Netflix has a documentary on Aspartame that scared me into stopping
Aspartame consumption.

Sorry, I don't recall the title.

industry scientists praise aspartame safety and benefits in Paris on
2006.05.30, Herve Nordmann, Andrew G. Renwick, Carlo La Vecchia, Tommy
Visscher, Jaap Seidell, France Bellisle, Adam Drewnowski, Margaret
Ashwell, Anne de la Hunty, Sigrid A. Gibson, Alan R. Boobis: Murray
2007.11.18
http://groups.yahoo.com/group/aspartameNM/message/1491

[ See also, given in full below:
details on 6 epidemiological studies since 2004 on diet soda (mainly
aspartame) correlations, as well as 14 other mainstream studies on
aspartame toxicity since summer 2005: Murray 2007.11.18
http://rmforall.blogspot.com/2007_11_01_archive.htm
Wednesday, November 14, 2007
http://groups.yahoo.com/group/aspartameNM/message/1490 ]

" AGR is a scientific consultant to
The International Sweeteners Association (ISA),
Avenue des Gaulois 9, 1040 Brussels, Belgium,
which is an organisation of producers and users of intense sweeteners.
"

Dr Hervé Nordman is Director, Scientific and Regulatory Affairs,
Ajinomoto Switzerland AG.

" The Conference was introduced and chaired by Dr Hervé Nordmann
(Chairman, ISA Working Group on Aspartame) who highlighted the fact
that
previous meetings had concentrated on safety aspects and that this was
the first comprehensive attempt in Europe to assess safety and
benefits
from the intake of an intense sweetener such as aspartame.

Aspartame was approved in countries world-wide
and its metabolism to normal dietary compounds
(aspartic acid, phenylalanine and methanol)
gave confidence in its safety.

The WHO/FAO Joint Expert Committee on Food Additives (JECFA) had
concluded that it was difficult to identify any dietary constituent
that
has been more thoroughly evaluated than aspartame.

Dr Nordmann stated that the continuing attention on unsubstantiated
safety issues served to divert interest and resources from more
important issues such as benefits in obesity and related diseases like
cardiovascular diseases and diabetes type 2. "

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6P-4N3WYRF-1&_user=1
0&_coverDate=07%2F31%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000
050221&_version=1&_urlVersion=0&_userid=10&md5=5b443166f3bd64a97a775137024a50f1

doi:10.1016/j.fct.2007.02.019
Copyright (c) 2007 Elsevier Ltd All rights reserved.

Food Chem Toxicol. 2007 Jul; 45(7): 1308-13. Epub 2007 Feb 22.
First European conference on aspartame: putting safety and benefits
into
perspective. Synopsis of presentations and conclusions.
Renwick AG, Nordmann H.
School of Medicine, University of Southampton, Bassett Crescent East,
Southampton SO16 7PX, UK. agr@soton.ac.uk
Received 24 January 2007;  accepted 16 February 2007.
Available online 22 February 2007.

By Andrew G. Renwick a
and Herve Nordmann b

a Emeritus Professor, School of Medicine, University of Southampton,
Bassett Crescent East, Southampton SO16 7PX, UK (author for
correspondence; Email agr@soton.ac.uk),

b Chairman, ISA Working Group on Aspartame, International Sweeteners
Association, Avenue des Gaulois 9, 1040 Brussels, Belgium.

[
http://72.14.253.104/search?q=cache:tNUPl3ZX3r8J:www.alliance-natural-health.org
/_docs/ANHwebsiteDoc_186.doc+%22Herve+Nordmann%22&hl=en&ct=clnk&cd=3&gl=us
JOINT FAO/WHO FOOD STANDARDS PROGRAMME
CODEX ALIMENTARIUS COMMISSION
Twenty-seventh Session
Geneva, 28 June - 3 July 2004
Dr Hervé NORDMANN
Director
Scientific and Regulatory Affairs
Ajinomoto Switzerland AG
Innere Güterstrasse 2-4
CH - 6304 Zug, Switzerland
Phone: 41-41 7286666  Fax: 41-41 7286565 herve.nordmann@ajimoto.com,
herve.nordmann@asg.ajinomota.com,herve.nordmann@asg.ajinomoto.com, ]

Running title ?- Conference on safety and benefits of aspartame

Key words ?- aspartame, safety, weight loss, benefit, obesity, health

Corresponding Author -- Private contact details for use by the Journal
only

Professor AG Renwick
XXXXXX
XXXXXX
XXXX
XXX

Tel XXXXXXX
Email agr@soton.ac.uk

Abstract

A Conference was held in Paris in 2006 to review the safety and
benefits
arising from the replacement of sucrose with the intense sweetener
aspartame.

The intakes of aspartame are only about 10% of the acceptable daily
intake, even by high consumers, so that the safety margin is about 3
orders of magnitude.

The safety of aspartame was confirmed in the EFSA Opinion of a recent
controversial rodent cancer bioassay.

There is increasing evidence that even modest reductions in the intake
of calories can reduce the risk factors associated with a number of
diseases, such as diabetes and cardiovascular disease.

A key issue addressed at the conference was whether the replacement of
sucrose with aspartame could result in a prolonged decrease in calorie
intake that was of similar magnitude to that necessary to produce a
health benefit.

A recent meta-analysis of published data showed that an adequate,
prolonged weight reduction could be achieved with aspartame.

It was recognised that risk assessment alone gave an unbalanced
impression to regulators and consumers,
and that in the future quantitative risk-benefit analyses should be
able
to provide more comprehensive advice.   PMID: 17397982

Introduction

On 30th May 2006, the International Sweeteners Association (ISA)
hosted
the ?First European Roundtable on Aspartame: Putting Benefits into
Perspective? in Paris.

The Conference brought together eminent experts to discuss the
scientific evidence of the safety and effectiveness of aspartame and
low
calorie sweeteners.

The Conference was introduced and chaired by Dr Hervé Nordmann
(Chairman, ISA Working Group on Aspartame) who highlighted the fact
that
previous meetings had concentrated on safety aspects and that this was
the first comprehensive attempt in Europe to assess safety and
benefits
from the intake of an intense sweetener such as aspartame.

Aspartame was approved in countries world-wide
and its metabolism to normal dietary compounds
(aspartic acid, phenylalanine and methanol)
gave confidence in its safety.

The WHO/FAO Joint Expert Committee on Food Additives (JECFA) had
concluded that it was difficult to identify any dietary constituent
that
has been more thoroughly evaluated than aspartame.

Dr Nordmann stated that the continuing attention on unsubstantiated
safety issues served to divert interest and resources from more
important issues such as benefits in obesity and related diseases like
cardiovascular diseases and diabetes type 2.

Risk assessment aspects

The initial presentation by Professor Andrew Renwick (University of
Southampton, UK) summarised the safety database on aspartame and
presented how the Acceptable Daily Intake (ADI) of 40mg/kg body weight
had been calculated by the traditional method of taking the No
Observed
Adverse Effect Level (NOAEL) from animal studies and dividing by an
uncertainty (safety) factor of 100.

However, there was a larger database of studies in humans (Stegink,
1987, Butchko and Stargel, 2001, Butchko et al., 2002) than was
available for any other approved food ingredient, and Professor
Renwick discussed the possibility of using these data directly to
determine the ADI, thereby avoiding issues of inter-species
extrapolation.

He concluded that any human study would have to fulfil criteria of
adequate duration, group size, group composition, daily dosage and
also investigate the endpoints detected in rats at intakes above the
NOAEL.

The 24 week study by Leon et al. (1989), which included 53 subjects
given 75 mg/kg body weight for 26 weeks, fulfilled many of these
criteria, but uncertainties would remain if it were used to establish
an ADI at the dose studied.

Although this study was restricted to healthy adults, other studies
had shown that other groups, such as children, individuals
heterozygous for phenylketonuria and patients with hepatic and renal
disease, would not be at greater risk since the absorption and
metabolism of aspartame were similar to healthy adults.

Professor Renwick concluded that the various human data could be used
to
support an ADI of 0-75 mg/kg/day, but that because daily intakes are
only about 10 % of the ADI it would be more logical to classify
aspartame as ?ADI not specified? (ADI not specified is used when the
compound is of such low toxicity in relation to intake that a
numerical ADI is not needed).

During the discussion of this paper it was pointed out that the
need for a numerical ADI for aspartame was based on policy rather than
science and that an ADI was not set for sucrose, which like aspartame
is
metabolized in the intestine prior to absorption as normal body
constituents (sucrose is hydrolyzed to glucose and fructose).

Further  discussion centred on the application of the ADI to children,
who have a higher intake of foods and beverages, on a body weight
basis, than adults.

Very young children generally do not consume carbonated beverages,
although there is use of diluted juice concentrates containing intense
sweeteners in the UK.

Diabetic children would represent the group with the highest potential
for intakes, and various intake studies have shown that the intakes
are below the ADI.

Professor Renwick then gave a presentation on the carcinogenicity
study
performed at the Ramazzini Institute (Soffritti et al., 2005, 2006).

The study included large group sizes (100-150/sex/treatment level) and
a
wide range of doses from less than the ADI to the maximum tolerated
dose.

However the study was of unusual design since the animals were from an
inbred colony with a high incidence of respiratory and other
infections
and were maintained until they died.

Differences in the survival of different groups complicated the
analysis
of the data.

In reality the protocol did not comply with testing guidelines, such
as
those of the OECD, and was similar to methods that had been abandoned
over 30 years ago because of problems of interpretation.

These two aspects meant that the data were not valid for risk
assessment
purposes.

The authors of the study had claimed that the study showed that
aspartame was a ?multipotential carcinogen?.

Professor Renwick cited the EFSA comprehensive evaluation of the study
(EFSA, 2006) which reached the conclusion that the data do not provide
evidence of a carcinogenic potential of aspartame and that there was
no
reason to revise the previously established ADI for aspartame of 40
mg/kg bodyweight.

During discussion of the paper it was questioned whether it was
ethical
to use massive numbers of animals in a study that from its inception
could not have provided useful data.

A major concern was that the study resulted in a large amount of
unbalanced media attention and public concern at the expense of the
extensive contrary information generated by more acceptable methods.

Although the EFSA Opinion (EFSA, 2006) was an invaluable scientific
contribution, it was thought that the media considered the Opinion a
?non-story? and gave it little coverage.

The discussion then moved to the recent studies performed by the NTP
in
the USA (NTP, 2005), which demonstrated that aspartame did not show
carcinogenic potential in studies in genetically modified animal
models.

It was pointed out that such studies were of limited value in the case
of aspartame as the models were of unknown specificity and sensitivity
for the endpoints of concern, and aspartame had proven negative in
more
conventional models.

In consequence this study also raised ethical issues related to the
use
of animals and sophisticated research resources.

The next paper was a particularly interesting presentation by
Professor
Carlo La Vecchia (Mario Negri Institute, Italy) in which he described
the findings of recent epidemiology investigations into any possible
link between intense sweeteners and cancer in humans using an
integrated
network of case-control studies, which were conducted in Italy between
1991 and 2004 (Gallus et al. 2006).

[ www.eastman.ucl.ac.uk/iaoo/founders/La%20Vecchia%20C_ShortCV.pdf
Date of birth: Feb. 27, 1955; Place of birth: Milano, Italy;
Citizienship: Italian; Languages: English, French (and Italian).
Current status: - Head, Laboratory of Epidemiology, Istituto di
Ricerche
Farmacologiche "Mario Negri", Milan (Italy)
(1989--).
- Associate Professor of Epidemiology, Istituto di Statistica Medica e
Biometria, Università di Milano
(1992--).
- Adjunct Professor of Epidemiology University of Lausanne,
Switzerland
(2002--).
- Adjunct Professor of Medicine, School of Medicine, Vanderbilt
University, Nashville, TN, (2002-2005).
Address: Istituto di Ricerche Farmacologiche"Mario Negri"
Via Eritrea 62 - 20157 Milan (Italy)      lavecchia@marionegri.it,
(Tel. +39-02-39014.1; Fax +39-02-33200231/02-39001916)
http://farmacologiasif.unito.it/ricerca04/ricerca/lavecchia_c.html  ;
Istituto di Statistica Medica e Biometria, Università di Milano, Via
Venezian 1 - 20133 Milan (Italy)
(Tel. +39-02-2361302; Fax +39-02-2362930). ]

Cases were
598 patients with histologically confirmed cancers of the oral cavity
and pharynx,
304 of the oesophagus,
1,953 of the colorectum,
460 of the larynx,
2,569 of the breast,
1,031 of the ovary,
1,294 of the prostate,
and 767 of the kidney.

Controls were 7,028 patients (3,301 men and 3,727 women) admitted to
the
same network of general and teaching hospitals, for acute non-
neoplastic
diseases.

Odds ratios (ORs) were obtained from multiple logistic regression
analyses, with allowance for total energy and major recognized risk
factors.

The ORs for consumption of saccharin and other sweeteners were not
significantly increased for cancers of the oral cavity and pharynx,
oesophagus, colon, rectum, larynx, breast, ovaries, prostate or
kidneys.

The absence of association between sweeteners and cancer risk was
reproduced across strata of sex, age, BMI and consumption of coffee,
alcohol or tobacco.

Professor La Vecchia then summarized the NIH-AARP and Health Study
( http://dietandhealth.cancer.gov ), which provided data for humans
that were relevant to the conclusions of the Ramazzini study in rats.

The NIH-AARP and Health Study was based on a large cohort of more than
500,000 subjects, including 2,106 hematopoietic cancers and 376 brain
cancer cases, and found no association with aspartame-containing
beverages:
the adjusted relative risk of consuming ?600 mg aspartame/day vs. none
for overall hematopoietic cancers was 0.93 (95% CI: 0.72-1.19) and for
?400mg aspartame/day
vs. none for brain cancer 0.74 (95% CI: 0.49-1.13) (Lim et al., 2006).

Professor La Vecchia concluded that the available data provide a
comprehensive, reassuring picture of sweeteners and the risk of
selected
cancers, and indicate no association between saccharin, aspartame and
other sweeteners, and the risk of several common neoplasms.

Benefit-related aspects

The Conference then moved on to discuss issues related to the benefits
associated with the replacement of sucrose by an intense sweetener
such
as aspartame.

A paper by Dr Tommy Visscher and Professor Jaap Seidell (Vrije
Universiteit Amsterdam) (presented by Dr Visscher) described the
relationship of energy balance and body weight.

[ http://www.bio.vu.nl/veng/staff.php
Tommy L.S. Visscher, PhD
phone: +31 (0)20-598 6948  fax: +31(0)20-598 6940
email: tommy.visscher@falw.vu.nl,
office: Bl 1085 O-551  working days: monday friday
position:
Postdoc epidemiology 'Weight gain prevention'. An integrated research
program subsidized by the Netherlands Heart Foundation (2002-2007).
Co-promotor Astrid JC Nooyens, MSc. 'Life-style predictors of weight
gain in prospective studies'. Implications for age-specific weight
gain
prevention trials.
Other affiliations:
Center for Prevention and Health Services Research (Head: Dr. H.S.
Smit). National Institute for Public Health and the Environment,
Bilthoven, The Netherlands.
Knowledge Center Overweight (Head: Prof. Dr. R.A. Hirasing).
EMGO-institute, Free University medical center, Amsterdam, The
Netherlands.
The International Journal of Behavioral Nutrition and Physical
Activity
Editorial Board
Assistant Professor, Department of Nutrition and Health
Free University, De Boelelaan 1085, 1081 HV, Amsterdam, Netherlands

Prof. Jaap C. Seidell
phone: +31 (0)20-598 6995  fax: +31(0)20-598 6940
email: jaap.seidell@falw.vu.nl,
office: Bl 1085 O-552
working days: monday tuesday wednesday thursday friday
position:
Full professor. Head of the Institute for Health Sciences and head of
the department of Nutrition and Health at the faculty of Earth and
Life
Sciences at Free University (80%) and the department of Internal
Medicine of the VU Medical Center (20%) in Amsterdam.  ]

Body mass index (BMI) had increased in recent years in all age groups,
indicating an increasing imbalance between energy intake and
expenditure.

An increase in body weight of 1kg extra fat could result if the daily
energy intake exceeded the energy expenditure by only 20 kcal.

Energy intake of 140 kcal per week was equivalent to a small beer, a
handful of peanuts, a croissant or a cookie, while 140 kcal could be
expended by 14 minutes jogging, 19 minutes cycling or 35 minutes
walking;
therefore even small changes in diet or activity could produce
profound
changes in BMI if maintained for prolonged periods.

Numerous personal and societal factors influence an individual?s diet
and activity.

The presentation then focused on the relationship between obesity and
disease, particularly cardiovascular disease and diabetes in relation
to
syndrome X, insulin insensitivity, hypertension and dyslipidaemias.

A BMI over 30 kg/m2 was a significant risk factor and was associated
with a large cost to the health services and to society and took up 6
%
of the health care budget in the USA.

Weight reduction causes a significant decrease in many risk factors
(triglyceride, total cholesterol, LDL and HDL cholesterol, and blood
pressure), and is associated with a decrease in risk of diabetes and
reduced morbidity.

The overall conclusion of the paper was that a relatively minor
decrease
in body weight could have a significant health benefit.

The discussion raised the issue that a small, 2-3 % decrease in body
weight caused by dieting could have a different effect on risk factors
than a 2-3 % difference in long-term maintenance of body weight.

Changes in body weight of 4-5 kg are achievable by relatively easy
changes in lifestyle, and it was encouraging to see that these were
associated with real health benefits.

For example, a reduction of 4.3 kg in body weight can reduce the risk
of
type-2 diabetes by 70 %.

There was also a link between obesity and cancer, with an increased
risk
for most sites when the BMI is >35 kg/m2 and for post-menopausal
breast
cancer and prostate cancer when the BMI is about 30 kg/m2 or more.

However most cancers develop only slowly and the average long-term BMI
would be important.

The subsequent presentation was by Dr France Bellisle (Institut
National
de Recherche Agronomique (INRA) in Paris) on the use of aspartame in
the
context of a weight reducing diet: effects on appetite and intake.

