The perils of fructose:

High fructose corn syrup (HFCS) has, over the past few decades, gradually displaced cane and beet sugar as the sweetener of choice for soft drinks, candy and prepared foods. In recent years, there have been a growing number claims that HFCS is a significant health risk to consumers, responsible for obesity, diabetes, heart disease and a wide variety of other illnesses. 

In fact, there are large amounts of experimental data supporting the claims that high levels of fructose in the diet can cause hyperlipidemia (high levels of fats — triglycerides primarily — in the blood), obesity and insulin resistance and may lead to cardiovascular disease and type 2 diabetes (for a good recent review, see [1]). A high-fructose diet is thought to cause hyperlipidemia (and probably visceral obesity) because fructose is preferentially “sent”  to fatty acid synthesis and it also reduces the activity of lipoprotein lipase (for a good review, see [2]). The mechanisms by which fructose causes insulin resistance and cardiovascular disease are less clear (see, for example [3], [4] and [5]), but there is no shortage of hypotheses. Despite the fact that some of the underlying mechanisms are not clear, the evidence seems pretty solid that there are real risks to high fructose consumption.

However, the question remains — is HFCS more of a health risk than other sweeteners? Many of the sources that demonize HFCS list alternative sweeteners — cane sugar, honey, agave syrup, etc. — that they claim are healthier than HFCS, but those claims usually rest primarily on the fact that these alternatives to HFCS are “natural” rather than any actual data showing that they are safer than HFCS. 

Sugar 101:

Before we can properly analyze these claims, we need to understand a bit about sugar. To begin with, what is sugar? To most people, sugar is the white granulated solid that they find in the sugar bowl. In reality, sugar is a much broader term. There are two general classes of sugars — aldose and ketose — and over twenty individual sugars (monosaccharides), if you limit yourself to only those found in nature. Of these, only a few play any significant role in human nutrition, primarily glucose, fructose and galactose (ribose, a sugar that forms the backbone of DNA and RNA, also plays a minor nutritional role). 

Further complicating the issue, there are also sugars — disaccharides — that are compounds made of two monosaccharides covalently bound together. The most common of these is sucrose, a compound made by joining one molecule of glucose to one molecule of  fructose. Sucrose is the sugar in the average sugar bowl. It is also the sugar in brown sugar, molasses, cane sugar, beet sugar and is the major component of maple syrup (and maple sugar). Another common disaccharide is lactose (milk sugar), which is a combination of glucose and galactose. Less commonly encountered is maltose, a combination of two molecules of glucose. 

Starches, such as corn starch, are also sugar. They are made up of long interlinked chains (polymers, also known as polysaccharides) of individual sugars (usually glucose). Cellulose, the major component of paper and wood, is also a polymer of glucose (with different bond geometries). Insect and crustacean shells are made of a sugar polymer known as chitin (also a major component of fungal cell walls). We literally live in a world of sugar. 

One final note about sugars — humans only absorb monosaccharides; no matter what form the sugar enters the digestive tract, it is only absorbed after it is broken down to its component monosaccharides (there are, as usual in biology, a few minor exceptions to this rule). There are a variety of enzymes — amylases, disaccharidases, etc. — that perform this function. Any disaccharide or polysaccharide that isn’t broken down (such as the raffinose and stachyose in beans and many other gas-causing foods) remains inside the gut, providing food for our gut bacteria.

“Natural” Sweeteners:

Now, let’s take a look at some of the sugar-based sweeteners in common use today. Honey was probably the first sweetener — at least in the part of the world where honey bees are native. Honey is about 82% sugar, with almost all the remainder being water. The sugar in honey is 43% glucose,  50% fructose, 4% galactose, 2% maltose, 1% sucrose and trace amounts of other sugars [6]. As mentioned earlier, it is considered by many to be a natural sweetener that is a healthy alternative to HFCS. 

