Fructose Hijacks the Liver to Grow Cancer

New research in Nature reveals how fructose can fuel the growth of cancer by hijacking the liver. We discuss what the data mean, and what they don't, and solutions.

Did you know that fructose can fuel cancer by hijacking your liver?

It sounds dramatic, but new research - published in Nature - has uncovered a chilling new connection between fructose — the sugar found in high-fructose corn syrup (HFCS) and, yes, fruit (more on that below) — and cancer growth.

And it’s not just about sugar making us gain weight; the effects are far deeper and more direct. Let me break it down for you.

There is now a video associated with this paper. If you prefer to watch, click below. If you prefer to read, continue onward! (And - yes - Newsletter subscribers get first access to my breakdowns).

Background

First, some background to hammer home the relevant of this finding.

High fructose diets are already associated with increased risks of certain cancer, like pancreatic cancer. And there are other known mechanisms whereby fructose can support cancer growth and survival.

In fact, information about the fructose-cancer connection appears itself to be metastasizing across the scientific literature.

What, too dark? Maybe fructose poisoned your sense of humor too ;).

Sorry! Back to “serious Nick”…

I particularly like these new data, because they reveal just how sneaky cancer can be, effectively hijacking our organs for its own purposes.

Fructose Fuels Tumor Growth

I’ll cut right to the chase… When they fed animals high-fructose corn syrup (HFCS) -- the most abundant and dense source of fructose in the modern human diet, they found:

“In all cases, diets supplemented with HFCS resulted in faster tumor growth compared with control diets.”

This included skin (melanoma), breast and cervical cancers in animal models, and across multiple species.

I will also emphasize that this happened independent of changes in body weight.

So, this is not simply an indirect effect of fructose from the slow insidious creeping negative effect fructose can have on metabolic health. (For a great paper on fructose and metabolic syndrome, click here).

No, what’s going on in this study is a direct effect of fructose consumption on cancer growth. Well, sort of...

The Mechanism: Liver Hijacked

The mechanism discovered is quite interesting and relies on the gatekeeper enzyme of fructose metabolism, ketohexokinase (KHK). Interestingly, many cancer cells themselves lack sufficient levels of KHK to process fructose.

Figure 2C from the paper, showing a Western blot of various cancer cell lines and hepatocytes (liver cells). Western blots stain for the presence of proteins, here a major form of the KHK enzyme, KHK-C. The beta-actin is a loading control. Clearly, there’s no visible KHK-C in the cancer cell lines, but plenty of KHK-C enzyme in the hepatocytes/liver cells.

However, cancer is very good at co-opting the body’s systems and organs for its own purposes.

In this case, the liver, when supplied with fructose, produces particular lipid molecules that go to the cancer cells and are converted to other lipid molecules called “phosphatidylcholines,” a major component of cell membranes.

In effect, the cancer is using your liver to convert fructose into the raw materials for cancer’s construction project.

This mechanism not only explains why fructose accelerates tumor growth but also highlights how tricky cancer can be in using your body’s normal systems for its gain.

Solutions

Understanding mechanism is turning the doorknob on the doorway of solutions.

One obvious solution to the threat of fructose is fructose reduction.

I’ll caveat, this does not mean fruit is poison, particularly lower sugar fruits like berries.

• In fact, as an interesting aside, more than 3X as much fructose is consumed in the United States from Sodas and Sugar-Sweetened beverages alone as compared to all fruits and fruit products.

• Furthermore, the lower doses of fructose in fruit, combined with slowed gastric emptying given the generally lower glycemic index of – say – berries versus a Frappuccino, actually allows time for the small intestine to transform fructose into other, less harmful, sugars before they traverse the portal vein to the liver.

However, our food supply is overflowing with fructose-containing processed foods.

Given that it’s unlikely these will disappear anytime soon, we need to innovate improvements in available options.

As an example, the mechanism described in this video relies on the fructose processing enzyme, ketohexokinase (KHK).

So, what if you used the rare sugar and low-calorie C-3 epimer of fructose, allulose, that can’t be processed by KHK? Well, obviously, the KHK-dependent risks, including fueling cancer, disappear.

If you want more on allulose and why I think it’s the best sugar and fructose substitute, see these videos:

But now, imagine if we did just that, scaled this up and displaced all the HFCS and added sugar with allulose.

For those who don’t need or want anything sweet, nothing has changed for us.

But at a broad public health level, the impact on metabolic health would be immense – perhaps even larger than the GLP-1 boom. I’m dead serious.

I speculate displacing all added sugar from the food supply would be a bigger boon for public health than any drug innovation I can imagine.

Health Company Disguised Itself as a Food Company

As a shameless but relevant plug, it’s no secret that’s this is the very mission of one health company, that’s disguised itself as a food company, RxSugar.

I’m on their scientific advisory board and, though I lack a sweet tooth myself, am happy to promote their products, including bars, syrups, brownie mix and now cereal, because it just makes sense from a public health perspective.

I’ve also had friends lose a tremendous amount of weight by leveraging allulose, and it’s super handy when cooking for big party’s at Thanksgiving.

I’ll link to their products with a discount code – NICK20 – if you or anyone you know wants to try.

But again, that’s not really the point. The point is high-sugar and high-fructose diets are a public health danger, and we need a multifaceted approach to reduce intake, including education (what we’re doing here), policy changes, and shifts in social norms.

Certainly a few blueberries or cake on your birthday won’t kill you… but routine intake of high dose fructose just might… and now we know just a little bit more about how it could.

Controversial Topics on My Social Media

Yesterday’s video on Seed Oils is getting some strong remarks. For a balanced and “provocatively reasonable” point of view:

And on the controversial topic of Food Dyes… but with a sensible twist: