More and more fructose is found in our drinks and foods, mostly in the form of fructose-containing corn syrup. As a result, we have consumed significantly more fructose in the last few decades. At the same time, the number of cancer cases rose. Now doctors have found a possible connection between these two trends. As they report in “Nature”, a diet containing fructose causes tumors to grow faster. The cancer cells cannot metabolize the sugar themselves. But you benefit from the fact that the liver can do it and produce lipids from it. The tumors of various types of cancer use these in turn as building blocks for their cell membrane. The findings could now help to develop tumor-inhibiting drugs and diets for cancer patients.
Glucose is found in many supermarket products, but over the past five decades it has increasingly been replaced by fructose. Both types of sugar, also known as glucose and fructose, are chemically very similar and both occur naturally in fruits, vegetables, dairy products and grains. In addition, they are also specifically added to many processed foods and drinks to sweeten them. Because fructose has a stronger sweetening power than glucose, it is being used more and more often, usually in the form of corn syrup. We therefore consume around 15 times more fructose today than we did in the 1960s.
During the same period, cancer cases increased. Since then, a number of cancers have become increasingly common in people under 50. Coincidence or is there a connection? It is known that cancer cells, like all our body cells, have a strong affinity for glucose. They use this simple sugar as an energy source. But do cancer cells and tumors also feed on fructose?
Diets containing fructose cause tumors to grow faster
A team led by Ronald Fowle-Grider from Washington University in St. Louis has now investigated this. To do this, the doctors fed zebrafish and mice with cancer either a normal diet or a high-fructose diet for several weeks and compared how quickly their tumors grew. It was shown that the tumors grew significantly faster when fructose was added to the animals’ food. The three tumor types studied – melanoma, breast cancer and cervical cancer – all responded strongly to the sugar: “We looked at many different types of cancer in different tissues throughout the body, and they all followed the same mechanism. In some cases, the growth rate of the tumors accelerated by twice or even more,” reports senior author Gary Patti from Washington University.
However, the body weight did not change as a result of the fructose administration, so the animals did not become fatter. The concentrations of glucose and insulin in the blood in the fasting state also did not change. This suggests that tumor growth is not due to altered sugar metabolism, but rather directly to fructose, as the researchers explain. To test this interpretation, the doctors fed fructose to animal and human cancer cells cultured in the laboratory in a follow-up experiment. Surprisingly, however, the cells did not react like the tumors and grew slower rather than faster. “In most cases, they grew almost as slowly as if we gave them no sugar at all,” says Patti. This suggests that the cancer cells – in contrast to glucose – cannot directly metabolize fructose themselves and use it as an energy source.
Is the liver to blame?
Fowle-Grider and his colleagues suspected that the animals’ livers instead convert the fructose into nutrients that the tumors can then use for themselves. To test this theory and find out which nutrients these are, the doctors again fed animals a diet rich in fructose and examined whether this changed the concentration of small metabolic products in the blood. It was shown that an increasing number of lipid molecules appear in the blood of these animals; Among other things, there were more lysophosphatidylcholines (LPCs). Additional tests on liver cells cultured in the laboratory showed that they release such LPCs after being fed fructose. This is made possible by two enzymes that occur in liver cells but not in tumor cells, as Fowle-Grider and his colleagues discovered.
The researchers conclude that the liver metabolizes fructose into lipids and releases them into the blood. The cancer tumors, in turn, then use these lipids as building material: They convert the LPCs into phosphatidylcholines (PCs) and incorporate them into their cell membrane. In co-cell cultures of liver and tumor cells, the cancer cells grew and divided more when the researchers added fructose. Getting the building blocks from the environment or the blood is more convenient for the cancer cells than producing them themselves, as previous studies have already shown. This appears to be particularly easy with unsaturated LPCs because, unlike other lipids, they are highly soluble and easy to transport, as the team found.
Low-sugar diet against the tumor?
The discovery that the liver converts fructose into usable nutrients for cancer cells could now change the treatment of many different types of cancer: cancer patients could be given a low-fructose diet to “starve” the tumors. “If you’re unlucky enough to have cancer, you should probably think about avoiding fructose,” says Patti. A clinical study will now show whether this actually works.
The idea of fighting cancer with targeted nutrition is not new. In this case, however, the effect would be indirect for the first time. “When we think about tumors, we have so far focused on what food components they consume directly. But humans are complex. “What we put into our bodies can be consumed by healthy tissue and then converted into something else that tumors use,” explains Patti.
Follow-up studies should also clarify whether drugs can prevent tumors from receiving the lipids. Instead of targeting cancer cells, the preparations could also target liver cells, or more precisely their fructose-degrading enzyme. The metabolism of healthy cells could potentially be used specifically to treat cancer.
Source: Ronald Fowle-Grider (Washington University) et al.; Nature, doi: 10.1038/s41586-024-08258-3