrate is actually quite beneficial in helping to fight disease pathogens in the mouth and gut. This is because it acts as an alternative source of nitric oxide [3], an important product in our bodies to help prevent stroke and ulcers (Lundberg 2008). Fascinatingly, its not our own bodies that does the conversion from nitrate to nitrite and nitric oxide, but rather symbiotic bacteria living in our mouths [4] and stomach (sounds gross, but is good!)(Duncan 1995). It seems in fact, that dietary nitrate presents no real health hazard to children or adults. There is also an entire book devoted to this question entitled Nitrate and Man: Toxic, Harmless or Beneficial by J. L’hirondel.

So it appears to be only infants < 6 months of age where there is any concern about nitrate levels, due to fears about methemoglobinemia (Greer 2005 [5]), and that is really only related to contanimated well water used for formula and some very high nitrate-level foods (beets, green beans, squash carrots). Those foods have high nitrates on their own, switching to organic certainly would have no effect in this case, and the recommendation for small infants is to simply avoid them.

Note that these aren’t just obscure arguments in scientific journals, it has in fact been picked up by the media mainstream media (Minkel 2004 [6]) and blogs (pponline [7]). So it makes sense for earlier reviews (such as Worthington’s) to have called out nitrate as being exceptional, but there is currently no real reason that I can discern for lower nitrate levels in organic to make it any “safer”, especially given the amounts already present. Finally, the European Food Safety Authority (similar to FDA) put out a finding in 2008 that affirms the safety of leafy fruits and vegetables, considering their nitrate content with no link with cancer and some potential positive side effects (EFSA 2008 [8]).

What the Science Says

Looking over the history of the studies in this area, I think it may be interesting to actually approach this in reverse chronological order, starting from the most recent and comprehensive review down to one in 2000 that actually seems much less systematic in its approach.

2009 – Dangour, American Journal of Clinical Nutrition

The most recent review is “Nutritional quality of organic foods: a systematic review” by Dangour et al, published September of 2009 in the American Journal of Clinical Nutrition. The study was sponsored by the UK Food Standards Agency (equivalent to US FDA). Their primary finding was that (Dangour 2009 [9]):

There is no evidence of a difference in nutrient quality between organically and conventionally produced foodstuffs. The small differences in nutrient content detected are biologically plausible and mostly relate to differences in production methods.

I hunted down the full text and found a preview (so reader should note that I cannot say for certain that it represents the final published version). All additional details come from that document[10]. For the statistically inclined, they have made the raw data available (Food Standards Agency 2010 [11]). Now, that’s open science for you!. In the full text we find the specific nutrients:

Analysis of satisfactory quality-crop studies found no evidence of a difference in 8 of the 11 nutrient categories (vitamin C, phenolic compounds, magnesium, potassium, calcium, zinc, copper, and total soluble solids)

Looking more into the paper, it mentions that Phosporous and “titratable acidity” went to organic and Nitrogen content went to conventional.

Their study filtered through more than 52,000 articles (covering the years 1958 to 2008) to find 162 studies purporting to compare organic and conventional foods (both food and livestock), to arrive at 55 that actual met the standards of the systematic review.

Those standards were:

“The quality of research and reporting in this area is extremely variable. Each study included in the review was graded for quality based on 5 criteria addressing key components of study design: a clear definition of the organic production methods, including the name of the organic certification body; specification of the cultivar of crop or breed of livestock; a statement of which nutrient or other nutritionally relevant substance was analyzed; a description of the laboratory analytic methods used; and a statement of the methods used for statistical analyses. Studies were defined as being of satisfactory quality if they met all 5 criteria. We did not grade further the quality of organic certifying bodies or analytic methods used”

One would think that all systematic reviews on this topic would follow similar standards, but that is not the case. It is possible that the lack of specific certification body filtered out quite a bit of them because “organic” is not a concrete term, but rather is defined in practice by whichever certification bodies have been approved by the national governments. Their criteria could be more or less “strict” for different parts of the definition of “organic” and, for the case of the US, might not be the same “organic” recognized by the USDA (which simply means they cannot use the official labelling (USDA 2010 [12]).

Not surprisingly, the UK Soil Association (organic food lobby) was none too pleased with the study. Their primary complaint was that it did not cover herbicide/pesticide content. The study was explicitly about nutritional content, so it is a rather strange complaint (Soil Association 2009 [13]). They attempt to discredit even the nutritional part by listing out the differences that were found in the study. However, the figures are misleading because the standard error is sometimes more than the difference! But the Soil Association doesn’t mention that. For instance, they show copper has having an 8.6% difference (in favor of organic). But if you look at the data in the Dangour study, the standard error is 11.5, making the difference meaningless. They do however make a fair point that organic food is not just about nutritional content (clearly) or pesticides, but about the whole lifecycle of production. This precludes “conventional” farmers from making use of the techniques that they feel will best optimize production without actually attempting to have organic certification, which I highly doubt is the case in the real world.

So it seems that the most recent, and certainly the most rigorous, systematic review finds no real nutritional difference between organic and conventional food. That study stretches back to studies in the 50s and has a very clear definition of its entry criteria.

2006 – Györéné, Orv Hetil

This study, “[A comparison of chemical composition and nutritional value of organically and conventionally grown plant derived foods]”, is actually in Hungarian but PubMed has an English version of its abstract. It has only been cited a single time (in a study by the Organic Center’s Charles Benbrook, which is my main reason for still including it here). That said, it is listed in PubMed, but I cannot tell if it is peer-reviewed or not. Part of the conclusions (Györéné 2006 [14]):

“Organic crops contain a significantly higher amount of certain antioxidants (vitamin C, polyphenols and flavonoids) and minerals, as well as have higher dry matter content than conventional ones.”

“Orv Hetil” appears to translation to something like “Health Weekly”.

So the results of this study are the organic crops are actually more nutritious. However, I don’t have a way of determining what studies they looked at, what criteria they used, or whether it was peer-reviewed.

2003 – Magkos, International Journal of Food Science And Nutrition

This study, “Organic food: nutritious food or food for thought? A review of the evidence” acknowledges (as do most) that quality studies in this area can be few and far between especially as you look at earlier studies. Their findings (Magkos 2003 [15]):

“In spite of these limitations, however, some differences can be identified. Although there is little evidence that organic and conventional foods differ in respect to the concentrations of the various micronutrients (vitamins, minerals and trace elements), there seems to be a slight trend towards higher ascorbic acid content in organically grown leafy vegetables and potatoes. There is also a trend towards lower protein concentration but of higher quality in some organic vegetables and cereal crops. “

I managed to track down what appears to the full text by searching for the first few words of the abstract. It is hosted on, so I won’t link to it here as I am not certain of the legality of documents uploaded there.

So the only real finding other than that organic and conventional are virtually identical is another case of the trend toward finding slightly higher ascorbic acid/Vitamin C content in organic food. It strikes me as being a well done study without obvious bias. The authors go item by item and provide overview of the findings.

2002 – Bourn, Critical Reviews in Food Science and Nutrition

This particular review (entitled “A comparison of the nutritional value, sensory qualities, and food safety of organically and conventionally produced foods”) was interesting in that it actually separated out the different types of studies and discussed them as units. For instance, the studies which looked only at fertilizer usage versus those that made retail purchases of “organic” and “conventional” products. 41 key studies were discussed and put into tables, but there are actually over 200 references. Part of their results (Bourn 2002 [16]):

With the possible exception of nitrate content, there is no strong evidence that organic and conventional foods differ in concentrations of various nutrients.

Google Scholar also identified the full text article (available as of July of 2010), which is where I found the information about how the study was done and the number of them. The review is a good read, especially as it goes into detail into the study design (or lack of) as well as tests of significance (or lack of) employed by the researchers. One thing that becomes quite clear from reading this study is the true variability and complexity in looking at the nutritional effects of the organic production process.

In the end, as you can see from the quote, there is no real difference between organic and conventional especially if you look at studies in their own context.

2001 – Worthington, Journal of Complementary and Alternative Medicine

This was an earlier “systematic” review performed by Virginia Worthington, a chiropractor from Washington DC. The review was entitled “Nutritional quality of organic versus conventional fruits, vegetables, and grains” and ended up using 41 studies (Worthington 2001 [17], Full Text [18]). The results:

Organic crops contained significantly more vitamin C, iron, magnesium, and phosphorus and significantly less nitrates than conventional crops. There were nonsignificant trends showing less protein but of a better quality and a higher content of nutritionally significant minerals with lower amounts of some heavy metals in organic crops compared to conventional ones.

I mention her profession because this is an alert to look closer at the study, and how it has been reviewed. By definition, a chiropractor who practices traditional chiropractic must ignore the majority of the science of illness in favor of the non-scientific idea of “subluxations” and “innate intelligence” as a basis for illness (Ernst 2008 [19]). So while her personal views do not actually make this study invalid, they lead to the reasonable suggestion that it may possibly cherry pick or otherwise perform improper analysis in the goal of coming up with a desired outcome. And if you read the article, she does seem to indicate that there was not much concern for how good a study was, rather they were just matched up. In any case, this is the earliest of the reviews and so did not have as good of studies to work with.

This one obviously found that trend for Vitamin C (and some others) in organic, as well as higher nitrate levels in conventional.


There does not appear to be any meaningful difference in nutrient content between organically-certified and “conventionally” grown produce. There is a possible trend toward higher Vitamin C content in organic, but for the levels found it would make no practical difference. The variance between any given two items of produce is so high that your specific organic fruit or vegetable is as likely to have less Vitamin C (or others) as any conventional one compared between themselves. Based on the scientific evidence, I see no reason to choose organically certified produce over conventional for purposes of obtaining higher nutrient content. This says nothing about other value/safety arguments that one might make (such as synthetic pesticide or sustainability), which I have not yet looked at, but plan to in a future article.

Appendix: Meta-meta review

For the reviews where I could get full text, or otherwise determine the the studies in use, I have created a table which has the reference, year and which reviewers used it. It is available as web page or as a CSV. It also includes a column for whether or not it found positive differences in organic, but I have not filled that out.

What I found intriguing is that there are only 4 studies that all of the reviews (except Gyorene, for which I could not find any full text version) agree was of high enough quality (or at least, met their criteria). A spattering more are in 2 studies, and the rest are in a single one, even for where the years overlap.

Just looking at these few studies you see that lack of meaningful trend. One might find organic higher for a given nutrient, and another will find organic lower for the same nutrient. Sometimes the same study had switches between the years the study was run.

The 4 that all “agree” on (though if you read Bourn, he references some more to point that they are frequently referenced but weren’t necessarily great studies):

Clarke RP, Merrow SB. Nutrient composition of tomatoes homegrown under different cultural procedures. Ecol Food Nutr 1979;8:37–46.

  • Long-term tomato study
  • 1 year higher Vitamin C in organic, others higher in conventional (but not statistically sig. difference)

Wolfson JL, Shearer G. Amino acid composition of grain protein of maize grown with and without pesticides and standard commercial fertilizers. Agron J 1981;73: 611–613.

  1. Proteins in maize
  2. From Bourn, protein and most amino acids lower in organic

Shier NW, Kelman J, Dunson JW. A comparison of Crude protein, moisture, ash and crop yield between organic and conventionally grown wheat. Nutr Rep Int 1984;30:337–349.

  • Found no difference in protein or moisture, difference in ash at a lower temperature
  • Conventional higher yield of grain

Smith B. Organic foods vs. supermarket foods: element levels. J Appl Nutr 1993;45:35–39.

