Aspartame Information replies to the New York Times (distributed with The Daily Telegraph)
Melanie Warner's article "New Research, New Fears About a Sweetener's Risks?"
which appears in the New York Times supplement circulated with the Daily
Telegraph today, makes many misleading allegations about the safety of
aspartame. This is not the first time that Ms Warner has chosen to attack the
safety of low calorie sweeteners. On 15 May, 2005, the New York Times carried an
article by Ms Warner that made allegations that Splenda was a possible
carcinogen. The Aspartame Information Service has prepared the following
point-by-point response to the allegations about aspartame as a service to
readers of the New York Times. The original text of the article is shown in
italics and the correct information appears below each quote.
When Dr. Morando Soffritti, a cancer researcher in Bologna, Italy, saw the
results of his team's seven-year study on aspartame, he knew he was about to be
injected into a bitter controversy over this sweetener, one of the most
contentiously debated substances ever added to foods and beverages.
There is a high level of scientific consensus about the safety of aspartame.
Aspartame is not only one of the most thoroughly tested ingredients in the food
supply but has been approved for use by the Food and Drug Administration, by
experts of the United Nations Food and Agriculture Organization and the World
Health Organization, by the European Union and by regulatory agencies in more
than one hundred countries. Furthermore, aspartame has been reviewed and found
to be safe for the general population by the Council of Scientific Affairs of
the American Medical Association. The Food and Drug Administration has affirmed
the safety of aspartame no fewer than twenty six times over a period of more
than a quarter of a century.
.Dr. Soffritti's study concluded that aspartame may cause the dreaded "c"
word: cancer. The research found that the sweetener was associated with
unusually high rates of lymphomas, leukemias and other cancers in rats that had
been given doses of it starting at what would be equivalent to four to five
20-ounce bottles of diet soda a day for a 150 pound person.
Dr Soffritti's allegation that aspartame is linked to cancer is not supported
by the data revealed in his paper. The claim that aspartame caused a higher
level of tumors in female rats (but not male rats) is based solely on a
comparison with the control group of female rats which had abnormally low levels
of tumors. Furthermore, the alleged effect only appears in the female rats when
the number of lymphomas and leukemia are combined. It is well known that these
diseases have different causes. Combining these symptoms is like combining
statistics on hay fever and the common cold and then asserting that they have
the same cause.
At the same time, Dr. Soffritti's findings have energized a vociferous
group of researchers, health advocates and others who say they are convinced
that aspartame is a toxin associated with a variety of health troubles,
including headaches, dizziness, blindness and seizures.
It is difficult to imagine how aspartame could be a toxin. Aspartame is a
simple food ingredient which is made from two amino acids, the building blocks
of protein that occur widely in the food we eat every day. They are found in
eggs, meat, cheese, fish, cereals, fruit and mother's milk. When we consume
aspartame, it is broken down in the digestive system to very small quantities of
common dietary components.
Dr Soffritti. says that since last July, he has been contacted by some of
these critics, including a member of Parliament in Britain and a number of
conspiracy theorists, some of whom say they have suffered from "aspartame
poisoning" and filled Web pages with cloak-and-dagger speculation about why the
FDA approved aspartame for sale a quarter-century ago.
The FDA's approval of aspartame for use in dry products in 1981 was followed
by further approvals for various product categories in the 1980s and 1990s. In
1996, the FDA approved the use of aspartame as a general purpose sweetener for
use in all foods and beverages.
No regulatory agency has yet acted on Dr. Soffritti's findings, although
Roger Williams, a member of Parliament, called for a ban on aspartame in Britain
The British parliamentary record shows that Roger Williams simply repeated a
series of extreme and absurd allegations from the conspiracy theorists. Caroline
Flint, the Parliamentary Under-Secretary of State for Health stated in her
response "The current advice from the Food Standards Agency remains in place,
namely that aspartame is safe for use in food."
Putting restrictions on aspartame would come at a significant
This statement is true, but not in the way that Ms Warner intends. There is
now a substantial body of scientific evidence which shows that aspartame helps
people to control their weight. The public health costs of scaring people about
a safe and wholesome food ingredient are indeed significant. Statistics from
Europe show that overweight and obesity are associated with 70,000 new cancer
cases every year.
