Dietary Fructose in Nonalcoholic Fatty Liver Disease

ByCrossFit March 7, 2019

Miriam Vos (Emory) and Joel Lavine (Columbia) present the evidence linking fructose to fatty liver disease in this 2013 review.

A healthy liver holds relatively little fat (<5.5% fat fraction). Fatty liver disease occurs when the liver stores too much fat, either by producing and importing too much, or by burning and exporting too little. Nonalcoholic fatty liver disease (NAFLD) is marked in particular by higher circulating fatty acids, greater liver fatty acid production (de novo lipogenesis, or DNL), and delayed liver fatty acid export.

When fructose is consumed, it passes through the small intestine and quickly is taken up by the liver, where it is either burned or converted to free fatty acids and/or glycerol and glycogen. Fructose has been shown to increase liver and visceral fat: the former through increased DNL and the latter as a potential consequence of liver insulin resistance (fatty livers become insulin resistant). Fructose similarly increases circulating triglyceride levels by increasing fat production within the liver. These effects may be exacerbated by the effects of fructose on the gut microbiome, which can trigger additional liver inflammation and the development or progression of NAFLD.

Figure 1: In NAFLD, ingested fructose may alter the microbiome, increasing movement of endotoxin into the portal system because of increased permeability of tight junctions. Endotoxin and fructose enter the liver where endotoxin increases inflammation and insulin resistance through activation of Toll‐like receptor 4 (TLR4). Fructose is rapidly metabolized, consuming adenosine triphosphate (ATP), which may result in increased adenosine monophosphate (AMP) and conversion to uric acid. Excess triglyceride produced through stimulation of de novolipogenesis (DNL) is packaged onto large, TG‐rich very low density lipoproteins (VLDL) or in the setting of imbalance can result in increased steatosis in the liver. Steatosis may also be driven by increased return of nonesterified free fatty acids (NEFA) from adipose tissue. From “Dietary fructose in nonalcoholic fatty liver disease“.

Patients with NAFLD tend to consume more fructose than their peers, and those with more severe NAFLD consume more than those with less severe NAFLD. However, Vos and Lavine note that evidence from direct clinical trials has been inconsistent and only clearly indicates that fructose increases liver fat content in the context of a hypercaloric diet. They conclude, however, “While the understanding of the role of fructose in NAFLD is evolving, the evidence demonstrating increased VAT, hypertriglyceridemia, and insulin resistance from high fructose is sufficient to support decreasing consumption as a clinical recommendation for patients with NAFLD.”

Note: This review was written in 2013. Subsequent evidence, to be presented elsewhere on, has more broadly illustrated a direct link between fructose consumption and NAFLD.

Comments on Dietary Fructose in Nonalcoholic Fatty Liver Disease


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Matthieu Dubreucq
December 5th, 2019 at 5:59 pm
Commented on: Dietary Fructose in Nonalcoholic Fatty Liver Disease

Thanks for the summary. I note that once again restricting food intake could again be good against Fatty Liver. Obviously cutting fructose also.

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Divjot Singh
April 23rd, 2019 at 4:11 pm
Commented on: Dietary Fructose in Nonalcoholic Fatty Liver Disease

Dear Author, Such wonderful information provided. Thank you so much for this.

I wanted to ask you, Why Herbalife product is filled with so much fructose in it and it is selling all over the world and become a market leader why is that?

Why people are consuming fructose so much when it's showing bad results?

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Charles Bergman
March 8th, 2019 at 1:16 pm
Commented on: Dietary Fructose in Nonalcoholic Fatty Liver Disease

Hey HQ- you note "subsequent evidence, to be presented elsewhere on"

Does that mean the articles are coming, but have not been released yet? Or do you already have them posted and I just can't find them?

This is certainly an interesting review, but it's far from a smoking gun. I'm looking forward to reading the rest of the evidence- it's no stretch to see the correlation, but I love the deep dives you all have been doing!

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Clarke Read
March 15th, 2019 at 6:28 pm

Hey Charles,

You nailed it, and I think you're seeing some of that already. We're going to be running quite a few articles on fatty liver disease in the remainder of March into April (and likely beyond that), and I think you'll see's a very important issue and one where diet and lifestyle likely plays a major role.

We're going to be bringing information from a variety of sources, ranging from mechanistic / metabolic information to some epidemiology, some editorial and opinion and some info about the broader statistics of the disease and their implications. Hopefully as it all comes together it'll paint a more comprehensive picture of what this condition is, why it matters, and what we may be able to do - individually and collectively - to reverse its course.

Thanks for following along!

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Charles Bergman
March 16th, 2019 at 2:20 am

Absolutely man! I saw yesterday's and today's articles and smiled! Awesome background research. I was doing NAFLD transplant research and decided to walk away to start an affiliate for this very reason. Working to prevent or reverse NAFLD is far more beneficially than trying to find ways to transplant a fatty liver.

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Clarke Read
March 17th, 2019 at 12:14 am

That's fantastic! And I think it's entirely aligned with where Crossfit is coming from in 2019. There is and always will be an enormous role for traditional medicine in health and well-being. At the same time, the tools favored by the Crossfit ecosystem - diet, exercise and a sense of community - can play a major part and for some conditions may even serve as treatments in themselves. These articles are in large part to illustrate how these factors can affect health, for good or ill, and so to empower community leaders like yourself to have a positive impact while bringing attention to these problems and potential solutions more broadly. (Other programs like the DDC and MDL1 build on this further)

It sounds like you’re way ahead of us on that front, and that’s amazing to hear. You’re a great example of the kind of positive impact the Crossfit community can have on our communities. Thank you.

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