A review of 500 studies conducted over a quarter century has turned up no credible evidence that the widely used artificial sweetener aspartame is unsafe, industry-funded research released on Tuesday showed.

A panel of American, British and Dutch experts rejected the notion that aspartame causes cancer, seizures, neurological damage or learning problems, or contributes to obesity. The panel did conclude that some people might be prone to headaches after consuming it.

The group did not conduct original research but assessed existing studies on the safety of aspartame, first approved by the U.S. Food and Drug Administration in 1981. It is widely used in diet soft drinks and sold in packets for use in coffee, tea or on food.

The panel found consumption of it increasing, but said it was safe even among the heaviest users, whether adults or children.

"Controlled and thorough scientific studies confirm aspartame's safety and find no credible link between consumption of aspartame at levels found in the human diet and conditions related to the nervous system and behavior, nor any other symptom or illness," the researchers said in a paper published in the journal Critical Reviews in Toxicology.

"There is no credible evidence that aspartame is carcinogenic," they added.

Since its approval, some people have argued that aspartame can cause a variety of illnesses, and various Web sites such as www.sweetpoison.com denounce the sweetener.

Read the entire article here.

Dr. Hull's Comment

I will never accept the news of aspartame safety. I think it is a "business" decision to discredit/discount the research results that aspartame DOES cause cancer, major nerve disorders, birth defects, and brain imbalances. Think about it - can you imagine the chaos that will occur when the truth of aspartame dangers is accredited. The FDA has known about the dangers, the corporations have known about the dangers, and the medical community (if it is really worth anything) has known about the dangers. The legal systems around the world aren't prepared for the number of lawsuits that will FLOOD the court systems if this truth is given life. The news reports have just released that acetaminophen found in Tylenol® has caused more deaths than any other substance in American drug history. But they dare to defend aspartame?? This CYA madness will stop one day and the truth about aspartame will become public knowledge - it has to. Never give up hope that the truth about the dangers of aspartame are real. One day, this will be common knowledge, but the "system" will take a major hit when it does.

Be very leery of the media and research groups, and the various government
agencies that have sold out in the past by telling you aspartame was safe.
The heat must be on them now; now they decide to come clean and deliver the
truth that aspartame has been proven to harm human health. Listen the most
to, and support those who have maintained aspartame dangers from the
beginning; illustrating their true integrity and sincere concern for human
health. These are the groups, organizations, and individuals to pay
attention to and trust. CSPI let us down in the past and publicly put forth
information that was not true. Why are they now deciding to come clean?

Read the entire New Aspartame Safety Review 'Perfectly Predictable' article.

Coca-Cola and food ingredient giant Cargill have teamed up to market a
new calorie-free natural sweetener they hope will shake up the global
market currently dominated by Tate & Lyle's sucralose and Splenda and
US company NutraSweet.

The sweetener, tentatively named rebiana, will be based on the Stevia
plant native to Paraguay but increasingly used as a health food in the
Far East and Hollywood, The Wall Street Journal reports today.

Coca-Cola has filed 24 patents applications in the past week around
extracting the tastiest parts of the Stevia plant and is seeking
exclusive rights to develop and market rebiana for use in drinks,
while Cargill, one of the world's largest agribusiness and trading
companies, owned by the founding Cargill and MacMillan families, will
market it for use in food such as yoghurt, cereals, ice cream and
sweets.

It has spent the past three years developing Stevia plantations in
China, Paraguay and Argentina.

However, the two companies acknowledge that they face regulatory
troubles since Stevia has been banned in the US and EU after a 1985
medical study linked the plant to liver problems.

They aim to market it first in countries where Stevia is not banned,
such as Japan and South America, and Cargill seeks to help regulatory
approval in the US by sponsoring more scientific studies.

Coca-Cola has been attempting to develop its own sweetener from the
Stevia plant for the past 10 years.

The beverages giant has resisted using Tate & Lyle's sucralose
sweetener in its diet fizzy drinks, it is thought because it believes
it leaves an aftertaste.

Instead it mainly used NutraSweet, made by the Chicago company of the
same name.

Tate & Lyle last week blamed a failure to penetrate the vast US
carbonated diet drinks market for disappointing sales of Splenda, its
artificial sweetener, which make up 20 per cent of group profits.

Iain Ferguson, the chief executive, admitted that US sales of Splenda,
had been "less than we had hoped for" during the year to March 30.

"We have not yet cracked any of the major lines there," he said and
warned that profits growth from the product would be only modest in
the current year.

Cargill is the second-largest privately held business in the United
States after Koch Industries.

In 2006, Cargill's sales of $75.2 billion would have ranked it 18th on
the Fortune 500 list.

It handles a quarter of all US grain exports, ships more than 6
million tonnes of sugar a year, and is a world leader in cocoa and
chocolate.

Through Degussa, it also has leading positions in ingredients, such as
salt, flour, malt, sweeteners, starches.

©Copyright 2007 Times Newspapers Ltd
Read the full story here.

COCA-COLA NORTH AMERICA ANNOUNCES
PLANS TO LAUNCH DIET COKE PLUS^™

"Great Taste Has Its Benefits"

ATLANTA, March 22, 2007 - Coca-Cola North America today announced it will launch Diet Coke Plus^™, a sparkling, calorie-free beverage with vitamins and minerals. In addition to providing great, refreshing taste, Diet Coke Plus is a good source of vitamins B3, B6, and B12, and the minerals zinc and magnesium. Diet Coke Plus will be available throughout the U.S. in April in retail stores where other Diet Coke products are sold.

"Consumers, including Diet Coke drinkers, are increasingly looking for more beverage options, and we wanted to offer them the convenience of a calorie-free beverage that is a good source of several essential vitamins and minerals, and one that delivers on the great taste that they have come to expect from us," said Katie Bayne, senior vice president, Coca-Cola Brands, Coca-Cola North America.

Each eight-ounce serving of Diet Coke Plus provides a good source of Niacin (vitamin B3), vitamins B6 and B12, zinc and magnesium (15% Daily Value [DV] for Niacin, B6 and B12, 10% DV for zinc and magnesium). Diet Coke Plus is the newest member of the Diet Coke family, which includes the flagship Diet Coke, Caffeine Free Diet Coke, Diet Coke with Lime, Diet Cherry Coke, and Diet Coke Sweetened with Splenda. Diet Coke lovers need not worry about their favorite sparkling beverage disappearing. "The millions of current Diet Coke devotees across America shouldn't be concerned - America's #1 diet sparkling beverage is staying just as it is," said Bayne.

Dr. Hull's Comments:

Vitamins mixed with chemical toxins...it's hard to make a logical comment on something so ridiculous. To start with, the vitamins added to this chemical drink are not natural, but manufactured replicas of real vitamins from foods. Mixed with the carbonation and the toxic acidic levels in a diet cola, any vitamins and minerals are quickly destroyed in the bottle. Then, the same toxins that make up aspartame, two manufactured amino acids connected by methanol, still make this diet cola just as nasty as it was before. Nothing's changed.

Sorry, folks, this new "vitamin" diet cola is another diet product with misleading marketing.

A second study conducted by the European Ramazzini Foundation (ERF) confirms the carcinogenicity of aspartame. The results of this study will be presented April 23, 2007 at the Mount Sinai Medical School of New York, where ERF Scientific Director Morando Soffritti will receive the third Irving J. Selikoff Award. [vedi testo completo per l'italiano]

Aspartame is an artificial sweetener consumed by hundreds of millions of people worldwide. It is used in over 6,000 diet products including soft drinks, chewing gum, candy, desserts, yogurt as well as in pharmaceuticals, in particular, syrups and antibiotics for children. In 2005, the European Ramazzini Foundation published important experimental data demonstrating the carcinogenicity of aspartame. These data demonstrated for the first time that aspartame is a carcinogenic agent, inducing various types of malignant tumors in rats, even at dose levels currently considered acceptable for humans.

As soon as carcinogenic effects were perceived during this first study, the ERF began a second long term experiment, administering aspartame at low doses in feed to rats beginning during fetal life.

In a world exclusive, Italian news station TG2 announced on April 13th that the European Ramazzini Foundation will present the results of this second study at the Mount Sinai School of Medicine at the end of April when Scientific Director Dr. Morando Soffritti will receive the third Irving J. Selikoff Award.

Ramazzini Foundation Portal on Research

We will publish the new study when it becomes available.

Rebecca Smithers, consumer affairs correspondent
The Guardian, May 8, 2007

Pressure is growing on supermarkets and retailers to ban artificial colours and flavourings from food and drink consumed by children, with most leading retailers reviewing their policies in the face of mounting consumer concern.

Sainsbury's will next month become the first major supermarket chain to ban artificial colours and flavourings from its own-label soft drinks.

The chain says the ban - in force from June 1 - is the result of "overwhelming" demand from parents concerned about E number additives and artificial flavours and their possible links with hyperactivity and behaviour problems among children, as well as allergies and breathing problems.

Other supermarkets and retailers are likely to follow, amid growing public concern about the health risks of artificial ingredients. Britain's biggest supermarket, Tesco, and Marks & Spencer are both moving to phase them out where they are still being used.

In the biggest single move of its kind Sainsbury's ban will apply to its entire range of more than 120 own-brand drinks - soft and fizzy drinks, squash and cordials, as well as mixers for use with alcohol, such as tonic water.