  • Of interest, Smith is actually from a company called Doctor’s Data, which is high on the list of Stephen Barrett’s “QuackWatch” and in fact they are currently suing him for calling them out on their invalid analysis of urine and the like. This does not mean their analysis is fruits are incorrect, and at the time they may have been totally legitimate. Small world I suppose.
  • Raw levels are not noted, neither are statistical significance levels (so “90% more” could mean almost anything). As an example of how you could choose to read the results to support whatever conclusion you want:
    • Organic potatoes had 10% more lead, but wheat 65% less, but sweet corn equal
    • Organic potatoes had 70% more mercury, but wheat 40% less, and sweet corn 80% more
    • Somehow they managed to calculate both as being less “on average” in organic, and all the “good” nutrients more in organic

There are are some more that at least 3 considered:

Pettersson BD. A comparison between the conventional and biodynamic farming systems as indicated by yields and quality. In: Lockeretz W, ed. Environmentally Sound Agriculture. New York: Praeger, 1983:87–94. (Not in Dangour)

  • Biodynamic potatoes had higher protein, Vitamin C (from Bourn)
  • Wheat and Barley had lower protein
  • Biodynamics is…interesting… and includes ideas from the “spiritual science of anthroposophy” (which is also what Waldorf education is based on) of Rudolf Steiner. What is strange is that one of their tenets is that holistically/biodynamically grown produce is more healthy and nutritious. Making it a tenet does not make it true.
  • “The concept of dynamic practic—those practices associated with non-physical forces in nature like vitality, life force, ki, subtle energy and related concepts—is a commonality that also underlies many systems of alternative and complementary medicine. It is this latter aspect of biodynamics which gives rise to the characterization of biodynamics as a spiritual or mystical approach to alternative agriculture. See the following table for a brief summary of biological and dynamic farming practices.”

Termine E, Lairon D, Taupier-Letage B, Gautier S, Lafont R, Lafont H. Yield and content in nitrates, minerals and ascorbic acid of leeks and turnips grown under mineral or organic nitrogen fertilizations. Plant Foods Hum Nutr 1987;37:321–32. (Not in Dangour, all details from Bourn)

  • Vitamin C higher in produce fertilized with manure versus woodchip compost
  • No consistent trends for organic versus conventional in either vegetable
  • Vogtmann H, Temperli AT, Kunsch U, Eichenberger M,Ott P. Accumulation of nitrates in leafy vegetablesgrown under contrasting agricultural systems. BiolAgric Hort 1984;2:51–68. (Not in Dangour)

    • Found no real difference in ascorbic acid or minerals
    • Organic had lower nitrate levels

    Stopes C, Woodward L, Forde G, Vogtmann H. The nitrate content of vegetable and salad crops offered to the consumer as from “organic” or “conventional” production systems. Biol Agric Hort 1988;5:215–221. (Not in Magkos)

    • (From Bourn) – no difference and generally wide variance

    Starling, W. and Richards, M.C., Quality of organically grown wheat and barley, Aspects Appl. Biology, 1990; 25: 193-8. (Not in Worthington)

    • (From Bourn) – Barley higher N in organic, wheat lower N and protein

    LeClerc J, Miller ML, Joliet E, Rocquelin G. Vitamin and mineral contents of carrot and celeriac grown under mineral or organic fertilization. Biol Agric Hort 1991;7:339–348. (Not in Magkos)

    • (From Bourn) – Higher beta-carotene in carrots
    • (From Bourn) – Celeriac lower Nitrate and zinc, higher P and vitamin C

    Warman PR, Havard KA. Yield, vitamin and mineral content of four vegetables grown with either composted manure or conventional fertilizer. J Vegetable Crop Production 1996;2:13–25. (Not in Bourn)

    • This is actually a combination of the results of the next 2 (not a distinct study)
    • Main finding across them: “Given the number of factors evaluated each year for each of the four crops, there were relatively few differences in the yield, vitamin and mineral content of the vegetables grown using the two different production systems. We believe this was related to the proper use of fertility amendments and pest control practices. When quality compost is analyzed prior to use, vegetables can be provided with approximately the same amount of essential nutrients from compost as from inorganic fertilizers.”

    Warman PR, Havard KA. Yield vitamin and mineral contents of organically and conventionally grown carrots and cabbage. Agric Ecosys Environ 1997;61:155–162. (Not in Magkos)

    • Three year study
    • Vitamin yield no different
    • Other minor differences in leaves

    Warman, P.R. and Havard, K.A., Yield, vitamin and mineral contents of organically and conventionally grown potatoes and sweet corn, Agric. Ecosys. Environ., 1998; 68: 207-16. (Not in Worthington)

    • Three year growing of potatoes and sweet corn
    • Vitamin C and E no different in corn
    • Phosphorous, Magenesium, Manganese higher in the organic potato tubers (as I read it), but others went to conventional (or were same)

    [1]USDA. “USDA National Nutrient Database for Standard Reference, Release 22”. Visited August 18, 2010

    [2]EPA. “Drinking Water Contaminants”. May 2009. Visited August 25, 2009. Available at

    [3]Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008 Feb;7(2):156-67. Review. PubMed PMID: 18167491

    [4]Duncan, C. “Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate”. Nature Medicine. 1(6):1 June 1995. pp546-551

    [5]Greer, FR. “Infant Methemoglobinemia: The Role of Dietary Nitrate in Food and Water”. Pediatric. Vol. 116 No. 3 September 2005, pp. 784-786 (doi:10.1542/peds.2005-1497)

    [6]Minkel, JR. Scientific American. “Bad Rap for Nitrate?”. September 6, 2004. Visited August 23, 2010. Available

    [7]Editors. Peak Performance Online. “Sports nutrition: Is dietery nitrate the key to enhanced endurance performance?”. Visited August 23, 2010. Available

    [8]European Food Safety Authority. “Nitrate in vegetables – Scientific Opinion of the Panel on Contaminants in the Food chain”. Published 5 June 2008. Visited 4 Sept 2010. Available at <;

    [9]Dangour, AD et al. “Nutritional quality of organic foods: a systematic review”. Am J Clin Nutr. 2009 Sep;90(3):680-5. Epub 2009 Jul 29. Review. PubMed PMID: 19640946.

    [10]Danger AD.“ajcn28041-1..6”.pdf. Ahead of print preview July 2009. Visited 7/23/2010.

    [11]Food Standards Agency. Report details. “Systematic review of differences in nutrient content of organically and conventionally produced food”. Published 5/12/2010. Visited 7/23/2010

    [12]National Organic Program (NOP). USDA. “NOP Regulations: Subpart D – Labels, Labeling, and Market Information”. Updated February 4, 2010. Visited August 18, 2010. Available at <;

    [13]Soil Association. “Soil Association response to the Food Standards Agency’s Organic Review”. Published 7/29/2009. Visited 7/23/2010. Available at <;

    [14]Györéné KG, Varga A, Lugasi A. [A comparison of chemical composition and nutritional value of organically and conventionally grown plant derived foods]. Orv Hetil. 2006 Oct 9;147(43):2081-90. Review. Hungarian. PubMed PMID: 17297755.

    [15]Magkos F, Arvaniti F, Zampelas A. Organic food:  nutritious food or food for thought? A review of the evidence. Int J Food Sci Nutr. 2003 Sep;54(5):357-71.Review. PubMed PMID: 12907407.

    [16]Bourn D, Prescott J. A comparison of the nutritional value, sensory qualities, and food safety of organically and conventionally produced foods. Crit Rev Food Sci Nutr. 2002 Jan;42(1):1-34. Review. PubMed PMID: 11833635.

    [17]Worthington V. Nutritional quality of organic versus conventional fruits, vegetables, and grains. J Altern Complement Med. 2001 Apr;7(2):161-73. PubMed PMID: 11327522.

    [18]Google Scholar found full text at, which is where I base my comments that are not in the abstract alone.Visited 7/25/2010

    [19]Ernst E. Chiropractic: a critical evaluation. J Pain Symptom Manage. 2008 May;35(5):544-62. Epub 2008 Feb 14. Review. PubMed PMID: 18280103.

    Extraordinary claims about Aspartame in the Huffington Post

    You can also get a PDF more suitable for printing.

    The Huffington Post recently posted an article by Joseph Mercola which appears to be intended to be about how aspartame manufacturers have rebranded it in an effort to mislead the public (Mercola 2010 [[1]]). The author uses this as a jumping off point to make a large number of claims about the dangers of aspartame, much of which is uncited or outdated. In this article, I will respond to the claims with updated information (when available) and point out where there appears to be no credible source at all for the claim. Carl Sagan put best what will be a major theme of this article: “extraordinary claims require extraordinary evidence.”

    The article starts light by stating the approval of aspartame was the “most contested” in FDA approval history. As proof, there is a link to the author’s own article (but not stated as such). I would not be surprised to find that nearly all major food additives go through a contentious process, and aspartame was no different. And they should, as this is a matter of safety and all concerns must be heard.

    There is certainly still controversy over aspartame and its history, but it seems to be the stuff of conspiracy, not science. In any case, aspartame has been approved by the FDA, and has been safely in use for more than 20 years.

    Mercola then moves on to the extraordinary claim (for which no references are provided) that aspartame was once listed as a “biochemical warfare agent claim”. I did manage to find another article on where he makes this claim and appears to cite a source as a footnote reference. But there is no actual list of footnotes on that article, so there is no way to check here. Aspartame is most definitely not listed as a biochemical warfare agent and, without credible evidence stating otherwise, it seems unlikely that it ever was in a meaningful way.

    Deceptive Marketing?

    There is a small section about how some manufacturers have chosen to rebrand aspartame. Based on the title of the whole article, it seemed that this was one of the major points, but it does not take up much space. The gist is that the manufacturer Ajinomoto has rebranded aspartame as “AminoSweet”. It is already also known as NutraSweet and Canderel, so I am not certain what the argument is here. I suppose if one is assuming that aspartame is dangerous and that manufacturers need to “hide” the true nature, then it seems like something he would be mad at. But in no way is the danger demonstrated in this article.

    Aspartame Wreaks “Havoc” On Your Health?

    After the initial remarks about the history and name change, Mercola moves onto the heart of the article: claims about the dangers of aspartame consumption. This section mainly makes the claim that there have been thousands of complaints to the FDA about side effects of aspartame, and that this demonstrates that it is not safe. In the words of Mercola:

    Did you know there have been more reports to the FDA for aspartame reactions than for all other food additives combined?

    In fact, there are over 10,000 official complaints, but by the FDA’s own admission, less than 1 percent of those who experience a reaction to a product ever report it. So in all likelihood, the toxic effects of aspartame may have affected roughly a million people already.

    This is another claim for which a reference (to the FDA in this case) would be appropriate. This one did not warrant even a link to despite forming the basis of the entire section. Searching the Internet a bit, it is possible his source is something like this apparent portion of an email from “Betty Martini” (a person or alias that you can find quite a bit of anti-aspartame content on the Internet). You may notice that this is a link to a page hosted on This is not FDA-sponsored material, but rather comments and documentation that consumers can submit (FDA 2010[[2]]) as part of the approval or petition process. In makes reference of an “official” FDA compilation of 10,000 complaints, but does not actually link to the list. Again, however, this extraordinary claim is not backed by actual evidence.