Dr Soffritti. was concerned about the large numbers of people who use
aspartame, particularly children and pregnant women. "If something is a
carcinogen in animals," he said, "then it should not be added to food,
especially if there are so many people that are going to be consuming
As noted above, Dr Soffritti's data do not support his allegation that
aspartame is a carcinogen. In the United Kingdom, the government's Department of
Health Committee on Carcinogenicity reviewed the Soffritti paper and recorded
the following conclusions in its minutes:
"Members considered that it was implausible that there should be only a small
increase in tumor incidence over such a wide range of doses. They also commented
that there may be a reasonable explanation for the differing historical control
figures but that the low incidence in the female control group compared to all
other groups cast doubt on the study. Members were critical of the study design
in that rats were allowed to live until a natural death. It was noted that the
statistical approach used, although survival-related, did not fully adjust for
The conclusions of the Committee on Carcinogenicity are available publicly
and were supplied to Ms Warner.
Lyn Nabors, executive vice president of the Calorie Control Council, said
Dr. Soffritti's study was not valid because the rats used in it had been allowed
to live longer than the two-year standard established by the United States
government's National Toxicology Program. "It's difficult to determine if the
cancers you find are due to something else," Ms. Nabors said. "Just as in
humans, the rat's body slows down later in life, and the aging process causes
all kinds of things." But John R. Bucher, deputy director of environmental
toxicology at the National Toxicology Program, the government's agency for
research on toxic chemicals, called the design of the Ramazzini study
"impressive" and "thorough," and said that he did not think the fact that rats
were allowed to live until their natural deaths had skewed the results. Dr. Jose
Russo, director of the breast cancer and environmental research center at the
Fox Chase Cancer Center in Philadelphia, says that lifetime studies are "ideal"
but that they are not done often, partly because they are more expensive than
Dr Soffritti did not follow the internationally established protocol for
animal carcinogenicity studies. A scientific consensus was established in the
1970s and was formalized in the publication in 1982 by the Food and Drug
Administration in its "Toxicological Principles for the Safety Assessment of
Direct Food Additives and Color Additives Used in Food." This document includes
"Guidelines for Oral Carcinogenicity Studies in Rodents" and specifically notes
on page 57 that "Animals should be exposed to the test substance 7 days per week
for at least 104 consecutive weeks" and that "Studies of greater than 130 weeks
duration are not recommended." Rats, like people, develop a range of cancers in
old age, and establishing cause and effect of tumors in rats which have died of
old age is not possible. Dr Soffritti's experiment was conducted on rats that
had died and therefore used an unreliable protocol which was abandoned by most
researchers thirty or more years ago.
Dr. Russo, however, criticized the Ramazzini study for not allowing
outside pathologists to analyze all of the tissue samples where cancerous tumors
were found. "People need to see every tumor," he said. Dr. Bucher of the
National Toxicology Program said pathologists at the program, with which
Ramazzini collaborates, looked at 70 tumor slides. But with the study producing
over 9,000 tumor-containing slides, James Swenberg, professor of environmental
science at the University of North Carolina at Chapel Hill, says that this falls
short of standard practice.
Previous findings by the Ramazzini researchers using a similar protocol to
that employed in the aspartame experiment have been reviewed by the FDA's Cancer
Assessment Committee, which noted that those reported data were "unreliable" due
to a "lack of critical details . and . questionable histopathological
While Dr. Soffritti's methods have drawn some criticism, the Ramazzini
cancer lab, which is financed by private bank foundations, governments and
17,000 individual members, has earned considerable credibility since it was
founded in 1971 for its pioneering research on chemicals.
Typically, an Italian not-for-profit organization is registered with an
appropriate regional registrar where it has to deposit its statute and accounts.
The Ramazzini Foundation does not appear to be registered with the relevant
regional registrar. On the contrary, the Ramazzini Foundation is registered with
the Bologna Chamber of Commerce as if it were a company. The Ramazzini group
regularly receives funding from industry.
Dr. Soffritti said he was inspired to look at aspartame because of what he
calls "inadequacies" in the cancer studies done by Searle in the 1970's. He said
that those studies did not involve large-enough numbers of rats and did not
allow them to live long enough to develop cancer. The Ramazzini study was
conducted with 1,900 rats, as opposed to the 280 to 688 rodents used in Searle's
studies, and the rats lived for up to three years instead of being sacrificed
after two, which is the human equivalent of age 53. "Cancer is a disease of the
third part of life," Dr. Soffritti said. "You have 75 percent of cancer
diagnoses for people who are 55 years old or older. So if you truncate the
experiments at 110 weeks and the rats are supposed to survive until 150 to 160
weeks, it means you avoid the development of cancer at the time when cancer
would be starting to arise."
