Research Review: Is Splenda safe? |

This is a great article, written by real researchers. It’s one thing to read about some great ideas on how to lose weight, but it’s another thing to see the results it gets you. In the case of Splenda, this article shows that people who took Splenda for weight loss showed similar weight loss to those taking fake sweeteners like aspartame. This is a great article, and it’s one you should read if you’re willing to put in the work.

The Splenda brand of artificial sweeteners has been a controversial topic in the nutrition world. The initial uses of the product were to help dieters and diabetics who were allergic to sugar or worried about the calories in sugar substitutes. But in the 2000’s, the campaign to ban the ingredient over concerns of the safety of consuming it began.

Splenda is a sugar substitute that has become popular in the United States. It is the second most popular artificial sweetener in the United Kingdom after aspartame. Splenda is also used in many other countries. It is made from the sweetener sucralose.

When it comes to satisfying their sweet appetite, many health-conscious folks choose artificial sweeteners over sugar. Splenda is a popular sweetener.

What exactly is Splenda?

It’s a combination of sucralose (also known as E955 by the European Union) and filler (maltodextose and dexose). Sucralose is a disaccharide (literally, “two sugars”) created by replacing three hydroxyl (OH – oxygen and hydrogen) groups with chlorine in sucrose (Cl). (All About Carbohydrates members can learn more about the different saccharides.)

That’s how Splenda got their original slogan, “Made from sugar so it tastes like sugar.” However, after getting some flack about misleading consumers, they changed the slogan to “Starts with sugar, tastes like sugar, but is not sugar.” Not sugar… good to know — though 47% of responders to a survey (by Johnson & Johnson, the parent company of Splenda) didn’t know Splenda wasn’t natural.


Compared to other artificial sweeteners, sucralose has three advantages:

  • It has hardly no aftertaste.
  • When heated, it remains stable, allowing you to cook and bake with it.
  • It may be added to items like lemon juice without changing its sweetness because it’s stable at varied acidities (pHs).

Sucralose was authorized by the FDA in 1998. The following is an excerpt from the FDA report:

“The agency calculated an ADI (acceptable daily intake) of 5 mg/kg bw/d for sucralose using the no-observed-effect level of 500 mg/kg bw/d* and a 100-fold safety factor. This ADI estimate for sucralose is significantly higher than the 90th percentile EDI (expected dietary intake) of 1.6 mg/kg bw/d”. [1]

*per kilogram of body weight each day in milligrams

Let’s take that technical jargon and apply it to an ordinary human weighing 68.2 kg (150 lbs).

  • The FDA estimates that the most regular sucralose users consume 1.6 milligrams per kilogram of body weight per day (mg/kg bw/d) (the top 10 percent )
    • This translates to 109 milligrams per day for our 68.2 kilogram person.
  • The FDA still considers 5 mg/kg/bw/d to be well within the safe amount of sucralose to use.
    • This equates to 341 milligrams per day for our 68.2 kilogram person.

What does that mean in terms of sweetness? Sucralose is approximately 600 times sweeter than sugar, so:

  • 109 mg sucralose is equivalent to 65.4 g sugar (15.9 teaspoons of sugar)
  • Sucralose (341 mg) is equivalent to 204.6 g sugar (48.7 teaspoons of sugar)

Because Splenda contains only 1.10 percent sucralose, you’d have to ingest 454.5mg/kg/d (or 31 g for our hypothetical person) to meet the FDA’s ADI of 5 mg/kg bw/d.

Sucralose’s discovery –- don’t try this at home

Professor Leslie Hough of Queen’s College, London, requested one of his foreign graduate students, Shashikant Phadnis, to “test” a chemical in his lab one day in 1976. Phadnis, on the other hand, misunderstood and believed he was supposed to “taste” this concoction!

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Luckily for Phadnis, the lab wasn’t working with toxins, but halogenated (a specific group in the periodic table that includes chlorine) sugars. So Phadnis tasted (instead of tested) the compound and found it to be incredibly sweet. Instead of having a lawsuit for the death of a grad student, Professor Hough (along with a British sugar company, Tate & Lyle), had a new artificial sweetener -– sucralose.

Interesting tidbit! Scientists seem to be tasting things they shouldn’t be tasting in the artificial sweetener industry. Constantin Fahlberg ate a sandwich tainted with saccharin, a chemical he was working with, which lead him to taste all of the substances he dealt with that day and discover saccharin was extremely sweet. Jim Schlatter was working when he licked his finger and felt the sweetness, so he went on a chemical tasting tour of his lab to find the culprit: aspartame.

