The sweetness profile of a food or beverage may be the most important determinant of whether a product is palatable and pleasant to consume. Sugar and other types of simple carbohydrates have long been used to not only enhance taste and acceptance, but also act as a preservative, add volume and form, provide stability, and offset the tartness or acidity of certain foods. The sugar, though, adds energy and will have implications for the caloric density and metabolic control for those who need to regulate their consumption of carbohydrate, e.g., people with diabetes. Artificial sweeteners, more appropriately described as non-nutritive sweeteners, began to appear in the human food chain in the early 1900s as a means to enhancing sweetness as a sugar substitute and containing calorie content of food. Generally these ingredients bind with the same receptors in the mouth that bind with glucose to elicit the perception of sweetness.
During the past five decades, use of nonnutritive sweeteners in foods and beverages has expanded dramatically. With this, a certain degree of lore has also evolved around nonnutritive sweeteners and generated misunderstandings among consumers. This brief review will identify and describe the non-nutritive sweeteners approved for use in the U.S. and summarize the general process used by the FDA to approve use of NNS in consumable products. The goal of this review is to inform the consumer for making educated choices and dispel inaccuracies and misconceptions about the nonnutritive sweeteners.
In 1958, the U.S. Food and Drug Administration (FDA) took on the role of evaluating the safety of the non-nutritive sweeteners and approving their use given supportive data on safety for humans.
Some may recall cyclamate, a sweetener used in the 1960s. It serves as an example of the conservativeness of the FDA and food and pharmaceutical companies. -In 1958, sodium cyclamate was approved by the FDA for human consumption in food products and medicines to mask bitterness. In the late 1960s, however, research indicated toxic and carcinogenic effects when cyclamate was combined with saccharin. In 1969, the FDA banned use of cyclamate. Subsequent research failed to replicate the adverse effects of cyclamate and companies petitioned the FDA change the ruling. -I personally recall my Biochemistry professor in 1981 stating the FDA had reacted too quickly. -The FDA denied the petition and to this day cyclamate continues to be banned in the U.S. Ironically it has been approved and is used in low amounts in other industrialized countries.
So what does it take to get approval to enter the food chain? To be approved for use in a food or beverage in the U.S., one of two options is required. The ingredient must be generally recognized as safe, i.e., GRAS, or it must undergo a rigorous evaluation to ensure safety for consumption by humans.
- A company proposing to use a new ingredient must petition the FDA and provide data on safety, including thorough scientific evaluation of sufficient quantity and quality using peer-reviewed published scientific evidence as well as unpublished studies that corroborate published findings. The scope of the science is described elsewhere in this review. Nonnutritive sweeteners would be an example of this.
- Widespread experience from common use in foods and beverages that provides a substantial history of consumption by significant samples of consumers; in essence evidence that the population does not react adversely to the ingredient. Soy protein isolates might be an example of this.
The first route applies primarily to new ingredients, additives to food and beverages that have not withstood the test of time of human consumption. The process requires an ingredient supplier or company in the food/beverage industry to submit scientific documentation, published and unpublished, to the FDA for review. Upon review, the FDA responds one of three ways:
- No questions are raised by FDA.
- The FDA decides the application lacks sufficient basis for a GRAS determination (e.g., appropriate data and information may be lacking or the provided data and information generates concerns about the safety of the notified ingredient.
- FDA indicates that it has ceased to evaluate the GRAS notice, at the notifier's request.
The evaluation required by the FDA is comprehensive, if not exhaustive, and includes an assessment of probable intake, effects of accumulation in the body from all sources, and toxicology studies. Probable intake considers all potential sources within a day; this is also known as estimated daily intake, an important factor in the FDA approval process described below.
As an initial step in the evaluation process, pharmacokinetics, or PK, studies are conducted to examine the degree of absorption, delivery and accumulation in tissues, rates and mechanisms of metabolism, and speed of eradication from the body. Information from the preliminary work is used to design the toxicology studies, which consist of acute subchronic toxicology, long-term subchronic toxicology, reproductive toxicity, and carcinogenicity. Additionally clinical trials on humans may be required.
The FDA approval process addresses three concepts when approve an ingredient:
- Highest no effect level (HNEL): data must allow the FDA to determine the highest threshold of intake at which no adverse outcomes occur.
- Acceptable daily intake (ADI): this is the amount thought to be safe to ingest daily over a lifetime. It is typically the HNEL divided by 100; 100 being a safety factor. Established by 10, for animal studies, x 10, for genetic variability among humans.
- Estimated daily intake (EDI): an overestimate of daily intake based on the amount of additive as a total (100%) replacement. Specifically for NNS, researchers will make the assumption that all sources of sweeteners, sugar included, originate exclusively from the candidate being evaluated as a nonnutritive sweetener. The dose becomes an extreme often wildly surpassing any amount a human could actually consume in a day.
Currently, the FDA has approved the use of five artificial sweeteners: saccharin, aspartame, acesulfame K, or AceK, sucralose, and neotame. Relatively recently, the FDA approved the use of stevia or Reb-A (stevia glycosides –rebaudioside A) as a natural sweetener. The adjacent table summarizes characteristics of each of these.