[ Ms. France Bellisle
INRA, Centre de Recherche en Nutrition Humaine, Hôtel Dieu Hospital,
Paris, France;
Nutrition, Hôtel-Dieu, 1 Place du Parvis Notre-Dame, 75181 Paris,
France.  f.bellisle@wanadoo.fr,f.bellisle@smbh.univ-paris13.fr,
bellisle@imaginet.fr,  ]

In theory, replacing sucrose (4 kcal/g) by a very low calorie
sweetener
(aspartame) should allow the pleasure of ingesting sweet-tasting foods
and drinks to be retained while decreasing energy intake, but the
issue
is complex.

Sucrose fulfils roles in food other than sweetness and removal of
sucrose from a solid food would require the introduction of other
ingredients, which might add calories back into the food.

In contrast, for beverages and semi-solid products like yoghurts the
main function of sucrose is to impart sweetness, so it could be
replaced
more readily with a reduction in calories (Bellisle & Drewnowski,
2007).

In the past, questions have been raised about whether intense
sweeteners
increase appetite or result in a craving for sweetened foods, but
these
suggestions have been disproved (Rolls, 1991).

In contrast a number of intervention studies have shown that replacing
sucrose with aspartame in the diet of those trying to reduce their
weight results in an increased weight loss (de la Hunty et al., 2006).

In discussion it was proposed that a general reduction in the
sweetness
of foods should be encouraged.

Dr Bellisle pointed out that we are born with an innate predisposition
to accept sweetness, which will be modulated by the child?s
experiences,
and we are all different in our responses to sugar concentrations;
some of us would find a given concentration extremely sweet, another
person would find it hardly sweet at all.

Individuals choose products that suit their sweetness perceptions and
preferences, and if only some products had reduced sweetness consumers
would still select products that satisfied their taste.

The general public should understand that although low-calorie foods
and
drinks may contain less energy than the regular products, they still
contain energy and too many calories can be consumed by eating
excessive
amounts of such products (Bellisle & Drewnowski, 2007).

If they are consumed in a sensible way in the context of a low-energy
diet, then they can help to control or prevent obesity.

But such products are not drugs that suppress appetite. Low-calorie
products will not help people if they believe that they can then eat
as
much as they like, without any consideration for the total amount of
energy that they ingest.

Further evidence on the relationship between aspartame, obesity and
weight loss was presented by Dr Margaret Ashwell
( www.ashwell.uk.com ),
who highlighted the increase in average body weights over the past 2
decades and then gave the results of a systematic review and the first
ever meta-analysis of published studies (De la Hunty et al., 2006).

The approach taken was a systematic review of primary studies that
used
explicit and reproducible methods to examine the effect of
substituting
sugar with aspartame (or a sweetener blend containing aspartame) on
energy intake or body weight.

Identification of studies that reached acceptable standards was
followed
by a meta-analysis.

The initial review identified 200 primary publications, but many of
these were excluded because they were not randomized control trials
and/or because the energy intake was not measured for at least 24 hrs.

A total of 15 studies on energy intake and 9 studies on weight loss
were
included in the meta-analysis.

Using the different studies and designs for energy intake, 32
comparisons were possible;
aspartame vs. baseline (n=8),
aspartame vs. non-sucrose control (n=7),
aspartame vs. sucrose crossover (n=5)
and aspartame vs. sucrose parallel (n=12).

Overall, aspartame produced a highly significant decrease in energy
intake (P<0.001) with an effect size of 0.4 standard deviations (SD).

The coefficient of variation of energy intakes in the human population
is about 25 %, so that this effect size ( 0.4SD ) would be equivalent
to
a 10 % energy reduction. A 10 % reduction in energy intake would be
equivalent to 1,560 kcal/week which would be stored in the body as 0.2
kg/adipose tissue per week.

Using the different studies and designs for weight loss, 20
comparisons
were possible;
aspartame vs. baseline (n=4),
aspartame vs. non-sucrose control (n=2),
aspartame vs. sucrose crossover (n=3)
and aspartame vs. sucrose parallel (n=11).

The analyses of the data were made under 3 sets of conditions:

i. least conservative ?-- used all weight outcomes including follow-up
weights,

ii. more conservative ?-- excluded studies in which the control group
gained weight

and iii. most conservative ?-- also excluded follow-up periods.

Each analysis showed a significant effect of aspartame, with P values
of
<0.001, 0.001 and 0.05 respectively
and effects sizes of 0.39, 0.30 and 0.22 respectively.

The coefficient of variation of body weight in populations studied is
about 15 %, so that the most conservative effect size ( 0.2SD ) would
be
equivalent to a 3 % reduction in body weight.

A 3 % reduction in body weight is equivalent to 2.3 kg for a 75 kg
person; over the average 12-week period this would be equal to 0.2
kg/adipose tissue per week.

Therefore, the analyses of the different data on weight loss and on
energy intake reach a remarkably consistent conclusion -? that
replacement of sucrose with aspartame can reduce body weight by about
0.2 kg/week.

Dr Ashwell then explored the practical implications of this research
conclusion.

The population of England has gained an average of 3.5 kg over the
period 1993 to 2003, or 0.35 kg/year, which is equivalent to 0.007
kg/week; therefore although a loss of 0.2 kg/week arising from the use
of aspartame is low, it would be enough to counteract the average
population rate of weight gain.

The issue of how much sucrose would need to be replaced by aspartame
was
considered in relation to the reduction of energy intake reported in
the
meta-analysis of 1,560 kcal/week or 220 kcal/day.

After allowing for the compensation of increasing calorie intake from
other sources, it was estimated that the 260 kcal replacement would be
achieve by the daily replacement
of 2 regular sucrose sweetened beverages with 2 diet beverages.

Dr Ashwell concluded her presentation with data showing that aspartame
was not only useful in reducing body weight, but in maintaining a
lower
body weight after dieting.

The discussion focused on "world" implications of the calculations
made
by Dr Ashwell.

It was suggested that 2 cans of carbonated beverage is the average
intake by Dutch boys, so that such a reduction in calorie intake is a
very real possibility, although it was also suggested that the average
in Europe was closer to 1 can/day

The issue of the possible extent of compensation was raised and
whether
individuals would simply consume the same total calories from other
sources, so that potential benefit of replacing a regular drink by a
carbonated drink would be lost.

This issue had also been raised following the presentation of Dr
Bellisle and again it was agreed that a reduction of calorie intake
from
one product would only work effectively if there was incomplete
compensation and the individual was thinking about their diet and
total
calorie intake.

The evidence to date shows that compensation with sweetened soft
drinks
is about 15.5 % and this value had been taken into account in Dr
Ashwell?s calculations.

A comment was also made that carbonated beverages are not an essential
part of the diet and could be simply avoided altogether;
while such an approach could be selected by one individual another
could
choose to consume a diet beverage instead ?-- so it all comes down to
consumer choice again.

The lack of good data from real-world intake and weight loss
investigations was discussed.

The presence of so many confounding factors, such as motivation, was
recognised.

The meta-analysis shows the real potential for weight reduction, but
whether or not that is achieved depends on the behaviour of the
individual.

The final presentation by Professor Alan R. Boobis (Imperial College
London) described approaches to risk-benefit analysis within the
context
of the scientific method (Root, 2003; Keiding and Budtz-Jorgensen,
2004).

Studies that investigate the safety of a compound may be considered to
start with the hypothesis that the compound is safe and then use
toxicity testing to try to reject the hypothesis.

If toxicity is not seen at multiples of human exposure, this means
that
the hypothesis cannot be rejected, i.e. the compound is not unsafe.

The data do not prove that the compound is safe, but simply that here
are no data to support the conclusion that it is unsafe.

In contrast a benefit arising from exposure can be demonstrated
positively with a certain degree of statistical confidence (Asp et
al.,
2004).

A risk and benefit comparison requires a common scale that includes
measures of quality of life, longevity and incidence (% of population
affected) (Ponce et al., 2001).

Comparisons should be made for the population at large, and for any
specific sub-populations, identified on basis of a difference in risk
or
a difference in benefit.

Health status is multi-dimensional and several descriptive systems
have
been developed to define health status, and have been widely used in
the
evaluation of medicines.

A typical scheme would assign a score (utility value) to each of the
health dimensions evaluated and derive an overall score, such as the
QALY (quality of life adjusted years) (Foran et al., 2005).

Societal concerns need to be addressed and these are distinct from the
scientific appraisal of risk and benefit, for example health and one?s
perception of health can be affected by psychological factors (Page et
al., 2006).

Professor Boobis then summarized the reported risk and benefits of
aspartame and highlighted the need for quantification of both aspects
on
a common scale before any comparison was possible.

He concluded that methods for systematic risk/benefit analysis should
be
developed because they would enable assessment of the overall balance
between risks and benefits, increase transparency, improve
communication
with, and understanding by, policy makers and consumers, and provide
greater defensibility of decisions made by policy makers.

The discussion supported such an approach, but a question was raised
as
to whether consumers would respond to the words ?risk? and ?benefit?
in
the same way?

This was triggered by the BSE issue and the resulting lack of public
confidence in the scientific process.

Professor Boobis pointed out that any risk/benefit analysis (or any
risk
assessment come to that) should spell out the uncertainties in the
data
and their interpretation --? such transparency about uncertainty would
avoid over-simplistic interpretations of complex issues.

Recognition of the scientific method would have prevented Ministerial
claims of absolute safety of beef products.

However, a fully transparent risk/benefit analysis could be a problem
for an essentially safe compound like aspartame, since the limitations
in the data (for both risk and benefit) would be spelled out, and the
carefully balanced analysis could be misrepresented if the media
focused
only on the limitations in the risk-related data.

There are always uncertainties in any risk assessment, and absolute
safety cannot be guaranteed for anything in life.

Professor Boobis highlighted the need to separate uncertainty in the
quality of the data, for example the Ramazzini study had major
limitations that could not be easily interpreted in relation to human
risk, from the general uncertainties such as inter-species
extrapolation
that are inherent in all risk assessments.

Interpretations of risks and benefits by individuals are idiosyncratic
and sometimes completely irrational.

Some people drink lots of alcohol, some smoke, some drive and drink at
the same time while some indulge in dangerous sports, and at the same
time such individuals claim to be concerned buying an apple with a
trace
of pesticide residue.

The point of having quantifiable evaluations of risks and benefits is
that both aspects can actually be quantified and then decisions can be
made on how to use these data, either as an individual or as a policy-
maker.

Conclusions

The meeting concluded with a discussion on risk communication.

Detailed consideration of how the Ramazzini study data were provided
to
the public as a press release (not the usual method of dissemination
of
academic data) and how industry and regulators responded showed the
need
for a planned strategy.

The release of the initial EFSA statement caused more concern than the
Ramazzini press conference itself, which had the effect of inflating a
non-study into a major media story.

The subsequent comprehensive EFSA Opinion arrived long after the
"storm had subsided".

It is vitally important for the future that government departments,
industry and academia improve their ability to communicate with
consumers, and gain the confidence of consumers as reliable sources of
information.

Responsible scientists working in the highly regulated area of food
safety should be willing to provide detailed information to food
safety
agencies of any new data they develop regarding food safety.

Communication of incomplete data to the wider public media or the slow
disclosure of study data over several months makes it impossible for
food safety agencies to deliver an informed scientific opinion.

Putting benefits and risk into perspective can help risk communication
and lead to greater understanding by the wider public by allowing an
objective hierarchy of risks to be weighted by the quantified
benefits.

Sound risk communication allows the consumer to put the real risk into
a
proper perspective.

Food safety authorities have a very important role to play as
independent bodies with responsibilities for risk assessment and risk
communication in the area of food safety, as do all members of the
risk
assessment chain.

Conflict of interest statement

AGR is a scientific consultant to
The International Sweeteners Association (ISA),
Avenue des Gaulois 9, 1040 Brussels, Belgium,
which is an organisation of producers and users of intense sweeteners.

References

Asp, N.G., Cummings, J.H., Howlett, J., Rafter, J., Riccardi, G.,
Westenhoefer, J. 2004.
PASSCLAIM: Process for the Assessment of Scientific Support for Claims
on Foods.  Phase Two: Moving Forward.
European Journal of Nutrition 43, 3-183.

Bellisle, F., Drewnowski, A. 2007.
Intense sweeteners, energy intake, and the control of body weight.
European Journal of Clinical Nutrition, in press.

[
http://www.nature.com/ejcn/journal/v61/n6/abs/1602649a.html;jsessionid=F0E21C01E
A28F03BF886A08A8A3178A6

Review

European Journal of Clinical Nutrition (2007) 61, 691?700;
doi:10.1038/sj.ejcn.1602649; published online 7 February 2007
Intense sweeteners, energy intake and the control of body weight
France Bellisle 1
and Adam Drewnowski 2

1. 1 France Bellisle, INRA, CRNH Ile-de-France, Paris XIII Leonard de
Vinci, Bobigny, France

2. 2 Center for Public Health Nutrition, School of Public Health and
Community Medicine, University of Washington, Seattle, WA, USA
uwcphn@u.washington.edu,adamdrew@u.washington.edu,

Correspondence: Dr F Bellisle, INRA, CRNH Ile-de-France, Paris XIII
Leonard de Vinci, Bobigny, France.  f.bellisle@smbh.univ-paris13.fr,

Received 25 October 2006; Accepted 4 December 2006;
Published online 7 February 2007.

Abstract

Replacing sugar with low-calorie sweeteners is a common strategy for
facilitating weight control.

By providing sweet taste without calories, intense sweeteners help
lower
energy density of beverages and some foods.

Reduced dietary energy density should result in lower energy intakes
-?
but are the energy reduction goals, in fact, achieved?

The uncoupling of sweetness and energy, afforded by intense
sweeteners,
has been the focus of numerous studies over the past two decades.

There are recurring arguments that intense sweeteners increase
appetite
for sweet foods, promote overeating, and may even lead to weight gain.

Does reducing energy density of sweet beverages and foods have a
measurable impact on appetite and energy intakes, as examined both in
short-term studies and over a longer period?

Can reductions in dietary energy density achieved with intense
sweeteners really affect body weight control?

This paper reviews evidence from laboratory, clinical and
epidemiological studies in the context of current research on energy
density, satiety and the control of food intake. PMID: 17299484

Keywords: intense sweeteners, energy density, hunger, satiety,
satiation, weight control ]

Butchko, H.H., Stargel, W.W. 2001.
Aspartame: scientific evaluation in the postmarketing period.
Regulatory Toxicology and Pharmacology 34, 221-233.

Butchko, H.H., Stargel, W.W., Comer, C.P., Mayhew, D.A., Benninger,
C.,
Blackburn, G.L., de Sonneville, L.M., Geha, R.S., Hertelendy, Z.,
Koestner, A., Leon, A.S., Liepa, G.U., McMartin, K.E., Mendenhall,
C.L.,
Munro, I.C., Novotny, E.J., Renwick, A.G., Schiffman, S.S., Schomer,
D.L., Shaywitz, B.A., Spiers, P.A., Tephly, T.R., Thomas, J.A., Trefz,
F.K. 2002.
Aspartame: review of safety.
Regulatory Toxicology and Pharmacology 35, S1-S93.

de la Hunty, A., Gibson, S., Ashwell, M. 2006.
A review of the effectiveness of aspartame in helping with weight
control.
British Nutrition Foundation Nutrition Bulletin 31, 115-128.
[ "The authors wish to thank the Ajinomoto Company for financial
support." ]
http://www.sig-nurture.com/papers/aspartame_nbu_564.pdf  PDF: 205 kB
[ text, but not tables, given below in this post ]

EFSA. 2006.
Opinion of the Scientific Panel on Food Additives, Flavourings,
Processing Aids and Materials in contact with Food (AFC) on a request
from the Commission related to a new long-term carcinogenicity study
on
aspartame.
The EFSA Journal 356, 1-44.

Foran, J.A., Good, D.H., Carpenter, D.O., Hamilton, M.C., Knuth, B.A.,
Schwager, S.J. 2005.
Quantitative analysis of the benefits and risks of consuming farmed
and
wild salmon.
Journal of Nutrition 135, 2639-2643.

Gallus, S., Scotti, L., Negri, E., Talamini, R., Franceschi, S.,
Montella, M., Giacosa, A., Dal Maso, L., La Vecchia, C. 2007.
Artificial sweeteners and cancer risk in a network of case?control
studies,
Annals of Oncology, Advance Access, in press.

Keiding, N., Budtz-Jorgensen, E. 2004.
The precautionary principle and statistical approaches to uncertainty.
International Journal of Occupational Medicine,
Environmental Health 17, 147-151.

Leon, A.S., Hunninghake, D.B., Bell, C., Rassin, D.K., Tephly, T.R.
1989.
Safety of long-term large doses of aspartame.
Archives of Internal Medicine 149, 2318-2324.

NTP. 2005. NTP report on the toxicology studies of aspartame (CAS NO.
22839-47-0) in genetically modified (FVB Tg.AC hemizygous) and
B6.129-Cdkn2atm1Rdp (N2) deficient mice and carcinogenicity studies of
aspartame in genetically modified [B6.129-Trp53tm1Brd (N5)
haploinsufficient] mice (feed studies).
NIH Publication No. 06-4459. U.S. Department Of Health And Human
Services, Public Health Service, National Institutes of Health.

Page, L.A., Petrie, K.J., Wessely, S.C. 2006.
Psychosocial responses to environmental incidents: a review and a
proposed typology.
Journal of Psychosomatic Research 60, 413-422.

Ponce, R.A., Wong, E.Y., Faustman, E.M. 2001.
Quality adjusted life years (QALYs) and dose-response models in
environmental health policy analysis -? methodological considerations.
Science of the Total Environment 274, 79-91.

Rolls, B.J. 1991.
Effects of intense sweeteners on hunger, food intake, and body weight:
a
review.
International Journal of Obesity 53, 872-878.

Root, D.H. 2003.
Bacon, Boole, the EPA, and scientific standards.
Risk Analysis 23, 663-668.

Soffritti, M., Belpoggi, F., Degli Esposti, D., Lambertini, L. 2005.
Aspartame induces lymphomas and leukaemias in rats.
European Journal of Oncology 10, 107-116.

Soffritti, M., Belpoggi, F., Degli Esposti, D., Lambertini, L.,
Tibaldi,
E., Rigano, A. 2006.
First experimental demonstration of the multipotential carcinogenic
effects of aspartame administered in the feed to Sprague-Dawley rats.
Environmental Health Perspectives 114, 379-85.