Sainsbury's is replacing aspartame with sucralose, a low-calorie sweetener made from sugar. It is also removing the widely used artificial colouring sulphite ammonia caramel (E150d) from its cola drinks, replacing it with barley malt extract. Sainsbury's said the chemicals will generally be replaced by natural colours and fruit and vegetable extracts, while flavourings will be from named fruits and other natural sources.

Marks & Spencer said none of its soft drinks contain aspartame - it uses sucralose in diet soft drinks - or artificial flavouring, while all its soft drinks except colas contain natural colours. It is working to remove the one remaining artificial colour from its colas. It said it had banned more than half the additives permitted by the EU, particularly those associated with concerns about food intolerance and children's diets including monosodium glutamate (MSG), cyclamates and tartrazine. Its children's range of ready meals do not contain added preservatives, artificial colours, flavourings or sweeteners, and the permitted additives used in the range had been agreed with the Hyperactive Children's Support Group (HCSG).

Tesco said in a statement: "We have a couple of fruit-flavoured fizzy drinks which contain artificial additives that will be removed by the summer. We use natural, fruit-based sweeteners in all of our drinks that are labelled for children or are in our 'kids' range.

"We have had an 'additives hit-list' for more than 20 years and in particular target colours and additives highlighted by the HCSG ... we are conducting a review regarding 'nature identical' additives in our drinks."

The founder of the HCSG, Sally Bunday, said Sainsbury's move was "fantastic news ... This is an important public health issue which manufacturers can no longer brush under the carpet. We hope that this announcement from Sainsbury's will lead other soft drink manufacturers and supermarkets to follow suit."

The HCSG is putting together a research project scrutinising the policies of supermarkets on artificial colours and flavourings, which will be published later this month.

Lizzy Vann, of the Organix range of babyfoods, said: "We would like to see more supermarkets and manufacturers launching an outright ban on additives in children's food ... The fact is that small children are being subjected to all sorts of ingredients that we just don't know enough about - they are being unfairly experimented on and their body mass also means that ... they are absorbing relatively large quantities."

Dr. Janet Starr Hull

___________________________________________________

An Unsweet Deal
Johnny J Burnham
The Bristol Press
Sept. 22, 2006

BRISTOL, Connecticut -- The Board of Education has decided to join the growing list of districts willing to give up some of its autonomy in exchange for financial incentives and participate in the state Department of Education's healthy food and beverage program.

The state will now reimburse the district 10 cents per meal served in its public schools. Bristol stands to gain an estimated $90,000 with nearly 900,000 meals served during the school year.

"We will no longer be able to sell anything to our students that is not approved by the state as being a healthy food or beverage," said Superintendent of Schools Michael J. Wasta.

The district had to move quickly, Wasta said, when it learned that the state needed a response by October or it would not provide reimbursement for the meals served from the start of the school year until the date it received official notification of the district's plan to participate. This would cost Bristol approximately $9,000 a month.

Although the district will gain financially, school fund-raising efforts may take a hit.

Whether it be a bake sale or the middle school cheesecake sale, students, may not participate in the selling or handling of any high-sugared, non-approved food that has any connection with the school or its programs.

Under Public Act No. 06-63, the only beverages permitted are "milk that may be flavored but contain no artificial sweeteners and no more than four grams of sugar per ounce; nondairy milks such as soy or rice milk, which may be flavored but contain no artificial sweeteners, no more than four grams of sugar per ounce, no more than 35 per cent of calories from fat per portion and no more than ten per cent of calories from saturated fat per portion; one hundred per cent fruit juice, vegetable juice or combination of such juices, containing no added sugars, sweeteners or artificial sweeteners; beverages that contain only water and fruit or vegetable juice and have no added sugars, sweeteners or artificial sweeteners; and water, which may be flavored but contain no added sugars, sweeteners, artificial sweeteners or caffeine."

All districts, whether taking advantage of the state's meal reimbursement plan or not, must abide by this new beverage law.

However, schools are still authorized to sell banned items at an event occurring after the end of the regular school day or on the weekend as long as the food or drink is not sold from a vending machine or school store.

According to the superintendent, soda and snack concessions are still permitted at Muzzy Field during sporting events.

Although the board voted in favor of participating, one commissioner, Christopher C. Wilson, said joining was a mistake.

"I certainly support the healthy lifestyle but [the state] is taking all autonomy away from the local school boards," he said. "We would only lose $90,000 if we turned this down but we would have the freedom to serve the students what we deem appropriate."

Wasta added that to his knowledge only three districts have declined to participate.

William Smyth, assistant to the superintendent for business, said that those that have chosen not to participate are small districts that do not serve a lot of meals and therefore reimbursement is minimal.

Johnny Burnham covers Bristol health, education, school and children's issues. Contact him at jburnham@bristolpress.com or 584-0504 ext. 250.

©The Bristol Press 2006

September 6, 2006

Confronting the criticism of health and environmental groups, three major nail polish manufacturers - including one on Long Island - say they've either removed or have begun the process of removing a trio of substances that have been deemed harmful.

The chemicals formaldehyde, toluene and dibutyl phthalate, or DBP, have been linked to cancer and birth defects. All were banned earlier this year in cosmetics by European Union regulators but have not been targeted for removal in this country by the Food and Drug Administration.

Manufacturers, all with markets abroad, said yesterday they have begun removing the compounds voluntarily under pressure from health and environmental advocacy organizations.

Executives at Del Laboratories in Uniondale, manufacturer of Sally Hansen brand nail polish, say their products are being reformulated to eliminate all three substances. The Sally Hansen brand is sold worldwide and is the No. 1 nail polish brand sold in drugstores.

"As a concerned manufacturer of products, we proactively respond to concerns and trends," said Bruce MacKay, Del Laboratories' vice president of scientific affairs, who insisted the products are safe.

Ann Nugent, a Del Laboratories spokeswoman, said the reformulated nail enamels should appear on store shelves early next year. Orly International Inc. and OPI Products, top salon brands with headquarters in Southern California, say they, too, will eliminate the compounds. Orly began the process last year and OPI started this year.

The companies had come under fire for several years from the Breast Cancer Fund, the Campaign for Safe Cosmetics and Women's Voices of the Earth, among a host of other advocacy groups.

"These are products that enter into the body in a way that is not dissimilar to the way that drugs do," said Jeanne Rizzo, a registered nurse and executive director of the San Francisco-based Breast Cancer Fund, a health advocacy organization that supports studies on the causes of breast cancer.

She said that DBP is an endocrine disrupter, associated with underdeveloped genitals in newborn males. Rizzo added that the compound belongs to a broad class of toxins that have been linked to accelerated puberty in girls, a factor that may be associated with an increased risk of breast cancer. Toluene has been linked to nervous system disorders, and formaldehyde is a suspected carcinogen.

The FDA doesn't require the rigorous scrutiny of cosmetics that is reserved for pharmaceuticals.

Rizzo said harmful substances have been allowed in nail polish because the expert panel advising the agency on cosmetics is made up of officials from the cosmetics industry.

FDA spokeswoman Veronica Castro said the agency could not respond to issues involving compounds in nail polish yesterday because the expert in the Cosmetics and Colors division was absent.

Arthur Levin, director of the Center for Medical Consumers, a health advocacy group in Manhattan, said the FDA is "understaffed and overworked," and cannot maintain appropriate vigilance over cosmetics.

Poison in the polish

Though the Food and Drug Administration does not require that cosmetics be rigorously tested for safety, three substances used in nail polish and treatment products have long been linked to cancer and birth defects.

Read more of this article.

Read more about formaldehyde.

Dr. Janet Hull

_____________________________________________________

Excess Soda Could Raise Esophageal Cancer Risk

Dear Mayo Clinic: Is there any connection between esophageal cancer and diet soda?

Answer: The quick answer is no: there's no direct connection between esophageal cancer and diet or regular soda. But the quick answer doesn't tell the whole story.

There are interconnections between soda, obesity, gastroesophagel reflux disease, or GERD, and esophageal cancer that may indicate it's best to go easy on soda.

The incidence of esophageal cancer continues to increase, and so far, researchers can't pinpoint a single reason for the increase.

Here are some of the known risk factors:

GERD: Frequent or constant heartburn is the most common symptom of gastroesophageal reflux disease.

While heartburn seems like just a nuisance, about 5 percent of people with GERD will develop Barrett's esophagus, a condition that occurs when acid reflux stimulates changes in the lining of the lower esophagus. Patients with Barrett's esophagus have a 30- to 125-fold increased risk of developing esophageal cancer.

And GERD is also associated with obesity.

Obesity: While soda alone doesn't cause obesity, it can contribute to weight gain. A 12-ounce regular soda contains about 10 teaspoons of sugar. Diet soda, though calorie free, could contribute to weight gain, too.

A study presented at last year's annual meeting of the American Diabetes Association found that for people who drank two or more cans of diet soda a day, the risk of becoming overweight or obese was 57.1 percent, compared with 47.2 percent for those who drank more than two cans of regular soda a day.

The study, done by researchers at Texas Health Science Center,tracked 622 people for about seven years.

It's not clear why diet soda consumption was associated with a higher risk of weight gain. The researchers speculated that diet soda drinkers fared worse because they opted for diet soda in an effort to lose weight. But drinking diet soda - without other changes - isn't enough to shed pounds. Or, it was theorized that perhaps the artificial sweeteners in diet soda somehow stimulate appetite.

