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Zero calorie sweeteners

Zero-calorie sweeteners. The lifesaver of diabetics and calorie counters everywhere. But have you ever questioned the safety or how they are made? There are both natural and artificial sweeteners available, we will go through them one by one and see what research says on any health effects. To access full studies simply input the url for the study you want to read into this website: http://sci-hub.tw/


Stevia is native to parts of Brazil and Paraguay, preferring moist, free-draining soil. The plant is a tender perennial cultivated for its leaves. Apparently, the leaves are the sweetest in the first couple years of growth. Unprocessed stevia leaves are 250 - 300 times sweeter than regular sugar. The sweet taste comes from glycosides rather than sugars so insulin is not activated because blood sugar levels are not altered. Some glucose is present when the digestive process breaks down the compounds, however, the little glucose that is present gets consumed by the gut bacteria before it can enter the bloodstream.

There are many stevia based sweeteners on the market, however, if the product can be used in a 1 to 1 ratio as a replacement for sugar then the company making it has added unknown ingredients. Alas, this natural option does come with some risks. The likelihood of these risks being a problem will differ for each person. Here are couple of studies to examine.

Effects of chronic administration of Stevia rebaudiana on fertility in rats

"Abstract A study conducted on prepubertal male rats showed that chronic administration (60 days) of a Stevia rebaudiana aqueous extract produced a decrease in final weight of testis, seminal vesicle and cauda epididymidis. In addition, the fructose content of the accessory sex glands and the epididymal sperm concentration are decreased. Stevia treatment tended to decrease the plasma testosterone level, probably by a putative affinity of glycosides of extract for a certain androgen receptor, and no alteration occurred in luteinizing hormone level. These data are consistent with the possibility that Stevia extracts may decrease the fertility of male rats."

Reduced fertility appears to be the main risk though some studies have seen a negative effect for specific types of cancer.

This document gives a good summary of studies to compare the relative risks without being a long read (2 pages).

About the safety of stevioside used as a sweetener


Technically xylitol is a low-calorie sweetener rather than zero calorie. It is typically advertised as safe for diabetics so I felt it was appropriate to include it. The glycemic index for xylitol is only 7 which is a strong contrast to glucose at 100 on the glycemic index. Xylitol is typically extracted from hardwoods and/or corncobs but it can be found at low concentrations in other plants. This sugar alcohol can be extracted in a couple of different ways. Fermentation with different bacteria and yeasts is one method, another method is a hydrogenation process to convert it into a primary alcohol. Research actually shows some potential benefits for mineralizing teeth and protecting against cavities. However, the research is currently considered of poor quality so we will need to keep an eye open to see what comes up. In the gut, we absorb xylitol poorly which lets the bacteria ferment and consume it. The fermentation is not an issue as long as you have regular bowel movements. In humans, there is no known toxicity threshold yet but higher doses can have a laxative effect. Some also experience bloating and flatulence before hitting the threshold for a laxative effect. For dogs, xylitol appears to be fatal when consumed and may be toxic to other animals as well.

Xylitol: A Review on Bioproduction, Application, Health Benefits, and Related Safety Issues

Can xylitol used in products like sweets, candy, chewing gum and toothpaste help prevent tooth decay in children and adults?

"This review has been produced to assess whether or not xylitol, a natural sweetener used in products such as sweets, candy, chewing gum and toothpaste, can help prevent tooth decay in children and adults."



Aspartame is a man-made chemical sweetener first synthesized in 1965 and sold under the brand name NutraSweet. The FDA initially approved it as a food additive in 1981 and has faced many controversies. The perceived sweetness is due to a specific protein binding sequence. Roughly 200 times sweeter than table sugar, very little is needed in a product, however, the flavor profile is not the same as sugar but remains the closest out of the currently approved artificial sweeteners. Under elevated temperatures and/or high pH aspartame breaks down into its constituent amino acids. Even under low pH conditions aspartame is not stable for long periods of time. This breakdown of the sweetener leads to the off flavors and bitter taste you may find in foods and beverages containing aspartame. Consuming aspartame has multiple effects on the human body including but not limited to neurological, cancer, changes in the gut biome and so forth.

Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice

"Aspartame (APM) is a well-known intense artificial sweetener used in more than 6,000 products. Among the major users of aspartame are children and women of childbearing age. In previous lifespan experiments conducted on Sprague–Dawley rats we have shown that APM is a carcinogenic agent in multiple sites and that its effects are increased when exposure starts from prenatal life.

"Translation: We have shown in previous experiments that aspartame can induce multiple cancers. Here we show that effect again and demonstrate that the longer the exposure through life, the worse the effect.

Effect of long term intake of aspartame on antioxidant defense status in liver

"The present study evaluates the effect of long term intake of aspartame, the artificial sweetener, on liver antioxidant system and hepatocellular injury in animal model. Eighteen adult male Wistar rats, weighing 150–175 g, were randomly divided into three groups as follows: first group was given aspartame dissolved in water in a dose of 500 mg/kg b.wt.; the second group was given a dose of 1000 mg/kg b.wt.; and controls were given water freely. Rats that had received aspartame (1000 mg/kg b.wt.) in the drinking water for 180 days showed a significant increase in activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT). The concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly reduced in the liver of rats that had received aspartame (1000 mg/kg b.wt.). Glutathione was significantly decreased in both the experimental groups. Histopathological examination revealed leukocyte infiltration in aspartame-treated rats (1000 mg/kg b.wt.). It can be concluded from these observations that long term consumption of aspartame leads to hepatocellular injury and alterations in liver antioxidant status mainly through glutathione dependent system."

Translation: Regular consumption of aspartame produced stress on the liver. How much stress depends on the dose. Glutathione is heavily depleted due to aspartame regardless of dosage.

Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat

"Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5–7 mg/kg/d in drinking water) treatments for 8 week (n = 10–12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation."

Translation: Aspartame changed the gut bacteria and showed evidence of stress on the body despite an outward appearance of health. We are not sure how serious a problem this is.

Effect of chronic exposure to aspartame on oxidative stress in brain discrete regions of albino rats

"This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions."

Translation: Breakdown products of aspartame can be detected in the blood even at moderate doses. Stress from exposure to these products can be found in the brain.


This artificial sweetener is 30 - 50 times sweeter than table sugar. This is the least potent of the sugar substitutes. Stays stable under heat and is typically combined with another artificial sweetener to disguise off tastes. Graduate student Michael Sveda discovered the sweet taste of cyclamate when he put his cigarette down while researching a new anti-fever medication in 1937. Originally the sweetener was intended to mask bitter flavors in medications however by 1958 the FDA gave it GRAS (Generally Recognized As Safe) status. Due to heavy usage in the following years, safety risks showing potential cancer links were found and by 1970 it was banned from all food and drug products in the USA. The full account of the FDA's decision can be found here: Cyclamate, commissioners decision. Cyclamate is still used in 130 countries.


This artificial sweetener has no effect on food energy (calories) and is 300 - 400 times sweeter than table sugar. It has a metallic aftertaste, especially at higher concentrations. Typically combined with other sweeteners it is the preferred choice to combine with cyclamate at a 10:1 ratio (cyclamate to saccharin) where both sweeteners are legal in food. It is also used in conjunction with aspartame to compensate for aspartame's short shelf life and low stability. First produced by chemist Constantin Fahlberg in 1879 at Johns Hopkins University, he noticed a sweet taste on his hand after working with the compound earlier that day. In 1886 saccharin started being produced in a factory in Germany, although widespread use would not occur until sugar shortages started during World War I. Due to the cost of importing sugar the British Saccharin Company was founded in 1917 to produce saccharin directly in Britain. Starting in 1907 research was started that would lead the director of the FDA, Harvey Wiley to decide he did not like saccharin because he viewed it as harmful to human health as well as lying to the consumer about what was in the food they were consuming. Research at this time shows there may be a negative effect on weight gain.

Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats

"In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats."


In 1976, scientists Tate & Lyle were working on uses for sugar and it's synthetic derivatives for industrial applications when one of them asked the other to "test" sucralose but the other heard "taste" and found it was exceptionally sweet. This synthetic sweetener is 320 - 1000 times sweeter than table sugar, heat and pH stable, with no caloric value. Sucralose is produced with a complicated process that replaces some of the hydroxyl atoms in sucrose (sugar) with chlorine atoms. Research by the Swedish Environmental Protection Agency has found that sewage cleanup does not remove sucralose from the water. Cumulative effects on the landscape are unknown at this time. Other research shows effects on insulin and gut bacteria.