Stegink, L.D. 1987.
The aspartame story: a model for the clinical testing of a food
additive.
American Journal of Clinical Nutrition 46, 204-215.

Food Chem Toxicol. 2007 Dec; 45(12): 2533-62. Epub 2007 Jun 26.
Application of the threshold of toxicological concern (TTC) to the
safety evaluation of cosmetic ingredients.
Kroes R, Renwick AG, Feron V, Galli CL, Gibney M, Greim H, Guy RH,
Lhuguenot JC, van de Sandt JJ.
Institute for Risk Assessment Sciences, Utrecht University, c/o
Seminariehof 38, NL- 3768 EE Soest, The Netherlands.

R. Kroes a,
A.G. Renwick b, Corresponding Author Contact Information, E-mail The
Corresponding Author,
V. Feron c,
C.L. Galli d,
M. Gibney e,
H. Greim f,
R.H. Guy g,
J.C. Lhuguenot h
and J.J.M. van de Sandt i

a Institute for Risk Assessment Sciences, Utrecht University, c/o
Seminariehof 38, NL- 3768 EE Soest, The Netherlands

b School of Medicine, University of Southampton, Biomedical Sciences
Building, Bassett Crescent East, Southampton SO16 7PX, UK

c Business Unit Toxicology and Applied Pharmacology, TNO Quality of
Life, P.O. Box 360, NL 3700 AJ Zeist, The Netherlands

d Laboratory of Toxicology, University of Milan, Via Balzaretti 9,
Milan
20133, Italy

e UCD Institute of Food and Health, University College Dublin,
Belfield,
Dublin 4, Ireland

f Technical University of Munich, Hohenbachernstrasse 15-17, D-85354
Freising-Weihenstephan, Germany

g University of Bath, Department of Pharmacy and Pharmacology,
Claverton
Down, Bath BA2 7AY, UK

h ENSBANA, Université de Bourgogne, 1 Esplanade Erasme, F-21000 Dijon,
France

i TNO Quality of Life, Utrechtseweg 48, 3704 HE Zeist, The Netherlands

Received 1 November 2006;  accepted 15 June 2007.
Available online 26 June 2007.

The threshold of toxicological concern (TTC) has been used for the
safety assessment of packaging migrants and flavouring agents that
occur
in food.

The approach compares the estimated oral intake with a TTC value
derived
from chronic oral toxicity data for structurally-related compounds

Application of the TTC approach to cosmetic ingredients and impurities
requires consideration of whether route-dependent differences in
first-pass metabolism could affect the applicability of TTC values
derived from oral data to the topical route.

The physicochemical characteristics of the chemical and the pattern of
cosmetic use would affect the long-term average internal dose that is
compared with the relevant TTC value.

Analysis has shown that the oral TTC values are valid for topical
exposures and that the relationship between the external topical dose
and the internal dose can be taken into account by conservative
default
adjustment factors.

The TTC approach relates to systemic effects, and use of the proposed
procedure would not provide an assessment of any local effects at the
site of application.

Overall the TTC approach provides a useful additional tool for the
safety evaluation of cosmetic ingredients and impurities of known
chemical structure in the absence of chemical-specific toxicology
data.
PMID: 17664037

Keywords: Risk assessment; Threshold of toxicological concern (TTC);
Cosmetic ingredients; Trans-dermal absorption

Abbreviations:
AUC, area under the plasma concentration?time curve;
BHA, butylated hydroxyl anisole;
BHT, butylated hydroxyl toluene;
Cmax, maximum observed concentration;
Csat, saturation concentration in water;
EFSA, European Food Safety Authority;
Jmax, maximum flux;
log Kp, permeability coefficient;
logP, log of the octanol: water partition coefficient;
MW, molecular weight;
NOAEL, no observed adverse effect level;
OP, organophosphate;
SCF, Scientific Committee on Food;
TTC, threshold of toxicological concern

star, open This paper is the output of an expert group organised by
Colipa (The European Cosmetic Toiletry and Perfumery Association;
Comité
de Liaison de la Parfumerie), Avenue Herrman Debroux 15A, B-1160
Auderghem, Brussels, Belgium;

observers who attended one or more meetings were
W. Aulmann, Henkel KGaA, 40191 Düsseldorf, Germany,
M. Bouvier d?Yvoire, European Commission, Joint Research Centre,
Institute for Health and Consumer Protection, European Centre for the
Validation of Alternative Methods,
via Enrico Fermi 1, 21020 Ispra (VA), Italy,
G. Nohynec, L?Oreal Recherche, Centre C. Zviak, 90 rue du General
Roguet, Clichy Cedex F ? 92583, France,
T. Peetso, European Commission, Health and Consumer Directorate, 1,
rue
de Genève, 1140 Brussels, Belgium
and P. Wagstaffe, European Commission, Management of Scientific
Committees, 200 rue de la Loi, 1049 Brussels, Belgium.

star, open star, open This paper is one of the last of the major
scientific publications of the late Professor Robert Kroes who died in
December 2006.

The participants at the meetings and his co-authors will remember him
as
an enthusiastic, stimulating and knowledgeable chairman, a renowned
toxicologist and pathologist, and a greatly missed colleague and
friend.

Corresponding Author Contact Information Corresponding author.
Tel.: +44 01229 588894.

A.W. Renwick in PubMed:

Items 1 - 20 of 187
Page 1 of 10

1: Kroes R, Renwick AG, Feron V, Galli CL, Gibney M, Greim H, Guy RH,
Lhuguenot JC, van de Sandt JJ.
Abstract
Application of the threshold of toxicological concern (TTC) to the
safety evaluation of cosmetic ingredients.
Food Chem Toxicol. 2007 Dec;45(12):2533-62. Epub 2007 Jun 26.
PMID: 17664037 [PubMed - in process]

2: Sved DW, Godsey JL, Ledyard SL, Mahoney AP, Stetson PL, Ho S, Myers
NR, Resnis P, Renwick AG.
Abstract
Absorption, tissue distribution, metabolism and elimination of taurine
given orally to rats.
Amino Acids. 2007;32(4):459-66. Epub 2007 Feb 16.
PMID: 17514497 [PubMed - indexed for MEDLINE]

3: Renwick AG, Nordmann H.
Abstract
First European conference on aspartame: putting safety and benefits
into
perspective. Synopsis of presentations and conclusions.
Food Chem Toxicol. 2007 Jul;45(7):1308-13. Epub 2007 Feb 22.
PMID: 17397982 [PubMed - indexed for MEDLINE]

4: Barlow S, Renwick AG, Kleiner J, Bridges JW, Busk L, Dybing E,
Edler
L, Eisenbrand G, Fink-Gremmels J, Knaap A, Kroes R, Liem D, Müller DJ,
Page S, Rolland V, Schlatter J, Tritscher A, Tueting W, Würtzen G.
Abstract
Risk assessment of substances that are both genotoxic and carcinogenic
report of an International Conference organized by EFSA and WHO with
support of ILSI Europe.
Food Chem Toxicol. 2006 Oct;44(10):1636-50. Epub 2006 Jul 8.
PMID: 16891049 [PubMed - indexed for MEDLINE]

5: O'Brien J, Renwick AG, Constable A, Dybing E, Müller DJ, Schlatter
J,
Slob W, Tueting W, van Benthem J, Williams GM, Wolfreys A.
Abstract
Approaches to the risk assessment of genotoxic carcinogens in food: a
critical appraisal.
Food Chem Toxicol. 2006 Oct;44(10):1613-35. Epub 2006 Jul 14. Review.
PMID: 16887251 [PubMed - indexed for MEDLINE]

6: Munro IC, Renwick AG.
Free Full Text
The 5th workshop on the assessment of adequate intake of dietary amino
acids: general discussion 2.
J Nutr. 2006 Jun;136(6 Suppl):1755S-1757S. No abstract available.
PMID: 16702351 [PubMed - indexed for MEDLINE]

7: Renwick AG.
Abstract
The intake of intense sweeteners - an update review.
Food Addit Contam. 2006 Apr;23(4):327-38. Review.
PMID: 16546879 [PubMed - indexed for MEDLINE]

8: Renwick AG.
Free Full Text
Toxicology of micronutrients: adverse effects and uncertainty.
J Nutr. 2006 Feb;136(2):493S-501S.
PMID: 16424134 [PubMed - indexed for MEDLINE]

9: Renwick AG.
Abstract
Structure-based thresholds of toxicological concern-guidance for
application to substances present at low levels in the diet.
Toxicol Appl Pharmacol. 2005 Sep 1;207(2 Suppl):585-91.
PMID: 16019047 [PubMed - in process]

10: Renwick AG, Walker R.
Free Full Text
The Fourth Workshop on the Assessment of Adequate Intake of Dietary
Amino Acids: general discussion of session 3 and overall workshop
discussion.
J Nutr. 2005 Jun;135(6 Suppl):1602S-6S. No abstract available.
PMID: 15930477 [PubMed - indexed for MEDLINE]

11: Dorne JL, Renwick AG.
Free Full Text
The refinement of uncertainty/safety factors in risk assessment by the
incorporation of data on toxicokinetic variability in humans.
Toxicol Sci. 2005 Jul;86(1):20-6. Epub 2005 Mar 30.
PMID: 15800035 [PubMed - indexed for MEDLINE]

12: Dorne JL, Walton K, Renwick AG.
Abstract
Human variability in xenobiotic metabolism and pathway-related
uncertainty factors for chemical risk assessment: a review.
Food Chem Toxicol. 2005 Feb;43(2):203-16. Review.
PMID: 15621332 [PubMed - indexed for MEDLINE]

13: Renwick AG, Flynn A, Fletcher RJ, Müller DJ, Tuijtelaars S,
Verhagen H.
Abstract
Risk-benefit analysis of micronutrients.
Food Chem Toxicol. 2004 Dec;42(12):1903-22. Review.
PMID: 15500928 [PubMed - indexed for MEDLINE]

14: Renwick AG.
Free Full Text
Establishing the upper end of the range of adequate and safe intakes
for
amino acids: a toxicologist's viewpoint.
J Nutr. 2004 Jun;134(6 Suppl):1617S-1624S; discussion 1630S-1632S,
1667S-1672S. Review.
PMID: 15173440 [PubMed - indexed for MEDLINE]

15: Renwick AG, Thompson JP, O'Shaughnessy M, Walter EJ.
Abstract
The metabolism of cyclamate to cyclohexylamine in humans during
long-term administration.
Toxicol Appl Pharmacol. 2004 May 1;196(3):367-80.
PMID: 15094307 [PubMed - indexed for MEDLINE]

16: Renwick AG.
Abstract
Toxicology databases and the concept of thresholds of toxicological
concern as used by the JECFA for the safety evaluation of flavouring
agents.
Toxicol Lett. 2004 Apr 1;149(1-3):223-34. Review.
PMID: 15093268 [PubMed - indexed for MEDLINE]

17: Renwick AG.
Abstract
Risk characterisation of chemicals in food.
Toxicol Lett. 2004 Apr 1;149(1-3):163-76. Review.
PMID: 15093262 [PubMed - indexed for MEDLINE]

18: Dorne JL, Walton K, Renwick AG.
Abstract
Human variability for metabolic pathways with limited data (CYP2A6,
CYP2C9, CYP2E1, ADH, esterases, glycine and sulphate conjugation).
Food Chem Toxicol. 2004 Mar;42(3):397-421.
PMID: 14871582 [PubMed - indexed for MEDLINE]

19: Serra-Majem L, Bassas L, García-Glosas R, Ribas L, Inglés C,
Casals
I, Saavedra P, Renwick AG.
Abstract
Cyclamate intake and cyclohexylamine excretion are not related to male
fertility in humans.
Food Addit Contam. 2003 Dec;20(12):1097-104.
PMID: 14726272 [PubMed - indexed for MEDLINE]

20: Dorne JL, Walton K, Renwick AG.
Abstract
Human variability in the renal elimination of foreign compounds and
renal excretion-related uncertainty factors for risk assessment.
Food Chem Toxicol. 2004 Feb;42(2):275-98. Review.
PMID: 14667473 [PubMed - indexed for MEDLINE]

http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=585516

Public Health Nutrition  (2006), 9: 523-530 Cambridge University Press
doi:10.1079/PHN2005874
Published online by Cambridge University Press 02Jan2007

   Research Article
National Diet and Nutrition Surveys: the British experience
Margaret Ashwell a1 c1,
Susan Barlow a2,
Sigrid Gibson a3
and Caroline Harris a4

a1 Ashwell Associates (Europe) Ltd, Ashwell Street, Ashwell,
Hertfordshire, SG7 5PZ and Oxford Brookes University, Headington
Campus,
Gipsy Lane, Oxford, OX3 0BP, UK

a2 Consultant in Toxicology, 8 Harrington Road, Brighton, East Sussex,
BN1 6RE, UK

a3 SiG-Nurture Ltd, 11 Woodway, Guildford, Surrey, GU1 2TF, UK
http://www.sig-nurture.com/whoarewe.htm
Sigrid A Gibson MA MSc RPHNutr.  sigridgibson@compuserve.com,
http://www.sig-nurture.com/contactus.htm
11 Woodway, Merrow, Guildford, Surrey GU1 2TF, UK
Telephone/fax: 01483 838018 (International: +44 1483 838018)
tel/fax +44 1483 838018,  sigrid@sig-nurture.com,sigridgibson@cs.com,
Director
Sigrid has degrees in Natural Sciences and Human Nutrition from
Cambridge and London Universities and is a registered public health
nutritionist.
She has over 20 years? experience in nutritional science, working with
government agencies, the food industry and universities.
Sigrid is the author of over 30 scientific publications on nutrition.
She is a member of the nutrition society and a founder member of the
freelance nutrition consultants? group SENSE.
[ vested interest clients:
Kellogg's
   *Breakfast cereal consumption and its associations with nutrient
intake and nutritional status in children (References  [22], [11],
[7] )

The Sugar Bureau
   *Further analyses of NDNS data on intakes of sugars and
associations with micronutrients, physical activity, obesity and
dental
caries (References [23],[13] [17-21], [10], [8]

The Biscuit, Cake, Chocolate and Confectionery Association (BCCCA)
   *Further analyses of NDNS data on food habits, physical activity
and body weight among young people (References [13], [5] )

The Meat and Livestock Commission
   *implications of reduced consumption of red meat for iron status
among women and children (References [15], [6], [4] ) ]

Scientific Publications since 1993

Sigrid A Gibson MA MSc RPHNutr.

1. De la Hunty, A., S. Gibson, and M. Ashwell (2006) ?A review of the
effectiveness of aspartame in helping with weight control?. Nutrition
Bulletin 31(2): p. 115-128. PDF: 205kB
http://www.sig-nurture.com/papers/aspartame_nbu_564.pdf

2. Ashwell, M., S. Barlow, S. Gibson and C. Harris (2006). "National
Diet and Nutrition Surveys: the British experience." Public Health
Nutrition 9 (4) 523-530. PDF:118kB

3. Gibson S (2005) Intake of sugars and soft drinks among young
people:
associations with body mass index and physical activity. Obesity
Reviews
6, S1, p46 WORD:47kB

4. Gibson, S & Ashwell, M (2004) Implications of low red meat
consumption for iron status of young people in Britain. Nutrition &
Food
Science 34 (6) 253-259. Abstract  PDF:163kB

5. Gibson, S, Lambert J & Neate, D (2004) Associations between weight
status, physical activity and consumption of biscuits, cakes and
confectionery among young people in Britain. British Nutrition
Foundation. Nutrition Bulletin 29 301-309. Abstract PDF:132kB

6. Gibson, S and Ashwell, M. (2003) The association between red and
processed meat consumption and iron intakes and status among British
adults. Public Health Nutrition 6 (4) 341-350. PDF:208kB

7. Gibson, S (2003) Micronutrient intakes, micronutrient status and
lipid profiles among young people consuming different amounts of
breakfast cereals: further analysis of data from the National Diet and
Nutrition Survey of Young People aged 4 to 18 years Public Health
Nutrition 6 (8) 815-820. PDF:129kB

8. Gibson S (2001) Dietary sugars and micronutrient dilution in normal
adults aged 65 years and over. Public Health Nutrition 4 (6)
1235-1244.
PDF:200kB

9. Lumbers, M., S. A. New, S. Gibson and M. C. Murphy (2001).
"Nutritional status in elderly female hip fracture patients:
comparison
with an age-matched home living group attending day centres." Br J
Nutr
85(6): 733-40.

10. Gibson SA (2000) Associations between energy density and
macronutrient composition in the diets of pre-school children: sugars
vs. starch. Int. J. Obesity 24, 633-638 Abstract

11. Gibson SA (2000) Breakfast cereal consumption in young children:
associations with non-milk extrinsic sugars and caries experience
further analysis of data from the UK National Diet and Nutrition
Survey
of children aged 1.5-4.5 years. . Public Health Nutrition 3 (2)
227-232.
PDF:119kB

12. Ashwell, M., G. Miller, and S. Gibson, (2000) A consensus review
of
the MAFF Lipids Programme: objectives and key achievements. British
Nutrition Foundation. Nutrition Bulletin 25, 155-158. Abstract

13. Gibson SA & Williams SA (1999) Dental caries in pre-school
children:
associations with social class, toothbrushing habit and consumption of
sugars and sugar-containing foods. Caries Research 33, 101-113.
Abstract

14. Gibson, S. (1999). "Iron status of pre-school children aged 1.5 to
4.5 years: associations with breakfast cereals, vitamin C and meat."
Proc Nutr. Soc 59: 49A.

15. Gibson SA (1999) Iron intake and iron status of pre-school
children:
associations with breakfast cereals, vitamin C and meat. Public Health
Nutrition 2 (4) 521-528. Abstract

16. Gibson, S. (1999). "The sugar:fat relationship revisited." Int J
Obes Relat Metab Disord 23(4): 441-3.

17. Gibson SA (1998) Hypothesis: parents may selectively restrict
sugar-containing foods for pre-school children with a high BMI. Int.
J.
Fd. Sci. Nutr. 49 , 65-70.