It is clear that maintaining a healthy body weight reduces your risk of many chronic illnesses, including some cancers. Although the interplay between soda, obesity and GERD hasn't been directly linked to esophageal cancer, there are enough connections to raise caution and watch what you drink.

- Claude Deschamps, M.D., Thoracic Surgery; and Jennifer Nelson, R.D., Clinical Dietetics, Mayo Clinic, Rochester, Minn.
Read more of this article.

You can email Oprah your Splenda story by filling out the Oprah.com online form. You can also email Bob Greene at Get With the Program.

Let's get the word out to these two very influential celebrities.

Dr. Janet Starr Hull

_______________________________________________
Artificial Sweeteners: No Calories ... Sweet!

Artificial sweeteners can help consumers cut down on calories and control weight, help to manage chronic conditions such as diabetes, and potentially prevent cavities, according to the American Dietetic Association (ADA).

To date, five artificial sweeteners are approved by the Food and Drug Administration: aspartame, saccharin, acesulfame-K, neotame, and sucralose. The agency regulates artificial sweeteners as food additives, which must be approved as safe before they can be marketed.

"The FDA evaluates a sweetener's composition and properties, how much of the substance is likely to be consumed, and various types of safety studies," says Laura Tarantino, Ph.D., director of the Office of Food Additive Safety in the FDA's Center for Food Safety and Applied Nutrition.

For each of the approved sweeteners, the typical amount used by U.S. consumers is well within designated "acceptable daily intake levels (ADI)," or levels that can be consumed safely every day over a lifetime. Here's a detailed look at each of the sweeteners.

Aspartame

Aspartame is 200 times sweeter than sugar. It has a caloric value similar to sugar (4 kcal/g), but the amounts used are small enough to consider aspartame essentially free of calories. Brand names include NutraSweet and Equal. Aspartame was first approved by the FDA in 1981 as a tabletop sweetener, and for use in gum, breakfast cereal, and other dry products. The use of aspartame was expanded to sodas in 1983, and then to use as a general-purpose sweetener in all foods and drinks in 1996.

Before approval, the FDA reviewed numerous studies showing that aspartame did not cause cancer or other adverse effects in laboratory animals. "This included three studies in which rats were fed aspartame in proportions more than 100 times higher than humans would likely consume," Tarantino says.

In the mid-1990s, a researcher raised concerns that a rise in brain cancer incidence in the United States was linked to aspartame use. According to FDA experts, there is no scientific evidence supporting a link between aspartame and any type of cancer. The National Toxicology Program, part of the U.S. Department of Health and Human Services, also conducted aspartame studies in mice and found no cancer link.

In 2005, the European Ramazzini Foundation (ERF) published new findings of a long-term feeding study on aspartame in rats. ERF scientists concluded that aspartame causes leukemia and lymphoma and that current uses of aspartame should be reevaluated. After reviewing the study data, however, the European Food Safety Authority (EFSA) released a statement in May 2006 that said the ERF's conclusion was not supported by the data. After learning of the ERF study results, the FDA requested the study data and received a portion of the data in February 2006. The FDA will announce its conclusions after completing its review.

"At this time, our position that aspartame is safe is based on the large body of information previously reviewed," Tarantino says. "Our conclusions are based on a detailed review of more than 100 toxicological and clinical studies on safety."

When ingested, aspartame is converted in the body to methanol and two amino acids--aspartic acid and phenylalanine. Tarantino says, "These substances are produced in much greater amounts in other common foods."

Because of the phenylalanine component, aspartame does carry a risk for people with the rare genetic disorder phenylketonuria. People who have this disorder should avoid or restrict aspartame use because of their body's difficulty in metabolizing phenylalanine. Its use can cause phenylalanine to build up in the blood at higher levels than normal. The aspartame regulation requires that a statement be placed on the label of all products containing aspartame specifically to alert phenylketonurics of the presence of phenylalanine.

Continue reading

The conclusions and summaries of this report begin on page 41. The FDA Review Board denied approval of aspartame September 30, 1980 based on a 50% rate of brain tumors from aspartame fed to the laboratory animals- rats, guinea pigs, monkeys and dogs. Large tumors appeared in the brains and in the nervous systems of the lab animals, and numerous deaths were recorded among mice under two years of age. According to the FDA Board of Inquiry, the number of recorded tumors from aspartame was in the hundreds. Aspartame surprisingly was "approved", nonetheless in 1981, despite the Board's recommendation to withdraw approval for aspartame.

After reading the FDA Petition, we ask you to revisit the April, 1995 list of 92 symptoms associated with aspartame use based on complaints submitted to the FDA.

The FDA puts a different spin on the topic these days. Please visit the FDA Web site FAQ section for their current position on aspartame. In order to find the FDA comments on aspartame safety, click on "Food Additives/Color Additives" on the menu at the left side of the page. After doing so, scroll down the list of Frequently Asked Questions and click on "Is aspartame safe?" The answer will appear in the right hand side of the FDA Web page.

The FDA Web site includes contact information for non-emergency food-related complaints, non-emergency reactions to medical products, and vaccinations. Click on the link provided on the FDA Web site to find the office with which to file your complaint.

For more information, please visit www.FDA.org for further information.

Dr. Janet Starr Hull

___________________________________________

Aspartame safe for consumption, food regulator concludes
By Ahmed ElAmin

05/05/2006 - The EU's food safety regulator today said aspartame is safe for consumption, contradicting a scientific study by the Ramazzini Foundation that claimed the artificial sweetener caused cancer.

The regulatory rejection of the study means food and beverage makers will not have to reformulate their products and find a substitute.

The European Food Safety Authority (EFSA) said it has evaluated the Ramazzini long-term study on the carcinogenicity of aspartame and concluded that "there is no need to further review the safety of aspartame nor to revise the previously established Acceptable Daily Intake (ADI)".

The current ADI for aspartame is 40 mg/kg body weight. Current average intakes of aspartame in Europe, including levels up to 10 mg/kg body weight per day, are well below the ADI, EFSA noted.

Read more of this article.

Dr. Janet Starr Hull

_______________________________

EUROPEAN RAMAZZINI FOUNDATION STANDS BEHIND ASPARTAME STUDY RESULTS, ANNOUNCES ONGOING RESEARCH ON ARTIFICIAL SWEETENERS
05 May 2006
Response to EFSA's AFC panel decision

The European Foundation of Oncology and Environmental Sciences "B. Ramazzini", the sole sponsor of a long-term carcinogenesis study demonstrating that aspartame is a multipotential carcinogenic agent in rodents, responded today to the opinion announced by the European Food Safety Authority's Panel on Food Additives, Flavorings, Processing Aids and Materials (AFC).

Scientific Director of the European Ramazzini Foundation and primary author of the aspartame study, Dr. Morando Soffritti, M.D., underlined the importance of EFSA's interest in the European Ramazzini Foundation's aspartame study saying, "as the Director of an independent, non-profit institution, I consider it an important recognition to have our data carefully considered by EFSA." Prior long-term carcinogenesis studies on aspartame (4 total) were conducted over 20 years ago by the producers of the artificial sweetener using a small number of animals per sex per group. The results of these studies provided the basis for the current opinion regarding the non-carcinogenicity of aspartame.

In responding to the AFC panel comments, Soffritti noted that "what the panel considers shortcomings of the study are instead distinctive and positive characteristics of our research protocol, research which has provided the scientific basis for changes in international regulations numerous times over the last 30 years." For instance, the European Ramazzini Foundation conducts what are known as lifespan mega-experiments, meaning that large groups of rodents are allowed to live out their natural lifespan and are examined for histopathological changes upon spontaneous death. This model is in contrast with most laboratories where rodents are sacrificed at 110 weeks of age (representing about 2/3 of the lifespan). The Ramazzini study design closely mirrors the human condition in which persons may be exposed to agents in the industrial and general environments from embryonic life until natural death. "Since 80% of cancer is diagnosed in humans over the age of 55, it is of paramount importance to observe how an agent affects laboratory animals in the last third of their lives", notes Soffritti. He added that "occurrence of chronic pulmonary inflammation is common in the natural dying process. Moreover, inflammation was observed in both animals who were treated with aspartame as well as in the control group."

With regard to a pathology review, it was not deemed appropriate or necessary to subject a small subset of the 34,000 slides to external review, especially given the statistical power of an experiment of this size. Slides of previous carcinogenesis studies on aspartame were not reviewed by the AFC panel, an action that Dr. Soffritti believes should have been obligatory in light of the European Ramazzini Foundation's results, at the very least those involving haemopoietic and lymphoid organs and tissues. At the highest dose level tested in the Ramazzini study, 25% of female rats bore lymphomas-leukemias compared with 8.7% in the controls.

Read more of this article.

Dr. Janet Starr Hull
_______________________________

PoughkeepsieJournal.com

Think twice before sipping that soft drink
By Evelyn Gezo

Soft drink companies recently announced they are voluntarily going to begin removing sweetened drinks from schools before the start of the 2008-2009 school year. Although a small step in the right direction, school food service directors, parents and school administrators will need to make smart decisions about the beverages that will be made available to students in the future.

There are so many beverages out on the market that may sound healthful but because of added nutrients or a clever name, they're anything but healthy.