    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[[3]]). 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 [[4]]):

    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[[5]].

    He lists the 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 there is no way to 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 [[6]]). 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 [[7]]).

    Mercola makes another remarkable claim:

    Unfortunately, aspartame toxicity is not well-known by doctors, despite its frequency. Diagnosis is also hampered by the fact that it mimics several other common health conditions, such as [Multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, Fibromyalgia, Arthritis, Chronic fatigue syndrome .. Birth defects..]

    In one statement, Mercola discounts the medical community at large’s ability to diagnose and recognize illnes and suggests and inability to recognize “aspartame toxicity”. This is a striking statement to make about the medical community. MDs (Dr. Mercola is a DO) are going to try their hardest to determine what causes ailments of their patients. If aspartame were a major concern, they would be aware of it.

    This section based its claims on the idea of a massive wealth of documented evidence of side effects. This evidence was not provided. That is not to say that the FDA does not receive complaints about aspartame (probably more so in the past shortly after it was approved). But the available data do not indicate that the complaints have continued, nor is it recognized as being any sort of potential danger by the FDA or the CDC.

    Diet Food and Drinks “Cause” Weight Problems?

    Mercola then moves onto the claim that low-calorie drinks actually lead to obesity and weight gain. He again makes what looks to be a reference to prove his claim, but it is in fact another link to one of his own articles on (which would be fine, except that it does not make it clear). Following the link, he references a study by Purdue University researchers published in Behavioral Neuroscience. In the study they tested whether or not rats would increase their calorie intake when a sweet taste was disconnected from actual energy content of the food (via non-nutritive sweeteners). They found that the results suggested the possibility that people could have increased obseity via those means (Swithers [[8]]).

    We at last have a situation where Mercola has (indirectly) cited an actual study to back his claims. However it represents a single study done on rats in a slightly contrived situation. A later systematic review of the larger body of research in humans (as well as rats) have found that in humans, non-nutritive sweeteners (NNS) do not generally seem to lead to increased energy intake due to confusing signals (emphasis mine) (Mattes [[9]]):

    Thus, short-term trials of NNS consumption provide mixed evidence supporting reduced energy intake, whereas longer-term trials consistently indicate that the use of NNS results in incomplete compensation and slightly lower energy intakes. The latter studies are arguably the more nutritionally relevant.”

    The authors response to that specific rat study:

    In one set of studies [Purdue]…It is unclear whether these findings can be extrapolated to humans who eat a more varied diet and when nonnutritively sweetened foods are ingested concurrently with high-energy foods (eg, diet soda with a hamburger, nonnutritively sweetened coffee with pie). Under such conditions, associative learning would be considerably more complicated and subtle. …

    Other recent evidence indicates that learning does occur in humans, but is counter to predictions from the animal studies (153)…In short-term tests, participants failed to report increased appetite or energy intake in response to consumption of NNS, whereas nonusers of NNS reported heightened appetite and energy intake after such stimulation. These findings indicate inconsistent exposure to NNS (paired or not paired with energy) from beverages results in blunted responses to their consumption and no elevation in risk of weight gain..The implications of chronic, widespread use of NNS on taste-energy associations and their influence on appetite and feeding are questions open to study.

    So based on a larger body of evidence, it seems that for users who do not frequently consume diet content, their senses won’t quite be used to the disconnect between the sweet signal and calorie content. However, it does not seem to actually lead to additional weight gain. Mercola did provide some evidence here, but it appears to be outweighed by a larger volume of studies directly relevant to humans though as always “more studies are needed.”

    It get worse?

    In the next section, Mercola continues about the apparent dangers of aspartame, which he has written a book about and encourages readers to get for their “loved ones”. He also restates that about two-thirds of side effects being neurological in nature, when more accurately it would be two-thirds (or whatever the figure might be) of claimed side effects. There are a couple of paragraphs discussing potential chemical reactions from aspartame that might lead to side effects in the brain. However the theories are un-sourced despite the specificity of the claims. Mercola mentions specifically migraine headaches and brain tumors.

    While there were some early very small studies that seemed to link aspartame and migraines (Koehler 1987[[10]]), larger controlled studies found aspartame no more likely to lead to migraines than placebo, including in those who already believed they had aspartame-caused headaches (Shiffman 1987[[11]], Garriga 1991[[12]]).

    As for brain tumors, it is likely that what Mercola has in mind is an infamous (and heavily criticised) data analysis performed by JW Olney (Olney 1996[[13]]). The study purported to demonstrate a marked increase in the incidence of brain tumors in the years following the approval of aspartame. The analysis has been criticised for choosing the years in such a way that the increase would seem to coincide with the approval, when in fact the increase started before aspartame was introduced, and has declined since (Butchko 2001[[14]]). Olney did not actually compare those who consumed aspartame with those who did not. A case-control study printed in the Journal of the National Cancer Institute was unable to reproduce any relationship between brain tumors (in children, who would be more sensitive) and aspartame (Gurney 1997[[15]]). It seems unlikely that the FDA would have kept aspartame on the market if there was any credible link between it and tumors, and presumably the Journal of the National Cancer Institute would not be pointing out the lack of effects.

    Given that there has been no credible causal link between aspartame and any actual disorder, it is interesting that the article continues: ”

    One of the reasons for this side effect, researchers have discovered, is because the phenylalanine in aspartame dissociates from the ester bond.”

    Again, no source is cited for this very specific claim, so it is hard to actually look into. Additionally, this is an argument about phenylalanine (a component of aspartame), not aspartame. Any relationship would need to be identified with the whole, not its parts. Before attempting to identify the causes of “aspartame toxicity”, it would seem prudent to first demonstrate that aspartame toxicity actually exists.

    Mercola then moves on to the idea of “excitotoxins”: “The aspartic acid in aspartame is a well-documented excitotoxin. Excitotoxins are usually amino acids, such as glutamate and aspartate. These special amino acids cause particular brain cells to become excessively excited, to the point that they die.”

    Note again that this is referring to specific components of aspartame, not the whole. In any case, if you perform Google search for “excitotoxin”, you won’t find results that suggest that this is a mainstream idea within the medical community. While excitotoxity may be a valid idea, it does really seem to be appropriate to link it to aspartame. Excitotoxity seems to be mainly used to claim harmful effects of MSG (via glutamate). The two main researchers in the area are John Olney (who coined the term) and Russell Blaylock. Searches on those names (especially Blaylock) turns up interesting results which, to me, do not put them into the mainstream.

    Dr. Mercola continues…

    Excitotoxins can also cause a loss of brain synapses and connecting fibers. A review conducted in 2008 by scientists from the University of Pretoria and the University of Limpopo found that consuming a lot of aspartame may inhibit the ability of enzymes in your brain to function normally, and may lead to neurodegeneration.

    According to the researchers, consuming a lot of aspartame can disturb:

    • The metabolism of amino acids
    • Protein structure and metabolism
    • The integrity of nucleic acids
    • Neuronal function
    • Endocrine balances

    The review cited brings up methanol and the other “suggested” cause of “certain mental disorders” (Humphries 2008). It is in a peer reviewed journal, and I am not qualified to analyze it (nor do I have access to the full text). That said, it is not frequently cited and one of the few citations is actually a printed response from the same journal: “The premise of the review, that the high-intensity sweetener aspartame is neurotoxic, ignores a very large scientific literature to the contrary“ (Fernstrom 2009[[16]]). Much of scientific credibility is based on the notion of having your results cited and reproduced. In the case of the Humphries study, there is already prior overwhelming evidence of no link and so their analysis is out of step.

    Mercola throws in a reference to the common claim about the dangers of aspartame with regard to formaldehyde. I just recently addressed this specific issue by looking at the studies around this claim, and there seems no reason to be concerned (Dewald 2010[[17]]). Despite the scary sound of “formaldehyde”, it is actually a completely normal part of the daily metabolic process, being produced in the amount of about 1.5oz a day (Formaldehyde Council 2007 [[18]]). Additionally, fruits and juices lead to a significantly higher volume of formaldehyde (Magnuson [[19]]) than aspartame.

    Dr. Mercola makes a quick foray into the claims that aspartame is a carcinogen. He links to his own article discussing a European Ramazzini Foundation study (Soffritti 2006 [[20]]) attempting to link aspartame to tumors in rats. The article mentions that the European Food agency and US FDA intended on reviewing the study. Well, they did review it (FDA 2007[[21]]) and found (European Commission 2002[[22]]) that it was not of sufficiently high quality or controls to demonstrate a cancer risk, and affirmed the continued safety of aspartame. So this is another case where the article does at least cite a source, but it is either outdated or heavily criticised by the scientific and health community.

    As part of his discussion on the apparent carcinogenicity of aspartame, Dr. Mercola makes reference (via to a “compelling case study” of a woman named Victoria Inness-Brown, who did a study of rats and demonstrated it caused tumors. It might strike you that the body of research on this topic is so sparse that he is forced to reference private citizens doing “research” which is even difficult for experts to perform. I challenge the reader to actually locate this study. It certainly wasn’t published in a journal (peer-reviewed or not). The only references I can find about it are old links to it, which now point to a generic landing page featuring credit card ads. But even reading his description I am suspicious. What happened in the control rats? The previously mentioned discredited Soffriti is the only study that seems to have legitimately attempted to look into this matter, and it was clearly found wanting.

    How does one cure oneself of the desire for sweets?

    In the next section, things take a bit of weird turn. Dr. Mercola discusses “Nutritional Typing™”, which is an offshoot of “Metabolic Typing” (a quiz-based approach apparently designed to determine the diet “tailored” to your metabolism). He provides a reference, which is again a link to an article on which seems to be a long form ad for a book written by Dr. Mercola on how to determine your “Nutritional Type”. It is also possible to become certified in this technique, for a sum of money.

    Dr. Mercola also mentions his solution for removing food cravings altogether in the form of his Meridian Tapping Technique (MTT). If you followed his reference (to a page), you will come across the following quote:

    Some people are initially wary of these principles that EFT [the former name for MTT] is based on – the electromagnetic energy that flows through the body and regulates our health is only recently becoming recognized in the West. Others are initially taken aback by (and sometimes amused by) the EFT tapping and affirmation methodology, whose basics you will learn here.

    There is absolutely no scientific basis for the concept of “meridians”. They, their purpose, or their effects have never been found. It would quite reasonable to be “wary” of those principles he espouses until such time as controlled studies have been done that actually detect meridians or their properties. Bringing up meridians brings to mind acupuncture and other alternative claims using “Qi” (the supposed “energy flow” or “vital energy” brought from traditional Chinese culture, and frequently used as explanation for non-scientific beliefs) for which there is no scientific basis and for which scientific studies can find no effect above that of a placebo (Madsen 2009 [[23]]).

    By way of evidence of how MTT is popular among practicing doctors, Dr. Mercola points out doctors who who have started using his MTT technique. The list does not include MDs (or even DOs as far as I can tell). The list is actually made up of:

    • Natural Health Clinics
    • Naturopathic Physicians
    • Pain Therapists
    • Emotional Therapists

    Dr. Mercola also sells books and DVDs available for purchase to be able to fully harness the power of EFT/MTT.

    This section seemed to be clearly the least objective of the article. The majority of it was made up of Dr. Mercola’s pointing to products and services made available by him and his company. No references are made to whether or not the techniques are scientifically credible or valid. They might be, but he offers no evidence. By now things have veered away from claims about the safety of aspartame.

    An “acceptable” alternative?

