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    High Fructose Corn Syrup, Genes And Global Trade Policy: A “Perfect Storm” For Fatty Liver Disease In Hispanics
    By Michael Goran | August 14th 2012 05:45 PM | 7 comments | Print | E-mail | Track Comments
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    Michael Goran is a professor of Preventive Medicine and Director of The Childhood Obesity Research Center at the University of Southern California...

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    As the prevalence of obesity rises around the world, non-alcoholic fatty liver disease(NAFLD) is a growing concern, especially among the vulnerable Hispanic population.  Perhaps most alarming is that NAFLD, traditionally a disease of middle age, has become increasingly prevalent in childhood, where studies show that ~38% of obese Hispanic children and adolescents have liver fat levels in the range of clinically diagnosed NAFLD.

    NAFLD is the most common cause of fatty liver disease in the U.S., serving as a precursor to non-alcoholic steatohepatitis, which can lead to cirrhosis, permanent liver damage and liver cancer.   Adding insult to injury, NAFLD is also associated with the development of type 2 diabetes and influenced by genetics.  Multiple studies have shown that Hispanics are genetically predisposed to fatty liver disease with a recent study identifying the PNPLA3 gene, which is linked with over 2-fold higher liver fat content.  Almost 50% of Hispanics carry this gene as opposed to around 20% of other populations. Furthermore, the impact of this gene is manifested in children as young as 8 years of age.

    Beyond genetics, fatty liver disease has another accomplice – dietary sugars,specifically fructose.  Most fructose is quickly converted into fat in the liver, and when consumed in abundance, thats ugar-turned-fat is stored in the liver, potentially leading to NAFLD.  It is important to note that fructose is also known as “fruit sugar” because it naturally occurs in most fruit.  Fructose in this form is housed in fiber-rich flesh, which serves as a sort of antidote to the negative effects of fructose breakdown.However, fructose is most commonly found as high fructose corn syrup (HFCS) and normal table sugar, which is not encased in a friendly fiber flesh, making it more likely to to wreak havoc on livers. This type of fructose is added to everything from breads, cookies, and chips to soda, yogurt, and sports drinks.

        Complicating matters is new evidence of a gene-diet interaction in Hispanics wherein higher liver fat is linked with higher sugar intake in subjects carrying a specific variant of the PNLPA3 gene. Thus, Hispanics carrying the PNPLA3 variant coupled with a high sugar diet (specifically high fructose which is a substrate for conversion to fat in the liver) are particularly susceptible to increased liver fat and subsequent disease.

        Further exacerbating the Hispanic vulnerability, sugar and fructose consumption in Mexico has increased dramatically. Of all countries, Mexico appears to have the“sweetest tooth” and has the highest per capita consumption of Coca Cola in the world (675 servings per capita per year, as compared to 394 in the U.S).   Just like it dominates the Mexican beverage industry, sugar also dominates marketing to children.  Food advertising in Mexico is over 10% more during children’s television programming compared to general audience programming with the majority of advertisements for sugar-sweetened beverages,sweets, and cereals with added sugar.   

        Consumption of sugar and HFCS in Mexico is strongly influenced not just by individual preferences but also by global trade policies. For a long time the US was banned from exporting HFCS to Mexico under a ruling from the North American Free Trade Agreement (NAFTA). However, after a long protracted legal case, this ruling was overturned by the World Trade Organization. This has resulted in an explosion of exports of HFCS from the US to Mexico, increasing exponentially in the last few years. This is likely going to have a huge impact on the“foodscape” in Mexico with the likely replacement of sugar by HFCS, introduction of a broader range of processed foods made with HFCS and a resulting dramatic increase in fructose exposure in the population. Couple this with the genetic predisposition and a gene by diet interaction and you have the makings of a“perfect storm” for fatty liver disease in Mexico. We are already seeing the beginnings of this in the Hispanic populations of the United States. For example, liver disease is now the 4th leading cause of death among Hispanic men in Los Angeles County.

        With a genetic tendency to deposit fat in the liver, an increasingly high sugar diet(namely fructose), and a rapid rise in childhood obesity, the Hispanic population in particular is highly vulnerable to fatty liver disease. A variety of public health measures are required to address this issue.

