While
driving home the other day I was tuned in to the local NPR affiliate (Radio IQ - WVTF) and heard an
interview with food columnist Tamar Haspel discussing her
Washington Post opinion piece titled 10 things I
know are true about food – that people don’t want to believe. Though I nodded along to most of
it, one of the 10 points in the list really dug under my skin. It was number 2 –
“Diet Soda is Fine”
Haspel points out a recent scientific study demonizing sucralose – the
artificial sweetener in Splenda – used doses of the sweetener that were
astronomically higher than those encountered by even the most extreme diet soda
consumers that the observation of cancer in the mouse cells was not really applicable
to real-world levels of exposure. She then questions the intent of the
scientists involved with the study saying that perhaps they were trying to
demonstrate a foregone conclusion about the ill-effects of sucralose.
First off, if you look at the study the researchers were mainly interested in the genotoxicity (cancer causing ability) of a modified version of sucralose called sucralose-6-acetate which is commercial impurity leftover in the manufacturing process of sucralose. Therefore, the amount of carcinogen a consumer might be exposed to would depend on the purity standards imposed by the FDA. For the sake of this piece, let’s assume Haspel’s point is valid and sucralose is not worth being afraid of for the possible increased cancer risk.
Full disclosure, I despise the taste of all artificial sweeteners and recoil in disgust every time I accidentally put any amount in my mouth. Maybe this distaste is the reason I feel compelled to write this but I think the main reason is the manner in which Haspel dismissed the science; by questioning the motives of the scientists. Here we have dueling conspiracy theories. On one side hardcore clean-eating advocates who think the soda giants have a secret plot to make people sick while they laugh all the way to the bank at the consumer paying $2.00 for a can of brown fizzy not-quite-sugar water that costs 10 cents to produce. On the other side is a skeptical food columnist thinking the nutrition scientists want to manipulate the data to match their preconceptions about how unhealthy artificial sweeteners are. I am an academic biochemist by training, not a nutritionist and not a shill for Big-POP (forgive me, I grew up in Western New York and that’s what we call soda there). I also lived in Fort Collins, Colorado for over a decade in my twenties and early thirties and was surrounded by crystal-healing propaganda that comes along with hanging around the bergamot and patchouli infused coffee shops and food-co-ops that make me nostalgic for my adopted home on the Front Range. I realize this background plus my inherent aversion for all artificial sweeteners may give me a negative point of view when thinking about this topic. Despite these admitted biases I’d like to present an argument against consuming artificial sweeteners backed by an underlying mechanistic biochemical explanation, not scare-mongering opinions from a water-is-best hippy, even if I am one.
During my second semester of graduate school in the biochemistry program at Colorado State University I audited a cell biology class that I had already taken the prior semester to prepare for my qualifying exam. During this class, a new professor to our department, Dr. Chaoping Chen, was teaching for the first time. When we got to the lecture about cell-surface receptors she used a fascinating example to illustrate mechanism of these transmembrane proteins – the sweet taste receptor. She made the point that artificial sweeteners work by binding to the sweet taste receptors in the cells of the tongue with a much higher affinity than do real sugars like sucrose. This means a molecule of sucralose (the artificial sweetener) binds to the receptor with approximately 500 times more tenacity than does a molecule of sucrose (table sugar). This explains why the artificial sweetener is ~500 times as sweet as sucrose on a gram per gram basis. Dr. Chen then warned us about consuming artificial sweeteners for the purpose of losing weight because though it is true that they are void of calories themselves they stimulate cells to absorb more calories from the rest of the food we consume. I’ll write this again because it is the crux of this whole piece. Artificial sweeteners stimulate our cells to absorb more calories from all the other food we consume.
Why does this happen? Understanding the changes cells under the influence of artificial sweeteners go through is a good first step to understanding this outcome. Taste receptors are more than just sensors at the tips of our taste buds. The very same receptors are present on the surface of our skeletal muscle cells and these receptors act as on/off switches that send chemical signals into a cell’s nucleus to change how much of a certain gene product is made. Without artificial sweeteners in the picture if you were to eat a cube of table sugar – sucrose – as the sugar molecules bind the receptors in your tongue cells a stimulating signal is passed from these cells through the nerves in your tongue up to your brain where you would think, “Oooooo that tastes sweet!”, then your tongue cells AND, more importantly, your skeletal muscle cells start to change gene expression, anticipating the spike in blood sugar that follows the sensation of sweet taste. More copies of the glucose transporter protein are made as a result of signals coming from the taste receptors in your tongue and muscle cells. These transporter proteins are tiny portals that selectively allow glucose to enter muscle cells. Making more of the glucose transporter protein in response to a sweet taste gives animals an adaptive advantage as the skeletal muscle cells act as local warehouses where the extra blood sugar can be stored for later use. After a sugary treat is ingested blood sugar levels usually drop in a few hours this results in the “on” switch flipping off because there is no longer enough sugar available to bind to the taste receptors on the muscles cells. A feeling of satisfaction washes over the eater and the level of glucose transporter protein made goes back to pre-sweet levels. Great! But now let’s look at what happens when these same taste receptors are activated by an artificial sweetener like sucralose. Recall me telling you that sucralose binds taste receptors much more tightly than sugar, with roughly 500 times the strength? This means sucralose molecules stay bound to taste receptors much longer. There is clear evidence that sucralose hangs out in the body for up to 5 days after ingestion.