    Considering the tone of the rest of the article, it was surprising that Dr. Mercola would actually endorse any artificial sweeteners. But he does at least approve of Stevia, because it is a “safe, natural alternative” sweetener from a plant.

    Yes, Stevia is “natural”, but is has had quite a bit of controversy itself. It was only in December of 2008 that the FDA gave it the “Generally Recognized as Safe” label (Curry 2008 [[24]]). Stevia is still banned from usage in the European Union (Stevia Association [[25]]). Recommending Stevia appears to me to be part of the common “natural fallacy” of regarding any substance that is closer to its original form as being somehow better than things which are “artificial” (even if the synthetic substance is chemically identical). There is plenty to be found in nature that is unsafe — arsenic, hemlock, poison ivy are some quick examples. While Stevia may actually be safe (and is approved in the US), it seems that Dr. Mercola recommends it purely on the grounds of it being “natural” despite having much less of a clinical track record of safety. Long term traditional usage is not the same as evidence.


    The most common response to this article may be personal anecdotes of those who believe they were/are adversely affected by aspartame. To those, I just ask that you carefully read the studies which have looked for evidence of the plausibility and occurrence of it, and found none. It is human nature to look for patterns, and aspartame is so prevalent that removing it from your diet is not an isolated situation. Making that change removes any number of other habits and substances. Only your doctor could really help you determine what is causing migraines, seizures, etc.

    Dr. Mercola’s article unfairly attacks aspartame, an artificial sweetener recognized and affirmed as safe by the FDA and used daily by millions of people without ill effects. I felt it important to point out the inaccuracies in the claims (and call for evidence of others) because if consumers get the impression that common products (be it food additives, medicines or medical practices) are unsafe they may seek out alternative treatments which have not been found to be safe, or may even have been found to be harmful.

    [1]Mercola, Joseph. Huffington Post, The. “America’s Deadliest Sweetener Betrays Millions, Then Hoodwinks You With Name Change.” July 6, 2010. Visited July 7, 2010.

    [2]US Food and Drug Administration. FDA. “Dockets Management”. Updated 2/1/2010. Visited 7/15/2010.

    [3]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”. Visited 7/12/2010

    [4]US Food And Drug Administration. “Adverse Event Reporting System (AERS).” Visited 7/9/2010

    [5]US Food And Drug Administration. “The Adverse Event Reporting System (AERS): Latest Quarterly Data Files”. Visited 7/9/2010

    [6]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.

    [7]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.

    [8]Swithers, E., Davidson TL. A Role for Sweet Taste: Caloire Predictive Relations in Energy Regulation by Rats. Behavioral Neuroscience 2008, Vol. 122, No. 1, 161–173

    [9]Mattes RD, Popkin BM. Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. Am J Clin Nutr. 2009 Jan;89(1):1-14. Epub 2008 Dec 3. Review. PubMed PMID: 19056571

    [10]Koehler SM, Glaros A. The effect of aspartame on migraine headache. Headache. 1988 Feb;28(1):10-4.

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

    [12]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.

    [13]Olney JW, Farber NB, Spitznagel E, Robins L, Increasing Brain Tumor Rates: Is There a Link to Aspartame? Journal of Neuropathology and Experimental Neurology 1996;55(11);1115-1123.

    [14]Butchko, Harriet, Frank Kotsonis, 1994. “Postmarketing Surveillance in the Food Industry: The Aspartame Case Study,” Nutritional Toxicology, edited by Frank Kotsonis, Maureen Mackey, and Jerry Hjelle, Raven Press, Ltd., New York, pages 235-249.

    [15]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.

    [16]Fernstrom, JD. “Aspartame effects on the brain”. European Journal of Clinical Nutrition 63, 698-699 (May 2009)

    [17]Dewald, Joshua. What does the science say? “Aspartame and Formaldehyde (or not…)”. 6/13/2010

    [18]Formaldehyde Council. “Formaldehyde: Facts and Background Information”. November 2007. Visited 7/16/2010.

    [19]Magnuson, B. “Straight facts on aspartame & health”. The Beverage Institute. Visited 6/13/2010.

    [20]Soffritti, M., Belpoggi F. et al. “First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats”. Environ Health Perspect. 2006 March; 114(3): 379–385.

    [21]US Food and Drug Administration. “FDA Statement on European Aspartame Study”. CFSAN/Office of Food Additive Safety. April 20, 2007. Accessed 6/13/2010

    [22]European Commission Scientific Committee on Feed. “Opinion of the Scientific Committee on Food:Update on the Safety of Aspartame”. December 4, 2002. Accessed 6/13/2010.

    [23]Madsen MV, Gøtzsche PC, Hróbjartsson A. Acupuncture treatment for pain:systematic review of randomised clinical trials with acupuncture, placebo

    acupuncture, and no acupuncture groups. BMJ. 2009 Jan 27;338:a3115.

    [24]Curry, L. CFSAN/Office of Food Additive Safety. “Agency Response Letter GRAS Notice No. GRN 000253”. December 17, 2008. Visited 7/12/2010.

    [25]European Stevia Association. “Status in the EU”. Visited 7/13/2010

    Aspartame and Formaldehyde (or not…)

    A possibly easier to read version of this better for pinting is available at

    There is also a separate entry which is a response to a Joe Mercola article posted to the Huffington Post which repeated some of the claims refuted here, as well as some additional ones.


    Aspartame, more commonly known as NutraSweet, is frequently claimed to have any number of ill effects in the body. This article will focus on the claim that aspartame contains formaldehyde, leading to toxic effects in the body (such as headaches), and will also touch on the claim that it is a carcinogen (cancer causing agent). There are additionally claims that aspartame leads to seizures, but this is a much less popular one (perhaps because the NutraSweet acknowledges the danger in the small amount of PKU sufferers for which it would affect). Hopefully the reader will be convinced it is true that one of the by-products of the breakdown of aspartame is formaldehyde, this does not represent any actual health hazard.

    Just what is aspartame?

    Aspartame is a low-caloric sweetener (i.e. alternative to sugar). Wikipedia describes aspartame as1

    a methyl ester of the dipeptide of the natural amino acids L-aspartic acid and L-phenylalanine. Under strongly acidic or alkaline conditions, aspartame may generate methanol by hydrolysis. Under more severe conditions, the peptide bonds are also hydrolyzed, resulting in the free amino acids

    Claims and Discussion

    A common claim is that aspartame contains formaldehyde which builds up in the body and creates all manner of ills. Others have claimed that it is a carcinogen (cancer causing agent) despite there being no studies that really demonstrate that.
    Mark D. Gold and Ralph Walton are two of the more prolific writers on this topic out there. Gold’s website has a section title “Formaldehyde Poisoning from Aspartame“, which has the following:

    In 1997 there was an increase in aspartame users reporting severe toxicity reactions and damage such as seizures, eye damage and vision loss, confusion, severe migraines, tremors, depression, anxiety attacks, insomnia, etc. In the same years, Ralph Walton, MD, Chairman, The Center for Behavioral Medicine showed that the only studies which didn’t find problems with aspartame where those funded by the manufacturer (Monsanto).

    Given the agreement amongst independent scientists about the toxicity of aspartame, the only question was whether the formaldehyde exposure from aspartame caused the toxicity. That question has now been largely answered because of research in the late 1990s.
    The following facts shown by recent scientific research:

    1. Aspartame (nutrasweet) breaks down into methanol (wood alcohol).
    2. Methanol quickly converts to formadehyde in the body.
    3. Formaldehyde causes gradual and eventually severe damage to the neurological system, immune system and causes permanent genetic damage at extremely low doses.
    4. Methanol from alcoholic beverages and from fruit and juices does not convert to formaldehyde and cause damage because there are protective chemicals in these traditionally ingested beverages.
    5. The most recent independent research in Europe demonstrates that ingestion of small amounts of aspartame leads to the accumulation of significant levels of formaldehyde (bound to protein) in organs (liver, kidneys, brain) and tissues.
    6. Excitotoxic amino acids such as the one which is immediately released from aspartame likely increases the damage caused by the formaldehyde.

    What the science says

    While it is true that aspartame does break down into methanol then formaldehyde, it actually happens much more in fruit juices (about 2x in a banana, or 6x in an 8oz glass of tomato juice2). Gold attempts to address this in item 4, but simply waves his hand as an explanation for why it can be ignored. The fact is that it simply is not enough to do anything and your body easily disposes of it.
    The above quoted article has one of the more untrue statements you can find. Not only do “non-independent” researchers find no problems, “independent” ones did not either. Instead what you will find are people making hypothetical claims which are not backed by anything. Gold and Walton are excellent at taking a statement by one scientist and using it as an explanation for why aspartame has been found to be bad, when in fact it has not. In other words, they start with the premise that aspartame is harmful then look for explanations for why it might be.

    The Walton set of research is frequently cited, but let’s break it down a bit. It actually was already rebutted here:

    Dr Walton’s paper reveals that of the 92 pieces of “research,” 85 (not 84) are said to identify an adverse reaction to aspartame. However, of the 85:

    • Ten studies actually involve aspartate and not aspartame. Aspartate is the salt of aspartic acid. Aspartic acid is a very common component of food. These studies are therefore irrelevant to aspartame safety.
    • 18 of the studies do not actually draw any negative conclusions about aspartame.
    • Five are review articles, not peer-reviewed studies.
    • Two are “brief reports” or “case reports”, not peer-reviewed studies.
    • Five are anecdotes, based on the writers’ observations of patients.
    • 11 are conference proceedings, which are not peer-reviewed studies.
    • 19 are letters to various medical journals.
    • Three are different reports of the same study.
    • Two are exact duplicates of other documents appearing in the list.
    • Three are different reports of the same allegations.

    Overwhelming indeed. My own analysis is available here. What I found entertaining is how many of them (18 or 19) don’t even find anything negative… yet Walton, either brazenly or unknowingly, still includes them in his number. All in all, Walton is quite sloppy.
    The only reasonable study (which I believe is also the one being referenced in #5 above), but still frequently questioned is:

    1. Trocho, C., et al., 1998. “Formaldehyde Derived From Dietary Aspartame Vinds(sic) to Tissue Components in vivo,” Life Sciences, Vol. 63, No. 5, pp. 337+, 1998
    Note the misspelling as “Vinds”… when it should be “Binds”. It’s generally cited as “Vinds” though.. a good indication that most of the sites claiming to do research are simply copy/pasting from this one guy.

    …The administration of labelled aspartame to a group of cirrhotic rats resulted in comparable label retention by tissue components, which suggests that liver function (or its defect) has little effect on formaldehyde formation from aspartame and binding to biological components. The chronic treatment of a series of rats with 200 mg/kg of non-labelled aspartame during 10 days resulted in the accumulation of even more label when given the radioactive bolus, suggesting that the amount of formaldehyde adducts coming from aspartame in tissue proteins and nucleic acids may be cumulative. It is concluded that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts.

    One of the primary responses is from Tephyl, quoted by Butchko et al3:

    However, according to Tephly (1999), the dose of aspartame used in the study (20 mg/kg body wt=2mg of methanol/kg body wt) would not yield blood methanol concentrations outside control values. Further, the administration of aspartame at 200 mg/kg body wt (equal to that in a single bolus of about 25 liters of beverage sweetened 100% with aspartame) to adult humans results in no detectable increase in blood formate concentrations (Stegink et al., 1981). Administration of [14C]methanol itself at 3000 mg/kg body wt to monkeys produces no detectable [14C]formaldehyde in body fluids and tissues (McMartin et al., 1979)…The lack of formaldehyde accumulation at very high doses of methanol question considerably the conclusion that formaldehyde adducts are forming from low doses of methanol (derived from high doses aspartame). Thus, Tephly (1999) concluded, “the normal flux of one-carbon moieties whether derived from pectin, aspartame, or fruit juices is a physiologic phenomenon and not a toxic event.”