18. Gibson SA (1997) Do diets high in sugars compromise micronutrient
intakes? Micronutrient intakes in the Dietary and Nutritional Survey
of
British Adults according to dietary concentration of added, non-milk
extrinsic or total sugars. J. Hum. Nutr. Diet. 10, 125-133. Abstract

19. Gibson SA (1997) Non-milk extrinsic sugars in the diets of
pre-school children:
association with intakes of micronutrients, energy , fat and NSP . Br.
J. Nutr. 78 367-378. Abstract

20. Gibson SA. (1996) Are diets high in non-milk extrinsic sugars
conducive to obesity? An analysis from the Dietary and Nutritional
Survey of British Adults. J. Hum. Nutr. Diet. 9, 283-292. Abstract

21. Gibson SA. (1996) Are high-fat, high-sugar foods and diets
conducive
to obesity? Int. J. Fd. Sci. Nutr. 47, 405-415. Abstract

22. Gibson SA & O?Sullivan K (1995) Breakfast cereal consumption
patterns and nutrient intakes of British schoolchildren. J. Roy. Soc.
Hlth 115 366-370. Abstract

23. Gibson SA (1993) Consumption and sources of sugars in the diets of
British schoolchildren: are high-sugar diets nutritionally inferior?
J.
Hum. Nutr. Diet. 6, 355-371

a4 Exponent International Ltd, 2D Hornbeam Park Oval, Harrogate, HG2
8RB, UK

Abstract

Objective
The National Diet and Nutrition Surveys (NDNS) are a series of
government-funded surveys of food intake, nutrient intake and
nutritional status of individuals, undertaken to support nutritional
policy and risk assessment.

This paper summarises a review that considered the extent to which
NDNS
met the needs of users and suggested options for the future.

The Food Standards Agency has since progressed favoured options.

This paper aims to help others wishing to obtain this type of
information within their own populations.

Design A detailed questionnaire was used to probe use of data and
gather
opinions from users, producers and managers of the NDNS.

It asked about general information needs from NDNS and changes that
might be made.

This was followed by a two-day workshop which included discussion of
the
main issues and the generation of 19 possible future options for
consideration by the Agency.

Results
Options to improve effectiveness included methods to prioritise
breadth
and depth of coverage and possible ways of improving response and
compliance.

Strategies to make surveys more efficient and timely, such as adopting
a
rolling programme, disaggregating survey components, integrating with
other studies and improving data access, were also suggested.

A rolling programme, in which data are collected continuously, was the
favoured option to address some of the concerns and a strategy is now
in
place to achieve this.

Conclusions
There is widespread support for the NDNS from its users.

There is no alternative source for such high-quality data on food and
nutrient consumption and nutritional status and physical measurements
in
the same individuals.

Useful information, such as the potential value of using a rolling
programme from the outset, can be gained from this British experience
by
others wishing to measure food and nutrient intakes and status in
their
own populations.   PMID: 16870026

(Received April 19 2005)  (Accepted August 31 2005)

Key Words: Diet; Surveys; Britain; Status; NDNS; Food Standards
Agency;
Nutrition; Food chemical exposure; Rolling programme; Lessons

Correspondence: c1 *Corresponding author:  margaret@ashwell.uk.com,

"The authors wish to thank the Ajinomoto Company for financial
support."

http://www.sig-nurture.com/papers/aspartame_nbu_564.pdf  PDF: 205 kB

Blackwell Publishing Ltd Oxford, UKNBU
(c) 2006 British Nutrition Foundation

Review Article

Correspondence: Anne de la Hunty, Ashwell Associates (Europe) Ltd,
Ashwell Street, Ashwell, Hertfordshire SG7 5PZ, UK.
E-mail: annedelahunty@btinternet.com,

REVIEW

1. De la Hunty, A., S. Gibson, and M. Ashwell (2006) ?A review of the
effectiveness of aspartame in helping with weight control?.
Nutrition Bulletin 31(2): p. 115-128.
A review of the effectiveness of aspartame in helping with weight
control
Anne de la Hunty *,
Sigrid Gibson ?,
and Margaret Ashwell *

* Ashwell Associates (Europe) Ltd, Ashwell, Hertfordshire, UK

? SiG-Nurture Ltd, Guildford, Surrey, UK

? Oxford Brookes University, Headington Campus, Oxford, UK

Summary

Strategies to reverse the upward trend in obesity rates need to focus
on
both reducing energy intake and increasing energy expenditure.

The provision of low- or reduced-energy-dense foods is one way of
helping people to reduce their energy intake and so enable weight
maintenance or weight loss to occur.

The use of intense sweeteners as a substitute for sucrose potentially
offers one way of helping people to reduce the energy density of their
diet without any loss of palatability.

This report reviews the evidence for the effect of aspartame on weight
loss, weight maintenance and energy intakes in adults and addresses
the
question of how much energy is compensated for and whether the use of
aspartame-sweetened foods and drinks is an effective way to lose
weight.

All studies which examined the effect of substituting sugar with
either
aspartame alone or aspartame in combination with other intense
sweeteners on energy intake or bodyweight were identified.

Studies which were not randomised controlled trials in healthy adults
and which did not measure energy intakes for at least 24 h (for those
with energy intakes as an outcome measure) were excluded from the
analysis.

A minimum of 24-h energy intake data was set as the cut-off to ensure
that the full extent of any compensatory effects was seen. A total of
16
studies were included in the analysis.

Of these 16 studies, 15 had energy intake as an outcome measure.

The studies which used soft drinks as the vehicle for aspartame used
between 500 and about 2000 ml which is equivalent to about two to six
cans or bottles of soft drinks every day.

A significant reduction in energy intakes was seen with aspartame
compared with all types of control except when aspartame was compared
with non-sucrose controls such as water.

The most relevant comparisons are the parallel design studies which
compare the effects of aspartame with sucrose.

These had an overall effect size of 0.4 standardised difference (SD).

This corresponds to a mean reduction of about 10% of energy intake.

At an average energy intake of 9.3 MJ/day (average of adult men and
women aged 19?50 years)
this is a deficit of 0.93 MJ/day (222 kcal/day or 1560 kcal/week),
which would be predicted (using an energy value for obese tissue of
7500
kcal/kg) to result in a weight loss of around 0.2 kg/week with a
confidence interval 50% either side of this estimate.

Information on the extent of compensation was available for 12 of the
15
studies.

The weighted average of these figures was 32 %.

Compensation is likely to vary with a number of factors such as the
size
of the caloric deficit, the type of food or drink manipulated, and
timescale.

An estimate of the amount of compensation with soft drinks was
calculated from the four studies which used soft drinks only as the
vehicle.

A weighted average of these figures was 15.5 %.

A significant reduction in weight was seen.

The combined effect figure of 0.2 SD is a conservative figure as it
excludes comparisons where the controls gained weight because of their
high-sucrose diet and the long-term follow-up data in which the
aspartame groups regained less weight than the control group.

An effect of 0.2 SD corresponds to about a 3 % reduction in bodyweight
(2.3 kg for an adult weighing 75 kg).

Given the weighted average study length was 12 weeks, this gives an
estimated rate of weight loss of around 0.2 kg/week for a 75-kg adult.

The meta-analyses demonstrate that using foods and drinks sweetened
with
aspartame instead of sucrose results in a significant reduction in
both
energy intakes and bodyweight.

Meta-analyses both of energy intake and of weight loss produced an
estimated rate of weight loss of about 0.2 kg/week.

This close agreement between the figure calculated from reductions in
energy intake and actual measures of weight loss gives confidence that
this is a true effect.

The two meta-analyses used different sets of studies with widely
differing designs and controls.

Although this makes comparisons between them difficult, it suggests
that
the final figure of around 0.2 kg/week is robust and is applicable to
the variety of ways aspartame-containing foods are used by consumers.

This review has shown that using foods and drinks sweetened with
aspartame instead of those sweetened with sucrose is an effective way
to
maintain and lose weight without reducing the palatability of the
diet.

The decrease in energy intakes and the rate of weight loss that can
reasonably be achieved is low but meaningful and, on a population
basis,
more than sufficient to counteract the current average rate of weight
gain of around 0.007 kg/week.

On an individual basis, it provides a useful adjunct to other weight
loss regimes.

Some compensation for the substituted energy does occur but this is
only
about one-third of the energy replaced and is probably less when using
soft drinks sweetened with aspartame.

Nevertheless, these compensation values are derived from short-term
studies.

More data are needed over the longer term to determine whether a
tolerance to the effects is acquired.

To achieve the average rate of weight loss seen in these studies of
0.2
kg/week will require around a 220-kcal (0.93 MJ) deficit per day based
on an energy value for obese tissue of 7500 kcal/kg.

Assuming the higher rate of compensation (32 %), this would require
the
substitution of around 330 kcal/day (1.4 MJ/day) from sucrose with
aspartame (which is equivalent to around 88 g of sucrose).

Using the lower estimated rate of compensation for soft drinks alone
(15.5 %) would require the substitution of about 260 kcal/day (1.1
MJ/day) from sucrose with aspartame.

This is equivalent to 70 g of sucrose or about two cans of soft drinks
every day.

Keywords:
aspartame,energy intakes,intense sweeteners,meta-
analysis,obesity,weight
loss

Introduction

Obesity is one of the major public health issues in the UK.

Around two-thirds of the population are now overweight or obese, a
quadruple increase in 25 years.

If the present rates of increase continue, obesity will soon overtake
smoking as the biggest cause of premature death in the UK.

The economic costs of obesity and overweight are estimated to be
between
6.6 and 7.4 billion pounds per year (Health Select Committee 2004).

Obesity increases the risk of cancers, including breast cancer,
endometrial cancer and colon cancer, diabetes, coronary heart disease,
hypertension, insulin resistance, gall bladder disease and
osteoarthritis.

The psychological consequences of obesity are also huge and include
anxiety, depression, low self-esteem and lack of confidence.

Suicide is more common in obese people than normal-weight people (WHO
1998).

Life expectancy is reduced by about 9 years in obese people, and by
even
more if they also smoke.

Strategies to reverse the upward trend in obesity rates need to focus
on
both reducing energy intake and increasing energy expenditure.

The provision of low- or reduced-energy-dense foods is one way of
helping people to reduce their energy intake and so enable weight
maintenance or weight loss to occur.

The use of intense sweeteners as a substitute for sucrose potentially
offers one way of helping people to reduce the energy density
of their diet without any loss of palatability.

This is particularly the case with soft drinks as it is possible to
reduce the energy content of the drink to practically zero as the
energy
content is almost entirely provided by sucrose or similar.

However, the usefulness of intense sweeteners as an aid to weight loss
was questioned after reports that subjects had higher hunger ratings
after drinking an aspartame-sweetened drink than after plain water
(Blundell & Hill 1986).

Blundell and Hill argued that any calorie savings achieved with
intense
sweeteners were false and were likely to be offset by increased energy
intakes at subsequent meals.

Although these findings were not replicated by other groups, the
question of how much energy compensation occurs with the use of
intense
sweeteners has been the subject of much research.

This report reviews the evidence for the effect of aspartame on weight
loss, weight maintenance and energy intakes in adults and addresses
the
question of how much energy is compensated for and whether the use of
aspartame-sweetened foods and drinks is an effective way to lose
weight.

Methods and summary of data

All studies which examined the effect of substituting sugar with
either
aspartame alone or aspartame in combination with other intense
sweeteners on energy intake or bodyweight in adults were identified.

Reviews by Kanders et al. (1996), Rolls and Shide (1996),
Drewnowski (1999), Vermunt et al. (2003) and Benton (2005) were used
as
a starting point for the search.

Studies which were not randomised controlled trials in healthy adults
and which did not measure energy intakes for at least 24 h (for those
with energy intakes as an outcome measure) were excluded from the
analysis.

A minimum of 24-h energy intake data was set as the cut-off to ensure
that the full extent of any compensatory effects was seen.

A total of 16 studies were included in the analysis.

Of these 16 studies, 15 had energy intake as an outcome measure
(Porikos et al. 1977, 1982;
Foltin et al. 1988, 1990, 1992;
Evans 1989;
Mattes 1990;
Tordoff & Alleva 1990;
Naismith & Rhodes 1995;
Blackburn et al. 1997;
Gatenby et al. 1997;
Lavin et al. 1997;
Reid & Hammersley 1998;
Raben et al. 2002;
Van Wymelbeke et al. 2004)

and 9 had weight loss
Porikos et al. 1977, 1982;
Kanders et al. 1988, 1990;
Tordoff & Alleva 1990;
Naismith & Rhodes 1995;
Blackburn et al. 1997;
Gatenby et al. 1997;
Reid & Hammersley 1998;
Raben et al. 2002).

The included studies show considerable variation in their design,
study
population, duration and type of control.

The studies with energy intake as the outcome measure are summarised
in
Table 1 while those with weight loss are summarised in Table 2.

Number of subjects

The largest trial had 163 subjects (Blackburn et al. 1997)
while the two smallest trials had six and eight subjects
(Porikos et al. 1977, 1982).

Most trials had between 10?30 subjects.

Table 1 Summary of studies with energy intakes as an outcome measure

Table 2 Summary of data of studies with weight as an outcome measure

Length of trials

The longest trial had an intervention period of 19 weeks, and then
followed up subjects for 3 years (Blackburn et al. 1997) while the
shortest trial had an intervention period of only 1 day
(Lavin et al. 1997).

Seven trials had an intervention period less than 1 week
while three trials lasted for 10 or 12 weeks.

Body mass index

Subjects in three of the trials were obese with body mass index over
30
kg/m2 (Porikos et al. 1977; Kanders et al. 1988; Blackburn et al.
1997).

Two of these trials were weight loss trials where average body mass
indices were around 37 kg/m2.

The other trials were in normalweight or overweight people.

Energy-restricted diet

Two trials tested the effectiveness of aspartame-containing products
in
people on an energy-restricted diet, who were trying to lose weight
(Kanders et al. 1988; Blackburn et al. 1997).

The other trials compared the effect of substituting foods and drinks
containing aspartame/intense sweeteners for similar foods containing
sugar in an ab libitum diet.

Setting

The studies were carried out in both metabolic ward situations and in
the free-living population.

Some of the studies in metabolic wards allowed subjects to determine
the
amount of food they consumed from a platter of foods offered to them
(Porikos et al. 1977, 1982) while other studies allowed them to select
the food they wanted from a list of available foods
(Foltin et al. 1988, 1990, 1992).

Studies in free-living populations either gave subjects daily food
supplements (Mattes 1990; Raben et al. 2002), provided meals on site
(Naismith & Rhodes 1995) or told subjects to replace items in their
diet with reduced sugar versions of their normal foods
(Gatenby et al. 1997).

Intervention vehicle

Four trials used soft drinks only as the vehicle for aspartame
substitution.

In one trial (Tordoff & Alleva 1990), subjects were required to drink
the equivalent of four bottles (1135 g/day) of soft drinks each day
while in another (Reid & Hammersley 1998), subjects were recruited on
the basis of habitually drinking at least two bottles (250 ml each) of
soft drinks a day.

In the study by Van Wymelbeke et al. (2004), subjects were required
to drink 2 l of a beverage on the study days while those in the study
by
Lavin et al. (1997) were given four cans (330 ml) of lemonade to drink
at defined times during the day.

In a fifth trial (Raben et al. 2002), 80 % by weight of the
substituted
foods were given as soft drinks as this reflects the distribution of
the
population?s intake of intense sweeteners.

The average intake of soft drinks in this study was 1285 g/day.

The other trials used breakfast cereals (Mattes 1990) or selections of
commercially available foods and drinks sweetened with aspartame
(Porikos et al. 1977, 1982; Kanders et al. 1988; Blackburn et al.
1997)
or a mixture of intense sweeteners (Foltin et al. 1988, 1990, 1992;
Naismith & Rhodes 1995; Gatenby et al. 1997; Raben et al. 2002).

Amount of food or energy substituted

This information was not always reported, nor was it reported in a
similar way in each study.

Some studies reported the amount of food that had been substituted
while others reported the amount of sucrose or the percentage of
energy
substituted by aspartame products.

The studies which used soft drinks as the vehicle for aspartame used
between 500 and about 2000 ml which is equivalent to about two to six
cans or bottles of soft drinks every day.

One study reported that about 2000 g of food per day was substituted
for
aspartamecontaining foods (Porikos et al. 1977) while another reported
that about 25 % of energy was substituted (Porikos et al. 1982).

The amount of energy substituted by aspartame ranged from
about 200 kcal/day (0.84 MJ) (Reid & Hammersley 1998)
to about 1000 kcal/day (4.2 MJ) (Foltin et al. 1992).

Controls

The choice of control has an important effect on the outcome of the
study and the relevance of the control diet to the ?normal? diet is
open
to question in many of the studies.

For a number of studies, the control diet involved the addition of a
large amount of sucrosecontaining foods which did not reflect the
subjects? previous diets and on which subjects gained weight
(Porikos et al. 1977, 1982).

Whether the control period was before or after the aspartame period
also
has an effect on the outcome.

Ten studies had a parallel sucrose-containing control while five
studies
compared aspartame with sucrose before and/or after
(Porikos et al. 1977, 1982; Foltin et al. 1988; Evans 1989;
Naismith & Rhodes 1995).

Three studies also had an additional control of carbonated mineral
water
(Lavin et al. 1997), plain cereal (Mattes 1990)
or no soda (Tordoff & Alleva 1990).

In a number of studies, comparisons were also made with baseline
values
(Mattes 1990; Foltin et al. 1992; Raben et al. 2002).

Results of meta-analysis

Energy intakes

The 15 studies with energy intake as an outcome measure were subjected
to a meta-analysis to calculate the combined effect (expressed as the
standardised difference or SD) of all the studies together (Fig. 1).

Effect sizes for each study were computed from the sample sizes, and
either group means and standard deviation or P-values.

Data presentation lacked statistical detail in a few studies,
requiring
standard deviations to be calculated or imputed.

Studies varied in their design, subjects and types of control, so we
used a random effects model (which allows that the true effect might
differ from study to study) rather than a fixed effect model (which
assumes that the true effect is the same for all studies).

Hedges? adjustment was used, which gave a more conservative estimate
of
effect size.

The plots illustrate the size and direction of effect for each study
and
the overall effect of all studies combined, with 95 % (lower and
upper)
confidence intervals.

All analyses were performed using the software package Comprehensive
Meta-analysis (Biostat Inc., Englewood, NJ, USA).

The studies were analysed according to the type of controls as this
affected the results.

The different controls were baseline diet, parallel sucrose control,
non-sucrose control (e.g. water) or the reintroduction of sucrose.