As noted above, rats, like people, develop cancers in old age. It is
precisely because of this fact that it is very difficult to interpret the
findings of life time rat studies. Four long-term carcinogenicity studies on
aspartame conducted in accordance with international standards have found no
relationship between aspartame and any form of cancer. In 2003, the U.S.
National Toxicology Program (NTP) completed three carcinogenicity studies in
which large amounts of aspartame were fed to groups of male and female
transgenic mice (cancer models). These studies, sponsored by the U.S. government
and conducted under accepted laboratory procedures, found no link between
aspartame and cancer. Aspartame has been used by hundreds of millions of
consumers around the world for over 20 years. With billions of man-years of safe
use, there is no indication of an association between aspartame and cancer in
Others have also challenged Searle's studies. Documents from the FDA and
records from the Federal Register indicate that, in the years before the FDA
approved aspartame, the agency had serious concerns about the accuracy and
credibility of Searle's aspartame studies. A 1976 report from an FDA task force,
for example, found that Searle's studies on aspartame and several of the
company's pharmaceutical drugs were "poorly conceived, carelessly executed, or
inaccurately analyzed or reported." It cited what it called a lack of training
by the scientists analyzing tissue samples, a "substantial" loss of information
because of tissue decomposition and inadequate monitoring of feeding
Searle's studies were evaluated independently by the FDA, the Universities
Associated for Research and Education in Pathology (UAREP) and by the Public
Board of Inquiry convened in 1980. All three bodies concluded that aspartame was
safe and not linked to cancer.
In response to the report, the FDA asked the Justice Department to open a
grand jury investigation into whether two of Searle's aspartame studies had been
falsified or were incomplete. In a 33-page letter in 1977, Richard A. Merrill,
the FDA's chief counsel at the time, recommended to Samuel K. Skinner, then the
United States attorney for the Northern District of Illinois, that a grand jury
investigate the company, which was based in the Chicago suburb of Skokie, for
"concealing material facts and making false statements in reports of animal
studies conducted to establish the safety of the drug Aldactone and the food
additive aspartame." A grand jury was never convened, however. Shortly after the
letter was sent, Mr. Skinner left the Justice Department to join Sidley &
Austin, a law firm that represented Searle. After 12 years at that firm, now
Sidley, Austin, Brown & Wood, Mr. Skinner was appointed to be President
George H. W. Bush's transportation secretary; later he became his chief of
staff. In 1978, a year and half after Mr. Skinner left the United States
attorney's office in Chicago, his deputy, William F. Conlon, also left to work
at Sidley & Austin. Mr. Skinner, now a lawyer at Greenberg Traurig LLP, said
that as soon as he began looking for a new job and interviewing with Sidley
& Austin, he recused himself from the Searle investigation. Mr. Conlon, who
is still at Sidley & Austin, did not return phone calls.
It is very difficult to take a political conspiracy theory seriously. The FDA
has affirmed the safety of aspartame twenty six times, culminating in the
agency's approval of aspartame as a general purpose sweetener in 1996.
Over the next few years, Searle's petition for aspartame approval led to
much disagreement within the FDA. The commissioner at the time, Alexander M.
Schmidt, convened a three-member public board of inquiry, which concluded that
one of Searle's studies on rats showed an increase in brain tumors from
aspartame. The board members - all of them scientists at universities - voted to
withhold approval of aspartame until more studies were done.
A further long term study on aspartame was completed in 1980. In a letter to
Commissioner Hayes regarding FDA approval of aspartame dated August 6, 1981, Dr.
Nauta, Chairman of the Public Board of Inquiry stated: "We wish to express our
endorsement of your final decision in this matter"
In any case, critics say that most of these studies were financed either
directly or indirectly by manufacturers of aspartame, and that the results of
aspartame studies tend to depend on who paid for them. In an analysis of 166
articles published in medical journals from 1980 to 1985, Dr. Ralph G. Walton, a
professor of psychiatry at Northeastern Ohio Universities College of Medicine
found that all 74 studies that were financed by the industry attested to
sweetener's safety. Of the 92 independently funded articles, 84 identified
adverse health effects. "Whenever you have studies that were not funded by the
industry, some sort of problem is identified," said Dr. Walton, adding that he
has not looked at studies performed since 1985. "It's far too much for it to be
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
- 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.
