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Aspartame sensitivity? A double blind randomised crossover study.

Sathyapalan T, Thatcher NJ, Hammersley R, Rigby AS, Courts FL, Pechlivanis A, Gooderham NJ, Holmes E, le Roux CW, Atkin SL - PLoS ONE (2015)

Bottom Line: Urine metabonomic studies showed no significant differences.This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans.ISRCTN Registry ISRCTN39650237.

View Article: PubMed Central - PubMed

Affiliation: Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, University of Hull, Hull, United Kingdom.

ABSTRACT

Background: Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation.

Methods: This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics.

Results: Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects.

Conclusion: Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans.

Trial registration: ISRCTN Registry ISRCTN39650237.

No MeSH data available.


Related in: MedlinePlus

Analysis of 600 MHz 1H NMR human serum baseline (pre-bar consumption) data from sensitive and control participants (A), and female and male participants (C).3A. OPLS-DA scores plot demonstrating that metabolic variation is dominated by inter-group (sensitive versus control) variation; 3B. OPLS-DA regression coefficient loadings plot (in the form of pseudo-NMR spectrum) of sensitive vs. non-sensitive confirming discriminatory peaks of interest identified by analysis of the raw spectra as being strongly associated with lipids. The signal orientation indicates a higher concentration of characteristic lipid metabolites in the sensitive population; 3C. OPLS-DA scores plot demonstrating clear separation of male (red symbols) from female (black symbols) subjects; 3D. OPLS-DA regression coefficient loadings plot (in the form of pseudo-NMR spectrum) male vs female confirming discriminatory peaks of interest identified by analysis of the raw spectra. The signal orientation indicates increased creatinine in males and increased choline-containing metabolites in females. For the loadings plots in B and D, the color-coded scale reflects the significance of the correlation of each metabolite with the separation (red indicates highest significance and blue indicates no significance).
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pone.0116212.g003: Analysis of 600 MHz 1H NMR human serum baseline (pre-bar consumption) data from sensitive and control participants (A), and female and male participants (C).3A. OPLS-DA scores plot demonstrating that metabolic variation is dominated by inter-group (sensitive versus control) variation; 3B. OPLS-DA regression coefficient loadings plot (in the form of pseudo-NMR spectrum) of sensitive vs. non-sensitive confirming discriminatory peaks of interest identified by analysis of the raw spectra as being strongly associated with lipids. The signal orientation indicates a higher concentration of characteristic lipid metabolites in the sensitive population; 3C. OPLS-DA scores plot demonstrating clear separation of male (red symbols) from female (black symbols) subjects; 3D. OPLS-DA regression coefficient loadings plot (in the form of pseudo-NMR spectrum) male vs female confirming discriminatory peaks of interest identified by analysis of the raw spectra. The signal orientation indicates increased creatinine in males and increased choline-containing metabolites in females. For the loadings plots in B and D, the color-coded scale reflects the significance of the correlation of each metabolite with the separation (red indicates highest significance and blue indicates no significance).

Mentions: The 1H NMR analysis indicated a metabolic difference in the blood serum samples attributed to variation in the serum lipid content between the two groups (AS vs NS). Fig. 3A and 3B, where the OPLS-DA scores plot along with the respective loadings plot in the form of a pseudo-NMR spectrum depicts these findings. Confirmation of the serum 1H NMR data was obtained using UPLC-MS lipidomics on a sample subset chosen randomly from each group (n = 12 per group). The sensitivity of this metabonomic approach was demonstrated as the models predicted the sex of individuals, irrespective of group (Fig. 3C and 3D).


Aspartame sensitivity? A double blind randomised crossover study.

Sathyapalan T, Thatcher NJ, Hammersley R, Rigby AS, Courts FL, Pechlivanis A, Gooderham NJ, Holmes E, le Roux CW, Atkin SL - PLoS ONE (2015)

Analysis of 600 MHz 1H NMR human serum baseline (pre-bar consumption) data from sensitive and control participants (A), and female and male participants (C).3A. OPLS-DA scores plot demonstrating that metabolic variation is dominated by inter-group (sensitive versus control) variation; 3B. OPLS-DA regression coefficient loadings plot (in the form of pseudo-NMR spectrum) of sensitive vs. non-sensitive confirming discriminatory peaks of interest identified by analysis of the raw spectra as being strongly associated with lipids. The signal orientation indicates a higher concentration of characteristic lipid metabolites in the sensitive population; 3C. OPLS-DA scores plot demonstrating clear separation of male (red symbols) from female (black symbols) subjects; 3D. OPLS-DA regression coefficient loadings plot (in the form of pseudo-NMR spectrum) male vs female confirming discriminatory peaks of interest identified by analysis of the raw spectra. The signal orientation indicates increased creatinine in males and increased choline-containing metabolites in females. For the loadings plots in B and D, the color-coded scale reflects the significance of the correlation of each metabolite with the separation (red indicates highest significance and blue indicates no significance).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4364783&req=5

pone.0116212.g003: Analysis of 600 MHz 1H NMR human serum baseline (pre-bar consumption) data from sensitive and control participants (A), and female and male participants (C).3A. OPLS-DA scores plot demonstrating that metabolic variation is dominated by inter-group (sensitive versus control) variation; 3B. OPLS-DA regression coefficient loadings plot (in the form of pseudo-NMR spectrum) of sensitive vs. non-sensitive confirming discriminatory peaks of interest identified by analysis of the raw spectra as being strongly associated with lipids. The signal orientation indicates a higher concentration of characteristic lipid metabolites in the sensitive population; 3C. OPLS-DA scores plot demonstrating clear separation of male (red symbols) from female (black symbols) subjects; 3D. OPLS-DA regression coefficient loadings plot (in the form of pseudo-NMR spectrum) male vs female confirming discriminatory peaks of interest identified by analysis of the raw spectra. The signal orientation indicates increased creatinine in males and increased choline-containing metabolites in females. For the loadings plots in B and D, the color-coded scale reflects the significance of the correlation of each metabolite with the separation (red indicates highest significance and blue indicates no significance).
Mentions: The 1H NMR analysis indicated a metabolic difference in the blood serum samples attributed to variation in the serum lipid content between the two groups (AS vs NS). Fig. 3A and 3B, where the OPLS-DA scores plot along with the respective loadings plot in the form of a pseudo-NMR spectrum depicts these findings. Confirmation of the serum 1H NMR data was obtained using UPLC-MS lipidomics on a sample subset chosen randomly from each group (n = 12 per group). The sensitivity of this metabonomic approach was demonstrated as the models predicted the sex of individuals, irrespective of group (Fig. 3C and 3D).

Bottom Line: Urine metabonomic studies showed no significant differences.This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans.ISRCTN Registry ISRCTN39650237.

View Article: PubMed Central - PubMed

Affiliation: Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, University of Hull, Hull, United Kingdom.

ABSTRACT

Background: Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation.

Methods: This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics.

Results: Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects.

Conclusion: Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans.

Trial registration: ISRCTN Registry ISRCTN39650237.

No MeSH data available.


Related in: MedlinePlus