Is It Bad For You?

There have been many unfounded rumors over the years about stuff that’s bad for you and many things that people thought were bad for you but are totally fine (butter for example) and things that people thought were totally fine for you but is actually terrible for you. I decided to take a look at some of these things and read the latest scientific research on them.

In this edition, I will be evaluating sugar substitutes. I tend to avoid them as much as possible anyway because they taste funny to me. But I recently noticed that the breakfast cereals we were eating were advertised as no sugar added and that instead they use sucralose to sweeten them. Some of the other common sweeteners are aspartame, acesulfame K, saccharin, Stevia, and maltitol.

Well, bad news for those of you who use sugar substitutes. Aspartame was shown to increase the risk of cancer in both female and male rats, especially of lymphomas, leukemias, and brain cancer in a study published back in 2006(1). This led to much controversy and various other groups, including the European Food Safety Agency, claiming that the animal unit was poorly run and that the animals often had infections, and that the histological exams of the animal tissues were analyzed incorrectly and that what was identified as cancer was actually just bacterial infections. In order to put this controversy to rest, the Ramazzini Institute that originally performed the study went back over the tissues 15 years later using state of the art techniques to reassess their previous findings. They found that there was no evidence of bacterial infections and what they had thought was cancer, was in fact cancer(2).

A French group (NutriNet-Sante) recently published a cohort study of almost 103,000 French people over a 12 year span who either consumed aspartame, acesulfame K, sucralose, or did not use sweeteners. Since many food products sneak artificial sweeteners in where we don’t expect them, the people kept detailed records of the foods they ate, including brand names and product names so the researchers could keep records of which sweeteners were being consumed. The group even validated the written records of the participants by making them photograph the meals, consulting with trained dieticians, and by test blood and urinary biomarkers. They also adjusted the data for different sociodemographic characteristics, lifestyle characteristics, physical characteristics, and personal and family medical history. These researchers were not kidding around.

They found that aspartame consumers had an overall 15% increase in cancer incidence, and acesulfame K consumers had an overall 13% increase in cancer. They did not find a significant difference in sucralose consumers, though these subjects only constituted about 10% of the test subjects of which only 37% were consumers of artificial sweeteners (less than 4,000 people, which is frankly not that many compared to the consumers of aspartame and acesulfame K).

As a result, the International Agency for Research on Cancer changed their categorization of aspartame as “possibly carcinogenic to humans” on July 14. The FDA still disagrees with these conclusions and does not think that there is any link to cancer.

Saccharin has been found to be carcinogenic only in male rats via a molecular mechanism that humans don’t have(3). In fact, saccharin may even kill cancer cells. A group is currently trying to optimize the molecular makeup of these compounds to target an enzyme that is expressed at much higher levels in hard to kill tumors(4). So unless you’re a male rat, you’re probably ok.

Stevia has been found to be carcinogenic if you have enough to sweeten 3,000 cups of coffee a day(5). So unless you have a worrisome caffeine addiction, you’re probably fine.

Maltitol is a sugar alcohol naturally found in some fruits and vegetables in small amounts. It’s almost as sweet as sugar but contains about half the calories. I couldn’t find much research on whether it is carcinogenic. I found one article showing that it lowers the risk of cecum and colon cancers in rats(6). It can however lead to “gastric disturbances” in some people (bloating, gas, and diarrhea)(7) so if you have gastric distress on a frequent basis, you might want to stay away from it.

Sucralose (Splenda) recently came under fire after an article came out claiming that there was evidence that it can give you cancer(8). And if you Google sucralose and cancer you will get an alarming number of research articles making similar claims. Apparently there have been quite a few findings on the subject that have been by and large ignored by large government bodies and organizations. So to summarize the recent article, yes, sucralose is genotoxic. Sucralose-6-acetate is one of the intermediary compounds in the production process which can still be found in small amounts in the finished product. It may also be produced naturally by the body during metabolism of sucralose.