Another sweetener used in ancient times — especially in regions where honey bees were not native — is tree sap. The most famous of these is the sap of sugar maple trees, used to make maple syrup and, when crystallized, maple sugar. Natural maple syrup is 60% sugar, with that sugar being 95% sucrose, 4% glucose and 1% fructose [6]

Fruit juices also have an ancient history of use as sweetening agents and — not surprisingly — are often cited as natural and healthy alternatives to HFCS. The sugar content of fruits varies with the type of fruit and even with the variety. Apples, for instance, are a bit over 10% sugar by weight, with that sugar being 57% fructose, 23% glucose and 20% sucrose. Peaches, in contrast, are 8.4% sugar by weight with that sugar being 57% sucrose, 23% glucose and 18% fructose. Pears – the most common fruit juice used in sweetening – are 9.8% sugar, with that sugar being 64% fructose, 28% glucose and 8% sucrose. Table grapes are about 15% sugar, with the sugars being 53% fructose and 47% glucose [6]

Sucrose, the disaccharide in common table sugar, was originally obtained in ralatively pure form from sugar cane, which can only grow in the tropics. The high cost of cane suger led to a search for alternative sources. As early as the 1700’s, sucrose was being extracted from sugar beets, but it took both selective breeding of sugar beets to increase their sucrose content and improvements in the extraction process to make beet sugar economically viable. By the late 1800’s and early 1900’s, sucrose from sugar beets had outstripped cane sugar in Europe and the U.S. Sugar beets have the advantage of growing throughout the temperate zone, closer to the demand. Just to be clear, beet sugar and case sugar are indistinguishable — they are exactly the same chemical compound (sucrose).

The rise of HFCS:

So, with all of these sugar-based sweeteners available, what prompted the development of HFCS?

Corn syrup is a relatively recent arrival as a sweetener; it had to wait until food processors discovered how to take corn starch (which, like most starches, is a polymer composed of long interlinked chains of glucose molecules) and break it down into isolated glucose molecules using the enzymes amylase and maltase. Commercial amounts of corn syrup were available by the middle of the 20th century [7]. Corn syrup was so much cheaper than sucrose that it saw extensive use as a sucrose substitute for thickening foods and to help retain moisture. It wasn’t much used solely as a sweetener because it isn’t as sweet as sucrose.

The fact is that not all sugars are equally sweet. If we assign sucrose (table sugar) a sweetness of 100%, glucose has a sweetness of 60 – 75% (on a gram-per-gram basis) and fructose has a sweetness of 140 – 170% [8][9][10]. (Note: the sweetness of fructose varies with its conformation, and so will differ under different circumstances [11]) Candy and soft drink manufacturers exploited the greater sweetness of fructose even before HFCS was available by using what is called “invert sugar”. Invert sugar is sucrose that has been treated with a weak acid solution and then recrystallized (to get rid of the acid). This treatment causes a portion of the sucrose to break apart into fructose and glucose. Although the glucose part is less sweet than sucrose, the fructose is so much sweeter that the overall effect is to get more sweetness with less sugar. This allowed the manufacturers to use less sugar and thereby save money, even though invert sugar was more expensive than plain sucrose.

In 1957, a process was developed to convert some of the glucose in corn syrup to fructose, yielding a product that was 42% fructose and 58% glucose [12]. This dramatically increased its sweetness, making a product that was a commercially viable competitor to sucrose as a sweetener. This was HFCS 42, which has a sweetness — gram-per-gram — slightly greater than sucrose (110%).

The primary advantage of HFCS 42 to food manufacturers was its low cost — much lower than the cost of sucrose. Secondary advantages were that it retained moisture better than sucrose (twice as many molecules), was slightly sweeter than sucrose (so less was needed), was in a liquid form and didn’t caramelize as readily as sucrose (this last one could be an advantage or a disadvantage, depending on the use).

Later, HFCS manufacturers began putting some of their HFCS 42 through separation columns to produce syrup that was 90% fructose (HFCS 90) [5]. Today, the bulk of the HFCS 90 production is used to make corn syrup with 55% fructose, known as HFCS 55, although a very small amount is used in some reduced-calorie confections (HFCS 90 is about 60% sweeter per gram than sucrose, which allows a 35% reduction in the amount of sugar used). 

With the introduction of HFCS 55, which is 25% sweeter than sucrose, food manufacturers found that the slightly increased price (which was still less than sucrose) was more than offset by the fact that they needed less of it to get the same level of sweetness. 

That’s right, HFCS allowed food manufacturers to use less sugar — and thus fewer sugar calories — in their products without compromising sweetness. Using sucrose — cane or beet sugar — would require 20% more sugar (and 20% more sugar calories) than using HFCS 55. 

How safe are other sweeteners compared to HFCS?:

Still, none of this alters the fact that a diet high in fructose has been shown to cause — or at least contribute to — hyperlipidemia, obesity, insulin resistance and cardiac disease. However, those who have been paying attention will have noticed that HFCS is not the ONLY sweetener that contains significant amounts of  fructose.

