Aspartame-Induced Lymphoma/Leukemia Seen in Rat Study, Other Cancers Ruled Out

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Cancer Epidemiol Biomarkers Prev. 2006 Sep; 15(9): 1654-9.

Comment in:

Cancer Epidemiol Biomarkers Prev. 2007 Jul; 16(7): 1527-8;

author reply 1528-9.

Consumption of aspartame-containin g beverages and incidence of

hematopoietic and brain malignancies.

Lim U, Subar AF, Mouw T, Hartge P, Morton LM, Stolzenberg- Solomon R,

Campbell D, Hollenbeck AR, Schatzkin A.

Division of Cancer Control and Population Sciences,

National Cancer Institute, 6130 Executive Boulevard, EPN 4005,

Rockville, MD 20852-7344, USA. PMID: 16985027

 

Unhee Lim 1,

Amy F. Subar 2, subara (AT) mail (DOT) 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 (AT) mail (DOT) nih.gov

 

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

 

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-containin g 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 over 600 mg/d, 0.98; 95% CI, 0.76 - 1.27 ),

glioma ( RR for over 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

( under 1% consuming over 1,200 mg/d ).

 

However, we did not detect any increase in risk estimates in the highest

categories ( over 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. "

 

[ This is the first good data about the percentage of aspartame users

who use over 6 cans daily, 1200 mg aspartame, which releases 132 mg

methanol, which becomes in many tissues durable cumulative toxic

products of formaldehyde and formic acid, about 30%, 40 mg daily.

Naturally this is a problematic level for obese diabetics and other

groups that are exposed to such high levels of potent toxins. ]

 

About 1% of 473,984 is 4,700 people, with a peak intake of 17 cans daily.

 

It would be worthwhile to investigate a wide variety of symptoms for the

0.1% of highest level users, about 470 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 %

 

aspartame use 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 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 12-oz cans diet soda 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.

 

http://groups. / group/aspartameN M/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.

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Naturally, I want to cut to the chase with pertinent critical comments,

often giving quotes from the ASE text and its 415 references:

 

" As aspartame is completely hydrolyzed following intake, studies

employing either intraperitoneal administration or direct exposure of

cells in vitro to intact aspartame do not reflect human exposures and

therefore, must be carefully interpreted. " [ Spot on! ]

 

3.1.1 [ 22 mg ingested aspartame releases 2.4 mg methanol, which is 11%

of the aspartame. Stegink, 1987

 

Fully 11% of aspartame is methanol -- 1,120 mg aspartame in 2 L diet

soda, almost six 12-oz cans, gives 123 mg methanol (wood alcohol). If

30% of the methanol is turned into formaldehyde, the amount of

formaldehyde, 37 mg, is 18 times the USA EPA limit for daily

formaldehyde in drinking water, 2 mg in 2 L water.

 

For instance, hangover researchers claim that it is the ~150 mg/L

methanol impurity, about one part in 10,000, twice the level from

aspartame in diet sodas, in dark wines and liquors that, turned into

formaldehyde and then formic acid, is the major cause of the dreadful

symptoms of " morning after " hangover " . ]

 

[reference 254:

J. Nutrition 1973 Oct; 103(10): 1454-1459.

Metabolism of aspartame in monkeys.

Oppermann JA, Muldoon E, Ranney RE.

Dept. of Biochemistry, Searle Laboratories,

Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680

 

They found that about 70% of the radioactive methanol in aspartame put

into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,

with little additional elimination, as carbon dioxide in exhaled air and

as water in the urine.

 

They did not mention that this means that about 30% of the methanol

naturally is quickly made into formaldehyde and then into formic acid,

with about 30% retention as durable cumulative toxic products in many

tissues.

 

They did not report any studies on the distribution of radioactivity in

body tissues, except that blood plasma proteins after 4 days held 4% of

the initial methanol.

 

[This study did not monitor long-term use of aspartame. ]

 

 

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