Fructose – The Role of Fructose in Metabolic Syndrome and Heart Disease

“Mark already ignores me. I think it is because I am in bed and I am a ‘stationary’ object, because once or twice at home when he saw me up and on the way to the toilet he evinced great interest at once. I am absolutely determined to check myself in any tendency to be sad when I see him forgetting and ignoring me, because what matters is that he shall be happy where he is. It is a mercy that he is at an age when ‘now’ is everything. It takes only a day or so to adjust himself completely to new people. I know Bill is right when he says that when I do come back to him he will, within a week, be as though I had never been away.”

From Sanatoriums to the Silent 'Sweet Killer'


… I feel hopeful about Mark remembering me again when I come back, because though last time he got quite out of the way of thinking about my being anything but an inanimate object, and used to distress me terribly by crying for someone else if I got him out of his pram or bathed him, yet within a week or so of our being back he was always trying to come to me.

These are the thoughts of a British woman of 32 who was suddenly separated from her husband, Bill, and fifteen-month-old baby, Mark in 1944, an era when those infected with tuberculosis were isolated from society and placed in sanatoriums. Extracts from her diary were published in the Journal of the Royal Society of Medicine in 2004 (1).

Tuberculosis – The Robber of Youth

Tuberculosis is an ancient plague that has flogged humankind throughout history. It has surged in great epidemics and then receded, thus behaving like other infectious diseases, but with a time scale that differs from many other known epidemic cycles.

The disease reached epidemic proportions in Europe and North America during the 18th and 19th centuries, earning the sobriquet, “Captain Among these Men of Death (2).” The bacterial species, Mycobacterium tuberculosis, may have killed more persons than any other microorganism.

Tuberculosis had many nicknames that produced despair and horror; the “great white plague”, “the robber of youth”, and “the graveyard cough”. Therapeutic options were limited, the mainstay of treatment was rest and fresh air.

In the late 19th and early 20th centuries, sanatoria were developed for the treatment of patients with tuberculosis. In 1859 Herman Brehmer opened his Heilenstat in the Silesian Mountain village of Gobersdorf in Germany, emphasizing a regimen of rest, a rich diet, and carefully supervised exercise (3). This facility is considered the first sanatorium devoted to the treatment of tuberculosis.

The first sanatorium in North America was opened in Asheville, North Carolina, by Joseph Gleitsman. Gleitsmann, a German-born and trained doctor, is believed to have selected Asheville because of its optimal combination of barometric pressure, temperature, humidity, and sunlight which he believed to be essential to healing tuberculosis (3).

Although the sanatoriums were supposed to provide treatment and care, they also isolated tuberculosis sufferers not only from those whom they might infect but also from matters of the world they lived in. In his famous novel, The Magic Mountain, Thomas Mann writes about Hans Castorp’s symbolical transport away from the everyday life and mundane obligations he has known, to the rarefied mountain air and introspective little world of the sanatorium

It is hard to comprehend the agony associated with being taken away from your loved ones and isolated from the rest of the world at the same time as realizing that death would be the most likely outcome. Thankfully, tuberculosis is not an epidemic anymore. Although not completely eradicated, it can be prevented and cured. Communicable diseases are no longer the most common cause of death and disability around the world.

Today’s Epidemic – The Metabolic Syndrome

Today’s epidemic is a horse of a different color.  The sanatoriums have been closed. Instead, we are facing a collection of noncommunicable diseases that to a large extent are caused by the way we live our lives, what we eat, whether we smoke, and whether we are couchbound or not.

There is abundant evidence that type-2 diabetes, cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), hypertension (high blood pressure), and some types of cancer may all be the result of biochemical alterations associated with the modern Western diet. These metabolic changes, collectively known as metabolic syndrome, are characterized by insulin resistance, derangements of glucose metabolism, hypertension, high blood triglycerides, and low blood levels of HDL cholesterol.

Of course, we might easily conclude that the metabolic syndrome is a consequence of the obesity epidemic. In fact, recent evidence shows that the worldwide prevalence of overweight and obesity combined rose by 27.5% for adults and 47.1% for children during the past three decades (4). Interestingly, these increases were seen in both developed and developing countries.

However, although metabolic syndrome often seems to travel with obesity, it occurs in normal-weight people as well. Furthermore, many obese individuals do not have the metabolic abnormalities that characterize the metabolic syndrome. Hence, it has to be assumed that it is not only about body weight and calories. But, if weight gain itself is not the culprit, what is?