Dr. Walton, who, like some other psychiatrists, has studied aspartame from
a neurological perspective, said he had also seen problems from the sweetener
firsthand. At Safe Harbor Behavioral Health, a mental health facility in Erie,
Pa., where he is clinical director, Dr. Walton said he had observed that for
many people with mood disorders, such as depression or bipolar disorder,
aspartame exacerbates the condition. "For people with panic disorders, for
instance, we've seen that when we eliminate aspartame, it's much easier to
control their illness," he said. "The number of panic attacks goes down." Dr.
Walton and others say that this is probably attributable to aspartame's
phenyalanine component. (Aspartame is made up of two amino acids, phenyalanine
and aspartic acid.) He said that an excess of phenyalanine could upset the
body's balance of neurotransmitters, causing a range of neurological symptoms.
Defenders of aspartame often point out that phenyalanine is naturally present in
many protein-intensive foods. But Dr. William M. Pardridge, a professor of
endocrinology at the David Geffen School of Medicine at the University of
California, Los Angeles, says that when it comes from food, phenyalanine is
absorbed into the brain more slowly. "If your blood phenyalanine level was
increased five times, in my view there would be a safety concern," Dr. Pardridge
said. "The question is whether aspartame use could ever increase levels that
much, and the answer is yes. We've known that for 20 years."
The two amino acids in aspartame are in fact aspartic acid and phenylalanine
(not phenyalanine). A serving of milk contains five times as much phenylalanine
and eleven times as much aspartic acid as a soft drink sweetened with aspartame.
People who frequently choose products with aspartame obtain over 98% of their
phenylalanine and aspartic acid from other dietary sources. Aspartame is broken
down by the digestive system to common dietary components and therefore brings
nothing new to our diet. In order to reach a five-fold increase in blood
phenylalanine levels, as suggested by William Pardridge, someone would have to
drink forty cans of diet soft drink with one hour. That is, of course,
Dr. Soffritti said he had not studied the effects of phenyalanine. He
theorized that the tumors in his study were related to the methanol, or wood
alcohol, that is produced as the body metabolizes aspartame. When the body
breaks down methanol, the result is formaldehyde, a known carcinogen. "I know
that when I treat animals with methanol, you end up with lymphomas and
leukemias," he said. But Dr. Kenneth E. McMartin, a methanol expert and
professor of pharmacology, toxicology and neuroscience at the Louisiana State
University Medical Center, said he believed that it was unlikely that someone
could consume enough aspartame to let harmful levels of formaldehyde build up in
The very small amount of methanol which is released when we eat or drink
products with aspartame is not anything to be concerned about. Methanol occurs
in fresh fruits and vegetables. There is as much methanol in a banana and more
than twice as much in a serving of tomato juice as there is in a soft drink
sweetened with aspartame. Traces of methanol also occur naturally in our blood,
in our saliva, and on our breath. The amount of methanol released when we drink
a soda sweetened with aspartame is about one twenty thousandth (1/20,000) of the
volume of the drink. Methanol from aspartame cannot be detected in the blood of
people who have consumed a single dose of aspartame equivalent to that in over
100 cans of soft drink.
Dr. Soffritti said he thought that more research and open debate were
needed on whether aspartame was a carcinogen. "It is very important to have
scientists who are independent and not funded by industry looking at this," he
said. Michael F. Jacobson, executive director of the Center for Science in the
Public Interest, a nutrition advocacy group, said he did not think that Dr.
Soffritti's study could be considered definitive, but that it should prompt an
"urgent re-examination. "For a chemical that is used by hundreds of millions of
people around the world, it should be absolutely safe," Mr. Jacobson said.
"There shouldn't be a cloud of doubt."
It is not surprising the Dr Soffritti or Michael Jacobson should urge a yet
another re-evaluation of aspartame. It is because aspartame is such a popular
ingredient that raising scare stories attracts media coverage, as this story in
the New York Times demonstrates. Aspartame remains one of the most thoroughly
tested and scrutinized ingredients in our food supply. It also has an important
role to play in helping people to avoid overweight and obesity, and their
related diseases, including cancer.
16 February 2006