Intestinal epithelial tissue samples exposed to it showed inflammation, oxidative stress, and cancer caused by double strand breaks in the DNA. Sucralose caused cancer in male mice fed it throughout their lifespans. It also disturbs the intestinal microbiome and the intestinal barrier, increases lipid accumulation, and decreases thyroid function. It can pass to nursing babies through the mother’s breastmilk and affect the baby’s microbiome too.

They even did a study on newborns born to mothers with similar medical backgrounds and weight who consumed either low levels or high levels of sucralose during pregnancy and found that the babies born to mothers who consumed high levels of sucralose were heavier and had higher levels of insulin than the babies born to the low-level group. These babies also showed signs of low-grade systemic inflammation in comparison to the other group(9).

Aside from whether or not these sweeteners cause cancer, there is conflicting evidence about whether or not it actually helps people lose weight. The answer seems to lie in whether or not you’re actively engaged in trying to lose weight. People that switch their regular sugar intake with sweeteners and are conscious about the other things they eat can lose weight with the help of sugar substitutes(10).

However, what actually happens in the body is that the sweetness of the sugar substitute itself activates the sweet receptors in our mouth(11) and causes the body to release insulin and insulin causes our body to store sugar in the muscle and adipose tissue. But since there was no actual sugar consumed, the body is moving glucose that it actually needed into the tissues, which leads to hypoglycemia. Hypoglycemia is your body telling you to eat something to replace the sugar in your body. So some people end up eating more when replacing sugar with synthetic sweeteners(3).

The FDA can say what it wants, but we stopped eating our “no sugar added” breakfast cereals. Better safe than sorry.

Bibliography

1. Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A. First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats. Environ Health Perspect. 2006 Mar;114(3):379–385.

2. Landrigan PJ, Straif K. Aspartame and cancer — new evidence for causation. Environ Health. 2021 Apr 12;20(1):42.

3. Tandel KR. Sugar substitutes: Health controversy over perceived benefits. J Pharmacol Pharmacother. 2011 Oct;2(4):236–243.

4. Bua S, Lomelino C, Murray AB, Osman SM, ALOthman ZA, Bozdag M, et al. A Sweet Combination”: Developing Saccharin and Acesulfame K Structures for Selectively Targeting the Tumor-Associated Carbonic Anhydrases IX and XII. J Med Chem. 2020 Jan 9;63(1):321–333.

5. Terai T, Ren H, Mori G, Yamaguchi Y, Hayashi T. Mutagenicity of steviol and its oxidative derivatives in Salmonella typhimurium TM677. Chem Pharm Bull. 2002 Jul;50(7):1007–1010.

6. Tsukamura M, Goto H, Arisawa T, Hayakawa T, Nakai N, Murakami T, et al. Dietary maltitol decreases the incidence of 1,2-dimethylhydrazine-induced cecum and proximal colon tumors in rats. J Nutr. 1998 Mar;128(3):536–540.

7. Mäkinen KK. Gastrointestinal Disturbances Associated with the Consumption of Sugar Alcohols with Special Consideration of Xylitol: Scientific Review and Instructions for Dentists and Other Health-Care Professionals. Int J Dent. 2016 Oct 20;2016:5967907.

8. Schiffman SS, Scholl EH, Furey TS, Nagle HT. Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: in vitro screening assays. J Toxicol Environ Health B Crit Rev. 2023 May 29;1–35.

9. Aguayo-Guerrero JA, Méndez-García LA, Manjarrez-Reyna AN, Esquivel-Velázquez M, León-Cabrera S, Meléndez G, et al. Newborns from Mothers Who Intensely Consumed Sucralose during Pregnancy Are Heavier and Exhibit Markers of Metabolic Alteration and Low-Grade Systemic Inflammation: A Cross-Sectional, Prospective Study. Biomedicines. 2023 Feb 21;11(3).

10. Sweet & Lowdown: Artificial Sweeteners & Weight Gain — Endocrine News [Internet]. [cited 2023 Jun 17]. Available from: https://endocrinenews.endocrine.org/sweet-lowdown-artificial-sweeteners-weight-gain/

11. Just T, Pau HW, Engel U, Hummel T. Cephalic phase insulin release in healthy humans after taste stimulation? Appetite. 2008 Nov;51(3):622–627.