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Aspartame: Sweet Or Bitter

Moses B. Ekong MSc
Lecturer
Department of Anatomy
Faculty of Basic Medical Sciences
University of Calabar Email address Physical Address

Citation: M. B. Ekong : Aspartame: Sweet Or Bitter. The Internet Journal of Health. 2009 Volume 9 Number 1

Keywords: Aspartame | Adverse effect | Metabolites | Safety

 

Abstract

Aspartame a non-saccharide sweetener has been surrounded with controversy for a long time. This review was to enlighten the public on its safety or otherwise. Several publications on aspartame and its metabolites were reviewed. Adverse effects of aspartame as reported were mostly on animal studies and in humans with certain dysfunction. Normal individuals were not affected though. These lead me to cautiously state that aspartame may be safe after all.


Introduction

Have you been using Equal, NutraSweet, Spoonful or Canderal? Do they really taste sweet? Are there really worth the patronage? Next time when you want to use them, try and take a look at their contents because you may not need them after all. The above-named products are few brand names for aspartame.

Aspartame (APT) is an artificial sweetener present in most diet drinks or soda and in other diet products, while some are sold alone in brands as mentioned earlier. It is a non saccharide alternative of sugar used by people including diabetics, and it is about 180 times sweeter than sugar in typical concentration with the energy value of sugar. It has caloric value of 4kilocalories or 17kilojoules per gram1, 2.

APT is a methyl ester of the di-peptide of the amino acid, aspartic acid and phenylalanine with IUPAC name: N-(L-α-Aspartyl)-L-phenylalanine, 1 methyl ester and molecular formula: C14H18N2O5. It has a molar mass of 294.3gmol with a melting point of 246-247°C and decomposes into its metabolites on boiling3.

Thumbnail: Figure 1: Chemical structure of aspartame3
Figure 1: Chemical structure of aspartame3

At room temperature, APT is stable at pH 4.3 where its half-life is approximately 300 days. At pH of 7, its half-life is only a few days. Under strongly acidic or alkaline conditions, APT may generate methanol by hydrolysis, with the peptide bonds being hydrolyzed into free amino acids under severe conditions3,4.

Background

Like most food taken into the body, aspartame (APT) is metabolized into its constituents: aspartic acid (ASP), phenylalanine (PHE) and methanol. These are further broken down into formaldehyde, formic acid and dikeptopiperazine5,6. ASP and PHE are not harmful per se, because both are amino acids useful in the body of every individual, but methanol is7,8.

Phenylalanine (PHE)

PHE is an essential amino acid present in breast milk and this is very important to young children. It is also found in other protein-rich foods such as eggs, beef, pork, fish, cheese as well as leafy vegetables and whole grains. PHE comprises about 50% of APT8, 9,10.

PHE is ketogenic and glucogenic, and serves in the synthesis of other tissue proteins. It is hydroxylated to tyrosine which serves as a precursor for epinephrine and nor epinephrine synthesis. Chemically it exists in three forms: L-Phenylalanine which is natural occurring; D-Phenylalanine is a mirror image of L-Phenylalanine and is artificially synthesized; DL-Phenylalanine is a combination of the two forms11.

Thumbnail: Figure 2: Chemical structure of phenylalanine12
Figure 2: Chemical structure of phenylalanine12

The D-Phenylalanine has been reported to help reduce chronic pain associated with certain health conditions by stimulating nerve pathways in the brain that control pain. It has also been reported to improve rigidity, walking, disabilities, speech difficulties and depression with Parkinson’s disease. In combination with ultraviolet radiation, its improve vitiligo11.

D-Phenylalanine undergoes bacterial breakdown in the intestine by bacterial enzymes and forms phenyl acetic acid, a toxin11. In individuals who suffer from phenylketonuria, APT is contraindicated as it contains PHE. Inability of these individuals to metabolize PHE results in its build up in the blood forming phenyl pyruvic acid which may lead to array of side effects including mental retardation, loss of pigmentation in skin, hair and eye11. PHE is metabolized into diketopiperazine, which has been implicated in brain tumor in animal experiment13,14.

Aspartic acid (ASP)

ASP is a non- essential amino acid that can be produce by our body. It comprises about 40% of APT. it is found in the brain, sprouting seeds, flakes, sausage meat, wild game, asparagus etc10, 15.