The effect of substituting aspartame-sweetened drinks with each of
these
controls is shown in Table 3.

A significant reduction in energy intakes was seen with aspartame
compared with all types of control except when aspartame was compared
with non-sucrose controls such as water.

The most relevant comparisons are the parallel design studies which
compare the effects of aspartame with sucrose.

These had an overall effect size of 0.4 SD.

As the coefficient of variation of energy intake is around 25 %, this
corresponds to a mean reduction of about 10% of energy intake.

At an average energy intake of 9.3 MJ/day
(average of adult men and women aged 19?50 years)
this is a deficit of 0.93 MJ/day (222 kcal/day or 1560 kcal/week),
which would be predicted
(using an energy value for obese tissue of 7500 kcal/kg)
to result in a weight loss of around 0.2 kg/week
with a confidence interval 50% either side of this estimate.

The strongest effect was found for comparisons in which the
aspartame/low-sugar period was followed by a normal/high-sucrose diet
(effect size > 1 SD).

This suggests that increases in energy intake are less well
compensated than decreases in energy intake.

Average level of compensation

Compensation is the explanation for the difference between the
theoretical energy intake and the actual energy intake in any study.

The extent of compensation that occurred in the different studies was
not reported for all studies, although it could be calculated for some
studies from information given in the paper.

Information on the extent of compensation was available for 12 of the
15
studies.

The weighted average of these figures was 32 % although they ranged
from
1 % to 111 % (see Table 1).

This estimate agrees well with the value of 36 % for solid food
calculated by Mattes (1996) in a meta-analysis of 42 studies.

Compensation is likely to vary with a number of factors such as the
size
of the caloric deficit, the type of food or drink manipulated, and
timescale.

An estimate of the amount of compensation with soft drinks was
calculated from the four studies which used soft drinks only as the
vehicle (Tordoff & Alleva 1990; Lavin et al. 1997;
Reid & Hammersley 1998; Van Wymelbeke et al. 2004).

A weighted average of these figures was 15.5 %.

This agrees with suggestions by other authors that compensation is
likely to be less where the substitution vehicle is a liquid.

This is because energy obtained from liquids is less satisfying than
energy from solid foods, making it easier to overconsume energy when
drinking liquids than when eating solids
(Beridot-Therond et al. 1998; Van Wymelbeke et al. 2004).

Table 3 Summary of meta-analysis of energy intake

Type of control;(number of study outcomes); -- P-value; Effect (SD);
--------------------------------- 95 % confidence limits: Lower;
Upper;

Baseline (8)------------------------------------- 0.017 0.58 0.10 1.05

Non-sucrose control (7)-------------------------- 0.377 0.18 -0.22
0.58

Sucrose after (5)-------------------------------- 0.000 1.14 0.52 1.76

Sucrose parallel (12)---------------------------- 0.033 0.40 0.03 0.77

All studies (32)--------------------------------- 0.000 0.47 0.24 0.70

SD, standardised difference.

Figure 1 Meta-analysis of studies of energy reduction with sweetener
vs.
other regime (subgroup analysis).
CI, confidence intervals; SD, standardised difference.

Figure 2 Meta-analysis of studies of weight loss with sweetener vs.
sucrose regime (all studies).
CI, confidence intervals; SD, standardised difference.

Weight loss

A meta-analysis of the 9 studies with weight loss as an outcome
measure
was also conducted to calculate the combined effect of aspartame on
weight loss.

The analysis was conducted in three stages.

The first stage used all weight outcomes including follow-up weights,
the second excluded studies in which the control group gained weight
and the third excluded follow-up periods as well.

Forrest plots for these analyses are shown in Figures 2?4.

The combined effects of the results for the different analyses are
shown
in Table 4.

A significant reduction in weight was seen for all three analyses.

The final combined effect figure of 0.221 SD (from Fig. 4) is a
conservative figure as it excludes comparisons where the controls
gained
weight because of their high-sucrose diet and the long-term follow-up
data in which the aspartame groups regained less weight than
the control group.

This gave the appearance of an increasing weight loss with aspartame.

As the coefficient of variation for bodyweight calculated from the
larger studies was 15 %, an effect of 0.2 SD corresponds to about a 3
%
reduction in bodyweight (2.3 kg for an adult weighing 75 kg

Figure 3 Meta-analysis of studies of weight loss with sweetener
(excluding outcomes with weight gain on sucrose regime).
CI, confidence intervals; SD, standardised difference.

Figure 4 Meta-analysis of studies of weight loss (intervention period
only, excluding studies with weight gain on sucrose regime).
CI, confidence intervals; SD, standardised difference.

Table 4 Summary of meta-analysis of weight loss:
effect size (as SD) by type of study
Studies; (number of study outcomes); P-value; Effect (SD)
---------------------------------- 95% confidence limits: Lower;
Upper;

All studies of weight loss (20)--------------- 0.0000 0.385 0.242
0.528
Excluding those
with a weight-gaining control (11) ------------ 0.001 0.295 0.129
0.460
Excluding weight-gaining controls
and follow-up data (8) ------------------------ 0.050 0.221 0.000
0.443

SD, standardised difference.

Given the weighted average study length was 12 weeks, this gives
an estimated rate of weight loss of around 0.2 kg/week
for a 75 kg adult.

Weight maintenance

The two weight loss studies followed participants up for 1 year
(Kanders et al. 1990) and 3 years (Blackburn et al. 1997)
after the initial weight loss phase of the study.

In the Kanders et al. study, weight maintenance was better in men who
consumed more aspartame products over the follow-up period but there
was
no difference for women.

The Blackburn et al. study found that weight regain was significantly
less in those consuming aspartame-sweetened products than in those who
were not.

After 3 years, those who consumed aspartame products had maintained a
weight loss of 5.1 kg compared with those in the no-aspartame group
who
had regained all their previous weight loss.

Conclusions

The meta-analyses demonstrate that using foods and drinks sweetened
with
aspartame instead of sucrose results in a significant reduction in
both
energy intakes and bodyweight.

The meta-analyses both of energy intake and of weight loss produced an
estimated rate of weight loss of about 0.2 kg/week.

This close agreement between the figure calculated from reductions in
energy intake and actual measures of weight loss gives confidence
that this is a true effect.

The two meta-analyses used different sets of studies with widely
differing designs and controls.

Although this makes comparisons between them difficult, it suggests
that
the final figure of around 0.2 kg/week is robust and is applicable to
the variety of ways aspartame-containing foods are used by consumers.

This is a low but meaningful rate of weight loss and, on a population
basis, more than sufficient to counteract the current average rate of
weight gain of around 0.007 kg/week
(NHS Health and Social Care Information Centre 2005).

On an individual basis, it provides a useful adjunct to other weight
loss regimes.

Unconscious compensation

An estimated compensation rate of around one-third of energy
substituted
was calculated from the studies which provided sufficient information.

However, basing the calculations only on studies which used soft
drinks
as the substitution vehicle gave a lower figure of about half this,
i.e.
around 15 %.

This is reasonable as it islikely that energy obtained from liquids is
less satiating than that obtained from foods and so the body is less
likely to adjust for the energy contained in a sucrosecontaining
drink than it would if the same amount of energy was provided in a
solid
food.

Nevertheless, these compensation values are derived from short-term
studies.

More data are needed over the longer term to determine whether a
tolerance to the effects is acquired.

Conscious adjustment

In addition to an unconscious compensatory effect, the effects of the
conscious adjustments and trade-offs that people consuming low-calorie
foods make also need to be considered.

Most of the studies included in the metaanalysis were blind and people
did not know whether they were consuming the sugar or the
aspartamecontaining version.

Therefore, these studies are not able to address this question.

Nevertheless, one study was not blind (Gatenby et al. 1997) and two
studies included an unblind comparison (Mattes 1990; Lavin et al.
1997).

In the Gatenby et al. study, subjects consuming the low-sugar versions
had a non-significantly lower energy intake than those consuming
the normal versions; however, some subjects increased their energy
intake suggesting that there was an element of adjustment.

In the Mattes study, both groups increased their energy intakes
(non-significantly) compared with the sucrose controls but those who
were aware they had consumed a low-calorie cereal did so more than
those
who were unaware.

In the Lavin et al. study, both informed and uninformed groups
compensated for the low-calorie drink (Lavin et al. 1997).

During the follow-up period of the Blackburn et al. trial, subjects
were
encouraged to continue using or not using aspartame-sweetened products
according to what they had been doing during the intervention period.

Over the next 3 years, those who used the aspartamesweetened foods
regained significantly less weight than those who did not
(Blackburn et al. 1997).

Therefore, although the effect of conscious adjustment might mitigate
against the expected reduction in energy intakes with casual aspartame
use, it is likely to be less important for people determinedly trying
to
control their weight.

Effectiveness of aspartame for weight loss

This review has shown that using foods and drinks sweetened with
aspartame instead of those sweetened with sucrose is an effective way
to
maintain and lose weight without losing the palatability of the diet.

The decrease in energy intakes and the rate of weight loss that can
reasonably be achieved is low but meaningful.

Some compensation for the substituted energy does occur but this is
only
about one-third of the energy replaced and is probably less when using
soft drinks sweetened with aspartame.

Nevertheless, these compensation values are derived from short-term
studies.

More data are needed over the longer term to determine whether a
tolerance to the effects is acquired.

To achieve the average rate of weight loss seen in these studies of
0.2
kg/week will require around a 220-kcal deficit (0.93 MJ) per day using
an energy value for obese tissue of 7500 kcal/kg.

Assuming the higher rate of compensation (32 %), this would require
the
substitution of around 330 kcal/day (1.4 MJ/day) from sucrose with
aspartame (which is equivalent to around 88 g of sucrose).

Using the lower estimated rate of compensation for soft drinks alone
(15.5 %) would require the substitution
of about 260 kcal/day (1.1 MJ/day) from sucrose with aspartame.

This is equivalent to 70 g of sucrose or about two cans of soft drinks
every day.

Acknowledgements

The authors wish to thank the Ajinomoto Company for financial support.

References

Benton D (2005) Can artificial sweeteners help control body
weight and prevent obesity? Nutrition Research Reviews 18:
63?76.

Beridot-Therond ME, Arts I, Fantino M et al. (1998) Short-term
effects of the flavour of drinks on ingestive behaviours in man.
Appetite 31: 67?81.

Blackburn GL, Kanders BS, Lavin PT et al. (1997) The effect of
aspartame
as part of a multidisciplinary weight-control program on
short- and long-term control of body weight. American Journal of
Clinical Nutrition 65: 409?18.

Blundell JE & Hill AJ (1986) Paradoxical effects of an intense
sweetener
(aspartame) on appetite. Lancet 1: 1092?3.

Drewnowski A (1999) Intense sweeteners and energy density of foods:
implications for weight control. European Journal of Clinical
Nutrition 53: 757?63.

Evans E (1989) Effect of withdrawal of artificial sweeteners on energy
intake of stabilized post-obese women. International Journal of
Obesity 13 (Suppl. 1): 111.

Foltin RW, Fischman MW, Emurian CS et al. (1988) Compensation
for caloric dilution in humans given unrestricted access to food in a
residential laboratory. Appetite 10: 13?24.

Foltin RW, Fischman MW, Moran TH et al. (1990) Caloric compensation
for lunches varying in fat and carbohydrate content by
humans in a residential laboratory. American Journal of Clinical
Nutrition 52: 969?80.

Foltin RW, Rolls BJ, Moran TH et al. (1992) Caloric, but not
macronutrient, compensation by humans for required-eating occasions
with meals and snack varying in fat and carbohydrate. American
Journal of Clinical Nutrition 55: 331?42.

Gatenby SJ, Aaron JI, Jack VA et al. (1997) Extended use of foods
modified in fat and sugar content: nutritional implications in a
freeliving female population. American Journal of Clinical Nutrition
65: 1867?73.

Health Select Committee (2004) Third Report: Obesity. H. O. Commons:
London.

Kanders BS, Lavin JH, Kowalchuk MB et al. (1990) Do aspartame
(APM)-sweetened foods and beverages in the long-term aid in longterm
control of body weight? American Journal of Clinical Nutrition
51: 515 (abstract).

Kanders BS, Blackburn GL, Lavin PT et al. (1996) Evaluation of
weight control. In: The Clinical Evaluation of a Food Additive:
Assessment of Aspartame (C Tschanz, HH Butchko, WW Stargel,
FM Kotsonsis eds), pp. 289?99. CRC Press: Boca Raton, FL.

Kanders BS, Lavin PT, Kowalchuk MB et al. (1988) An evaluation of
the effect of aspartame on weight loss. Appetite 11 (Suppl. 1): 73?
84.

Lavin JH, French SJ & Read NW (1997) The effect of sucrose- and
aspartame-sweetened drinks on energy intake, hunger and food
choice of female, moderately restrained eaters. International Journal
of Obesity and Related Metabolic Disorders 21: 37?42.

Mattes R (1990) Effects of aspartame and sucrose on hunger and
energy intake in humans. Physiology and Behavior 47: 1037?44.

Mattes RD (1996) Dietary compensation by humans for supplemental
energy provided as ethanol or carbohydrate in fluids. Physiology
and Behavior 59: 179?87.

Naismith D & Rhodes C (1995) Adjustment in energy intake following
the covert removal of sugar from the diet. Journal of Human
Nutrition and Dietetics 8: 167?75.

NHS Health and Social Care Information Centre (2005) Health Survey
for England 2004 ? Updating of Trend Data to Include 2004
Data. NHS. Available at:
http://www.ic.nhs.uk/pubs/hlthsvyeng2004upd.

Porikos KP, Booth G & Van Itallie TB (1977) Effect of covert
nutritive dilution on the spontaneous food intake of obese
individuals:
a pilot study. American Journal of Clinical Nutrition 30: 1638?44.

Porikos KP, Hesser MF & van Itallie TB (1982) Caloric regulation in
normal-weight men maintained on a palatable diet of conventional
foods. Physiology and Behavior 29: 293?300.

Raben A, Vasilaras TH, Moller AC et al. (2002) Sucrose compared
with artificial sweeteners: different effects on ad libitum food
intake
and body weight after 10 wk of supplementation in overweight subjects.
American Journal of Clinical Nutrition 76: 721?9.

Reid M & Hammersley R (1998) The effects of blind substitution of
aspartame-sweetened for sugar-sweetened soft drinks on appetite
and mood. British Food Journal 100: 254?9.

Rolls BJ & Shide DJ (1996) Evaluation of hunger, food intake and
body weight. In: The Clinical Evaluation of a Food Additive:
Assessment of Aspartame. (C Tschanz, HH Butchko, WW Stargel,
FM Kotsonsis eds), pp. 275?87. CRC Press: Boca Raton, FL.

Tordoff MG & Alleva AM (1990) Effect of drinking soda
sweetened with aspartame or high-fructose corn syrup on food
intake and body weight. American Journal of Clinical Nutrition 51:
963?9.

Van Wymelbeke V, Beridot-Therond ME, de La Gueronniere V et al.
(2004) Influence of repeated consumption of beverages containing
sucrose or intense sweeteners on food intake. European Journal of
Clinical Nutrition 58: 154?61.

Vermunt SH, Pasman WJ, Schaafsma G et al. (2003) Effects of sugar
intake on body weight: a review. Obesity Review 4: 91?9.

WHO (World Health Organization) (1998) Obesity: Preventing and
Managing the Global Epidemic. Report of WHO Consultation on
Obesity. WHO: Geneva.

[ http://www1.imperial.ac.uk/medicine/people/a.boobis/
Prof. Alan R. Boobis OBE +44 (0)20 8383 2041 a.boobis@imperial.ac.uk,
http://www1.imperial.ac.uk/medicine/people/a.boobis/
Section of Experimental Medicine and Toxicology, Division of Medicine,
Imperial College London, Hammersmith Campus, Ducane Road, London W12
0NN, UK.

Food Chem Toxicol. 2007 Nov; 45(11): 2126-37. Epub 2007 May 24.
Searching for novel biomarkers of centrally and peripehrally-acting
neurotoxicants, using surface-enhanced lasesorption/ionisation-time-of-
flight mass spectrometry (SELDI-TOF MS).
Min Fang  m.fang@imperial.ac.uk,
Alan R. Boobis  a.boobis@imperial.ac.uk,
Robert J. Edwards Tel.: +44 20 8383 2055; fax: +44 20 8383 2066.
r.edwards@imperial.ac.uk,
Section on Experimental Medicine & Toxicology, Division of Medicine,
Imperial College London, Hammersmith campus, Du Cane Road,
London W12 0NN, UK.

The neurotoxicity of chemicals to humans is difficult to monitor as
there are no suitable methods of detecting early neuronal dysfunction.

Here, a proof of principle study was designed to assess the potential
of identifying protein biomarkers in accessible biofluids for this
purpose.

Groups of rats were treated with a range of doses of the model
neurotoxicants, acrylamide (0, 2, 10, 50mg/kg) and methylmercury (0,
0.2, 1, 5mg/kg) for up to 3 weeks and samples of serum, urine, and
cerebral spinal fluid analysed by surface-enhanced laser desorption/
ionisation-time-of-flight mass spectrometry.

There was no neuropathology up to the highest dose tested.

Protein profiles were obtained from all samples and changes in the
levels of many proteins were detected in both serum and urine,
although not cerebral spinal fluid.

In serum, the combination of three protein ion levels with m/z values
of 4968, 9402 and 12,948 was able to correctly classify the treatment
groups thus: 88% control, 100% acrylamide, 92% methylmercury.

In urine, three protein ions with m/z values of 4944, 12,966 and
21,992 classified correctly the groups: 67% control, 94% acrylamide,
97% methylmercury.