Sucralose Affects Glycemic and Hormonal Responses to an Oral Glucose Load


Nonnutritive sweeteners (NNS), such as sucralose, have been reported to have metabolic effects in animal models. However, the relevance of these findings to human subjects is not clear. We evaluated the acute effects of sucralose ingestion on the metabolic response to an oral glucose load in obese subjects.


Seventeen obese subjects (BMI 42.3 ± 1.6 kg/m2) who did not use NNS and were insulin sensitive (based on a homeostasis model assessment of insulin resistance score ≤2.6) underwent a 5-h modified oral glucose tolerance test on two separate occasions preceded by consuming either sucralose (experimental condition) or water (control condition) 10 min before the glucose load in a randomized crossover design. Indices of β-cell function, insulin sensitivity (SI), and insulin clearance rates were estimated by using minimal models of glucose, insulin, and C-peptide kinetics.


Compared with the control condition, sucralose ingestion caused 1) a greater incremental increase in peak plasma glucose concentrations (4.2 ± 0.2 vs. 4.8 ± 0.3 mmol/L; P = 0.03), 2) a 20 ± 8% greater incremental increase in insulin area under the curve (AUC) (P < 0.03), 3) a 22 ± 7% greater peak insulin secretion rate (P < 0.02), 4) a 7 ± 4% decrease in insulin clearance (P = 0.04), and 5) a 23 ± 20% decrease in SI (P = 0.01). There were no significant differences between conditions in active glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, glucagon incremental AUC, or indices of the sensitivity of the β-cell response to glucose.


These data demonstrate that sucralose affects the glycemic and insulin responses to an oral glucose load in obese people who do not normally consume NNS."

Sucralose causes a concentration dependent metabolic inhibition of the gut flora Bacteroides, B. fragilis and B. uniformis not observed in the Firmicutes, E. faecalis and C. sordellii (1118.1)

"The gut microbiota is composed mainly of members from the phyla Bacteroides and Firmicutes. Others have shown a correlation of obesity with a reduction in the Bacteroides’ ability to grow normally and maintain their role in the gut. Sucralose is a ‘non-metabolizable’ chlorinated sucrose derivative and the synthesized ingredient in the artificial sweetener Splenda®. Turbidity data obtained from active cultures showed a differential effect of sucralose on the growth curves between members of these Phyla. Sucralose had little effect on two Firmicutes, E. faecalis and C. sordellii, while there was a concentration dependent inhibition of growth of Bacteroides, B. fragilis and B. uniformis. Preliminary results of sucrase enzyme assays may demonstrate considerable competitive inhibition in the presence of sucralose. Furthermore, preliminary transport tests may have displayed differential results between the two phyla suggesting two putative means of metabolic inhibition that explain the reported growth curves. It must be considered that sucralose has the ability to alter gut flora composition by these differential metabolic findings and the negative health impacts from this imbalance must be addressed."

Translation: Previous studies have shown reducing certain types of bacteria increases obesity. Sucralose reduced the growth of several different types of bacteria. These bacteria are known to exist in the human digestive tract. We believe that consuming this sweetener may have negative effects on human health because of these findings.

Acesulfame potassium:

Karl Clauss made the accidental discovery of this artificial sweetener in 1967 after he licked some off his fingers, not realizing the compound was on his hand. At 200 times sweeter than table sugar it is on par with aspartame but has a bitter aftertaste so it is often blended with other artificial sweeteners to give a more natural taste. Unlike aspartame, it remains stable under heat and has a longer shelf life. Despite the longer shelf life it can eventually break down into acetoacetamide which is toxic in high doses. Like other non-nutritive sweeteners, there is an association with weight gain which can lead to type II diabetes. Additionally, high doses have been shown to alter DNA (paper linked at the end of the article).

