Tag: fructose

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Fructose Identified as a Surprise Driver of Metastasis

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Photo by Sharon Mccutcheon on Unsplash

A new study from The Wistar Institute has uncovered an unexpected link between fructose and the spread of an aggressive form of ovarian cancer. Published in Nature Aging, the study found that cancer cells not killed by chemotherapy send signals to neighbouring tumour cells, driving metastasis. The researchers identified fructose as a key messenger in this process, revealing a previously unrecognised way that treatment-surviving cancer cells may promote metastasis.

“Some cancer cells that survive chemotherapy aren’t dividing anymore, but they’re still biologically active,” said Aidan Cole, PhD, a postdoctoral fellow in the lab of Katherine Aird, PhD, at The Wistar Institute and first author on the study. “Instead, they continue to release molecules that send signals to nearby cells. Our study is among the first to show that a nutrient – in this case, fructose – can act as one of those signals.”

Ovarian cancer is treated almost universally with platinum-based chemotherapy, and many patients respond well at first. However, the disease recurs in most patients and almost always spreads through the abdominal cavity. That spread, called metastasis, accounts for roughly 90% of deaths from the disease.

Prior research has suggested that cancer cells not killed by chemotherapy play a role in recurrence in part through the ability of these cells to release a complex mix of signalling molecules. Cole and his colleagues began their research by designing a unique experiment: they collected the molecules released by chemotherapy-surviving cells and found these factors alone could significantly increase the spread of cancer cells.

“As far as we know, this is the first time anyone has shown, in a preclinical model rather than just a dish, that it’s the molecules these cells release – not the cells themselves – that drive the cancer’s spread,” said Cole.

That finding sent the team looking for what was being released that caused the cancer cells to spread. Fructose, it turned out, was being made by the surviving cells and sent as the signal for increased spread. Even more interesting, they found that without chemotherapy treatment, consuming the high levels of fructose found in sugary drinks can also signal cancer to spread. The fructose finding is especially compelling because it raises the possibility that simple dietary changes could help shape how cancer progresses. This is particularly important given the prevalence of fructose consumption in the United States, with high fructose corn syrup accounting for ~8-20% of the daily caloric intake in some individuals. Unlike many cancer risk factors outside of patient control, fructose consumption can be modified by dietary choices. While the effectiveness of limiting fructose intake hasn’t yet been tested directly in patients, the study raises the possibility that nutrition could influence cancer progression in previously unrecognised ways.

The researchers next aimed to understand why fructose increases cancer cell spread. Through a variety of large-scale analytical techniques, including the use of a CRISPR screen, they discovered that fructose suppresses cholesterol within the neighbouring cells. Cholesterol is important for cells to stick to each other like a biological glue, so decreased cholesterol allows cells to more easily escape and spread.

The finding that fructose lowers cholesterol production has important clinical implications. Statins, which are taken by 39 million people in the United States, lower cholesterol production. The team found that statins alone decreased the glue between cells to promote escape. The research team is now examining whether these medications could be interfering with the effects of chemotherapy – though they stress this isn’t a reason for patients to stop taking them.

“We haven’t tested this effect in patients yet, but it raises questions about combining cholesterol-lowering drugs with chemotherapy, especially since ovarian cancer is most common in postmenopausal women who are often already on statins,” said Katherine Aird, PhD, professor and co-leader of the Molecular and Cellular Oncogenesis Program in the Ellen and Ronald Caplan Cancer Center at The Wistar Institute, and senior author of the study.

The researchers are also looking into how this mechanism might extend beyond ovarian cancer.

“We think other cancers that spread within the torso – pancreatic, colon, liver – could behave similarly. We can’t call it universal yet, but we think the effects are not just limited to ovarian cancer,” said Aird.

She and Cole have already started designing follow-up experiments to test the reproducibility of their findings in a variety of other cancer types.

Source: The Wistar Institute

Categories : Diet and Nutrition Metabolic DisordersTags :

New Report Highlights Fructose as a Key Driver of Metabolic Disease

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Researchers emphasise fructose’s unique role in obesity, metabolic syndrome and other chronic diseases

Photo by Kobby Mendez on Unsplash

A new report, published in Nature Metabolism, is shedding light on the distinct and underappreciated role of fructose in driving disease, separate from its role as a simple source of calories.

Researchers examine how common dietary sweeteners, including table sugar (sucrose) and high-fructose corn syrup, impact human health. While both contain glucose and fructose, fructose has unique metabolic effects that may more directly contribute to obesity and related conditions.

“Fructose is not just another calorie,” said Richard Johnson, MD, professor at the University of Colorado Anschutz and study lead author. “It acts as a metabolic signal that promotes fat production and storage in ways that differ fundamentally from glucose.”