The present guidelines established will allow elementary and middle schools to sell water, certain juices, low-fat and fat-free regular and flavored milks. The only difference between the two school levels will be portion sizes. Elementary schools will provide 8-ounce portions and the middle schools will have 10-ounce portions. The high schools will still be allowed to sell diet sodas, sport drinks, different types of waters and diet tea drinks.

But like any health intervention plan - and this one is no exception - choices begin with the individual, and in the case of young children and adolescents, with parental guidance. Here is an example.

Be careful what you buy

Coca-Cola just recently launched a new cola drink called Coca-Cola Blak, which is a combination of cola and coffee. Although Coca-Cola states it is for the adult market, the sleek packaging in itself is enticing to all age groups.

"The product is clearly not for young children, and adult consumers may be surprised if they look at the list of ingredients below the nutrition facts panel. An 8-ounce portion contains caffeine and high-fructose syrup like regular cola, but it also contains aspartame and acesulfame potassium, which are two non-nutritive sweeteners. The use of these two artificial sweeteners keeps the calories low, but there is no indication on the front label that these non-nutritive sweeteners are in the product. "

Read more of this article

Dr. Janet Starr Hull

__________________

Pharmaceutical Biology
(Formerly International Journal of Pharmacognosy)
Publisher: Taylor & Francis
Issue: Volume 42, Number 1 / February 2004 Pages: 1 - 7
URL: Linking Options DOI: 10.1080/13880200390500885

Circadian variations of biochemical variables in aspartame treated rats.
P. Rajasekar, P. Subramanian, T. Manivasagam
Department of Biochemistry, Faculty of Science Annamalai University
Annamalainagar Tamil Nadu, India

[ Perumal Subramanian, Thamilarasan Manivasagam ]

Accepted: May 4, 2004
Address correspondence to: P. Subramanian,
Department of Biochemistry,
Annamalai University, Annamalai Nagar - 608 002, Tamil Nadu,
India. E-mail: psub@rediffmail.com
DOI: 10.1080/13880200390500885 © 2004 Taylor & Francis Ltd.

Abstract
In a study of the impact of aspartame on biochemical oscillations, we examined the rhythms of blood glucose, plasma cholesterol, and protein and serum aspartate transaminase (AST) in experimental rats. Our results showed acrophase delays in glucose, total protein and advances in AST rhythms and increased mesor (in AST), amplitude (in cholesterol) and decreased amplitude values (in glucose, AST) in aspartame treated animals. Oral administration of aspartame might lead to increased levels of aspartate in brain which could alter the characteristics of biochemical variables possibly by modulating the transmission in several areas/nuclei in brain including retinohypothalamic tract (RHT) and suprachiasmatic nuclei (SCN).

Introduction

The biological clock in mammals is located in the suprachiasmatic nuclei (SCN). (Hannibal, 2002). Circadian clocks govern the timing of development, behaviour, physiology, endocrinology and biochemistry, as well as photoperiodic events (Forster et al., 2001). These biological rhythms are adjusted daily (entrained) to the environmental light/dark cycles via retinohypothalamic tract (RHT) (Hannibal, 2002). Many putative neurotransmitters have been identified in the SCN (Vandenpol, 1980).

Aspartate has been reported to be a putative excitatory neurotransmitter in retina (Yagub & Eldred, 1991) in the RHT (Honma et al., 1996) and SCN (Liou et al., 1986; Csaki et al., 2000). This excitatory amino acid is involved in the transmission of light information from retina to SCN via RHT (Takeuchi & Takahashi, 1994). Further, derivatives of aspartate (like N-acetyl aspartyl glutamate) also act as a neurotransmitter in RHT (Hannibal, 2002). Ingestion of L-aspartate into the SCN results in minor phase advances during a subjective day (Devries & Meijer, 1991).

Aspartame (ASP) is a dipeptide artificial sweetener; on oral administration, it is hydrolysed in the gastrointestinal tract to its constituent amino acids, L-phenylalanine and L-asartic acid (Ranney & Oppermann, 1979). Previous studies showed that dietary aspartame could alter the diurnal feeding patterns, meal size, distribution of diurnal pattern of spontaneous motor activity (Torie et al., 1985).

ASP reduced aggressive attack via a serotonergic meachanism (Goerss et al., 2000). The influences of chronic ASP ingestion on brain neuropeptide Y (NPY) concentration, plasma hormone, food intake and body fat in rats have been reported (Beck et al., 2002). The circadian nature of cholesterol synthesis (Jones & Schoeller, 1990) and total protein rhythms in humans and mice (Berezkin et al., 1992) and circadian variation of AST (Coll et al., 1993) were documented.

However, the influences of ASP on biochemical circadian rhythms has not been investigated intensively. In the present study, ASP administration to Wistar rats and its influence on circadian rhythms of blood variables glucose, cholesterol, total protein and AST) were monitored.

Materials and methods

Animals

Male Wistar rats (180-190 g) were obtained from the Central Animal House, Annamalai University. They were housed in polypropylene cages and provided food pellets (Agrocorporation Private Limited, Bangalore, India)
as a basal diet during the experiment. Animals were maintained at room tempertature (25 ± 2 °C) and under LD (12 : 12) conditions (Rajakrishnan et al., 1999; Subramanian & Balamurugan, 1999; Subramanian et al., 1998, 2000, 2001). Food and water were available ad libitum throughout the experimental period. Aspartame was obtained from SRL and all other biochemicals used in the study were of analytical grade.

Treatment schedule

The animals were randomized and grouped into experimental and control rats (n = 6 in each group). Group I rats act as control, which received standard food pellets. Group 2 animals were treated orally with aspartame (500 mg/kg body weight) every day (Sharma & Coulombe, 1987; Goerss et al., 2000) throughout the experimental period (11 weeks).

Biochemical oscillations

At the end of the experimental period, a minimal amount of blood (0.75ml) was collected from the orbital sinus using heparinized tubes from normal and aspartame treated groups every 4 hour (00:00, 04:00, 08:00, 12:00, 16:00, 20:00 and 24:00 hour) throughout the 24 hour period (Subrmanian & Balamurugan, 1998; Subramanian et al., 2000). Blood glucose (Fings et al., 1970), plasma cholesterol (Zlatkis et al., 1953), protein (Lowry et al., 1951) and serum AST (Reitman & Frankel, 1957) were estimated after blood collection. At the end of the study both control and ASP treated rats were killed by decapitation and aspartate levels in brain tissues (Pfleiderer, 1969) were measured.

Figure 1. Temporal oscillations of glucose at 4 hour intervals for a period of one day in Wistar rats [control (1A) and aspartame treated (1B)]. Dotted lines represent the raw data and solid lines represent the best fitting cosinor curves (obtained using "cosinorwin" computer software program). Note 6 hour delay of the acrophase in aspartame treated animals (Figure 1B).

Time series analysis

Time series analysis of the oscillation (measurements of acrophase, amplitude and mesor) were done by using "cosinorwin" computer software program. Acrophase is the measure of peak time of the total rhythmic variability in a 24 hour period. mplitude corresponds to half of the total rhythmic variability in a cycle. Mesor (M) is the rhythm adjusted mean. It is equal to the arithmetic mean for equidistant data covering the 24 hour period. The acrophase is expressed in h; mesor and amplitude values are expressed with the same units as the documented variables.

Table 1. Changes in the rhythm characteristics of glucose and cholesterol in control and aspartame treated rats.

Acrophase Amplitude Mesor Biochemical variable Groups (h) (mg/dl) (mg/dl) r-value p-value

Glucose I 00:35 7.3 109.1 0.71dr (p < 0.05)
---------II 7.32 5.3 106.2 -0.34ns (p < 0.50)

Cholesterol I 18:41 8.2 51.9 -0.67dr (p < 0.05)
-----------II 18:49 8.7 51.3 -0.67dr (p < 0.05)

dr -- detectable rhythmicity.
ns -- no significant rhythmicity.

Figure 2. Diurnal rhythms of cholesterol at 4 hour intervals for a period of one day in Wistar rats [control (2A)
and aspartame treated (2B)]. Note modulatory increase in amplitude of the rhythm. No significant changes in acrophase was observed in aspartame treated animals (Figure 2B). Other details as in Figures 1A and 1B.

Results

Aspartate levels in brain tissues (mean ± SD) were increased (4.212 ± 0.41) significantly (p < 0.001) in aspartame treated animals when compared to controls (1.40 ± 0.15).

The endogenous circadian rhythms of glucose showed acrophase at 00:35 hour in normal rats; in the case of aspartame treated animals (group II), maximum levels were found at 7:32 hour (Figure 1A, B). The amplitude, mesor and r-values were decreased significantly in group II when compared with controls (group I). Consinor analysis revealed detectable rhythmicity in normal group and this rhythmicity is affected in aspartame treated group (Table 1).

Cholesterol levels were maximum at 18:41 hour in normal and at 18:49 hour in aspartame treated animals (Figure 2A, 2B). Increased amplitude and decreased mesor values were found in aspartame treated rats than that of normal ones. Detectable cholesterol rhythms were observed in two groups (Table 1).

Table 2. Changes in the rhythm characteristics of total protein and AST in control and aspartame treated rats.

