X-Message-Number: 27628
Date: Fri, 17 Feb 2006 08:55:55 -0800 (PST)
From: Doug Skrecky <>
Subject: low cost of rodent longevity studies

[The most interesting item mentioned below was the lower than expected
cost of doing a lifelong study on rodents. At just one million dollars for
a test using 1900 rats, the economic benefits of mass production (26,937
animals used in all studies) is quite evident. Assuming just 19 rats were
to be used to screen a given intervention, then 100 longevity tests could
be completed for one million dollars, or just $10,000 each. Any
billionaires out there willing to invest? I do have some ideas to test!]

[BTW: In the controversial study discussed below, low dose aspartame
actually reduced the number of malignant tumors in male rats, and lifespan
was slightly increased by high dose aspartame in females. It is
interesting that neither of these facts was mentioned, and it all goes to
show that you can not always believe what you read, particularly when
people have axes to grind.]

February 12, 2006

The Lowdown on Sweet?

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

Aspartame is sold under the brand names Nutra-Sweet and Equal and is
found in such popular products as Diet Coke, Diet Pepsi, Diet Snapple
and Sugar Free Kool-Aid. Hundreds of millions of people consume it
worldwide. And 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. The study,
which involved 1,900 laboratory rats and cost $1 million, was conducted
at the European Ramazzini Foundation of Oncology and Environmental
Sciences, a nonprofit organization that studies cancer-causing
substances; Dr. Soffritti is its scientific director.

The findings, first released last July, prompted a flurry of criticism
from the Calorie Control Council, a trade group for makers of artificial
sweeteners that has spent the last 25 years trying to quell fears about
aspartame. It said Dr. Soffritti's study flew in the face of four
earlier cancer studies that aspartame's creator, G. D. Searle & Company,
had underwritten and used to persuade the Food and Drug Administration
to approve it for human consumption. "Aspartame has been safely consumed
for more than a quarter of a century and is one of the most thoroughly
studied food additives," read one news release from the council.

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.

DR. SOFFRITTI, who oversees 180 scientists and researchers in 30
countries who collaborate on toxin research, 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 F.D.A. approved
aspartame for sale a quarter-century ago.

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 last December. Last month, the European Food Safety Authority,
an advisory body for the European Commission, began to review 900 pages
of data from Dr. Soffritti; the goal is to finish by May. A commission
spokesman, Philip Tod, said it was too early to know what the next steps
would be if the scientists reviewing the data concurred with Dr.
Soffritti's findings.

In the United States, the Food and Drug Administration says it has also
taken note of the study, which is available online
(http://ehp.niehs.nih.gov/docs/2005/8711/abstract.html) and is scheduled
to be published next month in a medical journal financed by the National
Institutes of Health. F.D.A. officials say that they, too, intend to
conduct a thorough review.

But both the F.D.A. and the European Commission have cautioned that
there is no need for people to avoid aspartame. "We don't see any
concerns at this stage," said George H. Pauli, associate director for
science policy in the F.D.A.'s Office of Food Additive Safety. "We've
gone through a humongous amount of data on aspartame over the years."

Putting restrictions on aspartame would come at a significant cost. Food
companies and consumers around the world bought about $570 million worth
of it last year. New regulatory action on aspartame would also
jeopardize the billions of dollars worth of products sold with it.
Already, in the United States, many companies are opting to use
sucralose, or Splenda, in their new low-calorie products, in part
because it is less controversial.

Lance Collins, chief executive of Fuze Beverage in Englewood Cliffs,
N.J., said that safety concerns about aspartame were a "major
contributing factor" in his decision to use sucralose in his tea and
juice drinks. Sucralose, however, is made by under a patent by just one
company, Tate & Lyle of London, and is in desperately short supply.

Dr. Soffritti, who has spent 28 years doing research on potential
carcinogens, said he was trying to steer clear of the growing political
maelstrom. But he added that he 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 it."

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 limited-time tests. 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

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. It was
the first research body to do studies showing that vinyl chloride and
the gasoline additive methyl tertiary-butyl ether, or M.T.B.E., are
carcinogenic, research that eventually encouraged the United States to
strictly regulate vinyl chloride and that led 21 states to ban M.T.B.E.

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."

Others have also challenged Searle's studies. Documents from the F.D.A.
and records from the Federal Register indicate that, in the years before
the F.D.A. approved aspartame, the agency had serious concerns about the
accuracy and credibility of Searle's aspartame studies. From 1977 to
1985  during much of the approval process  Searle was headed by Donald
H. Rumsfeld, who is now the secretary of defense; Searle was acquired by
Monsanto in 1985. Monsanto later spun Searle's assets out into two
companies: Merisant, which owns the brands Equal and Canderel, and
NutraSweet, which is owned by J. W. Childs Equity Partners, an
investment firm in Boston.

A 1976 report from an F.D.A. 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 doses.

In response to the report, the F.D.A. 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 F.D.A.'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.

Over the next few years, Searle's petition for aspartame approval led to
much disagreement within the F.D.A. 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.

But yet another F.D.A. review, this one of Searle's tumor tissue slides
paid for by Searle and conducted by an academic group that is now
defunct  concluded that Searle's studies had demonstrated that aspartame
was safe. In 1981, a new F.D.A. commissioner, Arthur Hull Hayes,
concurred with this assessment and granted approval to aspartame shortly
after President Ronald Reagan appointed him to run the agency.

And in a move that fueled the conspiracy theories, Mr. Hayes left the
F.D.A. a little more than a year after approving aspartame and took a
job as a consultant to Burson-Marsteller, which at the time was Searle's
public relations agency. Mr. Hayes did not return calls seeking comment.

Ms. Nabors of the Calorie Control Council said that suggestions or
innuendoes that Searle was trying to influence government officials with
lucrative job offers were baseless. Artificial sweeteners are unfairly
targeted for suspicion, she said, citing the government's decision to
ban the sweetener cyclamate in 1969 after studies showed that it caused
cancer in animals. "Cyclamate was banned, saccharin was required to have
a warning label for a while, and there's all these conspiracy theories
on aspartame," she said.

She added that there were more than 100 published scientific studies
showing no adverse effects from aspartame, and said that in 2002, the
European Commission reviewed many of these studies and reaffirmed the
sweetener's safety. The bulk of the studies investigated neurological
effects; none were animal cancer studies, which are lengthy and

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 a coincidence."

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."

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 body.

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."

Dr. Soffritti's journal article on his findings is at

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=27628