    To break it down:
    1. Formaldehyde build-up has not in fact been detected even when 200mg/kg is given to humans (which is a huge amount)
    2. Even when large does of direct methanol (which is what breaks down into formaldehyde) were given to monkeys, it did not produce formaldehyde build-up
    3. There are other explanations for the labelled-carbon staying in the body, aside from formaldehyde build-up which will also occur with other substances (such as fruit pectin).
    Going back to the original comments about Gold and Walton, we have a situation of someone trying to explain the build-up for formaldehyde, when no other scientists are able to actually see a build-up in the first place. Instead it seems that the labelled molecules are making their way through the basic chemistry of the process, but the full molecule is not.

    Systematic Reviews

    Let’s continue one with some of the large overviews which discuss the overall safety of aspartame in the broader scope, and occasionally look at studies purporting to show harm.

    US Food and Drug Administration (FDA)

    Both the FDA and the European Commission have determined that aspartame is safe. However they kicked off additional reviews in response to a study done by the European Ramazzini Foundation (linked here4) that claimed to demonstrate that aspartame was a carcinogen. The European review found this to not at all be supported by the data. The US FDA decided to do its own separate review of the study and had similar findings5:

    FDA has completed its review concerning the long-term carcinogenicity study of aspartame entitled, “Long-Term Carcinogenicity Bioassays to Evaluate the Potential Biological Effects, in Particular Carcinogenic, of Aspartame Administered in Feed to Sprague-Dawley Rats,” conducted by the European Ramazzini Foundation (ERF), located in Bologna, Italy. FDA reviewed the study data made available to them by ERF and finds that it does not support ERF’s conclusion that aspartame is a carcinogen. Additionally, these data do not provide evidence to alter FDA’s conclusion that the use of aspartame is safe.


    Considering results from the large number of studies on aspartame’s safety, including five previously conducted negative chronic carcinogenicity studies, a recently reported large epidemiology study with negative associations between the use of aspartame and the occurrence of tumors, and negative findings from a series of three transgenic mouse assays, FDA finds no reason to alter its previous conclusion that aspartame is safe as a general purpose sweetener in food.

    Kind of interesting that the folks doing the study were not willing to actually submit it to a full review. If you take a look at the study’s tables (here and here), the bit that stands out to me is the lack of a consistent dose-response effect as you get higher doses of aspartame. They had to get up to an insane amount (2500mg/kg… or the equivalent of 500mg/kg for humans) to get a statistically significant effect.

    European Commission – Scientific Committee on Food

    For reasons unknown, people against Aspartame link to to the “European Commission updates their opinion” study as if the EC had determined that aspartame was now unsafe. The update was kicked off because of the Ramazzini Foundation study claiming carcinogenity. If you actually read the update, it is quite clear that they very much still find it to be safe.

    Some important bits from the text (in all cases emphasis is my own)6:

    The estimates of intake by mean and high level consumers are fairly consistent between European countries even though slightly different approaches were used. High level consumers, both adults and children, are unlikely to exceed the ADI of 40 mg/kg bw for aspartame. Special groups such as diabetics that are likely to be high consumers of foods containing aspartame are also well below the ADI. Therefore, from the available data it appears that no group is likely to exceed the ADI for aspartame on a regular basis.

    All this is really saying is that the actual amount that most people would consume is well below the worldwide maximum level allowed (40-50 mg/kg).

    If you view the table in the document, you can see that the mean is in the 2-3mg/kg bw/d, with high levels around 6-10.

    Animal studies have demonstrated that the metabolic breakdown products of aspartame are absorbed and metabolised similarly whether they are given alone or derived from aspartame. The extensive presystemic metabolism of aspartame results in little or no parent compound reaching the general circulation.

    This is in alignment to the Butchko/Tepyhl comments above: aspartame by-products (methanol, then formaldehyde) to not make it into the bloodstream.

    And the key parts:

    The aspartate component is rapidly metabolised and thus the plasma aspartate concentrations are not significantly elevated following aspartame doses of 34 to 50 mg/kg bw, whereas plasma Phe concentrations may increase depending on dose (Stegink, 1984). Methanol is also rapidly metabolised and blood levels are usually not detectable unless large bolus doses of aspartame (>50 mg/kg bw) are administered.

    Trocho is discussed:

    …Besides the fact that aspartame at high doses has never induced liver cancer in rats, Trocho’s studies did not identify the radioactivity found in the proteins and DNA. Consequently, the formation of adducts of formaldehyde on the proteins and nucleic acids from aspartame, in vivo, remains to be proved

    French Food Safety Agency (AFSSA)

    The AFSSA published its own systematic review (here hosted on the UK Food standards agency… FDA equivalent). They go over much of the same material as those above. On the subject of the aspartame leading to headaches, they have to say7:

    Another study…was also a randomised double-blind placebo-controlled cross-over trial, concluded that aspartame was no more likely than placebo to trigger headaches (Schiffman et al., 1987). This study consisted of 40 subjects who complained of aspartame-related headachesWhile 35% of subjects developed headaches while on aspartame, 45% developed headaches while on placebo.

    I found it interesting that the Shiffman study actually used people who were already pre-disposed to believe that they got headaches from aspartame, and even then it could not be demonstrated.


    The fact of the matter is there is not a convincing body of evidence (or none at all depending on how you look at it) to indicate that there is any reason to be concerned with normal intake of foods and beverages containing aspartame–unless you somehow manage to consume 12 liters of soda in a single sitting, in which case you have worse things to worry about. If there is interest, another article could focus on the supposed “excitotoxin” aspects of aspartame and some of the other proposed effects.The problem with these claims is that there is a large amount of urban myth around aspartame which do not have any studies (or reproduced studies) to back them up. They are essentially made up from whole cloth, which actually makes them more difficult to disprove. If there are specific studies that you have found convincing, then they could serve as a new jumping off point for another essay. Until then, there seems no reason to not consume diet beverages and other “light” foods.
    UPDATE July 15, 2012 – Corrected external link to rebuttal of Walton’s “independent” aspartame studies

    1 – Wikipedia page on aspartame. Used for general overview. Visited 3/5/2010

    2 Magnuson, B. “Straight facts on aspartame & health”. The Beverage Institute. Visited 6/13/2010. The actual numbers quoted come from the peer-reviewed paper by the same author, but I was unable to find a working full text link.

    3 Butchko, HH., Stargel, WW., Comer, CP., Mayhew, DA. “Aspartame: Review of Safety”. Regulatory Toxicology and Pharmacology 35, S1–S93 (2002)

    4 Soffritti, M., Belpoggi F. et al. “First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats”. Environ Health Perspect. 2006 March; 114(3): 379–385.

    5 US Food and Drug Administration. “FDA Statement on European Aspartame Study”. CFSAN/Office of Food Additive Safety. April 20, 2007. Accessed 6/13/2010

    6 European Commission Scientific Committee on Feed. “Opinion of the Scientific Committee on Food:Update on the Safety of Aspartame”. December 4, 2002. Accessed 6/13/2010.

    7 French Food Safety Agency (AFSSA). “Opinion on a possible link between the exposition to aspartame and the incidence of brain tumours in humans”. May 7, 2002. Accessed 6/13/2010.

    Water Bottles and Cancer

    A printable and easier to read version can be found at:



    I thought it would be interested to look into the oft-quoted idea that water bottles are not reusable and that if you do anything other than drink from them and toss them, that you would get cancer. I personally had not heard many of the claims and in even looking them up, the first few results were usually previous debunkings. This almost made be stop by I figured for my few readers I may as well summarize some of the results. Plus I thought it would be nice to look into something where there was nobody I could offend, which is nice. This is part of an ongoing series that has included energy drinks and water intake requirements.

    A comment-enabled version can be found on my blog at:

    Note: BPA will be covered in another essay, as the FDA and CDC are currently awaiting for new studies to be completed. They were supposed to report back Nov 30, but this has come and gone. Currently the official position is that BPA as it is currently used is safe.


    Your water bottle is not going to kill you. The best thing to do any time you hear that some every day item is going to kill you is to head on over to Snopes. Most stories like this are quickly found to be based on complete fabrications. This particular one happens to have very minute amounts of “real” science (e.g. dioxins and DEHA do exist and DEHA is in microwave-safe plastics) but that actual effects are in no way realistic. Additionally, DEHA is not actually carcinogenic as far as anyone can tell. Whether or not you personally believe in any claim of this sort, please refrain from passing it on before you have validated that it is credible.


    I am not a doctor or scientist, no words of mine should be construed as medical advice. My intent is only to find the best available scientific or medical evidence for or against claims that comes for authoritative sources. If you have credible studies that would contradict them, please let me know.


    Claim 1: Leaving a bottle of water in the car can make it cancerous

    Personally I had never really heard about this one, but I did some searching and it looks to be a popular one, having originated with an email hoax purporting to come from “Johns Hopkins” and claiming that leaving a water bottle in the car can cause it to leak “dioxins”. Occasionally the email will include the claim that Sheryl Crow was on Ellen to warn others about this happening to her.


    From one blog that has pasted the email (and claims it came from a breast cancer doctor): [1]

    Cancer Update from Johns-Hopkins

    Bottled water in your car isvery dangerous!

    On the Ellen show, Sheryl Crow said this is what caused her breast cancer. It has been identified as the most common cause of the high levels of dioxin in breast cancer tissue.

    Sheryl Crow’s oncologist told her:

    women should not drink bottled water that has been left in a car.The heat reacts with the chemicals in the plastic of the bottle which releases dioxin into the water. Dioxin is a toxin increasingly found in breast cancer tissue. So please be careful and do not drink bottled water that has been left in a car. Pass this on to all the women in your life.

    What the science says

    Let’s get the Sheryl Crow part of it out of the way right away. On her official site she posted real information about dioxins that specifically goes against the claim (i.e. she acknowledges that it is a hoax). It can currently be found on page 23 of her “news items” (the items are chronological, and this item is from October of 2006). It is a news item called “What You Need to Know About Dioxins (Updated with Notes from Gregg Dempsey”. In case that link doesn’t get you there, an Internet Archive version exists of her older site which had the same news item. She actually ends up quoting from some of the same stuff that will come below.
    Regardless, I think it should be stressed as always that celebrities should not be where you get your science or medical information from. This also goes for the ones I agree with.

    The Internet is flooded with messages warning against freezing water in plastic bottles or cooking with plastics in the microwave oven. These messages, frequently titled “Johns Hopkins Cancer News” or “Johns Hopkins Cancer Update,” are falsely attributed to Johns Hopkins and we do not endorse their content.

    Freezing water does not cause the release of chemicals from plastic bottles.

    Additionally, they have another response that goes into some more detail[3]:

    Question: What do you make of this recent email warning that claims dioxins can be released by freezing water in plastic bottles?

    Answer: No. This is an urban legend. There are no dioxins in plastics. In addition, freezing actually works against the release of chemicals. Chemicals do not diffuse as readily in cold temperatures, which would limit chemical release if there were dioxins in plastic, and we don’t think there are.

