Fructose sugar benefits and side effects info on intolerance, malabsorption, metabolism, use as sweetener, role in insulin resistance, is it healthy or harmful? by Ray Sahelian, M.D.
August 16 2017

Fructose is a sugar found widely in the diet as a free monosaccharide hexose, as the disaccharide, sucrose and in a polymerized form (fructans) as a component of plant oligosaccharides. Because fructose is considerably sweeter than sucrose or glucose, it is used to enhance the flavor, color stability, and freezing point depression of many foods and beverages. Fructose is also used in place of sucrose and other carbohydrates in dietetic products.
   Fructose is a simple sugar found in honey, fruit, table sugar (sucrose), and high-fructose corn syrup. Because of the worldwide increase in the consumption of these sweeteners, fructose intake has increase dramatically since the early 1900s. The past several decades have witnessed an even greater acceleration in consumption, in part because of the introduction of high-fructose corn syrup; this phenomenon is associated with the rise in obesity, diabetes, and high blood pressure. Studies in animals have shown that fructose can induce most features of the metabolic syndrome, including insulin resistance, elevated triglycerides, abdominal obesity, elevated blood pressure, inflammation, oxidative stress, endothelial dysfunction, kidney injury, and fatty liver. See natural ways to reduce levels of cholesterol.

Is it a good thing or a bad thing?
Human and animal studies suggest that fructose ingestion produces deleterious effects on the cardiovascular system, such as increase in blood pressure and also has adverse metabolic effects, for example insulin resistance and hypertriglyceridaemia. On the other hand it has also been determined that fructose, especially that is contained in natural sources as apples, dates and honey may produce beneficial effects on human health; smaller amounts may even help improve diabetic control. In conclusion, fructose appears to be not all that bad; is essential for male fertility, small amounts of fructose, specifically which comes from dietary sources appears to be beneficial for health.

High fructose intake harm
High intake of fructose is associated with the biochemical alterations that promote the development of metabolic syndrome, nonalcoholic fatty liver disease, and type 2 diabetes. It is metabolized by the liver, where it stimulates the production of fat molecules. The triglycerides synthesized lead to hepatic insulin resistance and high lipid levels in the blood. Fructose-derived advanced glycation end products (AGEs) can harm the body and age it quicker.

Fructose in diet, the foods that contain it
Most fructose in the American diet comes not from fresh fruit, but from high fructose corn syrup or sucrose (sugar) that is found in soft drinks and sweets. In 1966, refined sugar, also known as sucrose, held the No. 1 slot, accounting for 86 percent of sweeteners used. Today, sweeteners made from corn are the leader, racking up several billion in annual sales and accounting for more than half of the sweetener market. That switch largely reflects the steady growth of high fructose corn syrup, which climbed from zero consumption in 1966 to more than 60 pounds per person after the year 2000.

Fructose content in foods - benefit through eating fruits as opposed to processed foods and drinks
Honey, dates, raisins, molasses, and figs have a content of fructose greater than 10%. Grapes, raw apples, apple juice, persimmons, and blueberries have a fructose content of 5–10% by weight. Milk has hardly any fructose, nor do most vegetables and meats. When fructose is ingested from fruits, many other beneficial substances are also ingested including fiber and antioxidants, whereas when fructose is ingested through soft drinks or other processed foods, there is no fiber to slow the absorption of the fructose and few antioxidants to prevent or minimize the adverse effects of a high fructose intake on blood sugar or tissues.

Fructose absorption and metabolism
When ingested by itself, fructose is poorly absorbed from the gastrointestinal tract, and it is almost entirely cleared by the liver. Fructose differs in several ways from glucose, the other half of the sucrose (sugar) molecule. Fructose is absorbed from the gastrointestinal tract by a different mechanism than that for glucose. Glucose stimulates insulin release from the isolated pancreas, but fructose does not. Most cells have only low amounts of the glut-5 transporter, which transports fructose into cells. Fructose cannot enter most cells, because they lack glut-5, whereas glucose is transported into cells by glut-4, an insulin-dependent transport system. Finally, once inside the liver cell, fructose can enter the pathways that provide glycerol, the backbone for triacylglycerol.
   Fructose is easily metabolized and changed into fat. Studies in rodents, dogs, and nonhuman primates eating diets high in fructose or sucrose consistently show elevated blood lipids. The metabolism of fructose in the liver drives the production of uric acid, which utilizes nitric oxide, a key modulator of vascular function. George Bray, American Journal of Clinical Nutrition, 2007.

A high fructose diet increases lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreases hepatic insulin sensitivity.

Increase in cancer rate
Pancreatic tumor cells use fructose to divide and proliferate. Tumor cells fed both glucose and fructose use the two sugars in two different ways. Dr. Anthony Heaney of UCLA's Jonsson Cancer Center grew pancreatic cancer cells in lab dishes and fed them both glucose and fructose. Tumor cells thrive on sugar but they used the fructose to proliferate. Americans take in large amounts of fructose, mainly in high fructose corn syrup, a mix of fructose and glucose that is used in soft drinks, bread and a range of other foods. Cancer Research, 2010.

