Aspartame and its effects on health

In their editorial, "Aspartame and its effects on health" (1),
Professor Lean and Catherine Hankey described my web page
as "sensationalist journalism." That web page contains
nearly 400 pages of referenced discussion related to the
toxicity of aspartame and its metabolites. In addition,
there are several hundred pages of reports from individuals
detailing their experience of aspartame toxicity. I would
invite healthcare professionals to peruse a portion the
scientific sections that address both independent and
aspartame industry-funded research in detail:

http://www.holisticmed.com/aspartame/abuse/

http://www.holisticmed.com/aspartame/scf2002.html

http://www.holisticmed.com/aspartame/aspfaq.html

In addition, there are numerous reasoned articles
written by independent researchers and phsycians
that have been reproduced on the web:

http://www.dorway.com/doctors.html

Citations in the editorial that related to
aspartame and health effects included a web page
published by an aspartame industry-funded public
relations organization (2) and a published review
written by NutraSweet company employees and others
who have received funding from the manufacturer (3).
In is not surprising, therefore, that the authors
erroneously stated that "aspartame comprises just
two amino acids" and implied that the evidence does
not support the link between aspartame and health
effects. On the other hand, evidence from independent
research and published case reports (as detailed on
the above-mentioned web pages) demonstrates that
aspartame can cause a wide range of adverse health
effects.

Addressing the response by Dr. Finer, Medical Advisor
to Ajinomoto (aspartame manufacturer), he states that:

1) Individuals must consume 200 to 500 mg/kg of methanol in order to
cause toxicity. Kavet (4) estimated that as little as a single dose of 300
mg/kg of methanol can be lethal. Dr. Finer's comments related only to
single, lethal doses of methanol and not to chronic methanol and
formaldehyde toxicity.

2) Various manufacturer-sponsored studies of aspartame ingestion
showed no rise in plasma methanol levels. The methanol technique used in
the studies was a technique developed in 1969 (5) and incapable of
reading rises in plasma methanol less than 350 to 600%. Tephly (6) and
other aspartame manufacturer sponsored researchers involved in plasma
methanol measurements have refused to use sensitive testing methods
despite their availability for many years (7-9).

3) Dr. Briffa cited a study by Trocho et al. (10), that showed an
accumulation of significant levels formaldehyde adducts in various organs
and tissues (brain, liver, etc.) after ingestion of relatively small
amounts of aspartame. However, Dr. Briffa did not cite the letter by,
Tephly (11), a researcher involved in many of the aspartame manufacturer-
funded studies related to methanol and formate. However, the issues raised
by Tephly (such as items #1 and #2 above) have been refuted in numerous
forums and by using the data in the Trocho et al. study itself:

"The 'alternative' point expressed by Tephly, suggesting that
aspartame methanol-label goes all the way into formic acid and the C1
pathway was thoroughly refuted by us, using experimental data. There was
no labelled methionine nor thymine in protein and DNA respectively in the
rat protein we recovered from rats treated with aspartame. This means--
unequivocally-- that the label present in DNA and protein adducts was NOT
incorporated into amino acids or nucleic acid bases. The only explanation
for our data was that the label was in the form of formaldehyde adducts."
(12)

Dr. Finer did not discuss in detail other issues related to
aspartame and formaldehyde typically mentioned by the manufacturer:
methanol in fruits, formaldehyde in foods, long-term studies on
non-human primates and production of formaldehyde and methanol
in the body. The above-mentioned web pages addresses all of these
issues as well as various industry-sponsored double-blind studies
often cited by the manufacturer.

Dr. Finer is correct about me being an "excited" responder to
the editorial. I am excited that busy healthcare professionals are
finding the time to look at the independent research and, based
on case reports received, are beginning to warn their patients
off of aspartame. I am also excited that the World Health
Organization's recent approval of the sweetener stevia (13)
allows diabetics and others in Europe a healthier, time-tested
alternative.

1. Michael Lean, Catherine Hankey. Aspartame and its effects on
health BMJ 2004;329:755-756 (2nd October 2004).

2. Aspartame Information Center. http://www.aspartame.org/
Web site owned by the Calorie Control Council.
"It represents 60 manufacturers and suppliers of low-calorie,
low-fat and light foods and beverages, including the manufacturers
and suppliers of more than a dozen different dietary sweeteners,
fat replacers and other low-calorie ingredients."
http://www.caloriecontrol.org/aboutCCC.html (accessed 19 Oct 2004).

3. Butchko HH, Stargel WW. Aspartame: scientific evaluation
in the postmarketing period. Reg Toxic Pharma 2001;34: 221-233.