In fact, sucrose — even “natural” cane sugar — is 50% fructose once it is digested and absorbed. While this is 20% less than the fructose content of HFCS 55, food manufacturers need to use less (about 20% less) HFCS 55 to get the same sweetness, so it’s a wash as far as fructose content.

Honey, long touted as a “healthy” and “natural” alternative to evil HFCS, is also 50% fructose. Agave syrup (also called agave nectar), often promoted as a healthy alternative to HFCS (especially in diabetics),  is very high in fructose, although there is some disagreement over how much fructose it contains. According to the USDA, the sugar in cooked agave is 87% fructose (due to breakdown of fructans — a starch-like polymer of fructose — in the plant when it is cooked) [6]. A wholesale supplier of agave syrup, however, lists the fructose as 70 — 75% of the total sugar in their syrup [13]. Either way, agave syrup is higher in fructose than any other natural sweetener (and any form of HFCS except HFCS 90). 

Even fruit juices (and what could be more natural and healthy than fruit juice?) are 40 — 70% fructose, if you count the fructose in sucrose. And for those who argue that ingesting sucrose delays the absorption of fructose, Monsivais et al (2007) showed that sucrose breaks down spontaneously in carbonated beverages (and, presumably, all acid solutions), with 50% of the sucrose being hydrolyzed to fructose and glucose within the first 30 days after bottling [14].

Finally, a study that directly compared the short-term effects of fructose, HFCS and sucrose showed that they are indistinguishable [15]

What does all this mean?:

So, what are the take-home messages from all of this? 

  1. HFCS 42 and HFCS 55 have essentially the same amount of fructose, as a fraction of their total sugar, as honey, sucrose (cane or beet sugar) or maple syrup/sugar (to be agonizingly precise, HFCS has slightly less, and HCFS 55 has slightly more).
  2. HFCS 42 and HFCS 55 have an equal or smaller amount of fructose, as a fraction of their total sugar, as many commonly consumed fruits.
  3. Agave syrup has higher fructose content than any type of HFCS except HFCS 90. 

For people who are worried about their health or their children’s health — and who isn’t, these days — the data suggest that the best choice is to reduce intake of all sweeteners containing fructose. That includes not only the evil HFCS, but also natural cane sugar, molasses (which is just impure cane sugar), brown sugar (ditto) and honey. Even “unsweetened” (no added sugar) fruit juices need to be considered when limiting your family’s fructose intake. 

Finally, the best nutritional advice is to eat everything in moderation — and that includes sweets. While a diet high in fructose may increase your risk of obesity, diabetes and heart disease — maybe — a fructose-free diet is not guaranteed to prevent those diseases. Eat a variety of foods, including a small amount of sweets, get enough exercise, watch your (and your children’s) weight and see your doctor for regular health check-ups. 

And stop worrying that HFCS is poisoning you and your children. 

Until later,

Jim Laidler

 Jim Laidler, MD graduated from USC School of Medicine and went on to do an internship in Pediatrics before spending four years as a flight surgeon in the US Army. After his military service, he completed a residency in Anesthesiology and a fellowship in Pain Medicine at the University of Illinois. He practiced for several years in Alaska and Oregon before deciding to take up a new career in research. He is currently finishing his PhD thesis in Molecular Biology in Portland, Oregon.


DISCLAIMER:  The opinions expressed by Dr. Laidler are his own and not those of any organization or institution he is affiliated with. His writings are not meant to diagnose or treat any diseases or disorders except ignorance and misinformation.


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  14. Monsivais P et al. Sugars and satiety: does the type of sweetener make a difference? Am. J. Clin. Nutr. 2007; 86(1):116-123 
  15. Stanhope, KL et al. Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals. Am. J. Clin. Nutr. 2008 May; 87(5):1194-1203.

Posted by Jim Laidler

Jim Laidler, MD graduated from USC School of Medicine and went on to do an internship in Pediatrics before spending four years as a flight surgeon in the US Army. After his military service, he completed a residency in Anesthesiology and a fellowship in Pain Medicine at the University of Illinois. He practiced for several years in Alaska and Oregon before deciding to take up a new career in research. He is currently finishing his PhD thesis in Molecular Biology in Portland, Oregon. DISCLAIMER: The opinions expressed by Dr. Laidler are his own and not those of any organization or institution he is affiliated with. His writings are not meant to diagnose or treat any diseases or disorders other than ignorance and misinformation.