    The FDA has a page about dioxins. You are exposed to it quite often. Their page makes absolutely no mention of plastic bottles.

    Technically some studies have shown that high levels of exposure could potentially cause cancer[4]:

    G2. Why are people concerned about dioxins?

    One of the main concerns over health effects from dioxins is the risk of cancer in adults. Several studies suggest that workers exposed to high levels of dioxins at their workplace over many years have an increased risk of cancer. Animal studies have also shown an increased risk of cancer from long-term exposure to dioxins.

    G4. How might I be exposed to dioxins?

    Most of the population has low-level exposure to dioxins. Although dioxins are environmental contaminants, most dioxin exposure occurs through the diet, with over 95% coming through dietary intake of animal fats (see also F3 and F4). Small amounts of exposure occur from breathing air containing trace amounts of dioxins on particles and in vapor form, from inadvertent ingestion of soil containing dioxins, and from absorption through the skin contacting air, soil, or water containing minute levels of dioxins.

    But again it has absolutely nothing to do with plastic bottles (or even, as far as I know, any plastics you would use regularly).


    It is true that dioxins could be potentially hazardous, but it does not seem that the average person would be getting anywhere near the exposure that could be harmful. And it certainly has nothing whatsoever to do with water bottles.

    Claim 2: Heating of Freezing Water Bottles Causes them to Leach Chemicals such as DEHA


    As a seventh grade student, Claire Nelson learned that DEHA, di(ethylhexyl)adepate, considered a carcinogen, is found in plastic wrap. She also learned that the FDA had never studied the effect of microwave cooking on plastic-wrapped food. Claire began to wonder: “Can cancer-causing particles seep into food covered with household plastic wrap while it is being microwaved?”

    Three years later, with encouragement from her high school science teacher, Claire set out to test what the FDA had not. Although she had an idea for studying the effect of microwave radiation on plastic-wrapped food, she did not have the equipment. Eventually, Jon Wilkes at the National Center for Toxicological Research in Jefferson, Arkansas, agreed to help her. The research center, which is affiliated with the FDA, let her use its facilities to perform her experiments, which involved microwaving plastic wrap in virgin olive oil. Claire tested four different plastic wraps and “found not just the carcinogens but also xenoestrogen was migrating [into the oil]….” Xenoestrogens are linked to low sperm counts in men and to breast cancer in women.


    On Channel 2 (Huntsville, AL) this morning they had a Dr. Edward Fujimoto from Castle Hospital on the program. He is the manager of the Wellness Program at the hospital. He was talking about dioxins and how bad they are for us. He said that we should not be heating our food in the microwave using plastic containers. This applies to foods that contain fat. He said that the combination of fat, high heat and plastics releases dioxins into the food and ultimately into the cells of the body. Dioxins are carcinogens and highly toxic to the cells of our bodies.

    What the Science Says

    Others have done better research on this hoax (actually for both parts), a good one being at As usual, Snopes is a good source on this one ( Another one to take a look at
    I actually couldn’t put it better than Snopes:

    It’s a pretty good assumption that if using plastic containers in microwaves posed a significant risk of cancer, you’d be hearing it somewhere other than an e-mail forward of an anomymous summary of a morning news spot on a Hawaiin television station

    Replace the item and the danger, and you have a large percentage of all the supposed health hazards out there from normal household items.. which are also not backed by any actual science.
    From (arguably potentially biased) site[5]:

    The student’s thesis incorrectly identifies di(2-ethylhexyl) adipate (DEHA), a plastics additive, as a human carcinogen. DEHA is neither regulated nor classified as a human carcinogen by the U.S. Occupational Safety & Health Administration, the National Toxicology Program or the International Agency for Research on Cancer, the leading authorities on carcinogenic substances.

    In 1991, on the basis of very limited data, the U.S. Environmental Protection Agency classified DEHA as a “possible human carcinogen.” However, in 1995, EPA again evaluated the science and concluded that “…overall, the evidence is too limited to establish that DEHA is likely to cause cancer.”

    Further, DEHA is not inherent in PET as a raw material, byproduct or decomposition product. DEHA is a common plasticizer that is used in innumerable plastic items, many of which are found in the laboratory. For this reason, the student’s detection of DEHA is likely to have been the result of inadvertent lab contamination. This is supported by the fact that DEHA was detected infrequently (approximately 6% of the samples) and randomly, meaning that the frequency of detection bore no relationship to the test conditions.

    Moreover, DEHA has been cleared by FDA for food-contact applications and would not pose a health risk even if it were present.

    Finally, in June 2003, the Swiss Federal Laboratories for Materials Testing and Research conducted a scientific study of migration in new and reused plastic water bottles from three countries. The Swiss study did not find DEHA at concentrations significantly above the background levels detected in distilled water, indicating DEHA was unlikely to have migrated from the bottles. The study concluded that the levels of DEHA were distinctly below the World Health Organization guidelines for safe drinking water.

    Or if you don’t trust “”, how about the American Cancer Society[6].

    These emails are apparently based on a student’s college thesis. In fact, DEHA is not inherent in the plastic used to make these bottles, and even if it was the U.S. Environmental Protection Agency (EPA) says DEHA “cannot reasonably be anticipated to cause cancer, teratogenic effects, immunotoxicity, neurotoxicity, gene mutations, liver, kidney, reproductive, or developmental toxicity or other serious or irreversible chronic health effects.” Meanwhile, the International Agency for Research on Cancer (IARC), says diethylhexyl adipate “is not classifiable as to its carcinogenicity to humans.”

    The IARC study that both reference can be found online here. The above have already quoted it, so the link is just for reference.

    Or how about the EPA (you will note that they make no mention of water bottles)[7]:

    What is di(2-ethylhexyl) adipate?

    Di(2-ethylhexyl) adipate is a light-colored, oily liquid with an aromatic odor.

    What are di(2-ethylhexyl) adipate’s health effects?

    Some people who drink water containing di(2-ethylhexyl) adipate well in excess of the maximum contaminant level (MCL) for many years could experience toxic effects such as weight loss, liver enlargement, or possible reproductive difficulties.

    How does di(2-ethylhexyl) adipate get into my drinking water?

    The major source of di(2-ethylhexyl) adipate in drinking water is discharge from chemical factories.


    The FDA, EPA, and American Cancer Society are well aware of DEHA,water bottles and plastics. They make absolutely no claims about them being carcinogenic when frozen or heated. In fact they make sure to point that these claims are specifically untrue.

    Claim 3: Water bottles are unsafe for re-use because of bacteria


    Well, yeah. You should re-use any container without rinsing it with soap and water. Why would water bottles be any different. Claiming that water bottles are any different means that as soon as you open a bottle of water you must throw it away after the first drink if you don’t finish it. Does that make any sense?

    Further References

    Not surprisingly, Brian Dunning of Skeptoid covered this already (in 2007 no less) at:

    It has also been covered on pretty much every email-hoax debunking site.


    1 Smith-Batchen, Lisa. “Cancer Update from Johns Hopkins”. April 11, 2009.

    2 Johns Hopkins School of Public Health.


    4 Food and Drug Administration. “Questions and Answers about Dioxins”. Visited 2009/12/06

    5 American Chemistry Council. “FAQs: The Safety of Plastic Beverage Bottles”. Visited 12/6/2009

    6 American Cancer Society.

    7 Environmental Protection Agency. “Basic Information about Di(2-ethylhexyl) adipate in Drinking Water”.

    H1N1 (pandemic flu)

    What does the science say: H1N1

    Joshua DeWald (josh at 40two org)
    November 29, 2009
    As usual, an easier to read and printable version can be found at:
    Update (April 2012): Added portion (and link to) useful infographic on the cost of getting the flu vs the small cost of a vaccine. 


    It seemed like a good idea to do a quick entry addressing the H1N1 “swine flu” strain as well as the vaccine for it. A friend of mine suggested adding it to my previous entry on vaccines, but I thought I’d do a separate one instead so people’s eyes don’t glaze over from an already over-long article.

    I have no intention of promoting the quack H1N1 claims that are floating around the Internet, so I won’t be linking to them. What you will find here is the official information that is available about the disease and the vaccine. As usual, if you are convinced that the government is lying to us about the flu, then you may as well stop reading now, as I am really just summarizing CDC and FDA  data.

    As always, I welcome comments on my blog ( or to my email address (josh at 40two org). If anything in here seems factually inaccurate to you, please let me know, but cite your sources. I’m truly not interested in what “Mr. Fit” or any number of random Internet flu scare sites have to say unless they have any genuine science to back them up.


    The “pandemic” H1N1 (aka “swine flu”) is a very serious strain of flu. It is separate from the standard seasonal flu and to be protected for both you have to vaccinate from both. The actual effects are similar to the normal flu, which kills about 36000 people a year. The expected combined deaths of seasonal flu (3 strains) and H1N1 is about 65000 deaths. The H1N1 vaccine has been shown to be as safe and effective as the normal seasonal vaccine that people take yearly.


    I am not a doctor. None of my words should be construed at medical advice. If you still have questions about H1N1, speak with your own doctor. You may safely ignore any statements that appear to be opinion from me or not directly supported by any research or authority I cite.

    The H1N1 virus

    So what is H1N1 any way?

    There actually is already a different version of H1N1 that circulates as part of the seasonal flus.
    From the CDC’s Q&A about H1N1 (

    This virus was originally referred to as “swine flu” because laboratory testing showed that many of the genes in this new virus were very similar to influenza viruses that normally occur in pigs (swine) in North America. But further study has shown that this new virus is very different from what normally circulates in North American pigs. It has two genes from flu viruses that normally circulate in pigs in Europe and Asia and bird (avian) genes and human genes. Scientists call this a “quadruple reassortant” virus.


    The symptoms of 2009 H1N1 flu virus in people include fever, cough, sore throat, runny or stuffy nose, body aches, headache, chills and fatigue. Some people may have vomiting and diarrhea. People may be infected with the flu, including 2009 H1N1 and have respiratory symptoms without a fever. Severe illnesses and deaths have occurred as a result of illness associated with this virus.

    Severity, risk, infection rates:

    In seasonal flu, certain people are at “high risk” of serious complications. This includes people 65 years and older, children younger than five years old, pregnant women, and people of any age with certain chronic medical conditions. About 70 percent of people who have been hospitalized with this 2009 H1N1 virus have had one or more medical conditions previously recognized as placing people at “high risk” of serious seasonal flu-related complications. This includes pregnancy, diabetes, heart disease, asthma and kidney disease.

    With seasonal flu, we know that seasons vary in terms of timing, duration and severity. Seasonal influenza can cause mild to severe illness, and at times can lead to death. Each year, in the United States, on average 36,000 people die from flu-related complications and more than 200,000 people are hospitalized from flu-related causes. Of those hospitalized, 20,000 are children younger than 5 years old. Over 90% of deaths and about 60 percent of hospitalization occur in people older than 65.

    Is anybody really dying from H1N1?