4. Kavet R, et al. The Toxicity of Inhaled Methanol Vapors.
Critical Reviews in Toxicology 1990 21;1:21-50.

5. Baker, R.N., A.L. Alenty, J.F. Zack. Simultaneous
determination of lower alcohols, acetone and acetaldehyde in
blood by gas chromatography. Journal of Chromatographic Science,
1969; 7:312-314.

6. Stegink, Lewis D., Tephly, Thomas R., et al. Repeated
ingestion of aspartame-sweetended beverages: further
observations in individuals heterozygous for phenylketonuria.
Metabolism, 1990; 39(10):1076-1081.

7. d'Alessandro, Alessandra, et al. Formate in serum and
urine after controlled methanol exposure at the threshold limit
value. Environmental Health Perspectives, 1994; 102(2): 178-181.

8. Davoli, E., et al. Trace analysis of methanol in rat
serum by headspace high resolution gas chromatography/selected
ion monitoring," Journal of Chromatographic Science, 1986;
24:113-116.

9. Cook, M.R., F.J. Bergman, et al. Effects of methanol
vapor on human neurobehavioral measures. Research Report No. 42
(Peer Reviewed), Health Effects Institute, 141 Portland Street,
Suite 7300, Cambridge, MA 02139, +1-617-621-0266, August 1991.

10. Trocho C, et al. Formaldehyde derived from dietary aspartame
binds to tissue components in vivo. Life Sciences 1998 63;5:337.

11. Tephly TR. Comments on the purported generation of formaldehyde
and adduct formation from the sweetener aspartame. Life Sci., 1999,
65(13), 157-160.

12. Alemany 2002. Letter from Dr. Mari Alemany to Rich Murray,
September 8, 2002. http://groups.yahoo.com/group/aspartameNM/message/864 .

13. Joint FAO/WHO Expert Committee on Food Additives, 63rd Meeting,
Geneva, 8-17 June 2004:
http://www.who.int/ipcs/publications/jecfa/en/Summary63final.pdf

Competing interests:
None declared

It seems to me that there is a wider problem revealed by this debate,
namely the extent to which safety testing relies on population-level
studies which have not, thus far, paid much attention to the distribution
of harmful effects and the possibility that some genotypes are more
sensitive than others. Anecdotally, aspartame seems to be capable of
triggering me into migraine-like reactions, like those that I experience
from exposure to monosodium glutamate, cheap red wine and other known
triggers. People like me seem to be a relatively small proportion of the
population but can certainly experience serious adverse effects from
substances that are considered to be safe in population studies and are
widely employed by the food industry. Our sensitivity almost certainly
has a genetic basis, although I am not aware of any work that identifies
specific alleles or even proposes a plausible mechanism that might
precipitate such reactions. I suspect that a new generation of food safety
studies needs to be considered to take account of genetic variation and
that we should be moving towards a situation where it is easier for those
of us at-risk to identify ourselves and to determine from product and menu
labelling that we should not consumer certain products, both natural and
synthetically enhanced, that contain known triggers of adverse reactions
when encountering our metabolism. This does not necessarily imply that
products like aspartame are not safe for mass consumption - but I would
personally prefer to avoid a couple of hours intense pain and vomiting if
I inadvertently consume more than a fairly small amount.

Competing interests:
None declared

I read with interest Dr Finer’s riposte (1) to the rapid responses
relating to Lean and Hankey’s editorial (2). It is clearly an attempt to
discredit detractors and allay fears about aspartame. In his response, Dr
Finer strives to cast doubt on the validity of the criticisms of
aspartame, and states that "it is worth dissecting some of [sic]
statements to illustrate the often simplistic and selective approach to
evidence that detractors use". It seems only reasonable that Dr Finer’s
response should be subjected to the same scrutiny.

Dr Finer dismisses much of the evidence which shows aspartame has the
potential for harm by saying that the "issue is the quality of that
research of which a good test is whether it has been accepted for
publication in peer reviewed journals". Earlier in his response, however,
he cites a study that is not published in a peer-reviewed journal (3).
Also, I feel compelled to remind Dr Finer that of the 92 independently
funded aspartame safety studies referred to in the on-line review
referred to in my earlier response (4) (92 per cent of which suggested
that aspartame has the potential to cause harm), ALL were published in
peer-reviewed journals (5).