For many experts, the answer is obvious (5). It’s added sugar (6), fructose, the silent ‘sweet killer’.

The Silent ‘Sweet Killer’

Fructose is massively used by the food industry due to its very sweet taste and lack of inhibition of satiety compared with other types of sugar (7).

Fructose is a monosaccharide that is found naturally in fruits. It is typically consumed as sucrose (table sugar), a disaccharide composed of equal parts of fructose and glucose, or as a component of high-fructose corn syrup (HFCS). According to US Department of Agriculture (USDA) data, 60% of HFCS used is 55% fructose, and the remainder is typically 42% fructose (8).

For the last few decades, there has been an enormous rise in fructose consumption in the U.S. It is highest among adolescents (12–18 years). The largest source of fructose is sugar-sweetened beverages (30%) followed by grains (22%) and fruit or fruit juice (19%) (9)

There is strong evidence from both experimental and animal studies suggesting that high fructose consumption can lead to insulin resistance, high blood pressure, lipid abnormalities, and NAFLD.

The metabolic effects of fructose are very different from those of glucose. Fructose is metabolized almost exclusively in the liver whereas glucose can be metabolized by most cells of the body.

The entry of fructose into cells is not dependent on insulin and does not promote insulin secretion, unlike glucose. Fructose promotes an increase in blood levels of triglycerides (10). Elevated triglycerides caused by excessive fructose intake may be a precursor of insulin resistance (11).

Fructose-sweetened beverage consumption habits are associated with a central fat distribution and visceral obesity (12). Visceral fat tissue appears much more damaging to health than other types of fat tissue. Obese individuals with excess visceral obesity have a higher risk of diabetes, lipid disorders, and CVD than those with less visceral fat accumulation (13).

However, this may all be circumstantial evidence.  The question remaining is whether fructose plays a causative role in the biochemical abnormalities associated with obesity and metabolic syndrome? Does restricting fructose intake improve these metabolic abnormalities? Will reducing fructose reduce the risk of noncommunicable diseases such as diabetes, CVD, NAFLD, and cancer?

6349585_sInterestingly, these important questions were addressed recently in a very important paper published by Robert Lustig and colleagues from the University of California (14).

Lustig and coworkers studied 43 obese children (ages 8-19) with metabolic abnormalities typical of the metabolic syndrome. All were high consumers of added sugar in their diets (e.g. soft drinks, juices, pastries, breakfast cereals, salad dressings, etc.).

The children were fed the same calories and percent of each macronutrient as their home diet; but within the carbohydrate fraction, the added sugar was removed, and replaced with starch. For example, pastries were taken out, and bagels put in; yogurt was taken out, baked potato chips were put in; chicken teriyaki was taken out, turkey hot dogs were put in. Whole fruit was allowed. Dietary sugar consumption went from 28% to 10% of calories.

To dissociate the metabolic effects of dietary sugar from its calories and its effects on weight gain, it was important to keep weight constant. If the children were losing weight, they were told to eat more. The goal was to remain weight-stable over the ten days of study. On the final day, the children came back to the hospital for testing on their experimental low-added-sugar diet.

The Bottom Line

According to the World Health Organization (WHO), noncommunicable diseases kill 38 million people each year (15). Sixteen million of those deaths may be considered premature as they occur before the age of 70. CVD account for most of these deaths, followed by cancers, respiratory diseases, and diabetes. According to WHO, tobacco use, physical inactivity, the harmful use of alcohol, and unhealthy diets all increase the risk of premature death from noncommunicable diseases.

A worldwide study published last year suggests that sugary soft drinks kill 184,000 adults every year (16). The study shows that 133,000 deaths from diabetes, 45,000 deaths from CVD, and 6,450 deaths from cancer were caused by fizzy drinks, fruit drinks, energy drinks, and sweetened iced teas in the year 2010.

By now, it should be obvious that sugar-sweetened beverages are a single, modifiable component of our diet that can impact preventable death and disability in adults in high-, middle-, and low-income countries, indicating an urgent need for strong global prevention programs.

The success in preventing and treating communicable diseases like tuberculosis may be considered the biggest achievement in the history of medicine. However, it has left us with another enormous problem of a completely different nature. This time, we are not dealing with a ruthless microorganism but with an environment of our own creation, a culture that manages to encourage unhealthy lifestyle and junk food.

Defining our targets is the first step. It’s about time we realize that added sugar, fructose, in particular, is the silent ‘sweet killer,’ the 21st century’s white plague, today’s robber of youth.

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