ASP functions as neurotransmitter in the brain and helps improve the function of the immune system. It also plays a crucial role in generating cellular energy where it is easily converted to glucose when the demand for glucose exceeds supply. The L-aspartic acid helps promote a robust metabolism and is sometimes used to treat fatigue and depression, while too much of it in the brain produces free radicals10. D-aspartic acid increases thymus weight, depressed ventilation in males and females and helps regulate local testosterone production16,17.18.

Thumbnail: Figure 3: Chemical structure of DL-aspartic acid19
Figure 3: Chemical structure of DL-aspartic acid19

Methanol

Methanol also called wood alcohol comprises about 10% of APT. It is a deadly poison liberated from APT at temperature in excess of 30°C. It has a low excretion, hence build up within the body. It adverse effects include vision disorders, headache, tinnitus, dizziness, nausea, gastric and behavioral disturbances, numbness etc. methanol is further metabolize to formaldehyde, another toxic product. This is in turn metabolized into formic acid which is also toxic10.

Thumbnail: Figure 4: Chemical structure of methanol1
Figure 4: Chemical structure of methanol1

Discussion

Aspartame is metabolized into PHE, ASP and methanol5,6. Adverse effects of PHE, ASP and methanol arise when the normal plasma or general body levels are altered20,21, 22. The amino acids become toxic because their increased levels are not compensated by other amino acids necessary for the normal functioning of the body8. Koeppe et al21 reported that a balance in protein diet does not cause changes in brain amino acid uptake. The quantity and form of APT ingested usually determines the plasma levels of its metabolites20,23.

Another metabolite of APT, methanol has been implicated in the accumulation of aspartate, an excitotoxic amino acid affecting the optic nerve which may likely result in blindness24. Earlier reports have it that humans and other primates are not susceptible to excitotoxins as rodents and therefore the basis of comparison may be problematic25,26.

Reports also have it that about 10% by mass of APT is broken down into methanol in the small intestine and most of the methanol are absorbed and converted to formaldehyde and subsequently formic acid5,27. The accumulation of formaldehyde and formic acid in blood leads to blood acidosis28. Reports have it that the quantity of methanol produced is too small to disrupt normal physiological processes29,30.

There have been different reports of severe adverse effects of APT2, 22,24,31,32,33. some of these effects were reversed after stoppage of APT use or after adequate proteins were added to the diets of the individuals. Their reported effects include; multipotent carcinogenic properties, optic nerve damage, epileptic seizures, and other neurologic dysfunction, blindness and other ocular defects, tinnitus and other hearing defects, palpitations, tachycardia, nausea, diarrhea , skin allergies and endocrine and metabolic dysfunction and swelling at joints.

These reactions reported mimic, trigger or cause such diseases as chronic fatigue syndrome, Epstein-Barr, epilepsy, multiple sclerosis (MS), systemic lupus (ML), attention deficit disorder (ADD), lymphoma, Grave’s disease, Marnier’s disease etc2.

These results have caused agitations for the restriction and even ban of APT in the market and the resultant heated debates in different cycles34,35. Last year a bill was even sponsored with the aim of banning APT use36.

Proponents of the safety of APT have reported significant testing associated to National and International Health Organizations. Reviewed articles have shown that some human and animal studies have revealed no adverse effects of APT1,30,37, 38, 39, 40, 41. Speirs et al37 reported that large daily intake of APT had no effect on neuropsychologic, neurophysiologic, or behavioral functioning in healthy young adults. Others reported that changes in plasma amino acids and brain serotonin produced by APT are insufficient to cause brain functional deficit38.

Roman et al39 reported no significant modification of mono amine levels in rats administered doses of APT, while Schiffman et al40 stated that APT may cause headache but this is not different from any other normal cause of headache. Another report states that APT is beneficial in preventing destruction of brain tissue42. Even with increased brain tumor rate which some has ascribed to APT use43,44 Gallus et al45 stated that no such association existed between APT, saccharin and other sweeteners in several common neoplasms.

Conclusion

Aspartame (APT) is an artificial sweetener and a source of PHE, ASP and methanol. The harmful effects ascribed to its consumption are usually seen in individuals with metabolic, neurologic, endocrine or genetic dysfunction. Apparent normal individuals with reports of adverse effect may have underlying disorders that may not have been diagnose or that the quantity ingested is far too large that the presence of other amino acids cannot modulate them and the excretion rate is not as fast. Thus the safety of APT especially in normal/healthy individuals has been supported with this review. Though safe, the continuous use of APT as sweetener should be done with caution especially by the individuals who may be sure of their health status.