The argument from the sucralose is fine camp hinges on the fact that pure sucralose is not really metabolized in the body and leaves just as it entered. This is true but it hangs on to your tongue and your muscle cells for days and days whereas real sugar is used or stored by the body after just a few hours. The on switch I mentioned earlier is therefore on for much longer also. As the artificial sweetener molecule is stuck to the sweet taste receptor the signal of “make more glucose transporters, sugar incoming!” is also on. The real sugar molecules included in each meal a person eats after that initial flip of the on switch will be absorbed much more readily.
A study cited by the Cleveland Clinic concludes that overweight and obese adults who switched to artificially sweetened beverages consumed more total calories compared to overweight and obese people who drank traditionally sweetened beverages and therefore became even heavier. The increased binding affinity of artificial sweeteners provides a biochemical basis for understanding this otherwise backwards observation.
It may be true that artificial sweeteners do not pose a significant increase in cancer risk to the average consumer. However, I hope the mechanism explained here makes the reader think before loading their shopping cart up with diet soda thinking this will help with a weight loss goal.
A few afterthoughts. I’m picking on sucralose (Splenda) in this piece but there are six artificial sweeteners approved by the FDA including one you might recall – aspartame (aka NutraSweet). The structure of aspartame is much different than sucralose but it works the same way, by binding tightly the taste receptor proteins with much more strength than normal sugars. Aspartame is interesting as it does not really look like a sugar and is instead a dipeptide meaning two amino acids linked together. Aspartame has fascinated me for decades mostly due to the shady revolving door circumstances by which it was finally approved for human consumption in the United States in 1982. Prior to approval there was data indicating it as a carcinogen in mouse studies. This meant the FDA rejected it when the manufacturer, G.D. Searle and Company first attempted to get it approved. But, during the first years of the Regan administration one Mr. Donald Rumsfeld pushed through the approval. If that doesn’t leave a bad taste in your mouth, I’m not sure what will.
First off, if you look at the study the researchers were mainly interested in the genotoxicity (cancer causing ability) of a modified version of sucralose called sucralose-6-acetate which is commercial impurity leftover in the manufacturing process of sucralose. Therefore, the amount of carcinogen a consumer might be exposed to would depend on the purity standards imposed by the FDA. For the sake of this piece, let’s assume Haspel’s point is valid and sucralose is not worth being afraid of for the possible increased cancer risk.
Full disclosure, I despise the taste of all artificial sweeteners and recoil in disgust every time I accidentally put any amount in my mouth. Maybe this distaste is the reason I feel compelled to write this but I think the main reason is the manner in which Haspel dismissed the science; by questioning the motives of the scientists. Here we have dueling conspiracy theories. On one side hardcore clean-eating advocates who think the soda giants have a secret plot to make people sick while they laugh all the way to the bank at the consumer paying $2.00 for a can of brown fizzy not-quite-sugar water that costs 10 cents to produce. On the other side is a skeptical food columnist thinking the nutrition scientists want to manipulate the data to match their preconceptions about how unhealthy artificial sweeteners are. I am an academic biochemist by training, not a nutritionist and not a shill for Big-POP (forgive me, I grew up in Western New York and that’s what we call soda there). I also lived in Fort Collins, Colorado for over a decade in my twenties and early thirties and was surrounded by crystal-healing propaganda that comes along with hanging around the bergamot and patchouli infused coffee shops and food-co-ops that make me nostalgic for my adopted home on the Front Range. I realize this background plus my inherent aversion for all artificial sweeteners may give me a negative point of view when thinking about this topic. Despite these admitted biases I’d like to present an argument against consuming artificial sweeteners backed by an underlying mechanistic biochemical explanation, not scare-mongering opinions from a water-is-best hippy, even if I am one.
During my second semester of graduate school in the biochemistry program at Colorado State University I audited a cell biology class that I had already taken the prior semester to prepare for my qualifying exam. During this class, a new professor to our department, Dr. Chaoping Chen, was teaching for the first time. When we got to the lecture about cell-surface receptors she used a fascinating example to illustrate mechanism of these transmembrane proteins – the sweet taste receptor. She made the point that artificial sweeteners work by binding to the sweet taste receptors in the cells of the tongue with a much higher affinity than do real sugars like sucrose. This means a molecule of sucralose (the artificial sweetener) binds to the receptor with approximately 500 times more tenacity than does a molecule of sucrose (table sugar). This explains why the artificial sweetener is ~500 times as sweet as sucrose on a gram per gram basis. Dr. Chen then warned us about consuming artificial sweeteners for the purpose of losing weight because though it is true that they are void of calories themselves they stimulate cells to absorb more calories from the rest of the food we consume. I’ll write this again because it is the crux of this whole piece. Artificial sweeteners stimulate our cells to absorb more calories from all the other food we consume.
Why does this happen? Understanding the changes cells under the influence of artificial sweeteners go through is a good first step to understanding this outcome. Taste receptors are more than just sensors at the tips of our taste buds. The very same receptors are present on the surface of our skeletal muscle cells and these receptors act as on/off switches that send chemical signals into a cell’s nucleus to change how much of a certain gene product is made. Without artificial sweeteners in the picture if you were to eat a cube of table sugar – sucrose – as the sugar molecules bind the receptors in your tongue cells a stimulating signal is passed from these cells through the nerves in your tongue up to your brain where you would think, “Oooooo that tastes sweet!”, then your tongue cells AND, more importantly, your skeletal muscle cells start to change gene expression, anticipating the spike in blood sugar that follows the sensation of sweet taste. More copies of the glucose transporter protein are made as a result of signals coming from the taste receptors in your tongue and muscle cells. These transporter proteins are tiny portals that selectively allow glucose to enter muscle cells. Making more of the glucose transporter protein in response to a sweet taste gives animals an adaptive advantage as the skeletal muscle cells act as local warehouses where the extra blood sugar can be stored for later use. After a sugary treat is ingested blood sugar levels usually drop in a few hours this results in the “on” switch flipping off because there is no longer enough sugar available to bind to the taste receptors on the muscles cells. A feeling of satisfaction washes over the eater and the level of glucose transporter protein made goes back to pre-sweet levels. Great! But now let’s look at what happens when these same taste receptors are activated by an artificial sweetener like sucralose. Recall me telling you that sucralose binds taste receptors much more tightly than sugar, with roughly 500 times the strength? This means sucralose molecules stay bound to taste receptors much longer. There is clear evidence that sucralose hangs out in the body for up to 5 days after ingestion.
The argument from the sucralose is fine camp hinges on the fact that pure sucralose is not really metabolized in the body and leaves just as it entered. This is true but it hangs on to your tongue and your muscle cells for days and days whereas real sugar is used or stored by the body after just a few hours. The on switch I mentioned earlier is therefore on for much longer also. As the artificial sweetener molecule is stuck to the sweet taste receptor the signal of “make more glucose transporters, sugar incoming!” is also on. The real sugar molecules included in each meal a person eats after that initial flip of the on switch will be absorbed much more readily.
A study cited by the Cleveland Clinic concludes that overweight and obese adults who switched to artificially sweetened beverages consumed more total calories compared to overweight and obese people who drank traditionally sweetened beverages and therefore became even heavier. The increased binding affinity of artificial sweeteners provides a biochemical basis for understanding this otherwise backwards observation.
It may be true that artificial sweeteners do not pose a significant increase in cancer risk to the average consumer. However, I hope the mechanism explained here makes the reader think before loading their shopping cart up with diet soda thinking this will help with a weight loss goal.
A few afterthoughts. I’m picking on sucralose (Splenda) in this piece but there are six artificial sweeteners approved by the FDA including one you might recall – aspartame (aka NutraSweet). The structure of aspartame is much different than sucralose but it works the same way, by binding tightly the taste receptor proteins with much more strength than normal sugars. Aspartame is interesting as it does not really look like a sugar and is instead a dipeptide meaning two amino acids linked together. Aspartame has fascinated me for decades mostly due to the shady revolving door circumstances by which it was finally approved for human consumption in the United States in 1982. Prior to approval there was data indicating it as a carcinogen in mouse studies. This meant the FDA rejected it when the manufacturer, G.D. Searle and Company first attempted to get it approved. But, during the first years of the Regan administration one Mr. Donald Rumsfeld pushed through the approval. If that doesn’t leave a bad taste in your mouth, I’m not sure what will.
Sincerely,
Kristopher Hite Ph.D.
Note: I submitted a version of this post to the Washington Post Op-Ed section and it was rejected. So, to my long-dormant blog it goes!
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