Fructose: the new F word
We used to be told that fructose (aka “fruit sugar”) was the ideal sweetener for people with diabetes because it doesn’t cause blood sugar spikes. However, in recent years its reputation has tanked, as some experts have decided that fructose is the silently sinister sister of the sugar family, single-handedly responsible for obesity, diabetes, heart disease, fatty liver disease, gout, cancer, and worldwide destruction. In this popular lecture about the perils of fructose fructose has even been dubbed a poison largely responsible for the epidemic of childhood obesity.
Just a few weeks ago, yet another fructose study made headlines, including this New York Times article and a nicely balanced report in Science News claiming that fructose may make it harder to control appetite and food cravings than glucose, paving the way to overeating and obesity. [See article two in this series for a full breakdown of this study.]
Many of us had finally come to understand that excess refined carbohydrate intake, not saturated fat, is endangering our health, and some of us started cutting back on sugar and flour to protect ourselves. These changes aren’t easy—baked goods, pasta, ice cream and candy are cheap, convenient, and delicious! I personally would love to be told that I can safely eat all sugars except for fructose, and I bet I’m not alone. So what’s going on here?
It turns out that fructose is a fascinating and complicated topic, so what started out as a single blog post became a five-part series (my condolences in advance). Those of you already familiar with my pro-meat, pro-saturated fat, pro-cholesterol, anti-carbohydrate, plant-foods-are-not-to-be-trusted nutritional philosophy might guess fructose would be an easy target for me, but to my own surprise, the more I dug into the science, the more I found myself defending the the fruity little guy. Fructose is no health food, but it’s no poison either. Well, no more poisonous than any other sugar has the potential to be, anyway. Come with me to discover what fructose is, how it compares to other sugars, and how much you can safely consume. No time for details?
I’ve broken up the fructose fun into five articles to aid digestion:
- Fructose metabolism vs glucose metabolism. Today’s article reveals fun facts about fructose and how it behaves in your body compared to other sugars. If you had as much trouble following Dr. Lustig’s chemistry lesson as I did, read on to understand what the real differences are between fructose and glucose processing.
- Does fructose make you hungrier? In article two, "Fructose Raises Appetite . . . for Better Science," we look under the hood of the new study that claims fructose can cause overeating to see if we should be concerned.
- Fructose and your health. In article three, "Why Sugar Is Bad for You: A Summary of the Research," I review and summarize for you the latest research about fructose and diabetes, obesity, fatty liver, gout, heart disease and cancer.
- Fructose malabsorption. In article four, "Is Fructose Malabsorption Causing Your IBS?" we look at how to find out if fructose is the culprit of your IBS symptoms, and if so, how you can minimize fructose in your diet.
- Fructose in the real world. In the fifth article, "How to Diagnose, Prevent, and Treat Insulin Resistance," we finally look at real foods! We examine your favorite sweeteners, fruits, vegetables, grains and legumes to see how they measure up. I’ll share with you my dietary recommendations, provide a downloadable PDF with medical tests for insulin resistance that you can discuss with your health care provider, and include an infographic with helpful tips to guide you in your dietary decisions.
And away we go!
First, a bit of context. Where does fructose stand in relation to its natural simple sugar sisters?
Simple sugars: short and sweet
Glucose: aka blood sugar. A 6-carbon monosaccharide (single sugar ring) used by all plants and animals as their primary energy source, and therefore critically important to life. Glucose is not very sweet—less than half as sweet as fructose—which is why glucose isn’t used as a sweetener. All plants contain some pure glucose, and some plants also contain glucose linked together in long chains in the form of starch (amylose), which is not sweet at all. Dextrose is simply the name given to the glucose extracted from plant starch.
Fructose: aka fruit sugar. A 6-carbon monosaccharide (single sugar ring) used by plants to sweeten their fruits and make them more appealing to animals. Fructose is the sweetest of all the natural sugars and is found in its free form primarily in sweet fruits and vegetables. In humans, fructose is used by only a few cell types in the body for energy (notably sperm cells), but the body can make fructose from glucose where necessary.