Similar classifications using other serum and urinary protein ions
were also possible. This indicates the potential of serum and urine
protein biomarkers for the assessment of sub-clinical neurotoxicity.
PMID: 17602814

Carcinogenesis, Vol. 25, No. 6, 1053-1062, June 2004
Carcinogenesis vol.25 no.6 (c) Oxford University Press 2004; all rights
reserved.
ARTICLE
Urinary N2-(2'-deoxyguanosin-8-yl)PhIP as a biomarker for PhIP
exposure
Min Fang 1,
Robert J. Edwards 1,
Michael Bartlet-Jones 3,
Graham W. Taylor 2,
Stephen Murray 2,4  s.murray@imperial.ac.uk,
and Alan R. Boobis 1

1 Section of Experimental Medicine and Toxicology
2 Section on Proteomics, Division of Medicine, Imperial College
London, Hammersmith Campus, Du Cane Road, London W12 ONN, UK
3 Cancer Research UK, Lincoln's Inn Fields, London WC2A 3PX, UK

4 To whom correspondence should be addressed  s.murray@imperial.ac.uk,

Prof. R. Chen and Prof. S. Sun, Department of Medical Genetics, Second
Military Medical University, 800 Xiangyin Road, Shanghai 200433,
China. E-mail: rwchen@smmu.edu.cn, shsun@vip.sina.com, ]
////////////////////////////////////////////////////////////

details on 6 epidemiological studies since 2004 on diet soda (mainly
aspartame) correlations, as well as 14 other mainstream studies on
aspartame toxicity since summer 2005: Murray 2007.11.18
http://rmforall.blogspot.com/2007_11_01_archive.htm
Wednesday, November 14, 2007
http://groups.yahoo.com/group/aspartameNM/message/1490

"Of course, everyone chooses, as a natural priority, to enjoy peace,
joy, and love by helping to find, quickly share, and positively act
upon evidence about healthy and safe food, drink, and environment."

Rich Murray, MA Room For All rmforall@comcast.net
505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505

http://RMForAll.blogspot.com  new primary archive

http://groups.yahoo.com/group/aspartameNM/messages
group with 112 members, 1,491 posts in a public,
searchable archive

http://rmforall.blogspot.com/2007_09_01_archive.htm
Saturday, September 15, 2007
http://groups.yahoo.com/group/aspartameNM/message/1472
bias, omissions, incuriosity = opportunity, aspartame safety
evaluation, Magnuson BA, Burdock GA, Williams GM, 7 more, 2007 Sept,
Ajinomoto funded 98 pages  html [$ 32 781888262_content.pdf]: Murray
2007.09.15
////////////////////////////////////////////////////////////

[ This layman review gives detailed access to the gist of six
epidemiological studies since 2004, two in 2007, that show
correlations of diet soda (largely aspartame) with health issues.

Probably studies of the correlations at the top 0.1 to 1.0 % level of
use over periods of years by people in vulnerable groups are needed.

http://groups.yahoo.com/group/aspartameNM/message/1141
Nurses Health Study can quickly reveal the extent of aspartame
(methanol, formaldehyde, formic acid) toxicity: Murray 2004.11.21

The Nurses Health Study is a bonanza of information about the health
of
probably hundreds of nurses who use 6 or more cans daily of diet soft
drinks -- they have also stored blood and tissue samples from their
immense pool of subjects, over 100,000 for decades.

In total, there are 20 mainstream studies about negative effects with
aspartame since summer, 2005, listed in this review, included many
about the detailed biochemistry involved. ]
////////////////////////////////////////////////////////////

http://RMForAll.blogspot.com September 21, 2007
http://groups.yahoo.com/group/aspartameNM/message/1475

19,000 people, the 4% of users of aspartame who drink average 5 cans
daily, have more problems in NIH AARP study of 474,000 people: Murray
2007.09.21

This is the first good data about the percentage of aspartame users
who
use over 3 cans daily, averaging 5 cans daily at 200 mg per 12 oz can
diet soda.

About 4% of 473,984 is 19,000 people, with a peak intake of 17 cans
daily, and average 5 cans daily.

It would be worthwhile to investigate a wide variety of symptoms for
the
0.1% of highest level users, about 500 people.

For about 200 million USA aspartame users, this would be 200,000
people.

Table 1 reveals consistent increase in problems from

--------------------- zero to (400 - 600) to (over 600) mg/d
aspartame intake:

% of cohert ---------- 46 -------- 5 -------- 4 %

mean aspartame mg/d --- 0 -------441 ------ 986

16+ education -------- 37 ------- 40 ------- 34 %

diabetes history ------ 3 ------- 22 ------- 26 %

alcohol g/d ---------- 14 ------- 11 ------- 13

never smoke ---------- 36 ------- 31 ------- 29 %

Body Mass Index ------ 26 ------- 29 ------- 29

18.5 - 25 ------------ 42 ------- 21 ------- 19 %

30 - 35 -------------- 13 ------- 23 ------- 26 %

over 35 --------------- 4 ------- 10 ------- 13 %

Physical activity %:

under 3-4/mo --------- 32 ------- 32 ------- 37 %

under 1-2/wk --------- 22 ------- 21 ------- 19 %

over 3-4/wk ---------- 45 ------- 45 ------- 43 %

Calories kcal ----- 1,919 ---- 1,855 ---- 2,044 %

Caffeine mg/d ------- 393 ------ 364 ------ 424

There do seem to be many increases of problems
from the second to third row, as mean aspartame use doubles.

Granted, this is cherry picking the data, selecting interesting
patterns.

Correlations alone do not prove any direction of causation.

Nevertheless, it may be of value to study the correlations for
increasing aspartame intake among the 4 % using over 600 mg, the
equivalent of 3 cans 12-oz cans diet soda daily.
The average use for this group is 5 cans daily.

For instance, are a minority of these heavy users displaying the great
majority of the problems that are reflected in the mean for each level
of use, with most users only having little or no increase in problems?

This is a group of about 20,000 people.

"We cannot exclude the possibility that higher aspartame consumption
than that observed in this study may be associated with an elevated
risk
of hematopoietic or brain cancers."

http://cebp.aacrjournals.org/cgi/content/full/15/9/1654 free full text
http://cebp.aacrjournals.org/cgi/reprint/15/9/1654 free full text pdf

Cancer Epidemiology Biomarkers & Prevention Vol. 15, 1654-1659,
September 2006
(c) 2006 American Association for Cancer Research

Consumption of Aspartame-Containing Beverages and Incidence of
Hematopoietic and Brain Malignancies

Unhee Lim 1,
Amy F. Subar 2, subara@mail.nih.gov,
Traci Mouw 1,
Patricia Hartge 1,
Lindsay M. Morton 1,
Rachael Stolzenberg-Solomon 1,
David Campbell 3,
Albert R. Hollenbeck 4
and Arthur Schatzkin 1

1 Division of Cancer Epidemiology and Genetics,

2 Division of Cancer Control and Population Sciences, National Cancer
Institute, NIH, Department of Health and Human Services;

3 Information Management Services, Inc., Rockville, Maryland; and

4 AARP, Washington, District of Columbia

Requests for reprints: Amy Subar,
Division of Cancer Control and Population Sciences,
National Cancer Institute,
6130 Executive Boulevard, EPN 4005, Rockville, MD 20852-7344.
Phone: 301-594-0831; Fax: 301-435-3710. E-mail: subara@mail.nih.gov,

BACKGROUND:
In a few animal experiments, aspartame has been linked to
hematopoietic
and brain cancers.

Most animal studies have found no increase in the risk of these or
other
cancers.

Data on humans are sparse for either cancer.

Concern lingers regarding this widely used artificial sweetener.

OBJECTIVE:
We investigated prospectively whether aspartame consumption is
associated with the risk of hematopoietic cancers or gliomas
(malignant
brain cancer).

METHODS:
We examined 285,079 men and 188,905 women ages 50 to 71 years in the
NIH-AARP Diet and Health Study cohort

Daily aspartame intake was derived from responses to a baseline
self-administered food frequency questionnaire that queried
consumption
of four aspartame-containing beverages (soda, fruit drinks, sweetened
iced tea, and aspartame added to hot coffee and tea) during the past
year.

Histologically confirmed incident cancers were identified from eight
state cancer registries.

Multivariable-adjusted relative risks (RR) and 95% confidence
intervals
(CI) were estimated using Cox proportional hazards regression that
adjusted for age, sex, ethnicity, body mass index, and history of
diabetes.

RESULTS:
During over 5 years of follow-up (1995-2000), 1,888 hematopoietic
cancers and 315 malignant gliomas were ascertained.

Higher levels of aspartame intake were not associated with the risk of
overall hematopoietic cancer
(RR for >/=600 mg/d, 0.98; 95% CI, 0.76-1.27),
glioma (RR for >/=400 mg/d, 0.73; 95% CI, 0.46-1.15;
P for inverse linear trend = 0.05),
or their subtypes in men and women.

CONCLUSIONS:
Our findings do not support the hypothesis that aspartame increases
hematopoietic or brain cancer risk. PMID: 16985027

"We cannot exclude the possibility that higher aspartame consumption
than that observed in this study may be associated with an elevated
risk
of hematopoietic or brain cancers.

In the laboratory study with positive findings, animals were fed doses
starting from 4 mg up to 5,000 mg per kg body weight.

Significantly elevated lymphomas and leukemias were observed in female
rats fed 20 mg of aspartame and higher (e.g., 1,200 mg for humans
weighing 60 kg or 132 lb; refs. 13, 14).

The reported aspartame intake in our data ranged from 0 to 3,400 mg/d
with sparse numbers in the upper intake categories
(1,200 or 2,000 mg/d, which is equivalent to ~7 to 11 cans of soft
drinks daily) compared with the lowest categories,
and the associations were similarly null in both men and women."
////////////////////////////////////////////////////////////

http://RMForAll.blogspot.com October 12, 2007
http://groups.yahoo.com/group/aspartameNM/message/1479
13,620 seniors using more than 1 can/week artificially sweetened
[aspartame] soft drinks had 8% higher death risk, 1981-2004,
Paganini-Hill A, Kawas CH, Corrada MM, U. Southern Cal., Prev. Med.
2007
April 44(4) 305-10: Murray 2007.10.12

"Individuals who drank more than 1 can/week of artificially sweetened
(but not sugar-sweetened) soft drink (cola and other) had an 8 %
increased risk (95 % CI: 1.01-1.16)."

"The increased death risk with consumption of artificially sweetened,
but not sugar-sweetened, soft drinks suggests an effect of the
sweetener
rather than other components of the soft drinks, although residual
confounding remains a possibility."

Prev Med. 2007 Apr; 44(4): 305-10. Epub 2006 Dec 29.
Non-alcoholic beverage and caffeine consumption and mortality: the
Leisure World Cohort Study.
Paganini-Hill A, annliahi@usc.edu,
Kawas CH, ckawas@uci.edu,
Corrada MM. mcorrada@uci.edu,
Department of Preventive Medicine, Keck School of Medicine of the
University of Southern California, CA, USA.

OBJECTIVE:
To examine the effects of non-alcoholic beverage and caffeine
consumption on all-cause mortality in older adults.

METHODS:
The Leisure World Cohort Study is a prospective study of residents of
a
California retirement community.

A baseline postal health survey included details on coffee, tea, milk,
soft drink, and chocolate consumption.

Participants were followed for 23 years (1981-2004).

Risk ratios (RRs) of death were calculated using Cox regression for
8644
women and 4980 men (median age at entry, 74 years) and adjusted for
age,
gender, and multiple potential confounders.

RESULTS:
Caffeine consumption exhibited a U-shaped mortality curve.

Moderate caffeine consumers had a significantly reduced risk of death
(multivariable-adjusted RR = 0.94, 95 % CI: 0.89, 0.99 for 100-199 mg/
day
and RR = 0.90, 95 % CI: 0.85, 0.94 for 200-399 mg/day
compared with those consuming <50 mg/day).

Individuals who drank more than 1 can/week of artificially sweetened
(but not sugar-sweetened) soft drink (cola and other) had an 8 %
increased risk (95 % CI: 1.01-1.16).

Neither milk nor tea had a significant effect on mortality after
multivariable adjustment.

CONCLUSIONS:
Moderate caffeine consumption appeared beneficial in reducing risk of
death.

Attenuation in the observed associations between mortality and intake
of
tea and milk with adjustment for potential confounders suggests that
such consumption identifies those with other mortality-associated
lifestyle and health risks.

The increased death risk with consumption of artificially sweetened,
but
not sugar-sweetened, soft drinks suggests an effect of the sweetener
rather than other components of the soft drinks, although residual
confounding remains a possibility. PMID: 17275898

Age Ageing. 2007 Mar; 36(2): 203-9.
Type of alcohol consumed, changes in intake over time and mortality:
the
Leisure World Cohort Study.
Paganini-Hill A, Kawas CH, Corrada MM.
Department of Preventive Medicine,
Keck School of Medicine of University of Southern California, USA.
annliahi@usc.edu

BACKGROUND:
modifiable behavioural risk factors including smoking and alcohol
consumption are major contributing or actual causes of mortality.

OBJECTIVE:
to examine the effect of alcohol intake on all-cause mortality in
older
adults.

Design and SETTING:
prospective population-based cohort study of residents of a
California,
United States retirement community.

SUBJECTS:
8,877 women and 5,101 men (median age, 74 years) who in the early
1980s
completed a postal health survey incluing details on alcohol
consumption.

METHODS:
participants were followed for 23 years (1981-2004) including two
follow-up questionnaires (in 1992 and 1998) asking about current
alcohol
intake.

Age-adjusted and multivariate-adjusted risk ratios of death and 95 %
confidence intervals were calculated separately for men and women,
using
proportional hazard regression.

RESULTS:
of the 8,644 women and 4,980 men with complete information on the
variables of interest and potential confounders,
6,930 women and 4,456 men had died (median age, 87 years).

Both men and women who drank alcohol had decreased mortality compared
with non-drinkers.

Those who drank two or more drinks per day had a 15 % reduced risk of
death.

The reduced risk was not limited to one type of alcohol.

Stable drinkers (those who reported drinking both at baseline and
follow-up) had a significantly decreased risk of death compared with
stable non-drinkers.

Those who started drinking at follow-up also had a significantly lower
risk.

Women who quit drinking were at increased risk of death.

CONCLUSION:
in elderly men and women, moderate alcohol intake exhibits a
beneficial
effect on mortality.

Those who quit may do so for health reasons that affect mortality.
PMID: 17350977
////////////////////////////////////////////////////////////

" Analyses that used food frequency questionnaire data suggested that
intake of over 1 drink per day of either regular or diet soft drinks
was
associated with a over 50% higher incidence of metabolic syndrome
compared with intake of under 1 soft drink per week.

" Although the association of high fructose corn syrup intake and
insulin resistance may be a contributory mechanism, 31 in the present
study, both regular and diet soft drinks appeared to pose similar
metabolic hazards,
which suggests that other factors may be operational. "

" The caramel content of both regular and diet drinks may be a
potential
source of advanced glycation end products, 5 which may promote insulin
resistance 36 and can be proinflammatory. 37 "

" It is conceivable, though,
that there may be residual confounding caused by lifestyle factors not
adjusted for in the present analyses. "

" As noted above, it is conceivable that residual confounding by
lifestyle/dietary factors not adjusted for may have contributed to the
metabolic risks associated with soft drink intake. "

" The similar metabolic hazard posed by both regular and diet soft
drinks is noteworthy given the lack of calories in the latter;
however, other studies have also reported associations of diet soft
drinks with weight gain in boys 29 and with hypertension in adult
women. 7 "

29. Berkey CS, Rockett HRH, Field AE, Gillman MW, Colditz GA.
Sugar-added beverages and adolescent weight change.
Obesity Res. 2004; 12: 778-788.[Abstract/Free Full Text]

7. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC.
Habitual caffeine intake and the risk of hypertension in women.
JAMA. 2005; 294: 2330-2335.[Abstract/Free Full Text]

http://circ.ahajournals.org/cgi/content/full/116/5/480 free full text
[ Extracts ]

doi:10.1161/CIRCULATIONAHA.107.689935
CLINICAL PERSPECTIVE
Circulation. 2007; 116: 480-488.
(c) 2007 American Heart Association, Inc.
Epidemiology

Circulation. 2007 Jul 31; 116(5): 480-8. Epub 2007 Jul 23.
Soft drink consumption and risk of developing cardiometabolic risk
factors and the metabolic syndrome in middle-aged adults in the
community.
Ravi Dhingra, MD;
Lisa Sullivan, PhD;
Paul F. Jacques, PhD;
Thomas J. Wang, MD;
Caroline S. Fox, MD;  foxca@nhlbi.nih.gov,
James B. Meigs, MD, MPH;
Ralph B. D'Agostino, PhD;
J. Michael Gaziano, MD, MPH;
Ramachandran S. Vasan, MD  vasan@bu.edu,

From the National Heart, Lung, and Blood Institute's Framingham Heart
Study (R.D., T.J.W., C.S.F., R.S.V.), Framingham, Mass;

Massachusetts Veterans Epidemiology Research and Information Center
(R.D., J.M.G.), VA Boston Healthcare System, Boston, Mass;

Division of Aging (R.D., J.M.G.), Brigham and Women's Hospital,
Harvard
Medical School, Boston, Mass; Alice Peck Day Memorial Hospital (R.D.),
Lebanon, NH;

Department of Biostatistics (L.S., R.B.D.), Boston University School
of
Public Health, Boston, Mass;

Jean Mayer USDA Human Nutrition Research Center on Aging (P.F.J.),
Tufts
University, Boston, Mass; Division of Cardiology (T.J.W.) and
Department
of Medicine (J.B.M.), Massachusetts General Hospital, Harvard Medical
School, Boston, Mass;

National Heart, Lung, and Blood Institute (C.S.F.), Bethesda, Md;
Divisions of Preventive Medicine and Cardiovascular Medicine (J.M.G.),
Brigham and Women's Hospital, Boston, Mass;

and Cardiology Section and the Department of Preventive Medicine and
Epidemiology (R.S.V.), Boston University School of Medicine, Boston,
Mass.

Correspondence to Ramachandran S. Vasan, MD, Framingham Heart Study,
73
Mount Wayte Ave, Suite 2, Framingham, MA 01702-5803.  vasan@bu.edu,

Received January 12, 2007; accepted May 15, 2007.

BACKGROUND:
Consumption of soft drinks has been linked to obesity in children and
adolescents, but it is unclear whether it increases metabolic risk in
middle-aged individuals.

METHODS AND RESULTS:
We related the incidence of metabolic syndrome and its components to
soft drink consumption in participants in the Framingham Heart Study
(6,039 person-observations, 3,470 in women; mean age 52.9 years) who
were free of baseline metabolic syndrome.