    At the individual level, Hispanics in particular should avoid at all costs any foods or beverages made with high fructose corn syrup and also reduce consumption of foods with added sugar and other sweeteners. Food and beverage companies should be required to provide better labeling to indicate fructose content. And ultimately, at the broader macro level, trade and agricultural policies should consider not just the economic impact but also the public health impact of new policies. 

    MRI Image of Fatty Liver in a Teenager

    Comments

    Seems flaky to me. Extracting fructose from fruit fiber is not exactly a big challenge for the human digestive system. In fact, bioavailability is the goal of most "fruit," versus say extracting C5/C6 sugars bound in lignen.

    KevinFolta
    I've been really compelled by recent articles by Lustig et al and the potential problems associated with NAFLD and fructose.  Clearly the transport, uptake, metabolism and feedback are different than other sugars.  Two points that I think I'd like to expand on based on your writing here.  First, HFCS and sucrose (cane sugar) are chemically not that different once in the body. Each is about 50% fructose and 50% glucose (some HFCS is higher or lower in fructose).  So while we vilify HFCS, we need to avoid sugar.  Second, sugar in honey and fruit is predominantly fructose, so we might need to rethink these sources. Lustig et al suggest that the fiber in fruit changes the bioavailability of fructose therein, and I think there's likely something to that.  Important article and it will be interesting to see allelic breakdowns of populations and their sensitivities to these compounds. 
    Don't tell me it can't be done. Tell me how you are going to help me do it.
    Michael Goran
    Kevin - thanks for your note. Appreciate your comments. Couple of things. We have shown that there is almost twice as much fructose as glucose in off the shelf popular sodas like pepsi, coke and sprite. We published that paper a few years ago. Also, we have another paper about to be published where we analyzed global data on HFCS and diabetes. This shows that countries who use HFCS have 20% higher levels of diabetes.
    Hank
    The obvious question from laypeople (like me, who don't have the depth of knowledge of either of you) is, for example, why Coke in Mexico does not use HFCS but their obesity rate is much higher.  That's one example, of course, but if it looks like the data is being mapped to a cultural topology people are not going to be convinced.

    Two curves going up the same way is not a solid case, right?  Or am I missing something? 
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    Michael Goran
    Hank - situation in Mexico is changing rapidly. See paragraph 5 regarding the issue around trade policies. Overall sugar (including HFCS) consumption is strongly related to obesity. Hard to tease them apart because we dont really know how much HFCS individuals are consuming. The link between HFCS and health is more compelling to me for diabetes and other complications compared to obesity. Our new paper coming out soon shows that countries who use HFCS have 20% higher diabetes
    Hi Michael
    I really appreciate you taking time to share your expertise on dietary fructose and NAFLD with the world. PNPLA3 was news to me, thanks. It is great have a professor seeing the need for revoking GRAS status of fructose and need for fructose, galactose, glucose and sorbitol (sugar alcohol that metabolizes to fructose) labels. Surgeon General where are you? The Surgeon G is standing by while every child in USA is placed in harm’s way!
    Do you suspect NAFLD will eventually be recognized as hepatocyte dysfunction (similar to endothelial cell dysfunction replacing buildup of calcium plaque in arteries)? Since many cells can metabolize fructose, do you think of liver as protecting more fragile organs from toxin? drweaver@speed101.com

    The problem is that fructose is toxic and the liver removes toxins. If it can turn them into something with nutritional value it does. In this case fructose changes active liver enzymes so more of all carbohydrate is turned to fat. Some is metabolized to glucose. If that was all that happens we would have livers that store a lot of fat, but it wouldn’t be a disease. The problem comes because some of fructose is metabolized to glyceraldehyde (a 3-carbon sugar). Glyceraldehyde is the most reactive sugar in the body and can turn functional proteins within liver cells into junk. This leads to dysfunction (disease) of liver cells. Glyceraldehyde can also leave cell to react with lysine (most reactive protein in serum) and form the most toxic advanced glycation end product or TAGE. TAGE promotes inflammation via receptors for AGE and also is increases VegF which is associated with over 50 disease conditions.
    The answer is to avoid the molecule called fructose. It is found 55% or more by dry weight in many drinks, 50% in sugar (sucrose) and 40-50% by dry weight in fruit. The other thing to avoid is high blood glucose which creates abnormal fructose levels in all cells of body, not just the liver.