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The sweetest scandal

MagazineApril 2009 (Vol. 20 Issue 1)The sweetest scandal

It's one of the greatest lifestyle mysteries of modern times: Americans have the highest intake of low-fat and sugar-free foods in the world and, yet, they are among the most obese people on the planet

It's one of the greatest lifestyle mysteries of modern times: Americans have the highest intake of low-fat and sugar-free foods in the world and, yet, they are among the most obese people on the planet. Why? For years, doctors have puzzled over what they have come to call the 'American Paradox'.

In previous issues, WDDTY has offered one explanation: there is growing medical evidence that fat doesn't make you fat-and low-fat diets don't make you slim, either.

And now, there's new data that unravels the paradox even further and stands conventional thinking more than ever on its head. This latest bombshell finding is that sugar substitutes can make you fat. Indeed, the very reason for which people use low-calorie sweeteners may result in the opposite effect.

In addition to this bad news, there is also accumulating evidence that these ubiquitous food additives are not as innocuous as their manu-facturers-and the authorities-like to claim. For example, there's con-tinuing evidence that aspartame can cause cancer, a charge levelled at the substance as early as 30 years ago and only now finally vindicated.

So, is this the final nail in the coffin for aspartame and other artificial sweeteners?

Weighty issues

Professors Terry Davidson and Susan Swithers are psychobiologists working at Purdue University, Indiana, in the Ingestive Behavior Research Center (IBRC) within the Department of Psychological Sciences. As its name implies, the Center studies the food choices that individuals make. Five years ago, the two scientists, puzzled by the so-called American Paradox, came up with a theory. In a paper called 'A Pavlovian Approach to the Problem of Obesity', they speculated that the body may be using taste to control its food intake.

"Much as Pavlov's dogs learned that the sound of a bell signalled food, people may learn that both sweet-tasting and dense, viscous foods signal high calories," they suggested. "The body may use this information to determine how much food is required to meet its caloric needs." The crucial point, they theorized, was that this delicate act of self-regulation might be upset by artificial sweeteners (Int J Obes Relat Metab Disord, 2004; 28: 933-5).

To test their theory, the team used young laboratory rats, subjecting them to nothing more harmful than having to eat sweetened yoghurt mixed in with their normal feed. One batch of rats was given yoghurt sweetened with an artificial sweetener (saccharin), while the yoghurt given to another batch was sweetened with ordinary sugar.

The results were extraordinary. The researchers found that the saccharin-fed rats consumed more calories in total than the rats that had the normal sugar-so, of course, ended up gaining more weight. In fact, on average, they were a staggering 25-per-cent heavier after just five weeks.

In another, related study, the researchers again saw the same phenomenon. Two groups of rats were given two different, sweetened liquids-one using artificial sweet-eners, the other containing natural sugars-for 10 days. After that, the animals were allowed to eat as much as they wanted of a high-calorie chocolate-flavoured snack. Despite only the brief exposure to artificial sweeteners, there was a clear effecton the animals' appetites. The rats fed artificial sweeteners gobbled up more of the snack before deciding they had had enough.

In a third study, to measure energy expenditure, the researchers found that saccharin-fed rats had slightly lower energy expenditures after eating a high-calorie meal containing sugar.

"In addition to somehow stimula-ting food intake, we think that arti-ficial sweeteners may blunt the energy expenditure mechanism as well," say Davidson and Swithers.

Although these studies have used animal models and, therefore, may not necessarily apply to humans, the researchers see no reason why, in this case, their findings shouldn't hold true in people.

"Artificially sweetened foods seem to interfere with the natural ability of the body to use sweet taste to gauge caloric content of foods and beverages," they say. "When you substitute artificial sweeteners for real sugar, the body can no longer

use its sense of taste to gauge calories. So it may be fooled into thinking a product sweetened with sugar has no calories, and therefore people overeat" (Behav Neurosci, 2008; 122: 161-73).

Predictably, the industry and its cohorts of nutritionists have been quick to retaliate.

"Studies like this are a disservice to the consumer because they over-simplify the causes of obesity," says the US Calorie Control Council. "It is true that there has been an increase in the use of low-calorie sweeteners at the same time that we have seen an increase in obesity, but there has also been an increase in the use of cellphones and nobody is suggesting that they cause obesity."

Nevertheless, the data so far amassed by Davidson and Swithers appear to tally with observations made in the real world. Twenty years ago, Florida physician Dr H.J. Roberts, a passionate campaigner against artificial sweeteners, reported that 5 per cent of his patients showed "para-doxical weight gain" with low-calorie drinks, such as Diet Coke, that contain aspartame (J Appl Nutr, 1988; 40: 85-94).

