The extensive use of table sugar (sucrose) is being replaced by “sugar-free” products in order to avoid the health risks associated with dental problems, obesity and diabetes. Among these “sugar-free” products we are familiar with the “sugar-free” or “tooth-friendly” chewing gums and low-calorie “sugar-free” beverages. All these “sugar-free” foods are composed of artificial sweeteners like  Aspartame. The other products available in the market containing Aspartame are discussed in upcoming blogs. The present blog will help you to understand the features and health effects of foods containing Aspartame.

Aspartame

As discussed in my earlier blog, the primary reason for opting the sugar-free/ artificially sweetened sugar is to prevent weight gain and to become healthy. Aspartame is a widely used artificial non-saccharide sweetener, available in the market under the brand name Nutra Sweet, Equal, Natra Taste, Sugar-free Gold, and Candere and is labeled in products as E951. Due to its low calorie (4 calorie per gram) and long shelf life, Aspartame is widely used in low-calorie foods and beverages. In addition, Aspartame is highly acceptable due to its pleasant taste and flavor compared to the other artificial sweeteners. This artificial sweetener is reported to be approximately 200 times sweeter than our table sugar [1][2]. Hence, only a minimal amount of Aspartame is needed to sweeten our foods compared to natural sugar. A recent study reported that Aspartame is now being used in everyday products, which does not even have any “sugar-free” diet indications [3]. Aspartame is not stable at high temperatures and will break into its constituent amino acids during cooking or when stored at a higher temperature. Hence, it is widely used in cold foods rather than baked and cooked foods. Aspartame’s acceptable amount of daily intake (ADI) for both children and adults is 50 mg/kg [4].

Chemical composition

Aspartame is a chemical compound composed of phenylalanine (50%), aspartic acid (40%) and methanol (10%) and is chemically known as L-aspertyl L-phenylalanine methyl ester. The chemical name indicates that this compound contains methyl ester of dipeptide of amino acids aspartic acid and phenylalanine.

Regulatory approval

Aspartame is approved by many regulatory agencies such as Food and Drug Administration (FDA) under the “Generally Recognized As Safe” (GRAS) food additive category. Even though Aspartame has a high market demand, and the use of Aspartame is a subject of continuing controversy as many scientific and medical researchers have raised their concerns about Aspartame’s metabolic components.

Main concerns of scientists about Aspartame

Researchers suggest that Aspartame as such is not cytotoxic, but its metabolic components result in many health issues. During the digestion process, Aspartame breaks down into its metabolic components, such as aspartic acid, phenylalanine, and methanol. The further break down of methanol will lead to the formation of formaldehyde, formic acid, and decomposition of Aspartame will lead to the formation of a chemical compound, diketopiperazine [5].