Sucrose: aka table sugar, white sugar, cane sugar, beet sugar, or just plain old sugar. Sucrose is a disaccharide (double sugar ring) used by plants to transport and store energy. Each sucrose molecule consists of one glucose molecule bonded to one fructose molecule. We break this bond easily during digestion to free up glucose and fructose for absorption:
There are a few other simple natural sugars I’m not describing here for the sake of brevity: lactose and galactose (from milk), maltose (see article four), and trehalose (from mushrooms). All of them turn into glucose in our bodies. Even unnatural sugars such as high fructose corn syrup, brown rice syrup and agave syrup all turn into glucose and/or fructose in our bodies. [There’ll be more details about these sweeteners in article four.]
Since all of the sugars we eat ultimately break down into glucose, fructose, or some combination of the two, from here on we will focus on the differences between fructose and glucose.
The arguments in the fructose vs glucose war center around differences in how fructose and glucose are handled by the liver, so we unfortunately have to review some biochemistry. I’ll make this as painless as possible. Pretty pictures are included. Sit back, have yourself a nice baked potato, and we’ll get started.
You can think of your baked potato as a lovely lump of glucose. Baked potatoes are full of a starch called amylose, which is just long chains of glucose molecules. Your intestinal enzymes rapidly digest potato starch into pure glucose and your intestinal cells absorb it completely, causing your blood glucose (blood sugar) to spike. Fast on its heels, insulin rushes into your bloodstream to direct glucose traffic and bring your blood sugar back down.
Your liver is the first organ to see the blood glucose wave, and soaks up about 1/3 of the glucose for processing. The remaining 2/3 of the glucose circulates throughout your body to feed your cells. The absorption of glucose by liver cells does NOT require insulin, but insulin is required to keep the glucose inside liver cells.
Insulin is not simply a blood sugar regulator; it is a powerful growth hormone.
Once glucose is locked inside a liver cell, the cell can do a variety of things with it, depending on the circumstances. Remember that you have an insulin spike travelling with your glucose. Insulin is not simply a blood sugar regulator; it is a powerful growth hormone. Insulin sets the stage in the body for growth, and one of the ways it does this is by telling your liver: “build, grow and store!” If insulin is present, it will crank up the activity of a series of enzymes in the liver cell needed to process all the glucose rushing in.
The first liver cell enzyme turned on by insulin is glucokinase, which immediately slaps a phosphate onto glucose, trapping glucose inside the cell so it can’t leak back into the bloodstream. The phosphate comes from a molecule called ATP (adenosine TRI-phosphate), our body’s chief energy storage molecule. After ATP sacrifices one of its phosphates to glucose, it is then called ADP (adenosine DI-phosphate). When your insulin level is low, as it should be between meals, glucokinase will turn off so that the liver can release glucose back into the bloodstream to keep your blood sugar from dropping.
Which pathway glucose takes once it’s captured by a liver cell depends on MANY things, including levels of insulin, ATP, and a variety of other molecules that help the liver cell know what its needs are at any given moment. These molecules control glucose processing by turning enzymes on and off. The master regulator enzyme on the glucose conveyor belt is called PFK-1. One of the things that turns PFK-1 on is insulin, and one of the things that turns it off is ATP. When PFK-1 is turned on, glucose will be sent to the chopping block to be cut in half for further processing.
Under the influence of insulin, your liver can do any of following things with the new glucose load, depending on your body’s needs at the time:
Burn it or ferment it for energy (ATP). If liver cells need energy to conduct their cellular business, glucose will be chopped in half in preparation for burning in the mitochondria (your cellular furnace). Mitochondria require oxygen to turn glucose fragments into ATP; this process is called aerobic glycolysis. If there’s not enough oxygen around to burn it, glucose will be fermented instead, producing lactic acid (anaerobic glycolysis). The liver can release lactic acid into the bloodstream to be burned by working muscle or other oxygen-starved cells for energy.
Transform it into 5-carbon building blocks (ribulose-5-phosphate) plus powerful helper molecules (NADPH) required to build components of new or growing cells, such as proteins, RNA, and DNA. This “build and grow” route is called the “pentose phosphate pathway.”
Store it as glycogen or fat. In a process called glycogenesis, the liver strings glucose molecules into long chains of animal starch called glycogen, which is stored in the liver. If the liver’s glycogen tank is already full, glucose can be turned into fat instead (lipogenesis). The healthy liver doesn’t store much fat; it prefers to ship it out to other cells by releasing it into the bloodstream as triglycerides.
So, as you can see, glucose is a versatile molecule whose destiny depends on sophisticated signals between food, hormones, the liver, and the rest of the body. How is fructose different? Have a nice big swig of agave syrup (mostly fructose, as you’ll see in article four) and we’ll get started.