More recently, University of Texas Health Sciences Center researchers investigated the relationship between artificial sweeteners and people's weight. They monitored nearly 2000 people for eight years and found that, although all of these individuals had been normal weight at the start of the study, by the end of the observation period, about a third of them had become obese.

The researchers focused their analysis on the intake of soft drinks and sodas. Interestingly, although sugared drinks contain far more calories, it was those who chose diet sodas who put on more weight.

"There is a 41 per cent increase in risk of being overweight for every can or bottle of diet soft drink a person consumes each day," reported lead researcher Sharon Fowler, MPH, on presenting the results at the 65th Annual Scientific Sessions of the American Diabetes Association in San Diego in 2005 (Abstract 1058-P).

Of course, on their own, these findings are not proof of a causal relationship between artificial sweet-eners and weight gain, as one explanation may be that the fatter people get, the more they may feel obliged to switch to diet drinks. Nevertheless, it offers further food for thought.

Earlier this year, diet drinks were also implicated in a wide range of risk factors predisposing people to heart disease-the so-called Syndrome X or metabolic syndrome (MetSyn). A survey of nearly 10,000 Americans revealed that there is a 34-per-cent increased risk of developing the syndrome if you drink just one can of diet soda every day. Typical MetSyn problems include high blood pressure, a large waist size, incipient diabetes and high triglyceride levels (Circulation, 2008; 117: 754-61).

The role of aspartame

The world's best-selling artificial sweetener is aspartame. It's currently used in over 6000 products-from low-calorie drinks to toothpaste and even vitamin pills-often without our knowing it and, therefore, making it impossible for the average consumer to avoid. Given such widespread, un-acknowledged use, it is imperative that the substance be completely harmless and, indeed, most people are reassured by the clean bill of health it has been given by government agencies across the world. Documents released by the Food and Drug Admin-istration (FDA), the US government drugs watchdog, for example, are peppered with phrases describing aspartame as "innocuous", "one of the most thoroughly tested and studied food additives the agency has ever approved" and having "overwhel-ming documentation of aspartame's safety".

And yet, aspartame's track record has been anything but straight-forward. Throughout its history, there have been question marks over its safety (see box, this page).

From the beginning, critics have been suspicious of its chemical constituents. The major cause of concern is the amino acid phenylalanine, high levels of whichare known to cause brain damage. Although officialdom acknowledges this problem, it nevertheless points out that it only affects those who have phenylketonuria, a rare metabolic disorder where phenylalanine cannot be normally broken down in the body.

However, aspartame also contains aspartic acid and methanol, both of which can metabolize into potentially toxic compounds such as glutamate, asparagines and formaldehyde. Some of these are known to be neurotoxins as well as carcinogens.

In fact, early research claimed to have found a connection between aspartame and brain tumours. Soon after aspartame was discovered, Dr John Olney and his colleagues at the Washington University Medical School in St Louis, MO, as a result of finding an "exceedingly high incidence" of brain tumours in mice fed aspar-tame, decided to carry out an analysis of the brain tumour data gathered by the US National Cancer Institute. Looking at the data from 1975 to 1992, they found a 10 per cent increase in the prevalence of glioblastomas, corresponding to the introduction of aspartame (J Neuro-pathol Exp Neurol, 1996; 55: 1115-23).

Although the industry has countered this finding by arguing that the incidence of these brain cancers has now flattened out and even decreased, the evidence of aspartame's effects on both the brain and cancer continues to mount up.

Brain effects

Inevitably, much of the evidence has come from feeding aspartame to laboratory animals. This is because rats are considered to be appropriate test-beds as they metabolize aspar-tame in much the same way as do humans.

What has been clearly established is that aspartame has toxic effects on the rat brain; in particular, it inhibits neural growth-and does this at relatively low doses. Indeed, such "inhibition of neurite outgrowth" takes place at levels of additives found in the typical snack or soft drink, say a team of University of Liverpool toxicopathologists (Toxicol Sci, 2006; 90: 178-87). What's more, the toxic effects are made even worse when aspartame is combined with other additives such as food colourings.

Another brain effect of aspartame involves people with mood disorders. In a crossover, double-blind, placebo-controlled study of individuals witha history of depression, their adverse reactions on receiving 30 mg/kg of body weight/day of aspartame for one week were so severe that the study was prematurely stopped (Biol Psychiatry, 1993; 34: 13-7).

Equally worrying is the finding that aspartame can be dangerous for people with epilepsy, lowering their threshold for seizures-or prolonging them once they appear-at levels of intake over the recommended level of 40 mg/kg of body weight/day (Med Pregl, 2003; 56 Suppl 1: 27-9).