Acrophase Amplitude Mesor Biochemical variable Groups (h) (mg/dl) (mg/dl) r-value p-value

Total protein I 08:48 1.0 5.0 0.02ns (p < 0.5)
-------------II 12:00 0.9 5.2 0.97dr (p < 0.001)

AST I 23:49 10.1 50.9 0.88dr (p < 0.002)
------------II 12:33 4.0 61.9 0.91dr (p < 0.001)

dr -- detectable rhythmicity.
ns -- no significant rhythmicity.

Figure 3. Temporal oscillations of total protein at 4 hour intervals for a period of one day in Wistar rats [control (3A) and aspartame treated (3B)]. Note 4 hour delay of the acrophase in aspartame treated animals (Figure 3B). Other details as in Figures 1A and 1B.

Total protein levels showed the peak value at 8:48 hour and maximum value of aspartame treated animals was observed at 12:00 hour (Figure 3A, 3B). The amplitude and mesor values did not alter significantly in both cases. The rvalue is increased in treated animals than that of normal (Table 2). Analysis of serum AST activity over the 24 hour period revealed that the maximum activity at 23:49 hour in normal and at 12:33 hour in aspartame treated animals (Figure 4A, B). Low amplitude values and increased mesor and r-values were observed in aspartame treated animals, when compared with normal animals (Table 2).

Discussion

Neurotransmitters involving in regulation of circadian rhythms were normally used to probe the nature of circadian rhythms. Presence of aspartate in RHT (Liou et al., 1986), horizontal, amacrine and ganglion cells, in some photoreceptors and in some unidentified cells in the peripheral retina (Yagub & Eldred, 1991) was reported. The biochemical parameters chosen for this study showed marked fluctuations over a 24 hour period. From this study it can be concluded that light dark cycles are the most effective synchronizers for biochemical circadian rhythms studied in Wistar rats.

In the present study, peak time of glucose was at 3:00 hour in normal and at 7:32 hour in treated animals; this could be attributed to the food intake, digestion, and accumulation of glucose in blood. Rats administered aspartame with showed about 3 hour delays in glucose rhythms. However, no mesor value change was observed in group II when compared with normal rats. Aspartame could not alter glycemia (Ngugen et al., 1998).

Cholesterol levels in rats in the present study were increased at night as reported previously (Ueberberg et al., 1984). The whole body, free and total cholesterol syntheses oscillate periodically and predictably (Jones & Scholler, 1990).

In rats, the rate limiting enzyme (HMG CoA reductase) in the cholesterol synthesis pathway peak its activity at midnight (Mietenen, 1982; Pappu & Illingworth, 1994).

The peak level of transcription of cholesterol-7a-hydroxylse (7aH) gene was reported to occur in the evening. All these factors may contribute to the nocturnal increase of cholesterol.

Figure 4. Temporal variation of AST activity at 4 hour intervals for a period of one day in Wistar rats [control (4A) and aspartame treated (4B)].

Note 11 hour advance of the acrophase in aspartame treated animals (Figure 4B). Other details as in Figures 1A and 1B.

Circadian rhythms in total protein were reported in humans and mice (Touitou et al., 1986; Berezkin et al., 1992). The positive and negative balance between synthesis and degradation of protein might be responsible for the rhythmic phenomenon. In our experiment, AST levels are maximum at 23 hour in control and 11 hour advance in aspartame treated animals. The significant increase in mesor and amplitude of AST rhythm indicated that this may be due to the aspartame metabolites; aspartate might enter the TCA cycle via transamination of aspartate to oxaloacetate (Ranney & Oppermann, 1979).

In the present study, administration of aspsartame increased the brain aspartate levels corroborating the previous results (Moller, 1991; Burns et al., 1991). This increased brain aspartate might favour the transmission of light information to the SCN (Takeuchi & Takahashi, 1994)

Further, aspartame is known to act on NMDA receptors and has some neurological effects seen with glutamate (Disk, 2000; Abdollahi et al., 2001).

Activation of NMDA receptors tends to transmit photic information to the SCN (Mintz et al., 1999). This activation leads to increased production of nitric oxide (NO) (Meller & Gebhart, 1993). Involvement of NO in the transmission of light information to SCN is also suggested (Caillol et al., 2000).

Previous results showed that administration of aspartate into the SCN induced phase shifts in the free running rhythms of hamsters (Smith, 2000).

Hence, we speculate that increased aspartate levels in brain could alter the characteristics of biochemical rhythms studied, possibly by modulating the transmission in several areas/nuclei in brain including RHT and SCN.

References

Abdollahi M, Nikfar S, Abdoli N (2001): Potentiation by nitric oxide synthase inhibitor and calcium channel blocker of aspartame induced antinociception in the neouse formalin test. Funda Clin Pharmacol 15: 117-123. mabdol@yahoo.com

Beck B, Burlet A, Max JP, Stricker-Krongrad A. (2002): Effects of long-term ingestion of aspartame on hypothalamic neuropeptide Y, pasma leptin and body weight gain and composition. J Physiol Behav 75: 41-47. bernard.beck@nancy.inserm.fr; krongrad@mpi.com;

Berezkin MV, Grastisinskii EN, Kudinova VF, Batygov AN, Ponomareve LE, Prikazchikova O, Zhunkova GN (1992): Seasonal and circadian fluctuactions in blood biochemical indicators in mice in natural conditions and exposed to constant light. Bull EKSP Biol Med 114: 75-78.

Burns TS, Stargel WW, Tsehanz C, Kotdonis FN, Hurwitz A (1991): Aspartame and sucrose produce a similar increase in the plasma phenylalanine to large neutal amino acid ratio in healthy subjects. Pharmacology 43: 210-219.

Caillol M, Devinoy E, Lacroise MC, Schirar A (2000): Endothelial and neuronal nitric oxide synthases are present in the suprachiasmatic nuclei of syrian hamsters and rats. Eur J Neurosci 12: 649-61.

Coll AR, Arderiux F, Noguera AD (1993): Circadian rhythms of serum concentrations of 12 enzymes of clinical interest. Chronobiol Int 10: 190-202.

Csaki A, Kocsis K, Halasz B, Kiss J (2000): Localization of glutamatergic/aspartatergic neurons projecting to the hypothalamic paraventricular nucleus studied by retero grade transport. J Neurosci 101: 637-655.

Devries MJ, Meijer JH (1991): Aspartate injections into the suprachaismatic region of Syrian hamsters do not mimic the effects of light on the circadian activity rhythys. Neurosci Lett 127: 215-218.

Disk (2000): Micromedex international health series. Aspartame neurologic clinical effects. Toxicol Inf Poison: 105.

Fings CS, Toltiff CR, Duonin RT (1970): Glucose determination by o-toluidine method using glacial acetic acid. In: G Toro PG Ackermann eds., Practical Clinical Chemistry. Boston. Little Brown and Bronon CO 115-118.

Forster CH, Winter C, Hofbauer A, Hall JC, Stanewsky R (2001): The circadian clock of fruit flies is blind after
elimination of all known photoreceptor. J Neuron 30: 249-261.

Goerss AL, Wagner GC, Wendy L (2000): Acute effects of aspartame on aggression and neurochemistry of rats. Life Sci 67: 1325-1329.

Hannibal J (2002): Neurtransmitters of the retinohypothalamic tract. J Cell Tissue Res 309: 73-88.

Honma S, Katsuno Y, hinohara K, Abe H, Honma K [1996]: Circadian rhythm and response to light of extracellular glutamate and aspartate in rat suprachiasmatic nucleus. Am J Physiol 271: [Regulatory Integrative Comp Physiol 40]
R579-R585.

Jones PJH, Schoeller DA (1990): Evidence of diurnal periodicity in human cholesterol synthesis. J Lipid Res 37: 667-693.

Liou SY, Shibata S, Iwasaki K, Ueki (1986): Optic nerve stimulation-induced increase of release of 3H-glutamate and 3Haspartate but not 3H-GABA from the suprachiasmatic nucleus in slices of rat hypothalamus. Brain Res Bull 16: 527-531.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951): Protein measurement with the Folin-phenol reagent. J Biol Chem 193: 265-275.

Meller ST, Gebhart GF (1993): Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 2: 127- 136.

Mietencen TA (1982): Diurnal variation of cholesterol precursors squalene and methyl sterols in human plasma lipoproteins. J Lipid Res 23: 466-473.

Mintz EM, Marvel CL, Gillespie CF, Price KM, Albers HE (1999): Activation of NMDA receptors in the suprachiasmatic nucleus produces light-like phase shifts of the circadian clock in vivo. J Neurosci 19: 5124-5130.

Moller SE (1991): Effect of aspartame and protein administered in phenylalanine equivalence doses, on plasma netural amino acids, aspartate, insulin, and glucose in man. Pharmacol Toxicol 68: 408-412. sem@lundbeck.com

Nguyen UN, Dumoulin G, Henriet MT, Regnard J (1998): Aspartame ingestion increases urinary calcium, but not oxalate excretion, in healthy subjects. Clin Endocrinol Metabol 83: 165-168.

Pappu AS, Illingworth DR (1994): Diurnal variations in the plasma concentrations of mevalonicacid in patients with abeta lipoproteinaemia. Eur J Clin Invest 24: 698-702.

Pfleiderer G (1969): In: Methods of Enzymatic Analysis. Bergmeyer HU Ed, New York and London, Academic Press, pp. 381-383.

