How Fructose Makes Us Fat (and Accelerates Aging)

Graham Ryan

30 May 2014

Fruit is part of a healthy diet, right?

Recently, research into metabolic products called Advanced Glycation End Products (AGE’s) casts that assumption into a new light. AGE’s have been shown to be strongly pro-oxidative and pro-inflammatory and can accelerate several processes related to aging. Fructose (aka “fruit sugar”) is one of the primary dietary factors that drives production of AGE’s in the body.

Before we dive in to the specifics of how AGE’s affect the body, let’s take a moment to look critically at fruits and their nutritional value.

A Critical Look At Fruit

Most people assume fruits are valuable because they are nutrient-rich and loaded with antioxidants. While this may be true for a small handful of exotic fruits, almost none of the fruits eaten commonly in the western world can make this claim.

Apples, pears, grapes, peaches and other common fruits simply don’t supply meaningful levels of vitamins or minerals. To an extent, this has always been the reality of fruits. It should be pointed out, however, that the lack of nutrients in fruit has been exacerbated in recent decades by over-farming of nutrient-depleted soils.

As for antioxidants, common fruits again fall short. I’ll continue picking on apples and grapes, which both have pitiful antioxidant contents on par with lettuce, oats and bread. Common foods like chocolate, artichokes, nuts and even many beans have several times the levels of antioxidants per unit of weight.

There are notable exceptions, of course. Acai is remarkably antioxidant-dense, and raspberries and blueberries also score highly.

In addition to looking at what common fruits lack, we should look at what they do contain. Fruits are full of simple carbohydrates and sugars - particularly fructose. As an example, one large apple contains comparable amounts of both total sugar and fructose to 8oz of high-fructose-corn-syrup-sweetened soft drink.

If we’re being honest, most of the common fruits we buy in the produce section are essentially just natural high-fructose candy.

As a rule of thumb, berries tend to be lower in sugar and fructose and higher in antioxidants than other common fruits, making them easily the best choice among traditional fruit options.

High-Fructose Fruits - apples, pears, bananas, melons, dates, figs, grapes, raisins, prunes
Low-Fructose Fruits - blueberries, strawberries, blackberries, raspberries, oranges, apricots, nectarines

Problem #1 With Fructose: Triggers Fat Storage

When we eat fructose, our body treats it differently than other sugars and carbohydrates.

Fructose is one of the two primary monosaccharides found in foods (glucose is the other). This means all sugars and carbohydrates will be eventually broken down in the body into some mix of these two monosaccharides.

When we consume glucose, it will be absorbed directly into the bloodstream from the GI tract for use as energy, or to be stored for use later.

When we eat fructose on the other hand, our body does not allow it to pass directly in to the bloodstream but rather redirects it to the liver for further processing. Once fructose is in the liver, it will be converted in one of three ways:

Converted to glucose for immediate use.
Converted to glycogen (a polysaccharide) for storage in the liver.
Converted to triglycerides (fat) for storage.

Unless you're eating an excessive number of calories in a day, only a small portion of fructose you eat will be converted to triglycerides. If you're consuming excess calories, the percent of fructose converted to triglycerides in the liver increases sharply.

The bigger issue here is that when fructose is stored as fat in the liver, it activates the "hormonal trigger" that leads to increased fat storage in the rest of the body. Fat storage hormones are released and cells throughout the body are "instructed" to store nutrients as fat, rather than use them for immediate energy.

Over time, the effect of consistent moderate-to-high fructose consumption is to shift our hormones towards increased fat storage.

For this reason, researchers now attribute the huge increase in obesity that occurred in the mid-80's to 90's to an increased availability of high-fructose foods.

High fructose corn syrup (HFCS) is the obvious scapegoat here, but the reality is fructose has been slipped into our diets in many places you might not expect. Sucrose (table sugar) is a disaccharide that is 50% glucose, 50% fructose. Some "natural" sugars like agave are almost entirely fructose (honey is also quite high in fructose).

Our fruit has fundamentally changed in the past few decades as well. As plant breeding techniques have become more sophisticated, farmers are able to select for ever-sweeter fruits. As a result, fructose levels in fruit are significantly higher than they were 30 years ago.