Moreover, seizures can be triggered even in those without a history of epilepsy. Belgian emergency-room doctors recently reported "a case of epileptic seizures after a massive intake of Diet Coke" which they believe was triggered by the caffeine and aspartame contents of the drink (Eur J Emerg Med, 2008; 15: 51).

Some researchers are now sug-gesting that the direct and indirect effects of aspartame on cells of the brain and central nervous system may well be contributing to the epidemic of neurological and behavioural disturbances seen in young people today. There may also be a connection between aspartame and the develop-ment of certain mental disorders as well as impairments in learning and emotional functioning (Eur J Clin Nutr, 2008; 62: 451-62). This is supported by the fact that the long-term intake

of aspartame is known to impair memory in people (Psychol Today, 2001; 34: 20).

The link with cancer

The biggest concerns for long-term health have to do with the connection between aspartame and cancer. Much of the evidence has come from one institution-the European Ramazzini Foundation of Oncology and Environ-mental Sciences, based in Bologna, Italy. In March 2006, they reported the results of a three-year study of aspartame in 1800 rats, using a range of intakes designed to simulate normal human intakes.

Unlike previous studies, the researchers waited until the rats had died of natural causes before checking them for cancer-a sensible idea, given that cancer is primarily a disease of old age, which means that it takes time to become manifest. What they found was a statistically significant increase in lymphomas, leukaemias, and malignant tumours of the kidney, and peripheral and cranial nerves. The response was also dose-dependent: the higher the aspartame dose, the greater the incidence of cancer. The researchers' conclusion was stark: aspartame is a "multipotential car-cinogenic agent, even at a daily dose of 20 mg/kg body weight, much less than the current acceptable daily intake" (Environ Health Perspect, 2006; 114: 379-85).

The researchers then decided to take it one stage further. To more closely mimic human exposures, they fed aspartame to pregnant rats (from day 12 of fetal life) and continued to feed it to the newborns until their natural death. This preexposure to aspartame in the womb was found to result in even more cancers in later life, including a significant, dose-related increase in mammary cancer in the female rats (Environ Health Perspect, 2007; 115: 1293-7).

These findings are a powerful vin-dication of their previous findings, and have been further substantiated by the simultaneous discovery by Hungarian Institute of Public Health scientists, at the University of P'ecs, that aspartame can increase the expression of cancer-causing genes called 'oncogenes'-even when keep-ing to the recommended maximum daily dose (In Vivo, 2007; 21: 89-92).

Quo vadis: status quo?

However, even in the face of these powerful new data, the regulatory authorities have not budged. Al-though the Ramazzini laboratory has conducted the most extensive biological tests in the whole history of aspartame research, both the US FDA and the European Food Safety Authority (EFSA) have brushed them aside, mainly citing earlier animal experiments as disproof-despite the fact that some of these were carried out by the industry itself and were of questionable quality.

How long this stand-off will continue is anyone's guess. The word on the street is that aspartame may be in terminal decline anyway. Its patent has expired, and there is now such an oversupply that it's said to be no longer profitable and, thus, no longer worth manufacturing.

If so, good riddance. Meanwhile, to borrow from the advice usually doled out by drug com-panies, when it comes to low Aspartame (NutraSweet, Spoonful, Equal, Equal-Measure and Canderel) is one of the most money-making food additives ever produced. It can be found in over 6000 products and is consumed by over 200 million people, 10 per cent of whom ingest a staggering 125 g/year of the stuff, according to the Aspartame Information Center (see www.aspartame.org). Here are some of the highlights in the history of this ubiquitous additive.

- 1965 Accidental discovery of "an organic compound with a profound sucrose [sugar]-like taste" by drug giant G.D. Searle

- 1970 US neuroscientist Dr John W. Olney finds that aspartame causes brain damage in mice

- 1974 FDA approves aspartame for limited use in "dry foods", but then rescinds it

- 1980 FDA convenes a Public Board of Inquiry in response to Japanese data showing that aspartame may cause brain tumours in rats, and recommends against approval

- 1981 January G.D. Searle president and Republican Party supporter Donald Rumsfeld applies for full FDA approval the day after Republican President Ronald Reagan takes office

- 1981 July FDA approves aspartame for use in dry foods, with a stated acceptable daily intake (ADI) level of 50 mg/kg body weight/day

- 1982 UK approval given with an ADI of 40 mg/kg body weight/day

- 1983 FDA approves aspartame in drinks

- 1987 FDA Task Force reports that "Searle has not submitted all the facts of experiments to FDA . . . experiments have been poorly conceived, carelessly executed, or inaccurately analyzed or reported"