It’s odd because every scientist I know (including myself) would refuse to drink sterile distilled water from a laboratory. It simply does not appear to be a good concept. Oh then, perhaps that’s why I haven’t come up with a new artificial sweetener yet. (Or, as researcher Barry Marshall discovered when he deliberately infected himself with Helicobacter pylori bacteria, the cause of ulcers.) I don’t even want to know who discovered that diabetic urine has a pleasant flavor.)

Question for investigation

Today’s research review study, which evaluates the safety of Splenda in the gastrointestinal system of rats, is the result of either scientists’ folly or bravery.

MB Abou-Donia, EM El-Masry, AA Abdel-Rahman, RE McLendon, SS Schiffman. In male rats, splenda changes gut microbiota and increases intestinal p-glycoprotein and cytochrome p-450. 2008;71(21):1415-29. J Toxicol Environ Health A. 2008;71(21):1415-29.


Splenda® (“No Calorie Sweetener Granular”) was discovered to contain 1.10 percent sucralose, 1.08 percent glucose, 4.23 percent moisture, and 93.59 percent maltodextrin, according to the researchers. Because sucralose is such a sweet substance, there isn’t much of it in Splenda.

Subjects to research

Male adult rats were used in the experiment (Sprague-Dawley). Rats aren’t people, as we all know. (Though some people may have rat-like characteristics.) These types of experiments, however, are not permitted due to ethical concerns. The rats are sacrificed at the end, which is the most important ethical reason. Bumping someone off, for whatever cause, is frowned upon by ethics boards and the general public.


The rats were given different concentrations of Splenda for 12 weeks:

  • Water (0mg/kg/day sucralose) was used as a control.
  • Splenda 100 mg/kg/day or sucralose 1.1 mg/kg/day*
  • Splenda 300 mg/kg/day or sucralose 3.3 mg/kg/day
  • Splenda 500 mg/kg/day or sucralose 5.5 mg/kg/day**
  • Splenda 1000 mg/kg/day or sucralose 11 mg/kg/day

*The expected daily intake (EDI) is 1.6 mg/kg/day. *The FDA-approved ADI for sucralose is 5 mg/kg/day.

Fresh fecal pellets were collected every 12 weeks to measure pH and bacterial levels. The rats were also weighed on a weekly basis by the researchers. Half of the rats were sacrificed after 12 weeks, and the small and large intestines were taken for analysis. Water was provided to the other half of the rats for 12 weeks (dubbed “recovery”).


gaining weight

The most intriguing finding was that the rats gained more weight than the controls at the lowest dose of Splenda, 100mg/kg/day (below the normal daily intake) (Figure 1). However, the higher doses did not induce more weight gain, probably due to the body’s compensatory response of raising the amount of specific proteins to deal with the sucralose.

By the way, a recent study found no difference in food consumption between controls and sucralose-treated rats during a 26-week period [2], indicating that an increase in food intake is unlikely to be the cause of weight gain.

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The rats given 100 mg/kg/day and 500 mg/kg/day gained more weight than the control rats during the course of the 24 week study (12 weeks with sucralose + 12 weeks without, termed “recovery”) (Figure 2). However, there was no difference between 300 mg/kg/day and 1000 mg/kg/day, which is surprising because more sucralose should either a) raise weight even more, b) plateau, or c) show no change. Increasing the amount of sucralose alternates between increasing weight and having no effect. Hmmm. There is no explanation provided by the writers.

There is one idea that comes to mind: threshold levels of sucralose compensation. The first threshold is after 100 mg/kg/d but before 300 mg/kg/d –– because of compensation, you notice weight gain at 100 mg/kg/d but not at 300 mg/kg/d. After 500 mg/kg/d but before 1000 mg/kg/d, the second barrier is reached, resulting in weight gain before the next level of compensation is reached.

Weight gain after 12 weeks

After 12 weeks, you’ve gained weight.

Weight gain after 24 weeks

After 24 weeks, you’ve gained weight.


The rats had fewer “good” bacteria in their gastrointestinal tracts after 12 weeks of Splenda ingestion (at all dosages). The total quantity of anaerobes (non-oxygen-consuming bacteria) went down 49.8% in the 100 mg/kg/d dosage (the lowest dosage)! Even after 12 weeks of “recovery,” the bacteria had not recovered to normal levels: at 100 mg/kg/d, there were 53.9 percent fewer total anaerobes than at the start of the study.