Rajakrishnan V, Subramanian P, Viswanathan P, Menon VP (1999): Effect of chronic ethanol ingestion on biochemical circadian rhythms in Wistar rats. Alcohol 18: 147-152. [ Chronic ingestion of ethanol for 60 days was known to alter the characteristics of biochemical circadian rhythms in Wistar rats. Peak times of glucose, potassium and lactic acid rhythms were delayed by 18 h, 3 h, and 3 h respectively, whereas peak times of cholesterol and malondialdehyde rhythms were advanced by 3 h and 9 h respectively during ethanol treatment. Significant changes in range (p < 0.001 expect in calcium) and 24 h mean (p < 0.001) of all the biochemical circadian rhythms studied were observed during ethanol treatment. The alterations in the characteristics of these biochemical circadian rhythms could be principally due to the alterations on the hepatic cellular architecture; other plausible underlying reasons are also discussed. PMID: 10456565 ]

Ranney RE, Oppermann JA (1979): A review of the metabolism of the aspartyl moiety of aspartame in experimental animals and man. J Environ Pathol Toxicol 2: 979-985.

Reitman S, Frankel AS (1957): A colorimetric method for the determination of serum glutamic, oxaloacetic and glutamic pyruvic transaminases. Am J Clin Path 28: 53-56.

Sharma KP, Coulombe RA (1987): Effects of intense sweeteners on hunger, food intake and body weight. Food Chem Toxicol 25: 565-568.

Smith RQ (2000): Transport of glutamate and other aminoacids at the blood brain barrier. J Nutr 30: 1016S-1022S.

Takeuchi Y, Takahashi K (1994): Circadian variations of amino acid content of suprachiasmatic nucleus in rats. Neuroscience Lett 178: 275-278.

Torie K, Mimura T, Takasaki Y, Ichimura M (1985): Dietary aspartame with protein on plasma and brain amino acids, brain monoamines and behaviour in rats. J Physiol Behav 36: 765-771.

Vandenpol AN (1980): The hypothalamic suprachiasmatic nucleus of the rat intrinsic anatomy. J Comp Neurol 191: 661-702.

Yagub A, Eldred WD (1991): Localization of aspartate like immuno reactivity in the retina of the turtle (Pseudemys scripta). J Comp Neurol 312: 584-598.

Yokogoshi H, Roberts CH, Caballero B, Wurtman RJ (1984): Effects of aspartame and glucose administration on brain and plasma levels of large neutral amino acids and brain 5-hydroxy indoles. Am J Clin Nutr 40: 1-7.

[ Indian J Exp Biol. 2003 Aug; 41(8): 797-804. Circadian clock genes in Drosophila: recent developments. Subramanian P, Balamurugan E, Suthakar G. psub@rediffmail.com Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar 608 002, India.

Circadian rhythms provide a temporal framework to living organisms and are established in a majority of eukaryotes and in a few prokaryotes. The molecular mechanisms of circadian clock is constantly being investigated in Drosophila melanogaster. The core of the clock mechanism was described by a transcription-translation feedback loop model involving period (per), timeless (tim), dclock and cycle genes. However, recent research has identified multiple feedback loops controlling rhythm generation and expression. Novel mutations of timeless throw more light on the functions of per and tim products. Analysis of pdf neuropeptide gene (expressed in circadian pacemaker cells in Drosophila), indicate that PDF acts as the principal circadian transmitter and is involved in output pathways. The product of cryptochrome is known to function as a circadian photoreceptor as well as component of the circadian clock. This review focuses on the recent progress in the field of molecular rhythm research in the fruit fly. The gene(s) and the gene product(s) that are involved in the transmission of environmental information to the clock, as well as the timing signals from the clock outward to cellular functions are remain to be determined. Publication Types: Review PMID: 15248475 ]

Dr. Janet Starr Hull

_____________________________________

FDA Statement

FOR IMMEDIATE RELEASE
Statement
May 8, 2006 Media Inquiries:
Michael Herndon, 301-827-6242
Consumer Inquiries:
888-INFO-FDA

FDA Statement on European Aspartame Study

FDA is issuing this statement today in response to the European Food Safety Authority (EFSA) press release on its review of the long-term carcinogenicity study of aspartame conducted by the European Ramazzini Foundation (ERF).

Aspartame, a low-calorie sweetener, is composed primarily of two common amino acids, aspartic acid and phenylalanine. Each of these is also a building block for conventional foods such as protein and natural flavor molecules.

In 2005, ERF published new findings of a long-term feeding study on aspartame conducted in rats. Scientists from ERF concluded from their study that aspartame causes cancer and that current uses and consumption of the sweetener should be re-evaluated.

EFSA's review of ERF's study concluded, among other things, that on the basis of all evidence currently available to EFSA: ERF's conclusion that aspartame is a carcinogen is not supported by the data; and EFSA sees no need to further review its earlier scientific opinion on the safety of aspartame or to revise the Acceptable Daily Intake.

Upon learning of the ERF study results, FDA requested the study data from ERF to evaluate the findings. On February 28, 2006, the agency received a portion of the data requested. We are actively reviewing the data provided by ERF and will complete our review of those data as soon as possible. When FDA completes its review of the ERF study data, it will announce its conclusion.

Since it was first approved for use in the United States, the safety of aspartame has been questioned by some. To date, however, the agency has not been presented with scientific information that would support a change in our conclusions about the safety of aspartame. Those conclusions are based on a detailed review of a large body of information, including more than 100 toxicological and clinical studies regarding the sweetener's safety.

Critics Of Aspartame Warn Of Dangers
11:36 PM CDT on Monday, May 8, 2006
By JANET ST. JAMES / WFAA-TV

The Food and Drug Administration said it will do a review of a study that claims aspartame causes cancer.

Millions of people drink the popular artificial sweetener every day in their favorite diet soda and last year, an Italian study linked aspartame to higher rates of lymphoma and leukemia in rats.

An European union the equivalent to the FDA declined to support the conclusion, but many people claim aspartame has made them sick.

In fact, a number of medical professionals have urged people to stay away from it.

Painting is Gwenn Walden's joy, but she said a few years back the bright colors began to vanish before her eyes.

"I started having blind spots," she said. "Even if I waved the paint brush around, I could only see probably the top part. Anything below...would be out of sight, my hand, anything."

With fears of glaucoma or impending blindness, Walden went to the eye doctor.

"He's the one who said it was the brain spasm," she said.

Walden said she discovered the brain spasms occurred every time she drank a diet cola that contained aspartame.

Aspartame, known more commonly as NutraSweet or Equal, is the world's most popular artificial sweetener and found in more than 6,000 products from juice to Jell-O to jelly.

FDA approved it in the early 80's and it has been the source of growing controversy ever since. Early studies and thousands of consumer complaints to the government linked the

http://www.wfaa.com/

Consider saccharin. Research history proves that saccharin is safe for human use, and always has been. The pink stuff never caused cancer in humans after over one hundred years of use, nor was the 1960s laboratory study submitted for its public banishment ever proven to be legitimate.¹ Saccharin has merely received a total of six FDA complaints in its 100+ year history of use, whereas aspartame, found in the blue packet known as NutraSweet's Equal^®, had already received over 10,000 FDA complaints after ten years of use.  

Aspartame is proven in laboratory studies to eat holes in the brains of lab animals, cause mammary gland and testes tumors, lower fetal IQs and adversely affect fetal formation, yet it has no danger warning other than for Phenylketonuria (PKU), the inherited inability to process the amino acid phenylalanine.² Now we question the safety and approval process of Splenda's sucralose, which has been found in laboratory studies to shrink the thymus gland while enlarging the liver and kidneys, generate infertility in male rats, and create negative maternal gastrointestinal effects.³

So why, then, was the pink packet labeled a carcinogen and the blue and yellow packets deemed as safe when it actually appears the other way around?   And now the sweetener industry has gone a step further in their quest to capture your sweet addiction, by mixing together Splenda and NutraSweet and other artificial sweeteners, called "sweetener blends. One thing we know for sure, the race is on to win favor in the sweetener market, and the competition is extreme.

But, there's a catch to all the marketing hype touting sweetener safety - these sweeteners have not been proven safe for long-term use, nor safe for use during pregnancy, for fetuses, or for children. It's a "he said - she said" situation, and the one with the most money seems to win.

Equal^® began its first big advertising campaign using high profile celebrities like Cher, Lauren Hutton, and Raquel Welch who promoted the Blue-sweetener in the 1990s. Ads also featured B. Smith, the popular restaurant owner and celebrity chef, who touted Equal and his famous cheesecake recipe that now included the "newest sweetener product." Advertising spots took constant digs at saccharin's Sweet' N Low^® saying: "No aftertaste, like with some sweeteners."

One of the original television advertisements for NutraSweet /Equal was taken off the air shortly after its debut in the early 1980s due to its misleading implications that NutraSweet was all natural and produced from cow's milk.   Jersey cows were pictured grazing in a meadow. As one cow looked up at the camera, the announcer voiced-over: "NutraSweet.   It's made from pure ingredients."  