References

1. Aspartame. From Wikipedia, the free encyclopedia. Url: http://en.wikipedia.org. Assessed November 20, 2008. (s)

2. Hull JS. Aspartame Detox Program. Url: www.sweetpoison.com. Assessed November 20, 2008. (s)

3. Merck Index. 11 edition, 861. (s)

4. Ager DJ, Pantaleone DP, Henderson SA, Katritzky AR, Prakash I, Walters DE. Commercial, synthetic non-nutritive sweetener. Angewandte Chemie Intern Ed 1998; 37(13-24): 1802-1817. (s)

5. Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X, Fernández-López JA, Alemany M. Formaldehyde derived from dietary aspartame binds to tissue components in vivo. Life Sci1998; 63: 337–349. (s)

6. Fountain beverages in the US. The Coca-Cola Company, May 2007. (s)

7. Tsang WS, Clarke MA, Parrish FW. Determination of aspartame and its breakdown products in soft drinks by reverse-phase chromatography with UV detection. J Agric Food Chem 1985; 33: 734–738. (s)

8. Rodwell VW. Amino acid. In: Murray RK, Granner DK, Mayes PA, Rodwell VW (eds). Harper’s Biochemistry. New York: McGraw Hill 2000. pp 27-36. (s)

9. Zeratsky K. Phenylalanine. Url: www.MayoClinic.com. Assessed on November 20, 2008. (s)

10. Aspartame’s toxic contents. Ecologist Newsletter, August 9, 2005. Ecologist Magazine. Url: http://www.theecologist.org. (s)

11. Unknown author. Phenylalanine. http:// healthvitaminguide.com. Assessed on November 20, 2008. (s)

12. IUPAC-IUBMB Joint Commission on Biochemical Nomenclature. "Nomenclature and Symbolism for Amino Acids and Peptides". Recommendations on Organic & Biochemical Nomenclature, Symbols & Terminology etc. Retrieved on 2008/11/20. (s)

13. Olney JW, Farber NB, Spitznagel E, Robins LN (November 1996). "Increasing brain tumor rates: is there a link to aspartame?". Journal of neuropathology and experimental neurology 55 (11): 1115–1123. (s)

14. Shephard SE, Wakabayashi K, Nagao M. Mutagenic activity of peptides and the artificial sweetener aspartame after nitrosation. Food Chem Toxicol 1993; 31 (5): 323–329. (s)

15. Unknown author. Aspartic acid. Url: http://vitaminstuff.com. Assessed on November 20, 2008. (s)

16. Pipalová I, Pospíi M. The effect of dietary administration of aspartic acid on thymus weight in C57 black mice. Cell Mol Life Sci 1980; 36(7): 874-875. (s)

17. Schlenker EH, Goldman M, Holman G. Effect of aspartic acid on control of ventilation in androgenized and ovariectomized female rats. J Appl Physiol 1992; 72(6): 2255-2225. (s)

18. Di Fiore MM, Lamanna C, Assisi L, Botte V. opposing effects of D-aspartic acid and niticoxide on tuning of testosterone production in mallard testis during the productive cycle. Reprod Biol Endocrin 2008; 6. (s)

19. Dunn MS, Smart BW. DL-Aspartic acid. Organic Syntheses, Coll 1963; 4: 55. (s)

20. Stegink L, Filer L, Bell E, Ziegler E. Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. Metabolism 1987; 36 (5): 507–512. (s)

21. Koeppe RA, Shulkin BL, Rosenspire KC, et al. Effect of aspartame-derived phenylalanine on neutral amino acid uptake in human brain: a positron emission tomography study. J Neurochem 1991; 56 (5): 1526–1535. (s)

22. Møller S. Effect of aspartame and protein, administered in phenylalanine-equivalent doses, on plasma neutral amino acids, aspartate, insulin and glucose in man. Pharmacol Toxicol 1991; 68(5): 408–412. (s)

23. Stegink LD, Filer LJ, Bell EF, Ziegler EE. Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. Metabolism 1987; 36(5): 507-512. (s)

24. González-Quevedo A, Obregón F, Urbina M, Roussó T, Lima L. Effect of chronic methanol administration on amino acids and monoamines in retina, optic nerve, and brain of the rat. Toxicol Appl Pharmacol 2002; 185(2): 77–84. (s)

