The Not-So-Sweet Stuff: A Look at How Surplus Sugar Sabotages Our Cells’ Mitochondrial Efficiency

From sweetened lattes in the morning to surprisingly sugar-filled dressings topping your salad at lunch to an evening dessert (or two), many people typically consume much more sugar than they realize. With most Americans taking in roughly 22 teaspoons of added sugar per day (this doesn’t count the natural sugar in fruits, vegetables, and dairy), we are drowning in the sweet stuff — and so are our cells. 

While we know that excess sugar is detrimental to various health outcomes, it’s lesser-known what’s happening on a cellular level. Now, researchers find that high amounts of sugar inside cells reduce the quantity of fats called polyunsaturated fatty acids (PUFAs) in the membranes of mitochondria — our cells’ energy powerplants. Authored by Waldhart and colleagues and published in Cell Reports, this research team finds that the membrane alterations from excess sugar cause mitochondria to become less efficient, diminishing our myriad metabolic processes — and our health along with it.

How Sugar Changes Our Cells

Our bodies require correct proportions of PUFAs for many things, including cell-to-cell communication, mounting proper inflammatory responses, and supporting mitochondrial integrity. When we have too much sugar inside cells, the excess is formed into a different type of fat — a less flexible type than PUFAs. This change in lipid (fat) composition damages the mitochondrial membrane structure, causing it to become less efficient in producing energy. 

Although less-efficient mitochondria don’t always produce immediately recognizable effects, they can be attributed to many “typical” symptoms of our modern society, like fatigue or general lack of energy. As senior author of the study, Ning Wu, Ph.D., explains, "Although we may not always notice the difference in mitochondrial performance right away, our bodies do. If the [PUFA] balance is thrown off for long enough, we may begin to feel subtle changes, such as tiring more quickly."

With this in mind, the research team directly tested the effects of excessive intracellular sugar on mitochondrial function. To start, they genetically altered mice to not contain a protein called TXNIP (thioredoxin-interacting protein), which is a tight regulator of glucose (sugar) uptake from our bloodstream into our cells. Without TXNIP, glucose uptake is uncontrolled, and cells will contain too much sugar.

Excess Sugar Damages Mitochondrial Membranes

Waldhart and colleagues looked specifically at the effects of not having TXNIP on brown adipose tissue (BAT). Also known as brown fat, BAT ​​contains more mitochondria than other tissue because its primary function is to boost thermogenesis, or energy production through heat.

They found that mice without TXNIP — and thus had high amounts of intracellular sugar — had significantly lower PUFA concentrations in their brown fat cells’ membranes. These mice exhibited defective thermogenic activity after being exposed to cold treatment, or “cold stress.” Cold stress assesses mitochondrial capacity and ordinarily would lead to an uptick in BAT’s heat production if the mitochondria were functioning correctly. In this case, excessive sugar inside the mouse’s brown fat cells diminished this process and even damaged the structure of the mitochondria, causing swelling and breakages in the inner membrane folds.

The research team then successfully reversed these harmful effects by supplying the mice with a ketogenic diet — a very low carbohydrate diet with higher amounts of fat and protein. With this diet, the mouse’s cells could not have high amounts of glucose, even without TXNIP there to regulate it. These results indicate that poor mitochondrial integrity — and the diminished energy production that goes with it — can be rescued with simple dietary changes of lowering carbohydrate intake.

The authors describe, “Ultimately, our findings illustrate a clear, early connection between excess carbohydrate and mitochondrial function. They confirm mechanistically one detrimental aspect of a high-sugar diet. While such cellular changes induced by diet may not be obvious under normal conditions, we provide strong evidence that they indeed make a functional difference under stress.”

Sayonara, Sweet Tooth

So, can we never eat sugar again? Dr. Wu doesn’t necessarily think so, stating, "The body needs sugar, or glucose, to survive, but, as the saying goes: 'All good things in moderation.'" She continues, "We found that too much glucose in cells, which is directly linked to the amount of sugar consumed in one's diet, affects lipid composition throughout the body, which in turn affects the integrity of mitochondria. The overall effect is a loss of optimal function."

Essentially, not all sugar is bad (especially the types from fruit, vegetables, and dairy) but going overboard can seriously damage our mitochondria — and our energy production along with it. The American Heart Association recommends keeping added sugars to less than six teaspoons (100 calories worth) for women or nine teaspoons (150 calories) for men per day — but lower is definitely better when it comes to the sweet stuff. While maintaining a highly restrictive ketogenic diet is certainly not for everyone, lowering your overall sugar consumption is a sweet goal for most.

References: 

Waldhart AN, Muhire B, Johnson B, et al. Excess dietary carbohydrate affects mitochondrial integrity as observed in brown adipose tissue. Cell Rep. 2021;36(5):109488. doi:10.1016/j.celrep.2021.109488