Metabolic syndrome was defined as the presence of over of the
following:

waist circumference over 35 inches (women) or over 40 inches (men);
fasting blood glucose over 100 mg/dL;
serum triglycerides over 150 mg/dL;
blood pressure over 135/85 mm Hg;
and high-density lipoprotein cholesterol under 40 mg/dL (men)
or under 50 mg/dL (women).

Multivariable models included adjustments for age, sex, physical
activity, smoking, dietary intake of saturated fat, trans fat, fiber,
magnesium, total calories, and glycemic index.

Cross-sectionally, individuals consuming over 1 soft drink per day had
a
higher prevalence of metabolic syndrome
(odds ratio [OR], 1.48; 95 % CI, 1.30 to 1.69)
than those consuming under 1 drink per day.

On follow-up (mean of 4 years), new-onset metabolic syndrome developed
in 765 (18.7 %) of 4095 participants consuming under 1 drink per day
and
in 474 (22.6 %) of 2059 persons consuming over 1 soft drink per day.

Consumption of over 1 soft drink per day
was associated with increased odds of developing
metabolic syndrome (OR, 1.44; 95% CI, 1.20 to 1.74),
obesity (OR, 1.31; 95 % CI, 1.02 to 1.68),
increased waist circumference (OR, 1.30; 95 % CI, 1.09 to 1.56),
impaired fasting glucose (OR, 1.25; 95% CI, 1.05 to 1.48),
higher blood pressure (OR, 1.18; 95 % CI, 0.96 to 1.44),
hypertriglyceridemia (OR, 1.25; 95 % CI, 1.04 to 1.51), and
low high-density lipoprotein cholesterol
(OR, 1.32; 95 % CI 1.06 to 1.64).

CONCLUSIONS:
In middle-aged adults, soft drink consumption is associated with a
higher prevalence and incidence of multiple metabolic risk factors.
PMID: 17646581

Key Words: diabetes mellitus * metabolic syndrome * epidemiology *
obesity * risk factors * carbonated beverages

*        Introduction

Several reports from the United States and Europe indicate increasing
consumption of soft drinks among children, adolescents, and adults
over
the past 3 decades. 1,2

Many clinical studies have linked the rising consumption of soft
drinks
to the present epidemic of obesity and diabetes mellitus among
children
and adolescents 3-6 and to the development of hypertension in adults.
7

Furthermore, added sweeteners in soft drinks have been linked to an
increase in serum triglycerides levels in some reports 8,9 but not in
others. 10,11

The association of soft drink consumption with obesity and higher
insulin resistance has been attributed to multiple factors, including
greater caloric intake, the high fructose corn syrup content, 12 less
satiety and compensation, and a general effect of consuming refined
carbohydrates (see review by Drewnowski and Bellisle 13).

The aforementioned data raise the possibility that the consumption of
soft drinks can fuel metabolic derangements, including insulin
resistance, that can translate into a greater risk of developing
abdominal obesity, high triglyceride levels, low levels of high-
density
lipoprotein cholesterol (HDL-C), elevated blood pressure, and impaired
glucose tolerance; this constellation of metabolic traits has been
collectively referred to as the metabolic syndrome. 14

Higher prevalence of the metabolic syndrome poses greater risk for
cardiovascular disease in the community, 15 although the independent
contribution of this entity to vascular risk beyond its components has
been questioned 16

In the present prospective investigation, we tested the hypothesis
that
greater soft drink consumption increases the risk of developing
metabolic risk factors (alone and in combination [metabolic syndrome])
in middle-aged adults in the community.

Additionally, we evaluated whether metabolic risk varied on the basis
of
consumption of sugar-sweetened ("regular") versus artificially
sweetened
("diet") soft drinks.

*        Methods

Study Sample

The Framingham Heart Study began in 1948 with the enrollment of 5,209
participants into the original study cohort. 17

In 1971, children of the original cohort participants and the spouses
of
the children were enrolled into the Framingham Offspring Study
(n=5,124). 18

Offspring study participants are evaluated approximately every 4
years.

Information on daily consumption of soft drinks was collected via a
physician-administered questionnaire at each study visit from the
fourth
(1987-1991) through the sixth (1995-1998) examination cycles.

That examination questionnaire did not elicit information regarding
consumption of regular versus diet soft drinks; however, such
information was available from the self-administered food frequency
questionnaires (FFQ; Willett questionnaire) 19 completed by
participants
at the fifth (1992-1995) and sixth examination cycles (see below).

For the present investigation, we selected offspring cohort
participants
who attended any 2 consecutive examinations from the fourth through
the
seventh (1998-2001) examination cycles.

We excluded participants with missing data on covariates (n = 207) and
those with prevalent cardiovascular disease (n = 926).

After exclusions, a total of 8997 person-observations (4871 in women)
were eligible for the cross-sectional analyses.

For prospective analyses, we excluded individuals with baseline
metabolic syndrome (n = 2897 person-observations; metabolic syndrome
as
defined below) and those with any missing metabolic syndrome
components
on follow-up (n = 61 person-observations).

The schema for selection of individuals eligible for cross-sectional
and
longitudinal analyses is displayed in the Figure.

All participants provided written informed consent, and the protocol
for
the study was approved by institutional review board of Boston Medical
Center.

Figure 1185095

     Selection of study sample from baseline examinations using the
examination cola questionnaire and from the sample with available FFQ
data (within parentheses, for examinations 5 and 6).
Eligible participants and exclusions are indicated in the Figure.
CVD indicates cardiovascular disease.

Measurement of Covariates

At each Framingham Heart Study examination, participants provided a
medical history and underwent a complete standardized physical
examination that included anthropometry, blood pressure measurements,
and laboratory assessment of vascular risk factors.

Fasting levels of blood glucose, triglycerides, and HDL-C were
measured
with standard assays.

Blood pressure was measured by a physician using a mercury
sphygmomanometer and with the participant resting in a seated position
for 5 minutes; the average of 2 readings obtained on the participant's
left arm constituted the examination blood pressure.

Physical activity was assessed by calculating a "physical activity
index"; participants were asked specific questions regarding how many
hours in a typical day they spent sitting, sleeping, or performing
light-moderate or heavy physical activities. 20

Alcohol intake was assessed by averaging the number of alcoholic
beverages consumed per week.

Participants who reported smoking 1 or more cigarettes per day in the
year before the Framingham Heart Study examination were considered
current smokers.

Assessment of Soft Drink Consumption and Dietary Intake of Other Foods

At the index examinations, participants reported the average number of
12-oz servings of soft drinks (Coke, Pepsi, Sprite, or other
carbonated
soft drinks, separately categorized into caffeinated or decaffeinated
drinks) consumed per day in the year preceding the examination.

The responses to the questions were entered as integers (0 or more)
separately for caffeinated and decaffeinated soft drinks.

This questionnaire (referred to as the "examination cola
questionnaire")
did not separate nondrinkers from infrequent drinkers (<1 drink per
day).

Accordingly, we compared individuals who reported consuming 1, over 1,
or over 2 soft drinks per day with attendees who reported consuming
under 1 soft drink per day (infrequent drinkers and nondrinkers, who
served as the referent).

Intake of regular and diet soft drinks was assessed from FFQs 19 that
were administered at the fifth and sixth examinations.

We also assessed the dietary information on consumption of total
calories, saturated fat, trans fat, fiber, magnesium, and glycemic
index
from the FFQ. 19

Because a FFQ was not administered at the fourth examination cycle,
dietary covariate data from the fifth examination cycle were used for
analyses using information from the examination cola questionnaire at
all 3 examinations.

Data from the FFQ were considered valid only if total energy intakes
reported were over 2.51 MJ/d (600 kcal/d) for men and women but under
17.54 MJ/d (4200 kcal/d) for men or under 16.74 MJ/d (4000 kcal/d) for
women and if fewer than 13 food items were left blank.

Each food item was categorized in 9 categories that ranged from never
or
under 1 serving per month to over 6 servings per day.

For assessment of saturated fat, trans fat, or dietary fiber, the
nutrient intakes from all specific food items were multiplied by the
frequency of consumption.

The validity of the FFQ has been demonstrated previously. 21

Definition and Components of the Metabolic Syndrome

The metabolic syndrome was considered present if 3 or more of the
following individual components were present 14,22:
waist circumference over 35 inches (88 cm) for
or over 40 inches (102 cm) for men;
fasting blood sugar over 100 mg/dL (5.5 mmol/L) or treatment with oral
hypoglycemic agents or insulin;
blood pressure over 135/85 mm Hg or treatment for hypertension;
serum triglycerides over 150 mg/dL (1.7 mmol/L)
or treatment for hypertriglyceridemia (with niacin or fibrates);
and HDL-C under 40 mg/dL (1.03 mmol/L) in men
or under 50 mg/dL (1.3 mmol/L) in women.

Statistical Analyses

Age- and sex-adjusted baseline characteristics of the participant
groups
defined according to the number of soft drinks consumed in 1 day
(under 1, 1, or over 2 per day) were compared by multiple linear and
multiple logistic regression analysis for continuous and categorical
characteristics, respectively.
Data on consumption of soft drinks at each of the 3 eligible baseline
examinations (examination cola questionnaire) were used for this
purpose.
Tests for trend in baseline characteristics across soft drink
consumption categories were performed with multiple regression.
We also assessed the baseline characteristics after excluding
participants with prevalent metabolic syndrome at baseline
examinations (sample used for incidence analyses; see below).

Soft Drink Consumption and Prevalence of the Metabolic Syndrome

We used data from examinations 4, 5, and 6 (examination cola
questionnaire) and generalized estimating equations to compare the
prevalence of metabolic syndrome in participants who consumed over 1
soft drink per day with those who consumed under 1 soft drink per day
(referent).
Each participant could contribute up to 3 person-examinations of data
for analysis.
We also evaluated a dose response by comparing individuals
who consumed 1 soft drink per day and those who consumed over 2 soft
drinks per day with the referent group.
We constructed multivariable models in hierarchical fashion with
adjustment for age and sex (model I)
and for age, sex, physical activity index, smoking, dietary
consumption of saturated fat, trans fat, fiber, magnesium, total
calories, and glycemic index (model II).

We used soft drink consumption data from FFQs at examinations 5 and 6,
which yielded a smaller sample (Figure), to relate the prevalence of
metabolic syndrome across the following categories of intake of
regular
versus diet soft drinks using generalized estimating equations:
(1) under 1 diet or regular soft drink per week (referent),
(2) 1 to 6 diet soft drinks per week,
(3) over 1 diet soft drink per day,
(4) 1 to 6 regular soft drinks per week,
(5) 1 to 6 regular or diet soft drinks per week,
and (6) over 1 regular soft drink per day.
Individuals reporting consumption of both diet and regular soft drinks
over 1/d (n = 16) were grouped into the last category empirically.
We evaluated the 2 sets of models (I and II) noted above.

Soft Drink Consumption and Incidence of the Metabolic Syndrome

To assess the relations of soft drink consumption to the incidence of
metabolic syndrome, we excluded participants with prevalent metabolic
syndrome at each of examination cycles 4, 5, and 6 (n = 2,897
person-observations).
Then, we used pooled logistic regression analyses
by combining each 4-year follow-up period of observations to relate
the
number of soft drinks consumed per day (examination cola
questionnaire)
to the incidence of metabolic syndrome (from examination cycles 4 to
5,
5 to 6, and 6 to 7).23
The eligible participants were free of metabolic syndrome
at each baseline examination,
and in this setting, pooled logistic regression has been shown to
provide risk estimates similar to time-dependent Cox models.24
We compared the consumption of soft drinks  over 1 per day with
infrequent drinkers (under 1 per day; referent) and also
tested for a dose response by comparing groups consuming 1 and over 2
soft drinks per day with the referent group.
We evaluated 2 sets of models
(covariates as in models I and II above),
which paralleled the analyses of prevalence of metabolic syndrome.

Consumption of soft drinks varies with age and by sex.25
It has also been suggested that the effects of soft drinks and
carbohydrates on  metabolic traits may vary according to age, sex,26
and baseline body  weight.27
Therefore, we assessed for effect modification by age (modeled
as a continuous variable), sex, and body mass index
(under 30 versus over 30 kg/m2) by incorporating appropriate
interaction terms in the multivariable models.
We repeated analyses with additionally adjustment
for alcohol consumption and baseline levels of systolic and diastolic
blood pressure, blood glucose, serum triglycerides, and HDL-C.
These models were constructed to account for baseline levels of
metabolic traits.
Additionally, we repeated analyses to examine the association
between consumption of caffeinated and decaffeinated soft drinks,
considered separately, and incidence of the metabolic syndrome.
Because individuals with diabetes mellitus are a particularly high-
risk group for developing metabolic abnormalities, we also repeated
our analyses after excluding those with prevalent diabetes mellitus at
baseline.

To compare the risk of new-onset metabolic syndrome according to the
type of soft drink consumed (regular versus diet),
we used data from the FFQs at examinations 5 and 6
and evaluated the incidence of the metabolic syndrome across
categories of soft drinks consumed.
The 6 categories of regular and diet soft drinks were those noted
above (for the analyses of the prevalence of metabolic syndrome),
and 2 sets of models were evaluated
(models I and II, as described above).

Incidence of Individual Components of Metabolic Syndrome

We used multivariable logistic regression to evaluate the relations of
soft drink consumption to the incidence of each individual component
of
metabolic syndrome using data from the examination cola questionnaire.
We excluded participants who had the specific metabolic trait
prevalent
at baseline; for example, we excluded individuals with blood glucose
over 100 mg/dL (5.5 mmol/L) from the "at-risk" group for analysis that
examined the incidence of impaired fasting glucose.
Thus, we examined the incidence of increased waist circumference,
impaired fasting glucose, high blood pressure, hypertriglyceridemia,
and low HDL-C (all defined as above) according to the number of soft
drinks consumed per day.

We evaluated 2 sets of models (I and II, as noted above) and compared
the risk of developing metabolic traits associated with consumption of
over 1 soft drinks per day
with that in infrequent drinkers (under 1 soft drinks per day).
We also evaluated for a dose response as detailed above.
We did not perform analyses of development of individual metabolic
syndrome components in relation to regular versus diet soft drink
intake using the FFQ data at examinations 5 and 6 because the grouping
of incident events into 6 categories resulted in modest numbers of
events in each category.

All analyses were performed with SAS software version 9.0 (SAS
Institute, Cary, NC). A 2-sided probability value of under 0.05 was
considered statistically significant.

The authors had full access to and take full responsibility for the
integrity of the data. All authors have read and agree to the
manuscript
as written.

Results

The baseline characteristics of participants according to the
categories
of soft drinks consumed per day are presented in Table 1.

Approximately 35 % of the participants reported consuming over 1 soft
drink per day in response to the examination cola questionnaire
(data based on all 3 examinations).

In comparison, only 22 % of participants reported intake of at least 1
soft drink (diet or regular) per day in response to the FFQ (data
available for examinations 5 and 6 only).

The lower proportion reporting daily intake on the FFQ may be related
to
the greater number of options available to indicate soft drink intake;
participants drinking 1 to 6 soft drinks per week (also 22 % on the
FFQ)
may have rounded their responses on the examination cola questionnaire
to the nearest integer.

View this table:

     TABLE 1. Baseline Characteristics of Participants According to
Soft Drink Consumption (n = 8997)

In age- and sex-adjusted models, the prevalence of obesity (assessed
both by body mass index and by waist circumference), high blood
pressure, glucose intolerance, low HDL-C, and hypertriglyceridemia was
significantly higher in those who consumed a greater number of soft
drinks per day.

Serum total cholesterol, low-density lipoprotein cholesterol, physical
activity index, and alcohol consumption did not vary across categories
of soft drinks consumed.

Similar trends were obtained when we excluded individuals with
prevalent
metabolic syndrome (Data Supplement, Table I).

Prevalence of the Metabolic Syndrome

There was a 48 % higher adjusted prevalence of metabolic syndrome
among
those who consumed 1 or more soft drinks per day relative to
individuals
with infrequent soft drink consumption (Table 2).

We observed a rising prevalence of metabolic syndrome across
categories
of 1 and over 2 soft drinks per day

In parallel analyses with the data from the FFQ (Table 2),
participants
who consumed over 1 diet or regular soft drink per day had nearly a
1.8-fold adjusted prevalence of metabolic syndrome compared with
infrequent drinkers (under 1 per week).

TABLE 2. Cross-Sectional Relationships of Soft Drink Consumption With
Prevalence of Metabolic Syndrome

Incidence of the Metabolic Syndrome

Individuals who consumed at least 1 soft drink per day had a 44 %
higher
adjusted risk (95 % CI, 20 % to 74 %) of developing metabolic syndrome
compared with infrequent drinkers in multivariable-adjusted analyses
(Table 3).

There was no effect modification by age, body mass index, or sex
(interaction terms were not statistically significant).

After additional adjustment for baseline levels of covariates (blood
sugar, systolic and diastolic blood pressure, triglycerides, and HDL-
C)
and alcohol consumption in our models, the association of consumption
of
over 1 soft drink per day with incidence of metabolic syndrome
remained
robust (odds ratio [OR], 1.44; 95 % CI, 1.19 to 1.74).

Further exclusion of individuals with diabetes mellitus at baseline (n
=
138) attenuated the association (OR for over 1 soft drink per day,
1.16;
95% CI 1.00 to 1.34).

After stratification of analyses by caffeinated versus decaffeinated
drinks, results were consistent with the primary analyses; consumption
of over 1 soft drink per day was associated with incident metabolic
syndrome for both types of beverages (Data Supplement, Table II).

TABLE 3. Multiple Logistic Regression Examining Soft Drink Consumption
and Incidence of Metabolic Syndrome (n = 6154)

In analyses with FFQ data (Table 3), intake of at least 1 regular or
diet soft drink per day was associated with a over 50 % higher
incidence
of metabolic syndrome than among those who drank under 1 soft drink
per
week, although the association was borderline significant for intake
of
over 1 regular soft drink per day ( P = 0.07 ).

We also observed a graded increase in the risk of metabolic syndrome
from those who were consuming 1 to 6 diet or regular soft drinks per
week to those who drank over 1 soft drinks per day (diet or regular).

Incidence of Individual Components of the Metabolic Syndrome

Compared with infrequent drinkers, individuals who consumed over 1
soft
drink per day had a 25 % to 32 % higher adjusted risk of incidence of
each individual metabolic trait (Table 4), with the exception of
development of high blood pressure, for which there was a borderline
significant 18 % higher adjusted odds ( P = 0.10).

