Making Sense of Natural Non-Nutritive Sweeteners

The following article is an excerpt from, Supplementing Dietary Nutrients—A Guide for Healthcare Professionals, a new book by Thomas G. Guilliams, PhD.

Written with busy practitioners in mind, the book provides thorough, unbiased scientific reviews of more than 30 of the most commonly used dietary supplement ingredients, along with detailed recommendations for the clinical use of vitamins, minerals, probiotics, essential fatty acids and many other supplements.

Dr. Guilliams, a clinical instructor in the schools of pharmacy at the University of Wisconsin and the University of Minnesota, addresses many of the most challenging issues in nutrition-based practice, including: the role of nutrients in modulating gene expression; the merits and drawbacks of various diet regimens; the differences between natural versus synthetic forms of vitamins; the validity of RDAs; federal regulation of the dietary supplement industry, and more.

Supplementing Dietary Nutrients is available for purchase from Dr. Guilliams’ Point Institute.

In this section, Dr. Guilliams reviews the pros and cons of the most commonly used natural “non-nutritive” sweeteners. These ingredients are increasingly popular in foods and supplements marketed to people seeking to lose weight and minimize diabetes risk, but who want to avoid artificial sweeteners like aspartame or sucralose.

While controversy still remains about the risk of consuming artificial sweeteners, we recommend they be avoided by all individuals. We do know obesity and type 2 diabetes are more prevalent in subjects who consume more artificially sweetened beverages than their healthier counterparts, even though these compounds elicit no apparent insulin response. Whether these compounds are acting physiologically or psychologically, leading users to indulge in more extravagant eating habits, has yet to be determined.

Although less controversial, the role of “natural” non-nutritive sweeteners is also unsettled in the minds of many health-minded consumers and physicians. Frankly, while the general use of these compounds have been shown to be safe, extensive research on subtle changes in long-term glycemic control or insulin sensitivity are lacking in most cases.

More challenging is the idea that the use of any sweetening agent reinforces the “need for sweet” craving to which individuals have grown all too familiar. It is a delicate balancing act between consuming products designed to deliver healthy ingredients, while offsetting the bitter or off-putting flavors with something that is sweet on the tongue. The reality is many patients will simply not consume products they do not like (taste, smell, mouth-feel, aftertaste, etc.). For that reason, we will give a brief overview of some of the sweeteners commonly used in therapeutic products—functional foods, powders, bars and chewable tablets—available through healthcare professionals.

Agave nectar (syrup): We list this here only because some of the marketing material for products containing agave-derived sweeteners implies it is low in calories. In fact, agave syrup is one of many natural sweeteners mostly made of fructose, which is lower in Glycemic Index (GI) than glucose. We consider agave products to be similar in nature to honey and maple syrup, and do not consider it to be worse than HFCS. As with other natural sweeteners, the total amount used and the context of the food containing the ingredient will determine its overall glycemic impact. Agave syrup is often from organic-sourced plants.

Fructose: We are not talking here about natural fructose obtained from consuming fruits, but the commercially available fructose ingredients used as added sugar for bars, powders and tablets. Fructose is one of the most popular added sugars for these products because it is sweet, has a natural mouth-feel, dissolves well, has a relatively low GI and is cheap to use. Fructose is also commonly recommended over glucose and sucrose as a “diabetes-friendly” sugar because it results in less post-prandial glucose and insulin. However, regular and long-term consumption of fructose has been linked with insulin resistance, obesity, metabolic syndrome and diabetes.

Because data on added fructose alone are often combined with data on high-fructose corn syrup, it is difficult to distinguish the health-related outcomes of one from the other. Therefore, we advise fructose be used in moderation; and since other sweeteners are available, fructose should be limited when consuming products designed to promote health. Nearly all available commercial fructose is derived via a multistep process from cornstarch, although it may also be converted from cane or beet sugar sucrose or, sometimes, directly from fruit juice sources. While GMO-free fructose is becoming more available, most fructose available in the U.S. is likely to be derived from a genetically modified source.

Polyol sugars: Sugar alcohol molecules, or polyol sugars as they are called (e.g. xylitol, sorbitol), are technically counted as part of total carbohydrates (for label carbohydrate and calorie measurements), but are often subtracted, along with fiber, to produce what some call “net carbs” on food labels since these “sugars” contain fewer calories than the standard four calories per gram (Note: “Net carbs,” or similar terms, have no official definition for labeling and these terms are not recognized by the FDA. The use of this calculation (total carbs minus fiber and polyol sugars) became popular during the resurgence of diets emphasizing very-low-carbohydrate intake. This term can be misleading since the glycemic impact of a food product may be affected by other factors: fiber content, type of fiber, protein content and insulin-sensitizing nutrients).