Aspartame has been the low-calorie sweetener of choice for soft drink makers since 1981 when saccharin was falsely labeled a carcinogen. Here's a bit of news I discovered through my research that I bet you didn't know: the saccharin toxicity study was actually done using a blend of cyclamate and saccharin, and the results were "interpreted" as linking cyclamate - not saccharin - to the bladder cancer in rats.⁴

Researchers fed the laboratory mice sweetened water equivalent to 800 cans of saccharin/cyclamate every day from birth until death. In this one test, one mouse developed bladder cancer, and the results were submitted to the FDA requesting a cancer warning be placed on all saccharin products. Cyclamate was banned in 1970. No further testing was performed. So, it appears saccharin was sacrificed to make room in the market for a new more profitable sweetener, NutraSweet/Equal^®. Aspartame managed to hold the market until Splenda broke their monopoly in 2002.

And why don't we hear much about natural sweeteners such as stevia - are they safe? Preliminary scientific evidence (performed by independent researchers) shows stevia may improve the function of cells required for insulin production in the pancreas, and may also improve glucose tolerance in people with diabetes. But stevia isn't FDA approved as a "sweetener" in the USA. Actually, no one is allowed to label stevia a "sweetener" - you have to state that stevia is a dietary supplement that merely "tastes sweet."

Prior to the onslaught of chemical sugar substitutes, the need to "test" stevia for negative health effects had never been necessary after 1,500 years of its use. People have used stevia for generations in South America, Japan, China and Indonesian countries. Further research will be required for stevia safety, though, because as stevia becomes more competitive on the modern sweetener market, it will become more of a threat to the chemical sweetener companies. After years of political scrutiny and stonewalling in Europe, nonetheless in October 2004, stevia was finally approved by the European Commission for use as a "sweetener."⁵

So who and what do you believe concerning the safety of sweeteners?   Well, me, of course!

¹ Saccharin Final Rule Report On Safety. Rules and Regulations. 3357 Federal Register. Vol. 69, No. 115. Wednesday, June 16, 2004.

² Hull JS. Sweet Poison: How The World's Most Popular Artificial Sweetener Is Killing Us-My Story. New Horizon Press, 1997.

³ Bellin J. New Scientist. Pg 13. Nov 23, 1991.

⁴ Saccharin Final Rule Report On Safety. Rules and Regulations. 3357 Federal Register. Vol. 69, No. 115. Wednesday, June 16, 2004.

⁵ Stevia and Stevioside. Foods Stands Agency. March 27, 2002. http://www.food.gov.uk/multimedia/webpage/stevia

Big business - modern humans can't live without them, or can they? Don't forget that most big business has your money in mind.   Unfortunately, your health and wellness isn't always their primary goal, but it is important to learn about the companies that play such influential roles in your lives and the lives of your children.   After all, many of these corporations have reputable backgrounds, and it's everyone's hope that when they realize they may have jeopardized the health of their customers, they will repair any damage done.

So, who and what is Monsanto Chemical Company - the company that first brought us saccharin and then aspartame in the form of NutraSweet/Equal^®? Monsanto Chemical Company has recently applied to the FDA for commercial approval of genetically engineered wheat. This will have far-reaching effects on farmers, consumers, and the environment, but whether that's really safe or not is the topic of another article.   For now, let's just say there are great concerns with genetically engineered (GMO) grains products, such as:

• Organic farmers may face genetic cross-contamination
• Conventional farmers may lose the freedom to save their seed, as Monsanto will have the right to enforce its patents
• Farmers may also loose overseas markets because genetically engineered grains aren't accepted in most foreign countries
• Prices will probably fall, as have already occurred with corn

Monsanto's background is most attention grabbing and diverse. Monsanto Chemical Company is a leading provider of agricultural products and incorporated "solutions" for farmers. They make Roundup^®, the world's best-selling herbicide, as well as other herbicides. Monsanto produces leading seed brands, including DEKALB^® and Asgrow^®, and they provide farmers and other seed companies with biotechnology traits for insect protection and herbicide tolerance. They also are responsible for the creation and distribution of the Bovine Growth Hormone (BST), and have deep-rooted connections to the soft drink industry through the manufacturing of both saccharin and NutraSweet.

Monsanto Chemical Works opened its doors in St. Louis in 1901. In 2001, Monsanto celebrated its 100th anniversary as a business enterprise. So, what are the fine points behind this powerful company and how did it acquire such dominant world influence and diversity?

After thirty years in the pharmaceutical industry, John Francis Queeny, still an employee of Meyer Brothers Drug Company, sank his savings and monies borrowed from a Chicago soft drink supplier, into a new company to produce products for the food and pharmaceutical industries. He named the company after his wife, whose maiden name was Olga Monsanto. The corporate papers were filed on Nov. 29, 1901. ²

In 1902, Monsanto gained its reputation manufacturing saccharin, the company's first product. In 1903 to 1905, their entire saccharin output was shipped to the growing soft drink company in Georgia called Coca-Cola. In 1904, Monsanto introduced caffeine and vanillin as products for the escalating soft drink industry. Initially, vanillin was produced by extracting a chemical from cloves that were purchased from the Sultan of Zanzibar who insisted that the leftover spices be returned to him. Cloves had an important religious significance in the cremation of bodies, so there was importance in shipping them back to Zanzibar instead of disposing of them as waste in the United States.

By 1915, Monsanto's sales surpassed the one million dollar mark. Two years later, the company began the production of aspirin. Monsanto remained the largest U.S. producer of aspirin until the 1980s.

In 1917, the U.S. government filed suit over the safety of saccharin. Filed at Monsanto's request as a test case, the suit was dismissed in 1925, ending the government's unsuccessful attempts then to prove saccharin harmful. In 1981, saccharin was again questioned as a carcinogen, but no conclusive scientific proof was ever presented. In 2001, the cancer warning was removed from saccharin products as saccharin was shown, once again, to be safe for human consumption.

Despite saccharin's cancer "propaganda" in 1981, in 1985 G.D. Searle & Co. purchased Monsanto, taking the company deeper into pharmaceuticals and the sweetener industry. NutraSweet, saccharin's competitor, was now owned and marketed by the same company - Monsanto.

World War II brought Monsanto and the American government closer together as Monsanto became involved in research on uranium for the Manhattan Project, which led to the first nuclear bombs. Later, Monsanto operated the Mound (Ohio) Laboratory as a nuclear facility for the Federal government until the late 1980s, and their Dayton Laboratory was used as a research facility for nuclear-based and other government-funded projects.

Monsanto was in the petroleum business by 1955, having acquired Lion Oil primarily to provide themselves petrochemical raw materials. Lion Oil also put the company into the fertilizer business, and brought to Monsanto hydrocarbon technology, oil and gas reserves, and a retail gasoline business. The refinery and service stations were sold in 1972.

In 1977, Monsanto established a joint petrochemical venture with Conoco Oil Company at the Chocolate Bayou plant. They were eventually bought out and the money from the acquisition fueled their drive to acquire a pharmaceutical company.

At this time, G.D. Searle & Co. had succeeded in getting the U.S. Food and Drug Administration to finally approve NutraSweet (aspartame) for the second time, and prepared to purchase Monsanto in 1985. When Monsanto sold its sweetener business in 2000, including the NutraSweet brand sweetener, it brought Monsanto $440 million. ²

By 1998, Monsanto started buying seed companies and genetic laboratories. In December 1999, Monsanto and Pharmacia & Upjohn announced plans to merge the two companies. Monsanto and Pharmacia & Upjohn completed their merger on March 31 naming the new company the Pharmacia Corporation. The agricultural operations within Pharmacia retain the Monsanto name - the company renown for Roundup, the Bovine Growth Hormone, multifarious seed companies, saccharin and NutraSweet.

What's in Monsanto's future? The company has formed a wheat industry advisory committee to provide advice and counsel on how best to bring forward biotechnology products in wheat. They have begun posting product safety information for their current agricultural biotechnology products. Along with Round Up, they are marketing with widespread availability the drug, L-DOPA, used today for the treatment of Parkinson's disease. And they have placed the first U.S. corporate order to General Motors for pick-up trucks that use ethanol-based E85 fuel, part of a larger initiative to focus new research to enhance the use of bioenergy.

After numerous corporate exchanges and company buy-outs, Chicago-based Merisant Corporation is the latest "named" manufacturer of NutraSweet/ Equal. But who knows what tomorrow will bring ...

¹ http://www.monsanto.com/monsanto/layout/our_pledge/default.asp

² http://www.monsanto.com/monsanto/layout/about_us/ataglance.asp

All too often I hear people excuse the negative health effects of diet sweeteners because the products are "FDA approved."   Well, FDA approval may not be something the American consumer can actually depend upon anymore, like in days past. The FDA rules and regulations for the approval of food additives is a standard procedure for every applicant, but it has some serious flaws that need to be addressed. ¹

Basically, all the FDA is responsible for is reviewing the summaries of research conducted by the company applying for approval, typically from scientific studies the applicant has pay-rolled and performed in-house.   Then, the same company presents their explanation why their product should be allowed in the public food supply based on their research. At the very least, these research reports are debatable, yet rarely reviewed by independent researchers independent of the industry. ²

Interestingly, as with the case of aspartame approval, the FDA Bureau of Foods does not perform its own clinical testing, but the Bureau of Drugs does. The Bureau of Drugs reviewed the clinical tests for aspartame and found them to be unacceptable.   They then returned the test results to The Bureau of Foods with recommendations on how to conduct acceptable clinical tests.

Aspartame's FDA Approval Process Shows Significant Flaws: Aspartame's approval is a perfect example of what can be skewed and go wrong in the FDA approval process.