Much has been made of the putative adverse effects of artificial sweeteners. The test of time may be the best way of evaluating the safety of any new ingredient to which living organisms are repeatedly exposed for long periods. However, reflecting on the very conservative approach of the FDA to approve use, and the safe guards in place to prevent overexposure, the risks are low even in the event of a false negative conclusion, or type II error for the collective research findings on an ingredient; that an adverse outcome actually exists but just was not detected.
Consider a non-scientific but true observation, once broadcast on a popular television talk-show. The subject matter was one of “stealth calories,” those which slip by us and in time result in accumulating adiposity if not overt obesity because of the energy surplus. The guest of the show was filmed for her typical day, with the video later replayed for a calorie count. The replay revealed that while preparing for dinner, she consumed, in total unawareness, an entire six-pack of regular cola—again, before sitting down to eat dinner. One 12-oz can of regular soda contribute 35 g of simple sugars or 140 calories; the six-pack summed to 210 g of carbohydrates for 840 calories. Nice appetizer. Upon raising her consciousness, the guest agreed this was overexposure to an ingredient, sugar, which has been ingested throughout the history of mankind without pause for concern.
We would all agree; too much soda pop let alone whatever is in it. Now let’s assume that she was a light-weight 121 lb female (she was not) and that she had consumed diet soda that used nonnutritive sweetener. Using the Wikipedia posted amounts for diet soft drinks (http://en.wikipedia.org/wiki/Diet_soda
) and the ADI in the Table, she would have hit 50% of the acceptable daily intake if aspartame were the sweetener. If sucralose was the sole sweetener, she would have achieved 75% of the ADI, which would still be 100 fold less than the highest no-effect level (HNEL). The reality is that many of the formulations use a mix of NNS to achieve a better taste and thereby reduce the exposure of any one additive. What we lack here is the sources she ingests from other sources during the rest of the day. But that is not the point of this example. This example uses an excess by any reasonable person’s standards, and reveals it still falls short when we partial out a specific ingredient, that being the highest acceptable intake of the nonnutritive sweetener.
Given the crisis of obesity, metabolic syndrome and Type II diabetes currently faced by the U.S. and industrialized countries, nonnutritive sweeteners (NNS) are a valuable adjunct to managing energy balance in humans. The conservative nature and continuous diligence of the FDA and most food and pharma companies helps assure consumers that the NNS used in food, beverages, and medications is safe. A thorough examination of the science and rigorous requirements for approval reveal risks, if any, are very small given the vigilant control over exposure to specific ingredients. Introspection about excessiveness is recommended for those who continue to have doubts based on lore.
Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: Use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet 112:739-758, 2012.
Bray GA. Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some people. Adv Nutr. 2013 Mar 1;4(2):220-5. doi: 10.3945/an.112.002816.
Shankar, P. Ahuja S, Sriram K. Non-nutritive sweeteners: Review and update. Nutrition 29: 1293–1299, 2013.
Sylvetsky A, Rother KI, Brown R. Artificial Sweetener Use Among Children: Epidemiology, Recommendations, Metabolic Outcomes, and Future Directions. Pediatr Clin N Am 58 (2011) 1467–1480.
Table of Nonnutritive Sweeteners Cleared for Use in U.S.
|Sweetener (FDA approval) ||Sweetness Index ||Daily limit* ||Chemistry and Metabolism ||Product Use and Regulations |
|Saccharin (1958) ||200 to 700 x sucrose ||5 mg/kg || |
- Not metabolized by the body.
- Once thought to be a carcinogen, the type of tumor linked to saccharin in rats does not develop in humans.
- Rat studies, no human studies, indicate weight gain vs rats on sucrose.
- Originally GRAS but subsequently re-evaluated and regulated as a food additive.
- Heat resistant so can be used in baking and heat-processed foods.
- Can impart a bitter taste.
|Aspartame (1981) ||~200 x sucrose ||50 mg/kg || |
- Dipeptide of amino acids aspartic acid and phenylalanine.
- Metabolized in the gut into aspartate, methanol, and phenylalanine.
- Requires PKU warning for those unable to metabolize phenylalanine.
- Breaks down in heat dependent on pH and temperature.
- Links to side effects but with little or no scientific data to conclude true association or cause-and-effect.
|Acesulfame K (1998) ||200 x sucrose ||15 mg/kg || |
- An organic acid and potassium.
- Absorbed by body but is excreted in the urine non-metabolized.
- Heat stable.
- Commonly used in combination with aspartame or sucralose to reduce overall amount and achieve better taste profile.
|Sucralose (1998) ||600 x sucrose ||5 mg/kg || |
- Chlorinated sucrose
- Most is not absorbed; vast majority is excreted in feces.
- That absorbed is not metabolized and excreted in urine.
- Relatively recent approval by FDA
- Heat and acid stable.
|Neotame (2002) ||7,000 to 13,000 x sucrose ||2 mg/kg || |
- Partially absorbed.
- Quickly metabolized and excreted in urine and feces as methanol.
- Stables in foods and dry products
- Variable stability in liquids depend on acidity.
|Stevia (2008) ||300 x sucrose ||5 mg/kg || |
- Steviol glycosides –rebaudioside A, a natural sweetener extracted from Stevia rebaudiana Bertoni plant.
- GRAS status accepted by FDA in 2008; prior to that stevia was a dietary supplement.
- Stable in dry or liquid form.
- Can impart a bitter taste.
*Acceptable daily limit according to FDA.