TABLE 4. Multiple Logistic Regression Analysis Examining the Relations
of Incidence of Individual Components of Metabolic Syndrome According
to
Soft Drink Consumption (Data From All 3 Examinations [4, 5, and 6])

Discussion

In the present study, we observed a significantly higher prevalence of
metabolic syndrome among middle-aged adults who consumed over 1 soft
drink per day.

This association was consistent for intake of both regular and diet
soft
drinks.

Our prospective analyses corroborated the cross-sectional findings;
we observed an increase in the incidence of metabolic syndrome among
adults consuming at least 1 soft drink per day, regardless of whether
it was of the regular or diet type.

Additionally, consumption of soft drinks daily was associated with a
higher incidence of each metabolic syndrome component.

The present study extends results from prior studies that reported
that
a greater intake of soft drinks is associated with increased
prevalence
of metabolic syndrome, 28 higher risk of obesity, 4-6 high blood
pressure, 7 and diabetes mellitus. 5

The similar metabolic hazard posed by both regular and diet soft
drinks
is noteworthy given the lack of calories in the latter; however, other
studies have also reported associations of diet soft drinks with
weight
gain in boys 29 and with hypertension in adult women. 7

Mechanisms

There are several mechanisms that can explain the higher risk of
metabolic abnormalities associated with greater consumption of soft
drinks.

These can be broadly grouped under physiological effects, dietary
behavior, and the economics of food choice. 13

There are several physiological effects of soft drinks that may pose
an
adverse metabolic risk.

Larger consumption of added nutritive sweeteners such as high fructose
corn syrup (the primary sweetener in soft drinks) can lead to weight
gain, increased insulin resistance, 30,31 a lowering of HDL-C, 32 and
an
increase in triglyceride levels. 27

Typically, in the United States, the high fructose corn syrup added to
the beverages contains about 55 % fructose. 30,31

Although the association of high fructose corn syrup intake and
insulin
resistance may be a contributory mechanism, 31 in the present study,
both regular and diet soft drinks appeared to pose similar metabolic
hazards, which suggests that other factors may be operational.

Consumption of liquids is associated with a lesser degree of dietary
compensation (the adjustment in energy intake made in subsequent meals
in response to food intake).

Some investigators believe that intake of sugar-sweetened beverages
induces less compensation than intake of artificially sweetened soft
drinks, 33 but others disagree. 34

The high sweetness of diet or regular soft drinks may lead to
conditioning for a greater preference for intake of sweetened items,
35
although this explanation also has been questioned by some experts. 13

The caramel content of both regular and diet drinks may be a potential
source of advanced glycation end products, 5 which may promote insulin
resistance 36 and can be proinflammatory. 37

Dietary behavior among individuals consuming soft drinks may account
in
part for the clustering of metabolic risk factors in these people. 13

Individuals with greater intake of soft drinks also have a dietary
pattern characterized by greater intake of calories and saturated and
trans fats, lower consumption of fiber 38 and dairy products, 39 and a
sedentary life. 40

These observations were corroborated by the our findings of increased
consumption of saturated and trans fat, lower consumption of dietary
fiber, and higher rates of smoking in those with greater intake of
soft
drinks.

Nonetheless, in the present investigation, we adjusted for saturated
fat
and trans fat intake, dietary fiber consumption, smoking, and physical
activity in multivariable analyses and still observed a significant
association of soft drink consumption with the risk of developing
metabolic syndrome and its component traits.

It is conceivable, though, that there may be residual confounding
caused
by lifestyle factors not adjusted for in the present analyses.

Last, it has been suggested that the obesity-promoting effects of soft
drinks may be related in part to their costs, with less expensive
drinks
being associated with greater hazard by virtue of their preferential
selection for economic reasons. 13

The present investigation could not explore this explanation.

Strengths and Limitations

The strengths of the present study include the large community-based
sample of men and women and the adjustments for potential confounders;
however, several limitations merit comment.

We chose to use the modified definition of metabolic syndrome
recommended by the National Cholesterol Education Program 14 and did
not
use other criteria for the syndrome (such as those suggested by the
World Health Organization 41 or the European panel).

Researchers have found high correlation between these guidelines. 42

Given the observational nature of the present study, we cannot infer
that the observed associations are causal.

As noted above, it is conceivable that residual confounding by
lifestyle/dietary factors not adjusted for may have contributed to the
metabolic risks associated with soft drink intake.

Finally, participants in the present study were all white Americans,
which may limit the generalizability of our results to nonwhites.

Conclusions

In our large community-based sample of middle-aged adults, soft drink
consumption was associated with higher risk of developing adverse
metabolic traits and the metabolic syndrome.

The present observational data raise the possibility that public
health
policy measures to limit the rising consumption of soft drinks in the
community may be associated with a lowering of the burden of metabolic
risk factors in adults.

Acknowledgments

Sources of Funding

This work was supported through National Institutes of Health/National
Heart, Lung, and Blood Institute contracts N01-HC-25195, 1R01HL67288,
and 2K24HL04334 (Dr Vasan) and K23HL74077 (Dr Wang) and by a career
development award from the American Diabetes Association (Dr Meigs).

Disclosures

None.

References

  1. Nielsen SJ, Popkin BM. Changes in beverage intake between 1977
and 2001. Am J Prev Med. 2004; 27: 205-210.[CrossRef][Medline] [Order
article via Infotrieve]

  2. Vereecken CA, Inchley J, Subramanian SV, Hublet A, Maes L. The
relative influence of individual and contextual socio-economic status
on
consumption of fruit and soft drinks among adolescents in Europe. Eur
J
Public Health. 2005; 15: 224-232.[Abstract/Free Full Text]

  3. James J, Thomas P, Cavan D, Kerr D. Preventing childhood obesity
by reducing consumption of carbonated drinks: cluster randomised
controlled trial (published correction appears in BMJ. 2004;328:1236).
BMJ. 2004; 328: 1237.[Abstract/Free Full Text]

  4. Ludwig DS, Peterson KE, Gortmaker SL. Relation between
consumption of sugar-sweetened drinks and childhood obesity: a
prospective, observational analysis. Lancet. 2001; 357:
505-508.[CrossRef][Medline] [Order article via Infotrieve]

  5. Schulze MB, Manson JE, Ludwig DS, Colditz GA, Stampfer MJ,
Willett WC, Hu FB. Sugar-sweetened beverages, weight gain, and
incidence
of type 2 diabetes in young and middle-aged women. JAMA. 2004; 292:
927-934.[Abstract/Free Full Text]

  6. Troiano RP, Briefel RR, Carroll MD, Bialostosky K. Energy and
fat
intakes of children and adolescents in the United States: data from
the
National Health and Nutrition Examination Surveys. Am J Clin Nutr.
2000;
72: 1343S-1353S.[Abstract/Free Full Text]

  7. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual
caffeine intake and the risk of hypertension in women. JAMA. 2005;
294:
2330-2335.[Abstract/Free Full Text]

  8. Parks EJ, Hellerstein MK. Carbohydrate-induced
hypertriacylglycerolemia: historical perspective and review of
biological mechanisms. Am J Clin Nutr. 2000; 71: 412-433.[Abstract/
Free
Full Text]

  9. Smith JB, Niven BE, Mann JI. The effect of reduced extrinsic
sucrose intake on plasma triglyceride levels. Eur J Clin Nutr. 1996;
50:
498-504.[Medline] [Order article via Infotrieve]

 10. Surwit RS, Feinglos MN, McCaskill CC, Clay SL, Babyak MA,
Brownlow BS, Plaisted CS, Lin PH. Metabolic and behavioral effects of
a
high-sucrose diet during weight loss. Am J Clin Nutr. 1997; 65:
908-915.[Abstract/Free Full Text]

 11. Swanson JE, Laine DC, Thomas W, Bantle JP. Metabolic effects of
dietary fructose in healthy subjects. Am J Clin Nutr. 1992; 55:
851-856.[Abstract/Free Full Text]

 12. Jurgens H, Haass W, Castaneda TR, Schurmann A, Koebnick C,
Dombrowski F, Otto B, Nawrocki AR, Scherer PE, Spranger J, Ristow M,
Joost HG, Havel PJ, Tschop MH. Consuming fructose-sweetened beverages
increases body adiposity in mice. Obes Res. 2005; 13:
1146-1156.[Abstract/Free Full Text]

 13. Drewnowski A, Bellisle F. Liquid calories, sugar, and body
weight. Am J Clin Nutr. 2007; 85: 651-661.[Abstract/Free Full Text]

 14. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin
BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F.
Diagnosis and management of the metabolic syndrome: an American Heart
Association/National Heart, Lung, and Blood Institute scientific
statement. Circulation. 2005; 13: 322-327.

 15. Wilson PW, D'Agostino RB, Parise H, Sullivan L, Meigs JB.
Metabolic syndrome as a precursor of cardiovascular disease and type 2
diabetes mellitus. Circulation. 2005; 112: 3066-3072.[CrossRef]
[Medline]
[Order article via Infotrieve]

 16. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome:
time for a critical appraisal: joint statement from the American
Diabetes Association and the European Association for the Study of
Diabetes. Diabetes Care. 2005; 28: 2289-2304.[Abstract/Free Full Text]

 17. Dawber TR, Meadors GF, Moore FE. Epidemiologic approaches to
heart disease: the Framingham Study. Am J Public Health. 1951; 41:
279-286.[Free Full Text]

 18. Kannel WB, Feinleib M, McNamara PM, Garrison RJ, Castelli WP. An
investigation of coronary heart disease in families: the Framingham
Offspring Study. Am J Epidemiol. 1979; 110: 281-290.[Abstract/Free
Full
Text]

 19. Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J,
Hennekens CH, Speizer FE. Reproducibility and validity of a
semiquantitative food frequency questionnaire. Am J Epidemiol. 1985;
122: 51-65.[Abstract/Free Full Text]

 20. Kannel WB, Belanger A, D'Agostino R, Israel I. Physical activity
and physical demand on the job and risk of cardiovascular disease and
death: the Framingham Study. Am Heart J. 1986; 112:
820-825.[CrossRef][Medline] [Order article via Infotrieve]

 21. Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB,
Willett WC. Reproducibility and validity of an expanded
self-administered semiquantitative food frequency questionnaire among
male health professionals. Am J Epidemiol. 1992; 135:
1114-1126.[Abstract/Free Full Text]

 22. Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults. Executive Summary of the Third Report of
the National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults
(Adult Treatment Panel III). JAMA. 2001; 285: 2486-2497.[Free Full
Text]

 23. Cupples LA, D'Agostino RB, Anderson K, Kannel WB. Comparison of
baseline and repeated measure covariate techniques in the Framingham
Heart Study. Stat Med. 1988; 7: 205-222.[Medline] [Order article via
Infotrieve]

 24. D'Agostino RB, Lee ML, Belanger AJ, Cupples LA, Anderson K,
Kannel WB. Relation of pooled logistic regression to time dependent
Cox
regression analysis: the Framingham Heart Study. Stat Med. 1990; 9:
1501-1515.[Medline] [Order article via Infotrieve]

 25. Storey ML, Forshee RA, Anderson PA. Beverage consumption in the
US population. J Am Diet Assoc. 2006; 106: 1992-2000.[CrossRef]
[Medline]
[Order article via Infotrieve]

 26. Vartanian LR, Schwartz MB, Brownell KD. Effects of soft drink
consumption on nutrition and health: a systematic review and
meta-analysis. Am J Public Health. 2007; 97: 667-675.[Abstract/Free
Full
Text]

 27. Willett W, Manson J, Liu S. Glycemic index, glycemic load, and
risk of type 2 diabetes. Am J Clin Nutr. 2002; 76:
274S-280S.[Abstract/Free Full Text]

 28. Yoo S, Nicklas T, Baranowski T, Zakeri IF, Yang SJ, Srinivasan
SR, Berenson GS. Comparison of dietary intakes associated with
metabolic
syndrome risk factors in young adults: the Bogalusa Heart Study. Am J
Clin Nutr. 2004; 80: 841-848.[Abstract/Free Full Text]

 29. Berkey CS, Rockett HRH, Field AE, Gillman MW, Colditz GA.
Sugar-added beverages and adolescent weight change. Obesity Res. 2004;
12: 778-788.[Abstract/Free Full Text]

 30. Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose
corn
syrup in beverages may play a role in the epidemic of obesity. Am J
Clin
Nutr. 2004; 79: 537-543.[Abstract/Free Full Text]

 31. Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ. Fructose,
weight
gain, and the insulin resistance syndrome. Am J Clin Nutr. 2002; 76:
911-922.[Abstract/Free Full Text]

 32. Frost G, Leeds AA, Dore CJ, Madeiros S, Brading S, Dornhorst A.
Glycaemic index as a determinant of serum HDL-cholesterol
concentration.
Lancet. 1999; 353: 1045-1048.[CrossRef][Medline] [Order article via
Infotrieve]

 33. Van Wymelbeke V, Beridot-Therond ME, de LG, V, Fantino M.
Influence of repeated consumption of beverages containing sucrose or
intense sweeteners on food intake. Eur J Clin Nutr. 2004; 58:
154-161.[CrossRef][Medline] [Order article via Infotrieve]

 34. Holt SH, Sandona N, Brand-Miller JC. The effects of sugar-free
vs
sugar-rich beverages on feelings of fullness and subsequent food
intake.
Int J Food Sci Nutr. 2000; 51: 59-71.[CrossRef][Medline] [Order
article
via Infotrieve]

 35. Davidson TL, Swithers SE. A Pavlovian approach to the problem of
obesity. Int J Obes Relat Metab Disord. 2004; 28:
933-935.[CrossRef][Medline] [Order article via Infotrieve]

 36. Hofmann SM, Dong HJ, Li Z, Cai W, Altomonte J, Thung SN, Zeng F,
Fisher EA, Vlassara H. Improved insulin sensitivity is associated with
restricted intake of dietary glycoxidation products in the db/db
mouse.
Diabetes. 2002; 51: 2082-2089.[Abstract/Free Full Text]

 37. Vlassara H, Cai W, Crandall J, Goldberg T, Oberstein R, Dardaine
V, Peppa M, Rayfield EJ. Inflammatory mediators are induced by dietary
glycotoxins, a major risk factor for diabetic angiopathy (published
correction appears in Proc Natl Acad Sci U S A. 2003;100:763). Proc
Natl
Acad Sci U S A. 2002; 99: 15596-15601.[Abstract/Free Full Text]

 38. Pereira MA, Kartashov AI, Ebbeling CB, Van Horn L, Slattery ML,
Jacobs DR Jr, Ludwig DS. Fast-food habits, weight gain, and insulin
resistance (the CARDIA study): 15-year prospective analysis. Lancet.
2005; 365: 36-42.[CrossRef][Medline] [Order article via Infotrieve]

 39. Rampersaud GC, Bailey LB, Kauwell GP. National survey beverage
consumption data for children and adolescents indicate the need to
encourage a shift toward more nutritive beverages. J Am Diet Assoc.
2003; 103: 97-100.[CrossRef][Medline] [Order article via Infotrieve]

 40. Hu FB, Li TY, Colditz GA, Willett WC, Manson JE. Television
watching and other sedentary behaviors in relation to risk of obesity
and type 2 diabetes mellitus in women. JAMA. 2003; 289:
1785-1791.[Abstract/Free Full Text]

 41. World Health Organization. Definition, Diagnosis and
Classification of Diabetes Mellitus and Its Complications: Report of a
WHO Consultation, Part 1: Diagnosis and Classification of Diabetes
Mellitus. Geneva, Switzerland: World Health Organization; 1999: 1-59.

 42. Boronat M, Chirino R, Varillas VF, Saavedra P, Marrero D,
Fabregas M, Novoa J. Prevalence of the metabolic syndrome in the
island
of Gran Canaria: comparison of 3 major diagnostic proposals. Diabet
Med.
2005; 22: 1751-1756.[CrossRef][Medline] [Order article via Infotrieve]

p 488 CLINICAL PERSPECTIVE

Consumption of soft drinks among children, adolescents, and middle-
aged
adults has risen in the United States and Europe during the past 3
decades.

Prior studies have shown a higher prevalence of obesity and diabetes
mellitus in children who consume more soft drinks, although these
associations are less clear for adults.

We evaluated the relations of metabolic syndrome and its components to
soft drink consumption in Framingham participants.

Cross-sectionally, individuals consuming at least 1 soft drink per day
had about 50 % higher prevalence of the metabolic syndrome than those
consuming under 1 drink per day.

During a follow-up period of about 4 years, consumption of over 1 soft
drink per day was associated with a higher incidence of metabolic
syndrome and a higher incidence of each of its components, ie,
obesity,
increased waist circumference, impaired fasting glucose, higher blood
pressure, hypertriglyceridemia, and low high-density lipoprotein
cholesterol.

Analyses that used food frequency questionnaire data suggested that
intake of over 1 drink per day of either regular or diet soft drinks
was
associated with a over 50% higher incidence of metabolic syndrome
compared with intake of under 1 soft drink per week.

We conclude that consumption of more than 1 soft drink per day is
associated with a higher prevalence and incidence of multiple
metabolic
risk factors in middle-aged adults.

Our observational data raise the possibility that public health
measures
to limit consumption of soft drinks may be associated with a lowering
of
the burden of cardiometabolic risk factors in adults.

Footnotes

The online-only Data Supplement, consisting of tables, is available
with
this article at
http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.107.689935/DC1.

Guest Editor for this article was Gregory L. Burke, MD, MSc.

[ Dr. Gregory L. Burke is Professor and Chair of the Department of
Public Health Sciences at the Wake Forest University School of
Medicine. His research interests include epidemiology and
cardiovascular disease, atherosclerosis and subclinical CVD,
measurement issues in epidemiology, clinical trials of chronic disease
prevention, women's health, translation of scientific data for
physicians and the general public, and alternative strategies for
chronic disease prevention. Dr. Burke received his M.D. from the
University of Iowa in 1981.

Departments of Public Health Sciences, Pathology, and Obstetrics and
Gynecology, Wake Forest University School of Medicine,
and Lyndhurst Gynecology Associates, Winston-Salem, NC 27157, USA.
gburke@wfubmc.edu, ]

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