The cost of excessive sugar in the diet

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A new study from the MRC London Institute of Medical Sciences, in the UK, reports that while eating foods rich in sugar does not necessarily make you fat, they can make you very sick. They do this by increasing the level of a compound called uric acid in the blood. The study is published in the journal Cell Metabolism in March 2020.

It is well established that eating too much sugar isn’t a wise thing to do, as it increases the risk of early death. Excessive sugar consumption pushes up the chances of developing a metabolic disorder, including diabetes mellitus and obesity. It pushes down life expectancy by several years.

The question that motivated the current study was whether this reduction in life span was due to the impairment of metabolic functions or some other factors.

Study - Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila. Image Credit: Marcos Mesa Sam Wordley / Shutterstock

The study

The study was carried out in fruit flies fed a diet rich in sugar. As expected, the fruit flies had a shorter life span than those on a healthy diet.

Again, as expected from human studies, the flies showed many features of metabolic disease, such as obesity, and insulin resistance, according to investigator Helena Cocheme. These conditions are well known to be inducers of early death in humans. The natural conclusion was that premature death in fruit flies with excess sugar in their diets was the outcome of the development of these conditions.

The current study suggests otherwise. The researchers concentrated on identifying the role of water, sugar, and salt in the development of high mortality rates in the flies.

Sugar is a substance that causes severe dehydration, just like salt. Diabetes and pre-diabetic high sugar levels are signaled by increased thirst.

To combat this problem in flies with a high-sugar diet, the researchers provided them with more water to drink if they wanted. Cocheme reveals the outcome: “Water is vital for our health, yet its importance is often overlooked in metabolic studies. Therefore, we were surprised that flies fed a high-sugar diet did not show a reduced lifespan, simply by providing them with an extra source of water to drink. Unexpectedly, we found that these flies still exhibited the typical metabolic defects associated with high dietary sugar.”

In other words, even though the high sugar content of the diet still brought about the expected metabolic imbalances, it did not cause earlier death if the flies had more water to drink.

High sugar, dehydration, and high uric acid

In light of this finding, the team then looked at the fly’s renal system in greater detail. They found that when the flies were fed with too much sugar, their bodies built up a molecule called uric acid. This crystalline acid is generated from the process, which results in the breakdown of purines, which are one of the two types of nitrogen base compounds involved in building DNA.

Uric acid is the end-product of purine metabolism. This substance can form crystals if its concentration is too high. Such crystal formation in the fly’s renal system can give rise to renal calculi or kidney stones. In humans, too, uric acid accumulation is a prime cause of some types of kidney stones, as well as of inflammatory arthritis called gout. It is known to increase in concentration with age and may predict the development of diabetes and other metabolic conditions.

On the other hand, diluting the uric acid content of the blood by providing more water when required was an effective way of preventing the formation of kidney stones. Another way to prevent these stones from forming was to give the flies a drug that would block the uric acid synthesis pathway.

This intervention had a significant effect on the survival span of the fly, prolonging the lifespan even though the diet continued to be sugar-rich.

Implications

Unfortunately, this does not give the green light for people to eat all the sugar they can hold as long as they also drink plenty of water. In Cocheme’s insightful words, “The sugar-fed flies may live longer when we give them access to water, but they are still unhealthy.”

Moreover, she points out that obesity is a prime risk factor for heart disease in humans, but the current study hints that early death in people who eat too much sugar is not because of obesity. Instead, she says, “Our study suggests that disruption of the purine pathway is the limiting factor for survival in high-sugar-fed flies.”

To better explore how the sugar in the diet had an impact on human health, a parallel collaborative study in Germany looked at how healthy volunteers were affected by their diet. Co-researcher Christoph Kaleta reports, “Strikingly, just like flies, we found that dietary sugar intake in humans was associated with worse kidney function and higher purine levels in the blood.”

Cocheme sums up: “It will be very interesting to explore how our results from the fly translate to humans, and whether the purine pathway also contributes to regulating human survival. There is substantial evidence that what we eat influences our life expectancy and our risk for age-related diseases. By focusing on the purine pathway, our group hopes to find new therapeutic targets and strategies that promote healthy aging.”

Journal reference:

Esther van Dam, Lucie A.G. van Leeuwen, Eliano dos Santos, Joel James, Lena Best, Claudia Lennicke, Alec J. Vincent, Georgios Marinos, Andrea Foley, Marcela Buricova, Joao B. Mokochinski, Holger B. Kramer, Wolfgang Lieb, Matthias Laudes, Andre Franke, Christoph Kaleta, Helena M. Cochemé, Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila, Cell Metabolism, 2020, http://www.sciencedirect.com/science/article/pii/S1550413120300759

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