Fueling the Obesity Epidemic? Artificially Sweetened Beverage Use and Long-term Weight Gain

"We have examined the relationship between artificially sweetened beverage (ASB) consumption and long-term weight gain in the San Antonio Heart Study. From 1979 to 1988, height, weight, and ASB consumption were measured among 5,158 adult residents of San Antonio, Texas. Seven to eight years later, 3,682 participants (74% of survivors) were re-examined. Outcome measures were incidence of overweight/obesity (OW/OBinc) and obesity (OBinc) (BMI ≥ 25 and ≥ 30 kg/m2, respectively), and BMI change by follow-up (ΔBMI, kg/m2). A significant positive dose-response relationship emerged between baseline ASB consumption and all outcome measures, adjusted for baseline BMI and demographic/behavioral characteristics. Consuming >21 ASBs/week (vs. none) was associated with almost-doubled risk of OW/OB (odds ratio (OR) = 1.93, P = 0.007) among 1,250 baseline normal-weight (NW) individuals, and doubled risk of obesity (OR = 2.03, P = 0.0005) among 2,571 individuals with baseline BMIs <30 kg/m2. Compared with nonusers (+1.01 kg/m2), ΔBMIs were significantly higher for ASB quartiles 2–4: +1.46 (P = 0.003), +1.50 (P = 0.002), and +1.78 kg/m2 (P < 0.0001), respectively. Overall, adjusted ΔBMIs were 47% greater among artificial sweetner (AS) users than nonusers (+1.48 kg/m2 vs. +1.01 kg/m2, respectively, P < 0.0001). In separate analyses—stratified by gender; ethnicity; baseline weight category, dieting, or diabetes status; or exercise-change category—ΔBMIs were consistently greater among AS users. These differences, though not significant among exercise increasers, or those with baseline diabetes or BMI >30 kg/m2 (P = 0.069), were significant in all 13 remaining strata. These findings raise the question whether AS use might be fueling—rather than fighting—our escalating obesity epidemic."

Translation: Drinking 21 or more artificially sweetened beverages PER WEEK nearly doubled the risk of being overweight to fully obese.


These are extracted from a native Chinese fruit known as monk fruit or luo han kuo and is 300 - 400 times sweeter than sugar. Used in China, Australia, and Japan for ready-made products at this time. Some research is being done to investigate potential anti-cancer effects. Very little research is available in English but it is growing and so far this seems to be a medicinal sweetener and it is used on Traditional Chinese Medicine. Diabetics may find this study promising.

Insulin secretion stimulating effects of mogroside V and fruit extract of luo han kuo (Siraitia grosvenori Swingle) fruit extract..

"Luo han kuo fruit (Siraitia grosvenori Swingle), a fruit native to China, has been used as a natural sweetening agent for centuries and has been reported to be beneficial for diabetic population. However, limited research has been conducted to elucidate the relationship between the sweetening action and biological parameters that may be related to potential health benefits of LHK fruit (Luo Han Kuo fruit). The present study examined the effect of LHK fruit and its chemical components on insulin secretion using an in vitro cell model system. Mogroside V is the most abundant and the sweetest chemical component among the mogrosides in LHK fruit. The experimental data demonstrated that the crude LHK extract stimulated the secretion of insulin in pancreatic beta cells; furthermore, pure mogroside V isolated from LHK fruit also exhibited a significant activity in stimulating insulin secretion by the beta cells, which could partially be responsible for the insulin secretion activity of LHK fruit and fruit extract. The current study supports that LHK fruit/extract has the potential to be natural sweetener with a low glycemic index, and that mogroside V, possible other related mogrosides, can provide a positive health impact on stimulating insulin secretion."

Translation: this sweetener does not effect blood sugar but does encourage insulin production.

This 9 page paper goes over the artificial sweeteners one by one in plain language.

The Potential Toxicity of Artificial Sweeteners

"Since their discovery, the safety of artificial sweeteners has been controversial. Artificial sweeteners provide the sweet-ness of sugar without the calories. As public health attention has turned to reversing the obesity epidemic in the United States, more individuals of all ages are choosing to use these products. These choices may be beneficial for those who cannot tolerate sugar in their diets (e.g., diabetics). However, scientists disagree about the relationships between sweet-eners and lymphomas, leukemias, cancers of the bladder and brain, chronic fatigue syndrome, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, autism, and systemic lupus. Recently these substances have received increased attention due to their effects on glucose regulation. occupational health nurses need accurate and timely information to counsel individuals regarding the use of these substances. This article provides an overview of types of artificial sweet-eners, sweetener history, chemical structure, biological fate, physiological effects, published animal and human studies, and current standards and regulations."

If you would like to read any of the studies with a pay barrier simply cut and paste the URL into the website sci-hub.tw

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Hi, I'm Porche Berry

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