    Sadly, yes.
    As of October 17th (so a month before this writing), the CDC estimates that there have been 2500 to 6100 deaths. 63,000 to 153,000 people have been hospitalized. And the season is really just getting started.
    If you’re curious about why it’s an “estimate”, it mainly has to due with the fact that states don’t have to report all flu-related deaths, or the person might day later from complications. Specifically:
    • First, states are not required to report individual seasonal flu cases or deaths of people older than 18 years of age to CDC.
    • Second, seasonal influenza is infrequently listed on death certificates of people who die from flu-related complications.
    • Third, many seasonal flu-related deaths occur one or two weeks after a person’s initial infection, either because the person may develop a secondary bacterial co-infection (such as a staph infection) or because seasonal influenza can aggravate an existing chronic illness (such as congestive heart failure or chronic obstructive pulmonary disease).
    • Also, most people who die from seasonal flu-related complications are not tested for flu, or they seek medical care later in their illness when seasonal influenza can no longer be detected from respiratory samples. Influenza tests are most likely to detect influenza if performed soon after onset of illness.
    • For these reasons, many flu-related deaths may not be recorded on death certificates.

    The Vaccine

    Was the vaccine rushed?

    The key thing to know is that from a vaccine point of view, this is just another (better targeted) strain.
    “The flu” vaccine changes every year because of the evolution and recombination of the strains. Or from the CDC’s “key facts” about the seasonal flu1:

    The viruses in the vaccine change each year based on international surveillance and scientists’ estimations about which types and strains of viruses will circulate in a given year. About 2 weeks after vaccination, antibodies that provide protection against influenza virus infection develop in the body.

    My readers will probably agree that we don’t hear yearly conspiracy theories about the “rush” to create the current year flu vaccine. Or maybe they do and, rightfully, ignore them.
    The ones that circulate seasonally are:
    • H3N2
    • seasonal A (H1N1)
    • seasonal B
    “pandemic” H1N1 is the new version.
    Additionally, the FDA has a Q&A about the 2009 H1N1 which addresses this concern2.

    Vaccines used in the United States must be licensed by FDA. FDA approved these vaccines as a strain change to each manufacturer’s FDA-approved seasonal influenza vaccine. Each of the manufacturers will make the Influenza A (H1N1) 2009 Monovalent vaccines using its well-established, licensed egg-based manufacturing process that is used for seasonal influenza vaccine.

    There is considerable experience with seasonal influenza vaccine development and production and influenza vaccines produced by this technology have a long and successful track record of safety and effectiveness in the United States. The safety and effectiveness demonstrated for seasonal influenza vaccine also support the licensure of the Influenza A (H1N1) 2009 Monovalent vaccines produced using the same process as for seasonal vaccine.

    The Influenza A (H1N1) 2009 Monovalent vaccines will undergo the same rigorous testing and lot release procedures that are in place for seasonal influenza vaccines.


    Every year, it takes approximately 6 months to make the current season’s batch of flu vaccine. The pandemic H1N1 strain (an earlier version of which circulated in 1976) vaccine is being produced using the same process as the seasonal flu. To call it rushed is to also claim that every year the seasonal flu vaccine is “rushed”. I see no evidence of truth in that claim.

    But I heard that I might get Guillain-Barré?

    What is Guillain-Barré?

    From the CDC’s “Fact Sheet” on Guillain-Barré3:

    Guillain-Barré syndrome (GBS) is a rare disorder in which a person’s own immune system damages the nerves, causing muscle weakness and sometimes paralysis. GBS can cause symptoms that last for as little as a few weeks, or go on for several months. Most people recover fully from GBS, but some people have nerve damage that does not go away. In rare cases, people have died of GBS, usually from not being able to breathe due to weakness of their breathing muscles.

    A key item in there is the fact that “most people recover fully”.

    And the risk from the swine flu vaccine?

    Continuing in the same Fact Sheet:

    In very rare cases, someone may develop GBS in the days or weeks after getting a vaccination. In 1976, there was a small increased chance of GBS after getting a flu (swine flu) vaccination. This means about 1 more case per 100,000 people who got the swine flu vaccine

    Since 1976, many studies have been done to see if other flu vaccines may cause GBS. In most studies no link was found between the flu vaccine and GBS. However, two studies did suggest that about 1 more person out of 1 million people vaccinated with seasonal flu vaccine may develop GBS. This continues to be studied.  For the most part, the chance of getting very ill from flu is far higher than the chance of getting GBS after getting the flu vaccine.

    This 1976 increase is the part that scares people. In fact, as soon as the increase was noticed, they stopped doing mass vaccinations that year as a precaution (yes, despite what people would like to claim, the CDC is very concerned about the safety of vaccines and takes seriously any indication they they haphazardly vaccinate).
    Despite a continued lack of real risk in subsequent flu vaccination programs, the CDC definitely monitors for any illness following vaccination [from Fact Sheet above]:

    During the 2009-2010 flu season, CDC and FDA will be closely looking at reports of serious problems, including GBS, which may be linked to the use of the 2009 H1N1 flu vaccine and to the seasonal flu vaccine. These systems already include some vaccination safety systems, such as the Vaccine Adverse Event Reporting System (VAERS), and new systems, such as the CDC Emerging Infections Program and a partnership with the American Academy of Neurology, which includes doctors who are most likely to see people with GBS. None of these systems existed in 1976.

    If you’d like to take a look at some of the actual studies, the ones I found were:
    One study found the risk after swine flu vaccine in 1976 to be approximately 11.7/1M (or 1.7/100K)[4 ]. Another found 13.3/1M (or 1.3/100K) using a different methodology[5 ].
    Researches continued to look at the risk from the seasonal flu vaccine. I believe these are relevant because the process of creating the vaccine for seasonal and “pandemic” flu is the exact same. Nobody is quite sure what happened in 1976, but it has not been repeated and could have been a random blip.
    A study in Great Britain found no real evidence of increased risk from 1990-2005 following seasonal flu vaccine, but “greatly increased” risk following flu-like illnesses[6 ].
    There was a slight increase in the 1993-1994 season above the 1992-1993 which elicited a study that found: “There was no increase in the risk of vaccine-associated Guillain–Barré syndrome from 1992–1993 to 1993–1994. For the two seasons combined, the adjusted relative risk of 1.7 suggests slightly more than one additional case of Guillain–Barré syndrome per million persons vaccinated against influenza.”[7]

    Other insights

    In what I saw as a great example of a person really looking at the science and weighing the risks, even after recovering from Guillain-Barré, Laura Claire Price submitted an editorial (not a clinical study) published in the September 2009 British Medical Journal. After summarizing much of the findings (some I have quoted above), she closes8:

    In view of the potential risks of and likely exposure to flu infection as a health care professional, the lack of relapse of the syndrome in a sizable number of people who have had the flu vaccine, and the lack of a persistent causal association, my current view is to consider “having the jab” when it becomes available.

    In terms of the relative risks themselves, two statisticians did an analysis of relative risk and whether it necessarily indicates an actual association. The analysis seems generic to me, but it was specifically in response to a civil case regarding Guillain-Barré and flu vaccine (in tort law, 2.0 relative risk is used). They concluded9:

    The scientific connection between a relative risk of 2.0 and specific causation is doubtful. Large relative risks argue for general causation, while small ones argue against. If the relative risk is near 2.0, problems of bias and confounding in the underlying epidemiologic studies may be serious, perhaps intractable. Problems created by individual differences may be equally difficult. Bias and confounding affect the estimation of relative risk from the underlying data. By contrast, individual di fferences affect the interpretation of relative risk:namely, the application to any specific individual.

    In short, when the relative risk indicates an increased risk, but that relative risk is still low, then it is not necessarily indicative of an actual association.


    Guillain-Barré Syndrome is rare to get and generally a person recovers fully. Guillain-Barré appears to be triggered from many illnesses (including the flu) as well as other factors that affect the immune and nervous system. In rare causes (1/1,000,000) the flu vaccine itself can be this cause (as obviously the intent of the vaccine is the trigger an immune reaction). During the 1976 swine flu vaccination program, there appeared to be a 1/100,000 extra cases for those who were vaccinated. The health risks (as well as the incidence) of H1N1 itself is much higher and easily outweighs the risk of Guillain-Barré.

    But what about the crazy ingredients?

    General Overview

    Because people are unnecessarily scared, none of the US approved vaccines have adjuvants (basically they help to “annoy” the immune system into producing more antibodies) such as aluminum in them. But for some of the more “controversial” ingredients (for all US vaccines, not just flu), the FDA has produced a nice FAQ[10].

    They specifically cover formaldehyde, preservatives, amino acids, sugars, etc.

    I’ll quote from a portion of the section on formaldehyde (emphasis mine):

    Although high concentrations of formaldehyde can damage DNA (the building block of genes) and cause cancerous changes in cells in the laboratory, formaldehyde is an essential component in human metabolism and is required for the synthesis of DNA and amino acids (the building blocks of protein).  Therefore, all humans have detectable quantities of natural formaldehyde in their circulation. In addition, quantities of formaldehyde at least 600-fold greater than that contained in vaccines have been found to be safe in animals.

    Additionally, some of the sugars, proteins and amino acids:

    These materials may be added as stabilizers.  They help protect the vaccine from adverse conditions such as the freeze-drying process, for those vaccines that are freeze dried.  Stabilizers added to vaccines include: sugars such as sucrose and lactose, amino acids such as glycine or the monosodium salt of glutamic acid and proteins such as human serum albumin or gelatin.  Sugars, amino acids and proteins are not unique to vaccines and are encountered in everyday life in the diet and are components that are in the body naturally.

    The approved H1N1 vaccines for usage in the United States

    You can see this same list at the FDA’s “2009 Monovalent Descriptions and Ingredients” site[11].

    CSL Limited

    A single 0.5 mL dose of Influenza A (H1N1) 2009 Monovalent Vaccine contains:
    • sodium chloride (4.1 mg)
    • monobasic sodium phosphate (80 mcg)
    • dibasic sodium phosphate (300 mcg)
    • monobasic potassium phosphate (20 mcg)
    • potassium chloride (20 mcg)
    • calcium chloride (1.5 mcg)
    From the manufacturing process, each 0.5 mL dose may also contain residual amounts of:
    • sodium taurodeoxycholate (≤ 10 ppm),
    • ovalbumin (≤ 1 mcg),
    • neomycin sulfate (≤ 0.2 picograms [pg]),
    • polymyxin B (≤ 0.03 pg),
    • beta-propiolactone (< 25 nanograms)

    ID Biomedical Corporation of Quebec

    Influenza A (H1N1) 2009 Monovalent Vaccine, for intramuscular injection, is a homogenized, sterile, colorless to slightly opalescent suspension in a phosphate-buffered saline solution formulated to contain:
    • 15 mcg hemagglutinin per 0.5-mL dose of the influenza A/California/7/2009 (H1N1)v-like virus.
    • Thimerosal, a mercury derivative, is added as a preservative. Each dose contains 25 mcg mercury.
    Each dose may also contain residual amounts of:
    • egg proteins (≤1 mcg ovalbumin)
    • formaldehyde (≤25 mcg)
    • sodium deoxycholate (≤50 mcg)

    No doubt the first thing you will notice is the use of Thimerosal, which has absolutely not been found to be linked to Autism. However, this vaccine is still only used for adults over 18 years of age. I repeat, children do not receive this vaccine.

    MedImmune LLC

    Each 0.2 mL dose contains 106.5-7.5 FFU of the live attenuated influenza virus reassortant of the pandemic (H1N1) 2009 virus: A/California/7/2009 (H1N1)v.
    Each 0.2 mL dose also contains:
    • 0.188 mg/dose monosodium glutamate
    • 2.00 mg/dose hydrolyzed porcine gelatin
    • 2.42 mg/dose arginine
    • 13.68 mg/dose sucrose
    • 2.26 mg/dose dibasic potassium phosphate
    • 0.96 mg/dose monobasic potassium phosphate
    • <0.015 mcg/mL gentamicin sulfate.