Important proteins: P-Glycoprotein & Cytochrome P450

Changes in protein after 12 weeks of Splenda and 12 weeks of “healing” were the last thing the researchers looked at. P-glycoprotein and two cytochrome P-450 isoenzymes were the two proteins studied (enzymes that have different structure but the same or very similar functions.)

P-glycoprotein (p-gp) is a chemical transporter in the intestine. When it comes to Splenda, it turns out that 300mg/kg/day and 500mg/kg/day increase the amount of p-gp, while 1000mg/kg/day decreases it. You can transport more chemicals if you have more p-gp. Sucralose is most likely being carried in this scenario — but what does that mean? It means that your body tries to clear sucralose out of the gut at 300mg/kg/day and 500mg/kg/day, but at 1000mg/kg/day, another protein, cytochrome P450, comes into play.

Cytochrome p450 is a protein family. CYP3A4 and CYP2D1 were the two genes investigated in this study. Don’t fret about the letters and numbers; the two CYPs are fundamentally the same basic protein with somewhat different flavors. Both the intestine and the liver are responsible for breaking down external poisons (such as medications). The intestine was the only part of the body examined in this investigation. At 300mg/kg/day, 500mg/kg/day, and 1000mg/kg/day, both CYPs (CYP3A4 and CYP2D1) increase. With each increase in dosage, more protein is produced.

Because 1000mg/kg/day had the greatest CYP levels, the authors reasoned that there was no need for additional p-gp because there were so many CYPs breaking down sucralose (a major assumption). That’s why in the 1000 mg/kg/day Splenda group, p-gp didn’t rise. The CYPs appeared to be in charge.


What exactly does it all imply? To summarize, there are two essential elements to remember. For starters, even small doses of Splenda (100mg/kg/day) might promote weight gain. Second, Splenda has negative effects on your gut at moderate doses (300mg/kg/day and up), damaging both gut flora and proteins.

Why does this matter? Changes in gut bacteria can lead to problems with your immune system and ability to absorb nutrients. Changes in proteins levels, specifically p-gp and CYP3A4 & CYP2D1, seem to be a good thing -– you get rid of more foreign chemicals. But there are cases when this is bad. Say you’re undergoing some sort of treatment for cancer or are taking anti-depressants.  Then your body will remove the drugs you are taking more quickly, making the drugs less useful.

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This study has an easy counterargument: you are not a rat (if you are, send me an e-mail; I’m sure we can both earn a lot of money from a reading rat). As a result, it’s difficult to be certain that the outcomes would be the same in individuals. A comparable study examining sucralose consumption and weight growth in people is hoped to be conducted in the future, albeit the study would have to be longer than a year to transfer the 12 rat weeks into human weeks. Anyone interested in participating in a study that will last more than a year and could result in digestive issues and weight gain? At the very least, you’ll get to eat something sweet!

My advice is to avoid sucralose and Splenda if you have digestive difficulties or difficulty losing weight, or if you are taking any form of medicine. I’d also advise staying away from Splenda if you’re pregnant or breastfeeding, just to be safe. Use Splenda (and sucralose) sparingly if you don’t fall into any of these categories. By the way, finding out how much sucralose is in what you’re eating is extremely difficult unless you’re adding Splenda to your food (and can calculate your intake based on your new knowledge that Splenda is 1.10 percent sucralose) — good luck trying to figure out how much sucralose is in your protein powder!


To see the information sources mentioned in this article, go here.

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Splenda is a sugar substitute used by millions every day. It can be found in popular foods such as baked goods and soft drinks, and is the sweetener of choice in diet soft drinks, such as Diet Coke and Diet Dr Pepper. As a sugar substitute, it is used to replace table sugar, and acts as a low-calorie sweetener. But should you use Splenda?. Read more about sucralose vs stevia and let us know what you think.

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Frequently Asked Questions

Is Splenda Safe 2024?

Splenda is safe for consumption.

Is Splenda really that bad for you?

Splenda is a brand of artificial sweetener that has been around since the 1970s. It is made from sucralose, which is an artificial sweetener that does not break down in the body and can cause some health issues.

Is Splenda worse for you than sugar?

Splenda is not worse for you than sugar, but it does have a slightly different chemical composition.

Related Tags

This article broadly covered the following related topics:

  • splenda dangers
  • sucralose
  • splenda
  • sucralose side effects
  • is splenda safe

What do you think?


Written by Vaibhav Sharda