The quality of some of the science that Dr Finer uses to make his
case is also leaves a lot to be desired. For instance, he cites one study
(6) which involved giving aspartame to just 6 (six) healthy young adults
for just 1 (one) day (when it is the chronic, long-term exposure to the
constituents of aspartame and its metabolites that is consistently raised
as the real concern). Another study that Dr Finer cites (7) is also
critically flawed. This study assessed the effects of aspartame on
healthy subjects who may not be representative of individuals sensitive to
aspartame or its metabolites. Although 24 weeks in duration, this study
does not preclude health hazards that may come from consuming aspartame in
the long term. It should be noted that some individuals may be able to
ingest aspartame without clinically-obvious adverse effects for many
months or years (8). Also, in the Leon study (7), aspartame was given in
slow-dissolving capsules i.e. in a way that is not ‘bioequivalent’ to
aspartame ingested via food products, particularly beverages. This study
still actually turned up a greater than 50 per cent increase in adverse
reactions in the aspartame group. However, because the researchers split
the reactions into 14 small sub-categories, the chances of seeing
statistically significant differences in any one sub-category were very
low.

It seems utterly ironic to me that Dr Finer should emphasise the
importance of quality research, only for him to use such poor science in
an attempt to vindicate aspartame. And it appears somewhat hypocritical
that Dr Finer should accuse others of using a "simplistic and selective"
approach to the evidence they use.

Dr Finer seems dismissive of the potential for bias related to
industry funding in the area. Is he really blissfully unaware of the very
real issues that may pervert scientific objectivity, including publication
bias? Maybe he is ignorant of the published research which shows that
pharmaceutical industry funding can have a significant impact on the
apparent outcome of research (9). It may enlighten Dr Finer to know that
the authors of this study concluded that "systematic bias favours products
which are made by the company funding the research". It seems that in the
area of industry-related research, there’s an element of ‘he who pays the
piper, calls the tune’. And let us not imagine for one moment that the
food industry is not capable of underhand and cynical practices. Only
this week, BBC’s Panorama programme did a good job of exposing the food
industry’s attempts to influence the "official" findings of diet-related
reports and food policy, as well as its ability to coerce and corrupt at
the highest level (10).

It is perhaps worthy of note that the lead author of the editorial,
Professor Michael Lean, is not only Professor of human nutrition at the
Unversity of Glasgow, but also the Chairman of the Advisory Committee on
Research (ACR) that advises the Food Standards Agency (FSA) - the
organisation that plays a leading role in dictating food policy in the UK.
Personally, I am concerned that several members of the ACR have personal
interests in food companies or trade organisations that promote specific
foodstuffs (11). I am also perplexed at how Professor Lean (and his co-
author) managed to write an editorial that seemed to take aspartame's
safety so unquestioningly, in the face of considerable scientific evidence
to the contrary.

In his response, Finer cites another study that appears to exonerate
aspartame (12). He seems at great pains to point out that this study was
partly funded by the aspartame industry, and questions whether this study
should be regarded as industry funded or not. Does he really need someone
to answer this question for him? Finer’s own observations here are
utterly consistent with the findings of the on-line review that shows that
industry-funded (either whole or in part) research ALWAYS finds in favour
of aspartame (5).

Still further cause for concern comes from Dr Finer’s comments (or
rather, lack of them) regarding aspartame’s role in weight loss. He
congratulates Lean and Hankey on addressing "the evidence that suggests
aspartame may usefully protect consumers from some of the environmental
pressures that have been firmly implicated in the current epidemic of
obesity and diabetes". Dr Finer fails to acknowledge, however, that Lean
and Hankey’s appraisal in this respect was theoretical. I wonder what Dr
Finer thinks of the glaring lack of evidence that aspartame ingestion is
effective for weight loss. Perhaps he could explain his appetite for
aspartame, bearing in mind the fact that not one single double-blind
placebo-controlled study that attests to aspartame’s efficacy and a weight
loss aid has been published? I note that Professor Lean is quoted on the
FSA website as saying: "Very important policy decisions are being made by
the FSA and it is in the public interest that that these are based on top
quality research." Maybe he too would like to comment on the dearth of
"top quality research" that exists in support of aspartame’s supposed
health benefits?

The bias that pervades this area seems neatly mirrored in the
electronic responses to Lean and Hankey’s editorial. It is perhaps worth
noting that, to date, all but one of the rapid responses that pertain to
aspartame have been critical of the review and/or aspartame. Some may
take a rather cynical view of the fact that the only individual who has
leapt to aspartame’s defence is in the pay of its manufacturer
(Ajinomoto).

Dr Finer claims not to be surprised that there have been responses
from "excited nutritionists, wellness experts and journalists". Dr
Finer’s use of the adjective "excited" seems inappropriate to me. Perhaps
this was an attempt by him to portray genuinely concerned individuals as
somewhat hysterical? Also, perhaps Dr Finer could explain why he chose to
refer to the responses from "nutritionists, wellness experts or
journalists" when, in fact, the majority of responses, to date, have come
from doctors. I wonder whether Dr Finer calculated that this omission
might somehow make it easier for him to dismiss the "detractors".