The report outlines how fructose metabolism bypasses key regulatory steps in the body’s energy-processing pathways. This can lead to increased fat synthesis, depletion of cellular energy (ATP) and the production of compounds linked to metabolic dysfunction. Over time, these effects may contribute to metabolic syndrome, a cluster of conditions that includes obesity, insulin resistance and cardiovascular risk.

Importantly, the authors emphasise that fructose’s impact extends beyond dietary intake alone. The body can also produce fructose internally from glucose, suggesting that its role in disease may be broader than previously recognised.

The findings come amid ongoing concern about rising rates of obesity and diabetes worldwide. Although some countries have seen declines in sugary beverage consumption, overall intake of “free sugars” remains above recommended levels in many regions and continues to increase in others.

While fructose may have once served an evolutionary purpose, helping the body store energy that can aid survival during times of food scarcity, the researchers argue that in today’s environment of constant food availability, these same mechanisms now contribute to chronic disease.

“This review highlights fructose as a central player in metabolic health,” said Johnson. “Understanding its unique biological effects is critical for developing more effective strategies to prevent and treat metabolic disease.”

By Kelsea Pieters

Source: Colorado University Anschutz

Categories : Cancer Diet and NutritionTags :

Could Cutting Sugary Drinks Reduce Cancer Risk in Women?

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A higher intake of sugar-sweetened beverages (SSBs) in adulthood and adolescence was linked to an increased risk of early-onset colorectal cancer (CRC) in women, according to data from a large prospective study.

The Nurses’ Health Study II followed over 95 000 registered nurses from 1991 to 2015. Those consuming at least two SSB servings a day in adulthood had more than double the early-onset CRC risk of those consuming less than one serving a week. This rose by 16% with each extra serving per day.

In the adolescent years of ages 13 to 18, each serving-per-day increment was associated with a 32% higher risk of early-onset CRC. Meanwhile, replacing each SSB serving per day for adults with a serving of a non-SSB drink was associated with a 17-36% lower risk.

“Considering the well-established, adverse health consequences of SSBs and the highest consumption being characterized in adolescents and young adults under age 50 years, our findings reinforce the public health importance of limiting SSB intake for better health outcomes,” Yin Cao, ScD, MPH, of Washington University in St. Louis, and co-researchers wrote.

Although CRC has been on the decline, the age of early onset — that is, diagnosed before age 50 — has been increasing the past two decades. In comparison to adults born around 1950, those born around 1990 had twice the colon cancer risk and four times the rectal cancer risk.

An estimated 12% of the US population currently consume more than three SSB servings per day, as shown by National Health and Nutrition Examination Survey data. SSBs in the US are often include high fructose corn syrup as an ingredient, as opposed to South Africa which uses cane sugar.

In this study, the population consisted overwhelmingly of white females, ages 25 to 42, with an average age of approximately 42 at enrollment. Over up to 24-plus years of follow-up, 109 cases of early-onset CRC were recorded.

The researchers found that those with higher SSB intakes in adulthood tended to be less physically active and more likely to have a lower endoscopy history, to use non-steroidal anti-inflammatory drugs, and consume red and processed meats. They were also less likely to take multivitamins and to have a reduced intake of alcohol, fibre, folate, and calcium, and to have a poorer diet overall.

No association was found between intake of artificially sweetened beverages or fruit juice in adulthood and risk of early-onset CRC, mirroring past research.

The investigators listed a number of possible pathways for the effect of SSBs on early-onset CRC. 

For example, compared with isocaloric solid foods, energy-containing beverages do not create a feeling of satiation, leading to weight gain. SSBs also initiate rapid blood glucose response and insulin secretion, possibly leading to insulin resistance, inflammation, obesity, and type 2 diabetes — metabolic conditions which are linked to heightened CRC risk.

Other possibilities include intestinal dysbiosis and endotoxemia caused by high fructose levels , the principal sweetener in SSBs in the US and certain other countries, which can impair gut barrier function, increasing gut permeability, and possibly promote cancer formation. A recent experimental study suggested that the high-fructose corn syrup in SSBs from the US enhanced the growth of aggressive tumours in mice, regardless of weight and metabolic syndrome.

High-fructose corn syrup has also been linked to metabolic dysregulation, regardless of obesity.

Fortunately, overall SSB intake has been trending downward in recent years, and Dr Cao and co-authors concluded that further limiting consumption may be “an actionable strategy to curb the rising incidence of [early-onset] CRC.”

Study limitations, the researchers said, included possible unknown confounding variables, the few early-onset CRC cases prevented pinpointing the window of exposure, and there weren’t enough diabetic participants to stratify by a personal history of diabetes. Since the participants were mostly white women, the results were not readily generalisable to other ethnic groups or to men.

Source: MedPage Today

Source Reference: Hur J, et al “Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women” Gut 2021; DOI: 10.1136/gutjnl-2020-323450.