    Novartis Vaccines and Diagnostics Limited

    Influenza A (H1N1) 2009 Monovalent Vaccine is a homogenized, sterile, slightly opalescent suspension in a phosphate buffered saline. Influenza A (H1N1) 2009 Monovalent Vaccine is formulated to contain:
    • 15 mcg hemagglutinin (HA) per 0.5-mL dose of the following virus strain: A/California/7/2009 (H1N1)v-like virus.
    The 5-mL multidose vial formulation contains thimerosal, a mercury derivative, added as a preservative. Each 0.5-mL dose from the multidose vial contains 25 mcg mercury.
    Each dose from the multidose vial or from the prefilled syringe may also contain residual amounts of:
    • egg proteins (≤ 1 mcg ovalbumin)
    • polymyxin (≤ 3.75 mcg)
    • neomycin (≤ 2.5 mcg)
    • betapropiolactone (not more than 0.5 mcg)
    • nonylphenol ethoxylate (not more than 0.015% w/v)
    The multidose vial stopper and the syringe stopper/plunger do not contain latex.
    Again, notice the Thimerosal in the multidose version. This vaccine is itself only for children over 4 years of age. Also I suspect that due to the unnecessary fears, the single dose version is what is given to those under 18.

    Sanofi Pasteur, Inc.

    Influenza A (H1N1) 2009 Monovalent Vaccine is formulated to contain:

    15 mcg hemagglutinin (HA) of influenza A/California/07/2009 (H1N1) v-like virus per 0.5 mL dose.
    Gelatin 0.05% is added as a stabilizer.
    Each 0.5 mL dose may contain residual amounts of:
    • formaldehyde (not more than 100 mcg),
    • polyethylene glycol p-isooctylphenyl ether (not more than 0.02%) [Note: this is not anti-freeze, or even related to anti-freeze. Antifreeze is made from propylene glycol or ethylene glycol. It is non-toxic. It’s also in laxatives!]
    • sucrose (not more than 2.0%)
    There is no thimerosal used in the manufacturing process of the single-dose presentations of Influenza A (H1N1) 2009 Monovalent Vaccine.
    The multi-dose presentation of Influenza A (H1N1) 2009 Monovalent Vaccine contains thimerosal, a mercury derivative, added as a preservative.
    Each 0.5 mL dose of the multidose presentation contains 25 mcg mercury.
    Anything crazy? Didn’t think so.
    For those wondering why no adjuvants are present, it’s because they aren’t. Again, from the FDA’s Q&A about the swine flu vaccine:

    No, these vaccines are manufactured according to the same processes as the licensed (approved) seasonal influenza vaccines, which do not contain adjuvants.


    Except for the formaldehyde, which the CDC addresses, and the Thimerosal (which no valid scientific study has demonstrated has any causal link to Autism), which is only in vaccines meant for people over 18 (and possibly over 4 in one case), there are no ingredients which seem to me even worth looking up. Some of the online scare sites will attempt to link polyethylene glycol with “anti-freeze”, but this is a dishonest tactic.
    One sad side effect of the scare tactics are that there is actually less vaccine available because adjuvants aren’t being used (as they are in other countries). This means more attenuated virus and virus proteins must be used rather than a combination of proteins and adjuvants to stimulate the immune system. So less can be made and less live material is available for worldwide vaccines. Score one for pseudoscience.
    Another personal comment is that are people genuinely more trustworthy of random “herbal cures” that they find on the internet (or even a health food store) that is unregulated and not demonstrated to have any natural effect, then regulated and tested vaccines? Seriously?

    Is it safe for pregnant women?

    The Recommendation

    As usual, let’s go straight to the CDC’s statements about pregnant women and the flu vaccine[12 ]

    Additionally, because the vaccine cannot be given to babies less than 6 months old, the antibodies will protect the baby after it is born until they can get themselves vaccinated.

    Yes. Besides protecting her from infection, the shot may also help protect her infant. Flu shots are only given to infants 6 months of age and older. Everyone who lives with or gives care to an infant less than 6 months of age should get both the seasonal flu and 2009 H1N1 vaccines. A woman can get either the shots or the nasal spray after she delivers.

    It is true that the current swine flu vaccine has not been tested for pregnant women, as doing any clinical testing with pregnant women is not frequent.
    They are actually doing some clinical trials currently to be sure, which you can look for at the US Government’s There is currently a study in Phase II being done specifically for pregnant women[13].

    The studies

    A 2009 study (a literature review I believe, I can only get to the abstract) continues to find no risk to pregnant women from flu vaccines[14]:

    No study to date has demonstrated an increased risk of either maternal complications or adverse fetal outcomes associated with inactivated influenza vaccination. Moreover, no scientific evidence exists that thimerosal-containing vaccines are a cause of adverse events among children born to women who received influenza vaccine during pregnancy. In this article, we review the evidentiary basis for the recommendation of vaccination of all women who will be pregnant during the influenza season and safety data of influenza vaccination during pregnancy.

    A study done in 2004 comparing pregnant women getting vaccines with those who hadn’t between 1998 and 2003 and found no important statistically significant difference between them [15]:

    Among 7183 eligible mother-infant pairs, only 252 pregnant women (3.5%) received the influenza vaccine. Women with medical insurance were more likely to be vaccinated, although the rates for women with chronic underlying conditions were similar to those of healthy women, regardless of insurance status. The mean gestational age at the time of influenza vaccination was 26.1 weeks (range, 14-39 weeks). No serious adverse events occurred within 42 days of vaccination, and there was no difference between the groups in the outcomes of pregnancy (including cesarean delivery and premature delivery) and infant medical conditions from birth to 6 months of age.

    I dove into the study a bit and it should be noted that “abnormal glucose tolerance” test was just at the 95% CI p-value of .05, but there was no increased gestational diabetes. Additionally there was increased “transient hypertension”, but no additional preclampsia (which is what would normally follow). There was non-statistically significant increase in acute respiratory illnesses in the unvaccinated women, especially during the peak of flu season. And at the p-value of .05 (1.8% of cases), the children of unvaccinated women had congenital anomalies reported. The point here is really that there is no meaningful difference, as both as statistically insignificant increases in one form or another. They authors note: “Overall, a greater variety of pathologic conditions was observed in the group of infants of unvaccinated mothers throughout the first year of life.


    There is some unfortunate anecdotal stories of women who miscarry following flu vaccination. This is heartbreaking, but is a case of correlation without causation. There are thousands of spontaneous miscarriages a month (possibly daily), so it is not surprising that there will exist expectant mothers who will have happened to have gotten a vaccine recently (just as they might have had Burger King that morning, or gone to the gym, or been around a smoker, or any number of events that might correlate but are not the cause).

    I had a section where I attempted to calculate how many miscarriages might be occurring per day to demonstrate how likely it is. I’ve deleted this section because a) my math is probably wrong b) no matter the number it is heartbreaking. Instead I will simply provide the numbers of how many live births there are and the miscarriage rates.
    Every month there are approximately 320,000 successful live births (obviously depends on the year, this is from 2000)[16].
    While about 10-15% of pregnancies after the first few months end in spontaneous miscarriage, the rate is about 3% once in the 3rd trimester (unfortunately, I can’t seem to find a reliable source for this number, just various pregnancy sites mentioning it. The normal number is 10-15%, but that is across the entire pregnancy and not specifically for the 3rd trimester, which is what the anecdotal claims are about).
    Pregnant women should really speak with their physician. The CDC’s recommendation is for them to get vaccinated, due to the high risk of complications from the flu itself and as there is no indication that the vaccine would cause harm. There is anecdotal evidence, as there is for many things, of women who get a vaccination and then shortly afterwards miscarry. No study has been able to find this linkage.

    Further Resources

    The government’s flu information center:

    CDC’s “key facts” about the flu vaccines:

    As usual, Brian Dunning of Skeptoid manages to make the same topic entertaining:
    Additionally, the bloggers are Science-Based Medicine are in fact real doctors and genuinely know what they are talking about:
    Jason from Frugal Dad made a great infographic going over the “true cost” of the flu (in general), as it compares to the relatively low cost of getting vaccinated. Here is a small portion of it, I recommend you take a look at the whole thing. It covers both the cost to the individual as well as the a company, the economy as a whole and even the world overall.

    Cost of the Flu (


    1 “CDC: Seasonal Influenza Key Facts”. Visited 11/26/2009

    2 US Food and Drug Administration. “Influenza A (H1N1) 2009 Monovalent Vaccines Questions and Answers.” Published September 15, 2009. Visited 11/28/2009

    3 CDC. “Fact Sheet: Guillain-Barré Syndrome”. Published 11/2/2009. Visited 11/27/2009.

    4 Breman, Joel G. “GUILLAIN-BARRÉ SYNDROME AND ITS RELATIONSHIP TO SWINE INFLUENZA VACCINATION IN MICHIGAN, 1976–1977”. American Journal of Epidemiology Vol. 119, No. 6: 880-889

    5 Marks, James S. “Guillain-Barré Syndrome in Recipients of A/New Jersey Influenza Vaccine”. JAMA. 1980;243(24):2490-2494.

    6 Stowe, Julia et a. “Investigation of the Temporal Association of Guillain-Barré Syndrome With Influenza Vaccine and Influenzalike Illness Using the United Kingdom General Practice Research Database”. American Journal of Epidemiology 2009 169(3):382-388; doi:10.1093/aje/kwn310

    7 Lasky T, Terracciano GJ, Magder L, Koski CL, Ballesteros M, Nash D, Clark S, Haber P, Stolley PD, Schonberger LB, Chen RT. The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med. 1998 Dec 17;339(25):1797-802. PubMed PMID: 9854114.

    8 Price, Laura C. “Should I have an an H1N1 flu vaccination after Guillain-Barré syndrome?”. BMJ 2009;339:b3577. Visited 11/27/2009

    9 Freedman, D. A., Stark, P. B. (1999). The Swine Flu Vaccine and Guillain-Barré Syndrome: A Case Study in Relative Risk and Specific Causation. Eval Rev 23: 619-647

    10 “Common Ingredients in U.S. Licensed Vaccines”. Visited 11/27/2009

    11 US Food and Drug Administration. “Influenza A (H1N1) 2009 Monovalent Vaccines Descriptions and Ingredients”. Visited 11/27/2009

    12 Center for Disease Control. “2009 H1N1 Influenza Shots and Pregnant Women: Questions and Answers for Patients”. Updated November 2, 2009. Visited November 28, 2009.]:

    13 “H1N1 Vaccine in Pregnant Women”. Updated 11/25/2009. Visited 11/28/2009

    14 Tamma PD, Ault KA, Del Rio C, Steinhoff MC, Halsey NA, Omer SB. Safety of influenza vaccination during pregnancy. Am J Obstet Gynecol. 2009 Oct 20. [Epub ahead of print] PubMed PMID: 19850275.

    15 Flor M. Munoz, MD et al. “Safety of influenza vaccination during pregnancy”. American Journal of Obstetrics and Gynecology (2005) 192, 1098–106.

    16 CDC National Center for Health Statistics. “National Vital Statistics Reports. Births:Final data for 2000”. Vol:50,Number 5. February 12, 2002. Visited 11/29/2009.