Problem #2 With Fructose: AGE’s

In the body, fructose is a very reactive molecule, meaning that it will readily combine or interact with proteins, enzymes and other molecules. When fructose reacts with a protein or enzyme, it can form problematic byproducts known as AGE’s.

There are three primary monosaccharide sugars found in foods - glucose, fructose and galactose. All carbohydrates eventually are broken down into some combination of these three monosaccharides.

While each of these monosaccharides can potentially react with proteins to form AGE’s, it has been demonstrated that fructose is by far the most likely to react with proteins and form AGE’s, perhaps by an order of 10-fold. [1]

AGE’s and The Body

Advanced Glycation End Products have been shown to have a number of problematic effects in the body:

Pro-Oxidative - Once fructose reacts with a protein to form an AGE, that molecule becomes strongly oxidative. This means, AGE’s can, in turn, disrupt other enzymes and cellular functions. [2]
Pro-Inflammatory - In part due to their oxidative properties, AGE’s have been correlated with elevated levels of several of the primary markers of systemic inflammation, including high-sensitivity C-reactive protein (hsCRP). [2]
Insulin Resistance - Insulin is the primary hormone responsible for managing blood sugar levels as well as storage of fats and carbohydrates - making it a critical hormone in weight management and maintaining healthy energy levels. When your cells become desensitized (“resistant”) to insulin, conditions such as pre-diabetes and diabetes can result. Maintaining cellular sensitivity to insulin is critical to maintaining good health. High levels of AGE’s have been shown to decrease insulin sensitivity, perhaps by disrupting cellular insulin receptors. [3]
Collagen Cross-Linking - Collagen is the primary protein that comprises our connective tissues. When collagen becomes cross-linked in our connective tissues, we lose flexibility and strength. This is one of the primary mechanisms by which people tend to lose mobility and strength as they age. We’ve recently learned that AGE’s actively bind to and cross-link collagen proteins and are perhaps the primary cause for age-related muscle deterioration. [4]
Cardiovascular Disease - When AGE’s accumulate in the body, they can have a number of troubling effects on the cardiovascular system. AGE’s have been correlated with stiffening of vascular and myocardial vessels and dysfunction of the endothelium (the thin layer of cells on the interior of these vessels). AGE’s have also been implicated in the formation of atherosclerotic plaque, the problematic substance often responsible for blocking arteries. [5] Compounding these problems, AGE’s also seem to impair the synthesis of nitric oxide (NO) the chemical the body uses to dilate blood vessels and combat some of the effects of atherosclerosis.
Alzheimer’s Correlations - The research here is still developing, but it seems that the oxidative stress placed on the brain by accumulated AGE’s may play a central role in the development of Alzheimer’s disease. [7]

Should You Be Concerned?

AGE’s and fructose-toxicity are most significantly an issue for those over the age of 40. As we age, our kidneys become less efficient at removing AGE’s from the blood. When this happens, AGE’s accumulate and create issues.

The research done on AGE’s over the past decade-or-so seems to indicate that the accumulation of AGE’s may be one of the primary drivers of the aging process.

It should be noted, however, that the pro-oxidative, inflammatory and insulin-resistance effects of AGE’s were shown to affect people of all ages, although the effects were more pronounced in older participants.

Fruit: Worth The Risk?

It should be noted that AGE’s and fat storage are not the only issues of concern with fructose. Metabolism of fructose also produced more oxidative byproducts (like uric acid) relative to glucose.

When we eat glucose, it is absorbed by our GI tract and moves passively into the bloodstream for use as energy or to be stored. Fructose, on the other hand, is sent straight to the liver for processing when we consume it. Your body essentially treats fructose as toxic and sends it to the liver to be transformed before it can be used by the rest of the body. Shouldn’t this tell us something?

When you look at the cumulative risks that come with consuming fructose, fruit no longer looks like a healthy food - particularly when you consider the lack of nutritional value most fruits provide.

Keeping fructose consumption to a minimum is wise for individuals of any age, but particularly for those over 40 for whom accumulation of AGE’s can become a significant problem.

My recommendation to avoid the negative effects of fructose is to keep total consumption below 25g per day. Because fructose is found in SO many foods, this is actually quite a difficult figure to adhere to. If you're going to eat fruit on a regular basis, restricting yourself to a single serving of low-fructose fruits (blueberries, raspberries) is a good idea.