25. Abraham R, Swart J, Golberg L, Coulston F. Electron microscopic observations of hypothalami in neonatal rhesus monkeys (Macaca mulatta) after administration of monosodium-L-glutamate. Expt Mol Pathol 1975; 23(2): 203–213. (s)

26. Reynolds WA, Butler V, Lemkey-Johnston N. Hypothalamic morphology following ingestion of aspartame or MSG in the neonatal rodent and primate: a preliminary report. J Toxicol Environ Health 1976; 2(2): 471–480. (s)

27. McMartin KE, Martin-Amat G, Noker PE, Tephly TR. Lack of a role for formaldehyde in methanol poisoning in the monkey. Biochem. Pharmacol 1979; 28(5): 645–649. (s)

28. IARC Press Release, June 2004. Url: http://www.iarcfr/ENG/ PressRelease/archives. Assessed (s)

29. Lajtha A, Reilly MA, Dunlop DS. Aspartame consumption: lack of effects on neural function. J Nutr Biochem 1994; 5(6): 266–283. (s)

30. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL et al . Aspartame: review of safety". Regul Toxicol Pharmacol 2002; 35 (2 Pt 2): S1–93. (s)

31. Walton RG, Hudak R, Green-Waite RJ. Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population. Biol Psych 1993; 34: 13-17. (s)

32. Smith JD, Terpening CM, Schmidt SO, Gums JG, Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins. Ann Pharmacother 2001; 35: 702-706. (s)

33. Soffritti M, Belpoggi F, Esposti DD, Lambertini L. Aspartame induces lymphomas and leukaemias in rats (L’aspartame induce linfomi e leucemie nei ratti). Eur J Oncol 2005; 10(2): 107–116. (s)

34. Sugarman, C. Controversy Surrounds Sweetener. Washington Post 1983-07-03. pp. D1-2. Retrieved on 25 November 2008. (s)

35. Humphries P, Pretorius E, Naudé H. Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr 2008; 62(4): 451–462. (s)

36. American Bakers Association: New Mexico - Bill Introduced to Ban Aspartame in Foods 2007. (s)

37. Spiers PA, Sabounjian L, Reiner A, Myers DK, Wurtman J, Schomer DL. Aspartame: neuropsychologic and neurophysiologic evaluation of acute and chronic effects. Am J Clin Nutr 1998; 68: 531-537. (s)

38. Dailey JW, Lasley SM, Mishra PK, Bettendorf AF, Burger RL, Jobe PC. Aspartame fails to facilitate pentylenetetrazol-induced convulsions in CD-1 mice. Toxicol Applied Pharmacol 1989; 98(3): 475–486. (s)

39. Romano M, Diomede L, Guiso G, Caccia S, Perego C, Salmona M. Plasma and brain kinetics of large neutral amino acids and of striatum monoamines in rats given aspartame. Food Chem Toxicol 1990; 28 (5): 317–321. (s)

40. Schiffman SS, Buckley CE, Sampson HA, Massey EW, Baraniuk JN, Follett JV, Warwick ZS. Aspartame and susceptibility to headache," New Engl J Med 1987; 317: 1181–1185. (s)

41. Oppermann JA, Muldoon E, Ranney RE. Effect of aspartame on phenylalanine metabolism in monkey. J Nutr 1973; 103(10): 1460-1466. (s)

42. Belmadani A, Tramu G, Betbeder AM, Creppy EE. Subchronic effects of ochratoxin A on young adult rat brain and partial prevention by aspartame, a sweetener. Hum Expt Toxicol 1998; 17(7): 380-386 (s)

43. Olney, J.W., N.B. Farber, E. Spitznagel, L.N. Robins. Increasing Brain Tumor Rates: Is There a Link to Aspartame?" Journal of Neuropathology and Expt Neurol 1996; 55: 1115–1123. (s)

44. Gurney JG, Pogoda JM, Holly EA, Hecht SS, Preston-Martin S. Aspartame consumption in relation to childhood brain tumor risk: results from a case-control study. J National Cancer Institute 1997; 89: 1072–1074. (s)

45. Gallus S; Scotti L, Negri E, Talamini R, Franceschi S, Montella M, Giacosa A, Dal Maso L, La Vecchia C. Artificial sweeteners and cancer risk in a network of case–control studies. Ann Oncol 2007; 18(1): 40–44. (s)

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