Let me rewind the history tapes for a moment.   In 1965, Jim Schlatter, a chemist at G.D. Searle & Company was working on a project to discover new treatments for gastric ulcers . He accidentally spilled some of the heated chemical on his hand. Later he licked his finger as he reached for a piece of paper, and noticed the sweet taste. He and a friend decided to test some in coffee and both agreed the chemical had a sweet taste. The result: aspartame - two amino acids bonded by free methanol. The manufacturer (G.D. Searle) merely changed the paperwork submitted to the FDA from drug to food additive, but did not change the substance itself. But, the FDA did not go for it.

By March 1973, G.D. Searle submitted their final research on aspartame, along with the first petition to the FDA for aspartame approval in foods.   In 1974, the FDA approved aspartame for use in carbonated beverages and in dry products.   But in December 1975, the FDA task force concluded that some of Searle's studies were questionable and the FDA withdrew the 1973 aspartame approval. But G.D. Searle continued to push for re-approval of aspartame as a sweetener, not a drug.

In October 1980 after great controversy and corporate pressure to re-approve aspartame, a Public Board of Inquiry (PBOI) was impaneled by the FDA to evaluate aspartame safety. The Board found that aspartame caused an unacceptable level of brain tumors in animals tested.   Based on this fact, the PBOI ruled that aspartame should not be added to the food supply. One year later, aspartame was shockingly granted approval.

This debatable re-approval kicked-off over two decades of maneuvering, manipulating and dissembling of the truth behind aspartame's dangers and G.D. Searle 's (NutraSweet's) monopoly of the American sweetener market. Selling this "ulcer medication" as a food additive to hundreds of millions of healthy people every day meant many more dollars than limited sales to the much smaller group of ulcer sufferers. And, new medications were created to combat the side effects caused from aspartame use - side-effects such as migraine headaches, PMS, sexual dysfunction, sleep apnea, hair loss, and hyperactivity.

How could all this really happen? Well, there were apparently some questionable decisions behind the FDA approval of aspartame, no doubt, and it appears aspartame approval was not for the benefit of the consumer. Here's why, according to Jim Turner, Washington consumer attorney and author of The Chemical Feast: The Nadar Report on the Food and Drug Administration. Turner has actively opposed aspartame's approval since the 1970s.

"Searle, a drug company with little experience in food regulations, began studies on aspartame to comply with the FDA approval process -- but they failed to do so," states Turner. The early tests of the chemical additive showed it produced microscopic holes and tumors in the brains of experimental mice, epileptic seizures in monkeys, and was converted by animals into dangerous substances, including formaldehyde.

In 1974, however, in spite of the information in its files, the FDA approved aspartame as a dry-foods additive. But the agency also made public, for the first time, the data supporting the food-additive decision. This data was then reviewed by renowned brain researcher Dr. John Olney from Washington University in St. Louis, as well as other research scientists.

Dr. Olney discovered two studies showing brain tumors in rats and petitioned the FDA for a public hearing. Consumer Action for Improved Foods and Drugs, represented by Mr. Turner, also petitioned for a public hearing based on "the approval process having been founded on 'sloppy' science", and on the reports showing aspartame caused epileptic seizures in monkeys and damage to the human eye.

Dr. Olney had already demonstrated in laboratory studies that aspartic acid (forty percent aspartame) caused microscopic holes to form in the brains of rats after each feeding. Aspartame also includes fifty percent phenylalanine, which is proven to harm children with PKU, and methyl (wood) alcohol, which is a carcinogen and extremely neurotoxic in large amounts.

Faced with this array of possible health dangers, the FDA granted the hearing requests. In lieu of withdrawing its aspartame approval, the agency requested that Searle refrain from marketing the sweetener until after completion of the hearing. It then proposed that a Public Board of Inquiry (PBOI) review the matter.

In July of 1975, as the FDA prepared for the PBOI review - an FDA inspector conducted a routine inspection of Searle's Skokie, Ill. testing facilities, and found many "deviations" from proper procedure protocols.   This report led the FDA commissioner, at the time, to empanel a Special Commissioner's Task Force to review Searle's laboratories.

In December of 1975, the Task force reported serious problems with Searle's research on a wide range of products, including aspartame.   It found eleven other pivotal studies conducted in a manner so flawed that it raised more doubts concerning aspartame's safety, and created the possibility of serious criminal liability for G.D. Searle.

The FDA then delayed aspartame's approval.   It also contracted, over serious internal objection from several FDA representatives, a group of university pathologists (curiously at Searle's expense) to review most of the studies, and a task force was eventually set up to review three selected studies. The U.S. Attorney for Chicago requested a grand jury review of a 1960s monkey seizure study.

The pathologists paid by Searle only reviewed one part of Searle's laboratory protocols:

1. Searle's failure to properly report data

They did not re-open the study's design or conduct protocols.

The Searle-funded pathologists found no serious problems.   The FDA task force, on the other hand, found Searle's key tumor safety study unreliable, but their recommendations were ignored. FDA Chief Counsel Richard Merrill submitted a thirty-three-page letter to U.S. attorney Samuel Skinner recommending a grand jury investigation into G.D. Searle "for concealing material facts and making false statements in reports of animal studies to establish the safety of aspartame." Two specific studies of concern were cited. No action was taken, and Skinner allowed the statue of limitations to run out. Along with two of his aides, Skinner joined Searle's law firm shortly after that.

During the time period these committees met, the FDA organized the PBOI.   G.D. Searle and the FDA Bureau of Foods each nominated three members for the board, and the FDA commissioner selected one member from each list they submitted.   In October 1980, based on its limited review, the board blocked aspartame marketing until the tumor studies could be explained. Unless the FDA commissioner overruled the board, the matter was closed.

The next month in November 1980, Ronald Reagan was elected U.S. President. Donald Rumsfeld (former congressman from Skokie, Illinois, former White House Chief of Staff, and twice former Secretary of Defense) had been President of G.D. Searle since January 1977. He left Searle and joined the Reagan transition team.   A full court press began against the FDA's board decision to suspend aspartame approval.

In meetings a few months later in January 1981, Rumsfeld told a corporate sales meeting attendee that he would call in his chips and get aspartame approved by the end of the year. On January 25th, the day President Reagan took office, the previous FDA commissioner's authority was suspended, and the next month, the appointed commissioner's job went to Dr. Arthur Hull Hayes.

According to Turner, transition records do not show why the administration chose Dr. Hayes, a professor and Defense Department contract researcher.   In July of that year, Dr. Hayes, defying the FDA aspartame, approved aspartame for dry foods - his first major decision in office. In November 1983, the FDA approved aspartame for soft drinks - Hayes' last decision.

By November 1983, Hayes was under fire for accepting corporate gifts, and left the agency to work at Searle's public-relations firm as senior medical advisor. Shortly after the FDA soft-drink approval, Searle began test marketing, and complaints began to arrive at the FDA's doorstep, such as:

• Dizziness
• Blurred vision
• Headaches
• Seizures

The complaints were more serious than the agency had ever received on any food additive. At the same time, independent research scientists began looking more closely at the dangers of this manufactured chemical sweetener.

In 1985, the FDA asked the Centers for Disease Control (CDC) to review the first 650 complaints on aspartame (there were over 10,000 registered complaints as early as 1991).   The CDC realized that the symptoms in approximately twenty-five percent of the complainants stopped and then restarted, either purposely or by accident, when aspartame use was stopped and then restarted. The FDA discounted their report.

Time progressed and aspartame use increased, and according to data released by 1995, human brain tumors, like those in the animal studies, had risen ten percent, and previously benign tumors grew forcefully.   Searle and the FDA deputy commissioner defended that the data posed no problem. Two years later, this FDA deputy commissioner became vice president of clinical research for Searle. ³

From 1985 to 1995, approximately 400 aspartame research studies were performed both by Searle researchers and independent scientists. Most interestingly, those studies finding no problems with aspartame were one hundred percent funded by G.D. Searle. All studies funded by non-industry sources raised very serious questions and doubts concerning aspartame's safety in the public food supply.

"Given this record, it is little wonder that many health-conscious people believe avoiding NutraSweet improves their quality of life," states Turner, "If and when a scientific consensus concludes that aspartame puts some, if not all , of its consumers at risk, it will be much too late. The point is to eat safely now. Remember: the brain you save may be your own."

¹ Hull, JS. Sweet Poison: How The World's Most Popular Artificial Sweetener Is Killing Us-My Story. New Horizon Press, 1997.

² http://www.cfsan.fda.gov/~lrd/foodaddi.html

³ Hull, JS. Sweet Poison: How The World's Most Popular Artificial Sweetener Is Killing Us-My Story. New Horizon Press, 1997.

WASHINGTON - The news on aspartame was a little sweeter earlier this month, with one of the largest human studies so far finding no association with cancer.

Known by brand names such as NutraSweet and Equal, aspartame has been in and out of headlines since its approval in 1981, largely because of data raising the possibility of a link to brain cancer.

After years of relative quiet, the controversy revived in February, when a team of Italian researchers published disturbing data from an extensive animal study. The scientists, writing in the journal Environmental Health Perspectives, reported that rodents fed aspartame at levels under the daily acceptable limit appeared to have an increased risk of lymphoma, leukemia and brain cancers.

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