When a Sweet Tooth Helps Trigger Autoimmunity

Too much appeasing of a sweet tooth has been associated with an increased risk of developing autoimmunity.  While higher sugar consumption may do so, artificial sweeteners appear to increase the risk similarly.  This is a significant concern as either sugars or artificial sweeteners are added to almost all processed foods.

Humans have 3 primary taste drives which stimulate our interest in eating a particular food, the tastes of salt, fat, and sugar.  If you want to unconsciously drive someone to consume more of a particular food, simply add one or more of these tastes.  Compare your preference for a piece of bread plain or with peanut butter or butter.  Naturally, one with either of these fats added will taste better.  The taste of popcorn with and without salt is far different with the former much preferred.

The first caution with processed foods was that they contain too much salt which may contribute to hypertension risk.  We are now two decades into the “low fat food” craze which resulted in less tasteful food.  The only taste to rescue this need to increase the desire and consumption of a food – sugar or sweet taste.  When we have a patient going through the exercise of looking at the grams of sugar in any processed food they would consider and then scan the ingredient list for it or an artificial sweetener the result is almost universally, “they put sugar in everything”.

While this “eat” drive from these tastes served to help us find energy when for much of human existence we struggled to find enough to eat, it is purely an “over-eat” signal in the modern high food availability environment.  Many experts are of the opinion that the shift away from fats to the high consumption of sugars has caused the obesity and diabetes epidemics.

Increased consumption of sugars has been shown to increase the risk of multiple autoimmune diseases including rheumatoid arthritis, multiple sclerosis, psoriasis, and inflammatory bowel disease such as ulcerative colitis and Crohn’s disease.(1)  The mechanisms thought to be associated with this increased risk are multiple.  Increased sugar consumption causes an unhealthy shift in the microbiome living in the digestive tract to one that causes more inflammation.  These changes cause the gut barrier to weaken and leak, a major factor in autoimmune risk which we had discussed in a previous blog.

Another mechanism by which sugar may contribute to autoimmunity is that it increases activation of immune T cells, Th17 cells which are highly associated with autoimmunity.(2)  These T cells begin the attack against extra-cellular pathogens such as some bacteria and fungi as opposed to viruses which live inside of cells.  Too much activation of Th17 cells increases the risk that they will begin to react to self-tissue triggering autoimmunity.  

While artificial sweeteners contribute to autoimmunity through a somewhat different mechanism.  The activation of sweet taste receptors on the tongue induce loosening/leakage of the gut barrier to facilitate the transport of “sugars” across the intestinal barrier more easily.(3)  This is again thought to be a mechanism which facilitates getting energy into the system which helps when food and energy availability was low as it was during most of human existence.  This leakiness of the gut barrier allows bacterial toxins from the gut lumen to enter the system triggering inflammation and T cell activity.  It also allows poorly digested food peptides such as those in gluten to enter the system and trigger immune reactions against them.  The immune reaction to these food peptides can trigger cross-reactivity against self-tissue, autoimmunity.

As a side note on the artificial sweeteners, they were hailed as the cure for the obesity and diabetes epidemics.  A couple of decades later they are now thought to contribute to those problems.  The body has multiple layers of activating its functions.  The taste of “sweet” on the tongue causes about 1/3 of the insulin release that that food response will generate, a phenomenon called cephalic (at the head) phase insulin response.  The high insulin signaling in response to a high sugar or “sweet” diet food causes cells to respond less well to insulin, termed insulin resistance.  Insulin resistance is associated both with the excessive conversion of blood glucose to a storage fat, triglyceride (obesity) and also the inability to adequately lower blood glucose (diabetes).

Becoming aware of the sugar and sweeteners that are being consumed can lead to lower risks of several metabolic related diseases but also autoimmunity.  A good whole food diet will supply about 35-40 grams of natural sugars which are inherent to the foods.  The current U.S. diet supplies about 220 grams of sugar, or a 5-fold increase.  This is not done for our health benefit but rather to primarily drive excess food consumption.  In fact, it creates significant disease risk.

  1. Ma et al.  Excessive intake of sugar: An accomplice of inflammation.  Front. Immunol, 2022;13:988481.
  2. Zhang et al.  High glucose intake exacerbates autoimmunity through reactive oxygen species-mediated TGF-β cytokine activation.  Immunity. 2019;51(4):671–681.
  3. Shil et al.  Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3.  Nutrients, 2020;12:1862.