These polyol compounds are used to sweeten gum, chewable tablets, bars and powders; the sweetness and GI of each varies (see adjacent chart). Some people do not tolerate certain polyol sugars; GI complaints, such as bloating, gas, diarrhea, are not uncommon when these sugars are used in large amounts. Erythritol appears to be the best tolerated, but individual tolerance of each varies.

Polyol sugars can technically be made from a number of different vegetable materials, except lactitol, which is derived from cow’s milk. Corn is, by far, the most frequently used starting material. Other materials sometime used include cassava root, sucrose or hardwood pulp. If you are using products containing polyol sugars, you should be able to ask the supplier about the raw material source and the GMO-status of the raw material. Some of these products, even some corn-derived versions, are made from GMO-free sources.

Since many products with added flavorings are often bitter, requiring some form of additional sweeteners for palatability, modest levels of polyol sugars appear to be without documented issues in most people, though they are not calorie-free as some advertise.

 Ingredient  Sweetness  GI  Cal/g
 Sucrose (sugar)  100%  60  4
 Maltitol Syrup  75%  52  3
 Hydrogenated Starch Hydrolysate  33%  39  2.8
 Maltitol  75%  36  2.7
 Xylitol  100%  13  2.5
 Isomalt  55%  9  2.1
 Sorbitol  60%  9  2.5
 Lacitol  35%  6  2
 Mannitol  60%   0  1.5
 Erythritol  70%  0  0.2


Stevia: The leaves of Stevia rebaudiana are extracted to concentrate the naturally occurring steviol glycosides for use as a non-nutritive sweetener. Foremost amongst the sweet glycosides is rebaudioside A, often the only glycoside in highly purified products. After limiting how stevia could be used and labeled for years, the FDA approved the use of stevia extracts as an additive in food and supplements in 2008.

Stevia concentrates can be up to 300 times as sweet as sugar, yet appears to elicit no blood-glucose or insulin response. Concentrated stevia products can taste bitter to some consumers; most often it is used to accent the sweetness of other natural sweeteners.

Numerous studies have looked at various physiological effects of stevia extracts in humans and animal models. While long-term studies on glucose, insulin and other metabolic effects are limited, nearly all short-term studies, along with an abundance of animal studies exploring stevia’s metabolic effects, have suggested either no effect, or even an improvement in markers of insulin and metabolic function (Goyal SK, Samsher, Goyal RK. Stevia (Stevia rebaudiana) a bio-sweetener: a review. Int J Food Sci Nutr. 2010 Feb; 61(1):1-10).

Licorice root extracts (glycyrrhizin): Licorice root (Glycerrhiza glabra L.) has been used as both a sweetening agent in foods or candy and a medicinal plant for millennia (Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res. 2008 Jun; 22(6):709-24).

Glycyrrhizin can be concentrated and used in foods and supplements, as it is between 30 – 50 times sweeter than sugar. Unlike other sweeteners, the sweetness of glycyrrhizin lingers on the tongue for much longer. Excessive use of glycyrrhizin, as with overconsumption of black licorice candy, can result in water retention and hypertension. These symptoms may be an issue when consuming greater than 100 mg of glycyrrhizin per day, equivalent to 50 grams of licorice candy. Rarely would glycyrrhizin be used in quantities this high as an added sweetener in supplements.

A Balanced Approach

The use of both nutritive and non-nutritive sweeteners is often a concern for clinicians who believe these compounds are either unnecessary inactive excipients or downright harmful to consume.

It is our view that these sweeteners allow for the delivery of many agents in powders, liquids and chewable tablets that would be virtually impossible for some patients to consume in “tasteless” capsules and tablets. Clinicians need to be realistic with their expectation of their patients’ tolerances for consuming unsweetened products, realizing the amount of added sugars (or natural non-nutritive sweeteners) used in supplements is often miniscule compared to the USRDA allowance for added sugars.

A balanced combination of nutritive sweeteners—sucrose, fructose, agave syrup, rice syrup, honey —low-calorie/GI polyol sugars, and natural non-nutritive sweeteners, such as stevia and licorice root, can be part of the necessary delivery of health-promoting nutrient supplements.


Thomas G. Guilliams, PhD earned his doctorate in molecular immunology from the medical college of Wisconsin (Milwaukee). He is a clinical instructor at the University of Wisconsin School of Pharmacy, and also teaches at the University of Minnesota School of Pharmacy. He currently serves as Vice President of Scientific Affairs for Ortho Molecular Products, and has been involved in formulating a wide array of products and programs enabling clinicians to provide safe and effective supplements and lifestyle-based interventions.

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