Dr Finer does make one valid point, though: that some individuals
critical of aspartame have their own agendas. I’ll tell him what mine is:
that people should have access to balanced information about aspartame,
including the knowledge that:

a. aspartame has not been proven to help weight loss.

b. a considerable body of evidence exists which shows that this
synthetic chemical has potential for adverse effects on human health.

c. there is a glaring disparity between the findings of industry-
funded and non-industry funded research.

Dr Finer’s soothing reassurances do not change these basic facts.
While he may believe that there is ‘safety in science’, a closer, more
impartial look at the research into aspartame reveals that, in reality,
there is no place to hide.

References:

1. Finer, N. Aspartame - safety in science. Rapid response published
12th October 2004.

2. Lean MJ, Hankey C. Aspartame and its effects on health. BMJ 2004
328:755-756

3. Stegink LD, Filer LJ. Effects of aspartame ingestion on plasma
aspartate, phenylalanine and
methanol concentrations in potentially sensitive populations. In: The
clinical evaluation of a food additive. Assessment of Aspartame. Tschanz
C, Butchko HH, Stargel WW, Kotsonis FN, Edts, 1996(a), pp 87-113, CRC
Press, Boca Raton, New York, London, Tokyo.

4. Briffa J. It’s not just misleading websites that the public should
be protected from. BMJ Rapid response published 3rd October 2004.

5. http://www.dorway.com/peerrev.html

6. Stegink LD, et al. Effect of repeated ingestion of aspartame-
sweetened beverage on plasma amino acid, blood methanol and blood formate
concentrations in normal adults. Metabolism 1989, 38:357-363.

7. Roberts. Reactions Attributed to Aspartame-Containing Products:
551 Cases Journal of Applied Nutrition 1988 40; 85-94

8. Leon AS, et al. Safety of Long-term Large Doses of Aspartame. Arch
Intern Med. 1989;1 49:2318-2324

9. Lexchin J, et al. Pharmaceutical industry sponsorship and research
outcome and quality: systematic review. BMJ 2003 326(7400):1167-1170.

10. Panorama: The Trouble With Sugar BBC1 aired 10th October 2004

11. http://www.food.gov.uk/multimedia/pdfs/acr051_6.pdf

12. Spiers PA, et al. Aspartame: neuropsychologic and
neurophysiologic evaluation of acute and chronic effects. Am J Clin Nutr.
1998 68(3):531-537

Competing interests:
None declared

Dear Sir,

I agree with Professor Lean and Dr. Hankey that the proliferation of
sensationalist websites attributing any and every symptom a person might
have to the consumption of aspartame is not helpful. Such sites cloud the
issue for people like myself who would like to see a rational approach and
solution to the aspartame problem.

As one of the individuals who has a “frightening personal account” of
“multiple health disasters” which disappeared when I removed aspartame
from my diet (and which reappeared when inadvertently re-challenged), I
can assure all readers that I do not have an “opinion” “fuelled … by
anecdote”, nor by any website, but that I have experienced-based
knowledge. Duty or not, the government bodies are not monitoring health-
effects of aspartame: the necessary system for the reporting of such
problems does not exist; the medical profession has not been alerted to
the side-effects experienced from the many different forms of aspartame
and so cannot contribute useful clinical information.

After my own bad experiences of aspartame, I started to invite people
around me to talk about any awareness they had of ill-effects from the
sweetener. I very easily contacted over thirty individuals (in Scotland)
who told the same story of severe illness, of negligible help from medical
professionals, and of finally discovering for themselves what was the
cause. Consider the implications of this. If a private individual can
trace thirty people just by asking around, the total number of aspartame
‘survivors’ out there must be very large. Since, for every individual who
has managed to work out their aspartame problem for themselves, there must
be many more who have not, and the number of these sufferers must
therefore be staggering.

Professor Lean concludes “the public probably needs protection
against misleading websites”. I wholeheartedly agree, but, appearing
beside the article in the British Medical Journal website is a link to a
site claiming “reliable and official information about aspartame”. This
website belongs to the makers, and global distributors, of aspartame.
Like all commercial enterprises, it uses careful wording to appear to
answer questions on safety and to give reassurances without actually
acknowledging the problems which raised the safety questions in the first
place. The site is clearly neither ‘reliable’ nor ‘official’, it is a
commercial PR exercise, and is using advertisement in a respected medical
journal to camouflage its true nature..

The public definitely needs protection against ALL misleading
websites.

Yours faithfully,

Joanna Clarke
BSc. AIBMS MIBiol

Glasgow

Competing interests:
None declared