Fructose and diabetes, blood sugar
Diets high in fructose cause insulin resistance, a precursor to type 2 diabetes. A particular gene, known as PGC-1 beta, appears to play a key role in the development of insulin resistance in response to a high-fructose diet. Rats that had the gene's activity blocked were protected from insulin resistance despite feasting on a diet loaded with fructose. High-fructose corn syrup has been widely used in sodas and processed foods since the 1980s, and some researchers have blamed this trend at least in part for the concurrent rise in obesity and diabetes. Some studies have shown that fructose is metabolized differently than glucose is, being more readily converted into fat. Dr. Gerald Shulman and colleagues at Yale University School of Medicine. looked at PGC-1 beta because it activates another gene that governs the production of fat by the liver. When the researchers blocked the gene's activity in rats fed a high-fructose diet, the animals did not develop insulin resistance and elevated triglycerides. Inhibiting PGC-1 beta could help treat some cases of high triglycerides, fatty liver disease and insulin resistance. Cell Metabolism, 2009.

Excessive fructose intake from high-fructose corn syrup (HFCS) and sucrose has been implicated as a driving force behind the increasing prevalence of obesity and its downstream cardiometabolic complications including hypertension, gout, dyslidpidemia, metabolic syndrome, diabetes, and non-alcoholic fatty liver disease. Curr Hypertension Rep. 2013.

Diabetes. October 2013. Sugar, uric acid, and the etiology of diabetes and obesity. The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that "a calorie is just a calorie" and suggest that the metabolic effects of food may matter as much as its energy content.

Fructose consumption and gout
Consumption of sugar sweetened soft drinks and very high intake of fructose is associated with an increased risk of gout in men. Fructose rich fruits and fruit juices may also increase the risk when consumed as a high proportion of the diet.. Diet soft drinks are not associated with the risk of gout.

High fructose corn syrup and obesity
The intake of soft drinks containing high-fructose corn syrup or sucrose has risen in parallel with the epidemic of obesity. Made from corn starch, high-fructose corn syrup is a thick liquid that contains two basic sugar building blocks, fructose and glucose, in roughly equal amounts. While soft drinks and fruit beverages such as lemonade are the leading products containing high fructose corn syrup, plenty of other items -- including cookies, gum, jams, jellies and baked goods -- also contain this syrup.
   High fructose corn syrup is produced by processing corn starch to change its sugars from glucose to fructose. The sweetener became a popular replacement for table sugar (sucrose) in the 1980s when pricing controls and quotas made it expensive to import sugar into the U.S. Coca-Cola and Pepsi switched from sucrose to high-fructose corn syrup in 1984, and many other food manufacturers have since followed. Today, high-fructose corn syrup is found in everything from cookies to salad dressing to breakfast cereal. By 2005, the average American was consuming 60 pounds of high-fructose corn syrup each year, compared with 58 pounds of sugar.
   Dr. Elizabeth Parks, a physiologist and associate professor at the Center for Human Nutrition at the University of Texas' Southwestern Medical Center in Dallas has been studying this topic. Dr. Elizabeth Parks has found that our bodies turn fructose into fat more readily than glucose.

Consuming too much fructose -- a form of sugar found in corn syrup, honey and fruit -- appears to alter levels of hormones involved in appetite regulation in such a way as to encourage overeating, a new study suggests.After people in the study ate a meal followed by a drink flavored with the same amount of fructose found in two cans of soda, they showed relatively low levels of insulin and leptin, hormones that help people know that they are full. On the other hand, they showed relatively high levels of ghrelin, a hormone that stimulates eating. These hormonal changes could promote overeating,. Sugar occurs in two forms, fructose and glucose. Glucose, but not fructose, stimulates insulin secretion, which in turn regulates leptin production. Both fructose and glucose are naturally found in fruit and fruit juices. However, over the years manufacturers have sweetened sodas and some foods with corn syrup, which contains concentrated amounts of fructose. To investigate whether drinking fructose plays a role in obesity, Teff and her colleagues asked 12 normal-weight women to wash down balanced meals with drinks sweetened with either fructose or glucose. When the women drank the fructose drink, their levels of insulin and leptin were lower than when they consumed a drink flavored with glucose, and levels of ghrelin were higher, the researchers report in the Journal of Clinical Endocrinology and Metabolism. In addition, drinking the fructose drink was associated with a spike in levels of blood fats, a known risk factor for cardiovascular disease.