• The excessive use of Aspartame elevates the levels of phenylalanine and aspartic acid in the brain, which affect the neurophysiological activities by inhibiting the development and release of neurotransmitters, such as dopamine, norepinephrine, and serotonin [6]. This will lead to many neurological and behavioral disorders such as headache, anxiety, depression, attention deficit disorder, etc.
• In addition, the high level of phenylalanine is harmful to those who have inherited diseases such as phenylketonuria (a genetic disorder of building up of phenylalanine to potentially toxic level). The individuals who have this disease possess insufficient amounts of the enzyme (phenylalanine hydroxylase), which is responsible for the breakdown of phenylalanine to tyrosine. Hence, the amount of phenylalanine accumulates in parts of the brain, which will cause disorders in human brain functions. In order to avoid this risk to phenylketonuria patients, FDA mandated all food manufacturers to specify the presence of phenylalanine in the warning label. There are also reports of an increase in phenylalanine level in normal humans without the phenylketonuria disease due to the regular consumption of Aspartame-rich foods [7].
• The second metabolic component aspartic acid is also a naturally found nonessential amino acid, which human body can produce by its own. This amino acid boosts the production of the excitatory neurotransmitter (testosterone) and is also widely promoted as a sugar-free supplement for improving the athletic performance. However, there are speculations (with limited clinical studies) that higher dose of Aspartame foods will naturally increase the amount of aspartic acid level and may cause excitotoxicity in conjunction with another amino acid (such as glutamate) and thus inflicts damage on brain and nerves [8][9].
• The presence of methanol or methanol-rich beverages cause methanol poisoning (toxicity) and results in human blindness and death. However, studies reveal that the amount of methanol produced due to the breakdown of Aspartame is comparatively less to cause toxicity in human being. But during the hot weather, and after physical exercising or exertion results in a large amount of fluid loss and hence people drink more amount of Aspartame-rich (sugar–free) beverages. This may result in methanol poisoning as the consumption level may exceed the Aspartame daily intake limit [10].
• The component methanol produced by the metabolism of Aspartame will further be converted to formaldehyde and then oxidized to formic acid. The formaldehyde produced is a significant danger to human health and is a known carcinogen (a chemical that is cancer causing) and mutagenic (a chemical which affects genetic material like DNA), which can affect human vision, DNA damage, and cause birth defects [11]. Further, the significant increase in formic acid levels in the blood will cause the development of metabolic acidosis [8][12]. Metabolic acidosis arises due to the production of excessive quantity of acid in our body, and our kidneys are not capable of removing these acid residues from our body [13].   
• In addition, at a higher temperature (while heating or baking at 180^o) Aspartame undergoes decomposition and forms derivatives of diketopiperazine. Diketopiperazine is a cancer-causing component in Aspartame, which mainly affects the central nervous system (CNS). Since this component forms tumors in the CNS, Aspartame is not highly recommended to use in cooked or baked foods [14].

In addition, studies reveal that the excessive consumption of Aspartame causes nausea, omitting, headache, dizziness, risks of Alzheimer’s disease, behavioral disorders, birth-defects, cancer, and other Gastro Intestinal issues. However, there are many mixed reports available regarding the safety of Aspartame sugar substitute [15][16].

Recommendations

Even though research work initiated by the industry found no adverse effects, several academic independent studies conducted in animals claim a number of health issues associated with the consumption of Aspartame. In fact, majority of these scientific studies indicate that the long-term excessive consumption foods with artificial sweetener (sugar-free) such as Aspartame, do not significantly improve our health, instead will contribute to high risks on human health. The controversy about Aspartame continues and still sugar substituted products such as Aspartame are widely used in more than 90 countries worldwide and 6000 food products either in the form of sugar-free diet and even with sugar-rich products. Hence, for an optimal healthy life, it is recommended to use moderate amounts of sugar-free substitute products and minimize the use of processed foods and additives in our diet.

References

[1] https://en.wikipedia.org/wiki/Aspartame.

[2] Sanchari Chattopadhyay et al., Journal of Food Science and Technology, 51, 2014, 611-621.

[3] Humphries P et al.,European Journal of Clinical Nutrition, 62, 2008, 451-464.

[4] Muzafar Maqsood Wani et al., Journal of Medical Sciences, 22, 2019, e046-e048

[5] George V et al., Journal of Food Science and Technology, 47, 2010, 408-413.

[6] Arbind Kumar Choudhary et al., An International Journal on Nutrition, Diet and Nervous System, 21, 2018, 306-316.

[7] https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=172.804

[8] Farzad Roshanzamir et al., International Journal of Reproductive BioMedicine, 15, 2017, 1-10.

[9] Louise M Burke et al., British Journal of Sports Medicine, 43, 2009, 1088-1090.

[10] Humphries P et al., European Journal of Clinical Nutrition, 62, 2008, 451-462.

[11] Swenberg J A et al., Toxicologic Pathology, 41, 2013, 181-189

[12] Palese M et al.,Journal of Toxicology and Environmental Health, 1, 1975, 13-24.

[13] McMartin K E et al., The American Journal of Medicine, 68, 1980, 414-418.

[14] Rycerz K et al., Folia Neuropathology,51, 2013, 10-17.

[15] https://www.cancer.org/cancer/cancer-causes/aspartame.html

[16] Shankar P et al., Nutrition, 29, 2013, 1293-1299.