Fructose: All-Natural, or Natural Disaster??

I set out last week to write an article about how to enjoy a drink or two over the holidays without paying too steep a metabolic price, so to speak. But as I got further in, I realized I need to explain something first: I need to explain why fructose is almost as toxic to your liver as alcohol. So bear with me for a little biochemistry. If you survive this post, I will reward you by teaching you how to drink alcohol without getting nearly as drunk as your friends… What is Fructose? Fructose is a sugar found in honey, agave nectar, and fruit. It looks very similar to glucose, but unfortunately it’s metabolized very differently. If

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you stick a molecule of glucose and fructose together, you get sucrose— also known as table sugar. (Sucrose is also found naturally in sugarcane and sugar beets.) High Fructose Corn Syrup is pretty similar to table sugar, except the blend of fructose:glucose is not 50:50— it’s 55% fructose/ 45% glucose: hence, “high fructose”. (So, a few years ago when Snapple switched from HFCS to sucrose in their tea, they were really just changing from 55% fructose to 50%: insignificant to your body, but quite significant to their marketing.) Your body needs sugar for energy, but not all sugar is created equal. Glucose is the sugar you metabolize most efficiently. Unless you ingest it in small doses, your liver gets overwhelmed by fructose very easily. When you eat whole fruit, the fructose doesn’t hit your liver all at once –it is slowed down by the fiber in the fruit. But when you drink sugar, whether as sucrose (in orange juice or Snapple) or High Fructose Corn Syrup (in soda and many

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other processed foods), the fructose comes at your liver like a speeding bullet. Any time your liver gets more than 25g of fructose at a time, bad things start to happen. How is the metabolism of fructose different from glucose? Here’s a diagram of how the two are metabolized below. Don’t let the diagram freak you out—I added a few words to it to show what is important:

CLICK DIAGRAM TO ENLARGE
You can see fructose on the top left and glucose on the top right. On the glucose side, I circled the enzyme “phosphofructokinase,” which plays a key role in glucose metabolism. When you have enough energy, that enzyme gets slowed down: ATP and Citrate put the brakes on. But on the left side, that enzyme doesn’t exist: Fructose metabolism bypasses it entirely. You see the end result on the bottom left: Lots of triglycerides get made in your liver. In addition (not shown on the chart), eating glucose results in the release of leptin, a hormone that makes you less hungry. Fructose does NOT cause leptin release, so you keep feeling hungry. Result: More eating + more triglycerides = more You. In medical terms, you become a fatty—literally: you develop what’s called Non-Alcoholic Fatty Liver Disease (NAFLD). What is really interesting about this is that fructose isn’t just bad for you—your liver metabolizes it almost exactly the same way it metabolizes alcohol. Here’s a stripped-down version of the metabolism of Alcohol:
Adapted from: Alcohol Research & Health Vol. 29, No. 4, 2006 p 246.
The alcohol you

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drink is Ethanol. When you drink it, an enzyme called Alcohol Dehydrogenase (ADH) helps make Acetaldehyde. Acetaldehyde is a real troublemaker, generating free radicals that cause liver damage unless you have enough antioxidants (glutathione or Vitamin C) available to mop it up. Luckily, another enzyme

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called Aldehyde Dehydrogenase (ALDH2) helps out by converting Acetaldehyde to Acetate… …but that Acetate jumps right into the same pathway as Fructose metabolism: As you can see, Acetate is used instead of Pyruvate when alcohol is in your

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system, which leads to the same Fatty Liver disease (except now it’s called Alcoholic Fatty Liver)! I know, that’s a lot to swallow. For those of you who want to know more, there is a great series of very short videos by UCSF endocrinologist Robert Lustig which you can watch here: …as well as a 75 minute lecture with all the biochemistry you could ever ask for, here: http://www.youtube.com/watch?v=dBnniua6-oM So, lesson of the day: No high fructose corn syrup! If you want fruit, eat whole fruit once a day– preferably berries, which are higher in antioxidants and lower in sugar. (Cantaloupe is the worst choice: highest in sugar, lowest in antioxidants.) Similarly, fruit juice is usually just concentrated sugar—orange juice is not actually good for you. However, if you want to have some pomegranate juice or blueberry juice, the antioxidant benefits probably make it worth your while. Stay tuned– my next post will be just for fun: How to use your new knowledge of fructose biochem to survive New Years’ Eve!

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