Sucrose or high fructose corn syrup have similar effect on satiety
Sugars and satiety: does the type of sweetener make a difference?
American Journal of Clinical Nutrition, 2007.
The objective of the study was to compare the relative effect of commercial beverages containing sucrose or high fructose corn syrup on hunger, satiety, and energy intakes at the next meal with the use of a within-subject design.
Thirty-seven volunteers (19 men, 18 women) aged 20–29 y consumed isocaloric cola beverages (215 kcal) sweetened with sucrose, high fructose corn syrup 42, or high fructose corn syrup 55. High fructose corn syrup 42 contains 42% fructose, and high fructose corn syrup 55 contains 55% fructose. Diet cola (2 kcal), 1%-fat milk (215 kcal), and no beverage were the control conditions. The 5 beverages were consumed 2 h after a standard breakfast. Participants rated hunger, thirst, and satiety at baseline and at 20-min intervals after ingestion. A tray lunch (1708 kcal) was served at 1230, and energy intakes were measured. There was no differences between sucrose- and high fructose corn syrup -sweetened colas in perceived sweetness, hunger and satiety profiles, or energy intakes at lunch. The 4 caloric beverages tended to partially suppress energy intakes at lunch, whereas the no-beverage and diet beverage conditions did not; the effect was significant only for 1%-fat milk. Energy intakes in the diet cola and the no-beverage conditions did not differ significantly. There was no evidence that commercial cola beverages sweetened with either sucrose or high fructose corn syrup have significantly different effects on hunger, satiety, or short-term energy intakes.

Fructose -- a kind of sugar found in a wide variety of foods and beverages -- may encourage overeating. Fructose may be best known to consumers in the form of high-fructose corn syrup, which has long been added to manufactured foods from sodas to cookies. Distinct from sugar known as glucose (produced by the natural breakdown of complex carbohydrates), fructose is also a "simple" sugar and a natural component of fruit. However, "in a series of studies we have found that when compared to glucose, the simple sugar, fructose, is a weaker suppressor of brain areas that help control appetite and the motivation to eat," said study co-author Dr. Kathleen Page, an assistant professor of clinical medicine at the Keck School of Medicine of the University of Southern California in Los Angeles.

Fructose and glucose consumption compared to whey protein ingestion
Appetite hormones and energy intake in obese men after consumption of fructose, glucose and whey protein beverages.
Int J Obes (Lond). 2007.
Commonwealth Scientific and Industrial Research Organisation (CSIRO), Human Nutrition, Adelaide, Australia, Department of Physiology, University of Adelaide, Adelaide, Australia.
To investigate appetite responses over 4 hour to fructose beverages in obese men, relative to glucose and whey protein. Second, to investigate the effect of combining whey and fructose on postprandial appetite hormones. Randomized, double-blind crossover study of four beverages containing 50 g of whey, fructose, glucose or 25 g whey+25 g fructose. Blood samples and appetite ratings were collected for 4 h then a buffet meal was offered. Subjects were twenty-eight obese men. Measurements were done of plasma ghrelin (total), glucagon-like peptide-1 (GLP-1 7-36), cholecystokinin-8, glucose, insulin and appetite ratings were assessed at baseline and 30, 45, 60, 90, 120, 180, 240 min after beverages, followed by measurement of ad libitum energy intake. Results: Fructose produced lower glycemia and insulinemia compared to the glucose treatment; whereas postprandial ghrelin, GLP-1 and cholecystokinin responses were similar after both treatments. Whey protein produced a prolonged (2-4 h) suppression of ghrelin and elevation of GLP-1 and cholecystokinin that were reduced when combined with fructose, while glucose and insulin responses were similar. Energy intake after 4 h was independent of beverage type. Conclusion:In obese men, fructose- and glucose-based beverages had similar effects on appetite and associated regulatory hormones, independent of the differing glycemic and insulinemic responses. The contrasting profile of plasma ghrelin, GLP-1 and cholecystokinin after whey protein consumption did not impact on ad libitum intake 4 h later and was attenuated when 50% of whey was replaced with fructose.

Fructose absorption
Free fructose has limited absorption in the small intestine, with up to one half of the population unable to completely absorb a load of 25 g. Average daily intake of fructose varies from 11 to 54 g around the world. Fructans are not hydrolysed or absorbed in the small intestine. The physiological consequences of their malabsorption include increasing osmotic load, providing substrate for rapid bacterial fermentation, changing gastrointestinal motility, promoting mucosal biofilm and altering the profile of bacteria. These effects are additive with other short-chain poorly absorbed carbohydrates such as sorbitol. The clinical significance of these events depends upon the response of the bowel to such changes; they have a higher chance of inducing symptoms in patients with functional gut disorders than asymptomatic subjects. Restricting dietary intake of free fructose and/or fructans may have durable symptomatic benefits in a high proportion of patients with functional gut disorders, but high quality evidence is lacking. It is proposed that confusion over the clinical relevance of fructose malabsorption may be reduced by regarding it not as an abnormality but as a physiological process offering an opportunity to improve functional gastrointestinal symptoms by dietary change.

Fructose malabsorption
Dietary fructose induces abdominal symptoms in patients with fructose malabsorption.

I am diagnosed with fructose malabsorption disorder by Dr. Satish Rao of the University of Iowa. My gastroenterologist was unable to accurately diagnose me (after 10 years and many tests) and sent me to Dr. Satish Rao. I have been doing a lot of research on the dangers of excess fructose in your body (diabetes, cancer and liver disease).

Fructose and flatulence
Increased consumption of fructose can cause gastrointestinal distress, resulting in symptoms such as bloating, flatulence and diarrhea. Individuals with altered gastrointestinal function, such as inflammatory bowel disease or irritable bowel, therefore need to limit the amount of fructose consumed. