Fake Sugar — Does the Body Rebel?

Nutritive sugar is sucrose, the kind that Nature provides; the kind with calories. A non-nutritive sweetener (or NNS) is the other kind.

What sort of neural response is provoked by each type? What kind of metabolic reaction, and what kind of eating behaviors follow the consumption of one or the other? The whole point of an NNS is to quench the desire for sweets by tricking the body into believing it has consumed some natural sugar, while not adding to the caloric load.

What effect does the fake stuff have on appetite, and on the reward mechanism that is supposed to be persuaded that sugar has been delivered? Does the body, like a cheated user who paid for cocaine, get angry and protest, “Hey, this stuff is just baby laxative”? Turns out, the answers have to do with both sex and obesity.

Why does anyone care?

The authors explain that something like 40% of American adults are into the NNSs, even though a basic understanding of the health consequences is somewhat wobbly or, as scientists put it, “shows mixed results.” Aside from the substances’ effect on appetite, there is the all-important question of whether body weight is even affected. Most of all, what about glucose metabolism, which is a rather significant factor in overall health?

It is known that the areas of the brain having to do with taste, reward, and homeostasis are involved, and make their own judgments about nutritive sugars versus NNSs. Yet, previous studies have mainly been of normal-weight humans — and males, at that. Which brings us to the crux of the matter, and the reason for this particular research endeavor: If female rats have already been overfed to induce obesity, it looks like an NNS tends to make them eat more (increased energy intake) and get fatter (weight gain). What? Isn’t that contrary to the whole point and purpose of ingesting the fake stuff in the first place? Exactly!

A small study

The researchers recruited 74 subjects (58% female) aged 18 to 35 and tried to make sure they were uniformly matched in many ways — right-handed non-smokers and non-dieters whose weight had been stable for at least three months; taking no meds except the women who were on birth control; with no history of eating disorders, illicit drug use, or medical diagnoses.

(Side note: The amazing part is that they found any such people in Southern California! Apparently, it took almost four years to recruit even this number of qualified participants. A puzzling question is what being right-handed has to do with anything, which does not seem to be explained.) The study had to be cut short when the Coronavirus pandemic set in, and then analysis of the data took a year:

Our findings indicate that female individuals and those with obesity, and especially female individuals with obesity, might be particularly sensitive to greater neural responsivity elicited by sucralose compared with sucrose consumption. This study highlights the need to consider individual biological factors in research studies and potentially in dietary recommendations regarding the use and efficacy of NNS for body weight management.

Worldhealth.net asked an uninvolved third party, behavioral scientist Susan Swithers, what it all means. She said,

You are supposed to get sugar after something tastes sweet. Your body has been conditioned to that… [This could mean] when you get the sweet taste without the sugar, that changes how you respond to sugar the next time, because you don’t know whether it’s coming or not.

How does this relate to obesity? Swithers suggests that an NNS scams the organism into thinking that sugar is incoming (much like the hopeful cocaine customer). But when sucrose does not arrive in the system, the body somehow begins to lose its ability to prepare for the metabolization of the next load of actual sugar that comes along.

Your responses and feedback are welcome!

Source: “Obesity and Sex-Related Associations With Differential Effects of Sucralose vs Sucrose on Appetite and Reward Processing,” JAMANetwork.com, 09/28/21
Source: “Diet soda may prompt food cravings, especially in women and people with obesity,” WorldHealth.net, 10/11/21
Image by David Martín/CC BY-SA 2.0

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About Dr. Robert A. Pretlow

Dr. Robert A. Pretlow is a pediatrician and childhood obesity specialist. He has been researching and spreading awareness on the childhood obesity epidemic in the US for more than a decade.
You can contact Dr. Pretlow at:


Dr. Pretlow’s invited presentation at the American Society of Animal Science 2020 Conference
What’s Causing Obesity in Companion Animals and What Can We Do About It

Dr. Pretlow’s invited presentation at the World Obesity Federation 2019 Conference:
Food/Eating Addiction and the Displacement Mechanism

Dr. Pretlow’s Multi-Center Clinical Trial Kick-off Speech 2018:
Obesity: Tackling the Root Cause

Dr. Pretlow’s 2017 Workshop on
Treatment of Obesity Using the Addiction Model

Dr. Pretlow’s invited presentation for
TEC and UNC 2016

Dr. Pretlow’s invited presentation at the 2015 Obesity Summit in London, UK.

Dr. Pretlow’s invited keynote at the 2014 European Childhood Obesity Group Congress in Salzburg, Austria.

Dr. Pretlow’s presentation at the 2013 European Congress on Obesity in Liverpool, UK.

Dr. Pretlow’s presentation at the 2011 International Conference on Childhood Obesity in Lisbon, Portugal.

Dr. Pretlow’s presentation at the 2010 Uniting Against Childhood Obesity Conference in Houston, TX.

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