- 1998 US clinical psychologist Professor Ralph Walton analyzes 166 peer-reviewed studies of aspartame: the industry-funded studies all say that aspartame is safe, but 91 per cent of the independent studies conclude it is not

- 1988 EU gives approval, and its additive number is E951

- 2006 January In the UK, 46 MPs sign an Early Day Motion calling for aspartame to be removed from the list of permitted food additives

- 2006 March Italian researchers claim that aspartame is carcinogenic

- 2006 May The European Food Safety Authority (EFSA) declares that "there is no need to further review the safety of aspartame"

- 2007 April The FDA "finds no reason to alter its previous conclusion that aspartame is safe as a general purpose sweetener in food"

- 2007 November International scientists employed by the Washington, DC-based Burdock Group ("our Food Industry solutions help you bring your products to market safely and profitably") declare that "the weight of existing evidence is that aspartame is safe at current levels of consumption" (Crit Rev Toxicol, 2007; 37: 629-727).-calorie products, always read the label.

Tony Edwards

Aspartame side-effects

In 1993 under the Freedom of Information Act, the US Food and Drug Administration (FDA) was forced to release their database of adverse symptoms, comprising reports from over 10,000 members of the general public. Aspartame was reported to be the subject of the most consumer complaints. What follows is the FDA's list of reported side-effects, presented in the order of frequency:

- Headache

- Dizziness, poor equilibrium

- Change in mood

- Vomiting or nausea

- Abdominal pain and cramps

- Change in vision

- Diarrhoea

- Seizures and convulsions

- Grand mal seizures

- Memory loss

- Fatigue and weakness

- Other neurological symptoms

- Rash

- Sleep problems

- Hives

- Change in heart rate

- Itching

- Change in sensation (numbness, tingling)

- Local swelling

- Change in activity level

- Difficulty breathing

- Oral sensory changes

- Change in menstrual pattern.

Clinically reported adverse reactions from the scientific literature include:

- Headaches (Neurology, 1994; 44: 1787-93)

- Depression (Biol Psychiatry, 1993; 34: 13-7)

- Thrombocytopenia (South Med J, 2007; 100: 543)

- Sj"ogren syndrome (South Med J, 2006; 99: 631-2)

- Fibromyalgia (Ann Pharmacother, 2001; 35: 702-6).

Safer sugar substitutes

Xylitol

This natural carbohydrate is mainly found in birch trees and, in its manu-factured form, looks and tastes just like sugar. However, it is not a complete alternative to chemical sweeteners as it still has as many as half the calories of sugar. On the other hand, its glycaemic index (GI) score is a mere 8, making it an extremely slowly absorbed carbohydrate and, therefore, good for diabetics and slimmers.

It's also claimed to be a probiotic-a promoter of friendly bacteria in the gut-and able to increase bone density. The best evidence of its usefulness is in preventing both tooth decay (J Dent Educ, 2001; 65: 1106-9) and middle-ear infections (Pediatrics, 1998; 102: 879-84).

However, its good safety record has recently come into question after some mysterious cases of dog poisoning-some of which were fatal. The theory is that it causes a marked surge in insulin leading to collapse, seizures and severe liver damage-but only in dogs (J Am Vet Med Assoc, 2006; 229: 1113-7; Vet Hum Toxicol, 2004; 46: 87-8; Veterinary Medicine, 2006; 101: 791-7). In humans, it can cause diarrhoea in high doses.

Lo han kuo

Derived from a Chinese fruit, lo han kuo (magic fruit, luo han guo) can be up to 250 times sweeter than sugar, but with barely measurable calories.

It is traditionally used in China as a medicinal herb for treating cough and sore throat; folk medicine believes it increases longevity. In the West, one of its best-known trade names is SlimSweet.

Stevia

Derived from the South American shrub Stevia rebaudiana, this is said tobe up to 300 times sweeter than sugar, but it can't be sold as an officially approved sweetener because the US Food and Drug Administration considers its safety to be unproven. However, even a cursory study of the literature reveals that stevia is not only harmless, but may even have positive medical benefits, such as boosting immune function (Chem Biol Interact, 2008; 173: 115-21).

Fructo-oligosaccharides (FOS)

These carbohydrates, extracted from certain plants such as Jerusalem artichokes, onions and bananas, are not only a useful sweetener, but have additional probiotic effects in the gut, promoting bifidobacteria (Dig Liver Dis, 2006; 38 Suppl 2: S283-7). It is often used to help prevent Candida infections.

Agave nectar

Made from the Agave cactus plant, this honey-like substance is far sweeter than sugar, but with half the carbohydrates. However, its GI score is 48, which considerably reduces its value in a weight-loss regime.


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