Differences between glucose and fructose metabolism
Difference #1: The intestine does not absorb fructose as well as it absorbs glucose. There’ll be more details about fructose absorption issues in articles two and three, but for now suffice it to say that pure fructose is difficult for most of us to absorb completely.
Difference #2: The liver absorbs a LOT more fructose than glucose. Since you don’t need fructose to feed your cells, there’s no need to keep any of it in circulation, so your liver removes as much of it as it possibly can, like a big sponge.
Difference #3: Glucose triggers insulin release, but fructose doesn’t. Insulin plays a major role in turning key enzymes on or off, so without an insulin spike, the enzyme environment within the liver cell may be very different, and therefore the processing pathways available to fructose bits may be very different. (The important truth is that all foods that contain fructose also contain glucose, and some fructose gets converted into glucose, so when you consume fructose there usually WILL be some insulin around, but just for now, let’s stick with pure fructose for now to highlight the metabolic differences).
Difference #4: The first two steps in fructose processing are completely separate from glucose processing, unregulated, and irreversible. Once inside the liver cell, ATP tags fructose with a phosphate no matter what, trapping it inside the cell. The enzyme responsible for this step is fructokinase, which is turned on by fructose, and doesn’t listen to insulin. Next, an enzyme called aldolase B unceremoniously chops fructose in half. These first two steps completely bypass PFK-1, the master enzyme that controls glucose processing, so regardless of what your body needs or wants at the moment, fructose will be broken down, because, unlike glucose, fructose molecules can’t be stored, and can’t be released back into the bloodstream. The liver cell has no choice but to break down every molecule of fructose it receives.
Similarities between glucose and fructose metabolism
Glucose and fructose travel separate roads for just the first few steps of processing. However, as soon as fructose gets chopped in half, it turns into the very same 3-carbon molecule that glucose forms when glucose is chopped in half (glyceraldehyde-3-phosphate, or G3P for short). All G3P molecules, whether they come from fructose or glucose, get funneled into a single common pathway. From that point on, you can’t tell the difference between them; fructose bits can turn into ATP, lactic acid, building blocks, glycogen, or fat, just like glucose bits can, because the bits are identical. Fructose pieces can even turn into glucose! Which pathway fructose and glucose take is determined by your body’s needs at that moment and by the amount of fructose and glucose you eat.
This illustration highlights the key differences between glucose and fructose metabolism in the liver. Fructose follows its own unidirectional, unregulated pathway until it is cleaved into Glyceraldehyde-3-Phosphate (G3P), which is identical to G3P from glucose. At that point, the G3P from fructose enters the glucose metabolic pathway and can become lactic acid, ATP, or fat, or can cycle back through the glucose pathway to enter the Pentose Phosphate Pathway, become glycogen, or re-enter the bloodstream as glucose.
The gist of the fructophobes’ argument is that fructose is dangerous because it bypasses the usual checks and balances that control glucose (namely insulin and PFK-1), heads straight to the liver, and turns instantly into fat, slashing and burning precious ATP (energy molecules) along the way, leaving piles of toxic waste (uric acid) in its wake.
Uric acid? What’s that? Under normal circumstances, whenever ATP donates a phosphate to fructose or glucose, the ADP leftover is recycled back into ATP. However, the liver absorbs only a portion of the glucose you consume, whereas it absorbs almost all of the fructose you consume. If too many fructose molecules flood the liver, they could theoretically use up too much ATP too fast, and ADP leftovers could overwhelm the recycling machinery. If ADP can’t be recycled, cells can turn it into a waste product called uric acid and send it out via the bloodstream to the kidneys for removal from the body. High levels of uric acid in the blood can trigger gout in some people. For more information about gout see article three of this series, and also my post "Got Gout but Love Meat?"
Scary claim #1: Fructose is fast fat
Those in the fructose-phobia camp would say that the liver turns all the fructose we eat instantly into fat, and that the fat either pours into the bloodstream (raising bad cholesterol and triglyceride levels and increasing risk for heart disease) or getting trapped in the liver, causing fatty liver disease.
As you now know, fructose can turn into anything that glucose can. There’s no evidence in humans that a realistic amount of fructose under ordinary circumstances causes an increase in fat production by the liver compared to glucose.
