Aspartame (also known as Nutrasweet or Aminosweet) is a popular sugar substitute that is commonly found in “diet” foods and beverages, most notably, diet soda. Since it’s discovery in 1965 and debut into the food supply in 1982, aspartame has made its way into an estimated 6,000 products including baby food, chewable multivitamins, powdered beverage mixes, toothpaste, frozen meals, soda, and gum (1). Currently aspartame is considered to be safe as a non-nutritive sweetener by the FDA, but in the last twenty years there has been much debate over its safety.

The term “non-nutritive sweetener” is an inaccurate way to describe aspartame- non-nutritive implies that the substance passes through the digestive tract unchanged. However, aspartame is readily absorbed and metabolized in the human GI tract into it’s three components: phenylalanine, aspartic acid (aspartate), and methanol. Each of these components have their share of bad press, which adds up to one dangerous artificial sweetener. Don’t believe me? Read on, dear reader…

Aspartame has has the reputation for being a carcinogen (cancer causative agent) for quite some time, mostly due to the fact that 10% of it’s byproduct, methanol, is metabolized to form formeldahyde, a known human carcinogen. However, studies to prove or disprove aspartame’s role in cancer have thus far been largely unclear. In 2006 a “mega-experiment” was performed on 1,800 rodents, in which the animals were given various doses of aspartame in their chow from the age of eight weeks until natural death (4). That last part is of crucial importance- All the other studies that were done until that point were done on rodents that were sacrificed (killed) between 104 and 110 weeks of age, which corresponds to about 2/3 of the animals’ lifespan. This is important because approximately 80% of human cancers (and animals) are diagnosed in the last 1/3 of the lifespan (5)- so in all the other experiments they were killing the animals before the cancer would have had a chance to develop! In this study the authors found an increase in cancers of various types in doses as low as 400 ppm, which is equivalent to 20 mg/kg body weight. The FDA’s acceptable daily intake for aspartame is currently set to 50 mg/kg in the United States and 40 mg/kg in Europe- nearly twice the dose seen to increase cancer risk in this study. Here are the authors comments on their results:
    “The results of this mega-experiment indicate that APM (aspartame) is multipotential
      carcinogenic agent, even at daily doses of 20 mg/kg body weight, much less than than
     currently acceptable intake. On the basis of these results, a reevaluation of the present
     guidelines on the use and consumption of APM is urgent and cannot be delayed.”(4)

Artificial sweeteners are commonly seen in “diet” and diabetic friendly foods- everything from diet soda to frozen “diet” dinners. However, there is a large body of evidence that shows a correlation between artificial sweetener use and weight gain (2). Sweet taste enhances human appetite, regardless of caloric value. Actually, the authors of the study I am now referencing go on to say that “inconsistent coupling between sweet taste and caloric content can lead to compensatory overeating and positive energy balance” (2). They believe this is because of the disruption between the two ways our brains interpret food reward. The first starts in the taste buds, then the sweet taste sensory stimulation is perceived by the brain. This is called the sensory part of the food reward. The second part (the postingestive food reward pathway) depends on the metabolic products of the food, which is ultimately relayed to the hypothalamus, the part of the brain that controls the autonomic nervous system. It has been shown that artificial sweeteners do not activate the postingestive pathway, thus giving your brain two conflicting signals about what it just ate. This just goes to show ya, you can’t outsmart the body. Furthermore, because of the increased carbohydrate cravings and subsequent weight gain resulting from aspartame ingestion, “aspartame is believed to cause problems in diabetic control” (3). 

(Nikki’s note: I personally don’t recommend you drink milk either!.. More on that another time.)

For those of you who don’t mind the occasional tumor or diabetes, perhaps the effects aspartame might have on your brain will be the one to tip the scale for you. A recent study in the journal of Drug and Chemical Toxicology (1) demonstrated that aspartame significantly reduces the amount of glutathione (remember that really important antioxidant?) and glutathione reductase (the enzyme that “recycles” glutathione) in the rat brain. Granted, this particular study did use a much higher dose than say, the cancer study, but I personally wouldn’t want to chance decreasing my precious glutathione.
    “The results of this study indicate that long-term consumption of aspartame leads to an
      imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the
      mechanism involving the glutathione-dependant system.” (1) 
In another study the authors found that samples of rat brain tissue that were damaged by aspartame were completely or partially restored to normal upon incubation of glutathione or L-cysteine (a glutathione precursor) (6). A different study outlined the various ways aspartame interferes with normal neurotransmitter synthesis and function (3). Neurotransmitters that may be effected by aspartame include serotonin (most famous for it’s role, or lack there of, in depression), dopamine (decreased in Parkinson’s disease), acetylcholine (Alzheimer’s), and norepinephrine. So, not only does aspartame cause generalized inflammation and depletion of antioxidants in the brain, but it can lead to a multitude of neurological symptoms via it’s effects on numerous neurotransmitters.

To add insult to injury, most processed foods have more than one artificial dye or sweetener in them. Several studies have looked at the synergistic effects of artificial sweeteners with each other and artificial colors. In 2006 a study found “significant synergy” between MSG and the food dye Brilliant Blue in various proportions, as well as aspartame and Quinoline Yellow. All four substances decreased neurite outgrowth on their own, but seemed to have a more profound effect when used together (7). Another study looked at the combined effects of MSG and aspartame on disruption of glucose homeostasis (blood sugar regulation) and found that the two did indeed work together (8). Again, both substances increased fat deposition and insulin resistance on their own, but the effects were magnified when the two acted together.

Many skeptics will say that these results are not convincing because they are almost exclusively based on animal (rodent) studies. I agree- humans and rodents are different. For instance, it has been shown that (because of enzymatic differences) test animals are 60 times less sensitive to phenylalanine, 10-20 times less sensitive to methanol poisoning, and 8-10 times less sensitive to aspartic acid and glutamate than us humans (3).

I hope that I have convinced you all to avoid artificial sweeteners, particularly aspartame. Friends, don’t be surprised if i take that diet soda away next time we hang out together!

Nikki

References:
(1) M Abhilash “Long-term consumption of aspartame and brain antioxidant defense status” Drug and Chemical Toxicology 2012 (PMID: 22385158)
(2) Yang Q “Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings” Journal of biology and medicine 2010 (PMID: 20589192)
(3) P Humphries “Direct and indirect cellular effects of aspartame on the brain” European Journal of Clinical Nutrition 2008 (PMID: 17684524)
(4) Soffritti M “First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to sprague-dawley rats” (PMID 16507461)
(5) Mead, N. Sour findings on popular sweetener, Enviromental Health Perspectives 2006 vol 114 number 3 pg 76
(6) Simintzi I “L-Cysteine and glutathione restore the modulation of the rat frontal cortex Na+, K+ ATPase activity induced by aspartame metabolites” Food and Chemical Toxicology 46 (2008) 2074-2079 (PMID: 18343556)
(7) Lau K “Synergistic interactions between commonly used food additives in a developmental neurotoxicity test” Toxicological Sciences 2006; 90(1) 178-187 (PMID: 16352620)
(8) Collison KS “Interactive effects of neonatal exposure to MSG and aspartame on glucose homeostasis” Nutrition and Metabolism (London) 2012 June 14;9(1):58 (PMID: 22697049)

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