In fact, a review of studies that used radioactive tracers to stalk fructose as it traveled through people’s bodies found that less than 1% of the fructose consumed by the research subjects ended up as fat! A decent amount of the fructose, as much as 54%, actually turned into glucose! Why did so little of the fructose turn into fat? Fructose doesn’t trigger insulin spikes, and you need insulin to turn on fat-building pathways. Insulin is a growth hormone that tells the liver to grow and store; when insulin levels are low, fat-building pathways are turned off.
Scary claim #2: Fructose drains cells of ATP, our precious energy molecules
There is no evidence that ATP depletion occurs in humans except when fructose is injected directly into someone’s veins (don’t try this at home . . .).
Scary claim #3: Fructose raises uric acid levels, which can cause gout.
While there are human studies showing that fructose can raise uric acid levels more than glucose can, all of these studies used extremely high doses of fructose (approximately 215 grams)—this is roughly the amount of fructose in 2-1/2 liters of Mountain Dew or grape juice (don’t try this at home either). In addition, people in these studies were given these mega-doses of fructose on top of their usual diet, increasing their daily calorie intake by about 1/3. Therefore it is impossible to say whether it was the extreme fructose exposure or simply the excess calories that caused uric acid levels to rise in these cases. Human studies of fructose under normal calorie conditions found no increase in uric acid production.
Summary of key points
- All of the sugars and starches in our diet, whether natural or artificial, ultimately break down into glucose, fructose, or a combination of the two.
- Glucose from sweets and starches spike in the bloodstream, triggering an insulin spike. Fructose spikes in the liver, and does not directly trigger an insulin response.
- Insulin is a powerful hormone that puts your liver in growth and storage mode.
- The first phase of glucose processing is very tightly controlled because glucose must obey both insulin and the regulatory enzyme PFK-1, whereas fructose bypasses these important checks and balances.
- The remaining phases of glucose and fructose processing merge and become identical. Therefore both glucose and fructose can turn into ATP (energy), lactic acid (energy), glycogen (storage), ribulose-5-phosphate (building blocks for new/growing cells), or fat, depending on the body’s needs.
- Very little of the fructose we eat turns into fat in the absence of glucose/insulin.
- There is no evidence that fructose drains cells of ATP unless you inject it into your veins.
- Fructose only raises uric acid levels in the blood at high doses under high calorie conditions.
Yes, fructose is handled differently by the body than glucose in a variety of ways. It is absorbed less well by the intestines, absorbed in far greater amounts by the liver, and the first two steps of its processing in the liver are unregulated, meaning that fructose gets broken down by the liver no matter what. However, there is no reason to believe that these metabolic differences make ordinary amounts of fructose any worse than ordinary amounts of glucose when it comes to ATP reserves, fat production, or uric acid levels. Fructose byproducts are identical to glucose byproducts and can turn into all of the same things that glucose can. Fructose is primarily just another source of glucose in the diet.
How do I know fructose is not a poison? The body has a variety of sugar receptor molecules that help simple sugars enter cells. One of them, called GLUT-5, is specific for fructose alone. We also turn a good deal of the fructose we eat into glucose, a molecule critical to life. We do not require fructose (or any sugar) to live or be healthy, but fructose can certainly be used as a source of nourishment, and in my book, that means it’s not a poison. If fructose were an actual poison, Mother Nature would not have installed receptors in our intestines designed specifically to welcome fructose into our bodies. Yes, too much fructose, like too much of anything, can be potentially harmful, but that doesn’t make it poisonous. If you drink too much water, your sodium levels will drop, you will have a seizure, and you could die. But water is clearly not a poison. In the case of fructose, as in the case of water, the dose makes the poison. How much fructose can you safely eat? it all depends on who you are…find out more in article four!
I don’t believe that the fact that fructose is handled differently than glucose by the body makes fructose any worse than glucose when it comes to the health of our cells. As you’ll see in the rest of the series (if you’re still alive after having slogged through this basic science article), fructose is not the nutritional super-villain it’s been made out to be. What is the dietary scourge of our time? Sugar. Excessive sugar of any type, including fructose, but perhaps glucose worst of all. If you don’t believe me, stay tuned for more!
There you have it. Did that make sense? Are you any more or less afraid of fructose than you were before? Please share your thoughts and questions below so we can continue to learn from one another.
In article two, "Fructose Raises Appetite . . . for Better Science," we answer the following questions:
Is the new study about fructose and appetite worth your attention? How good are scientific studies of fructose in general? Can we count on them to give us useful information about what we should eat to be healthy?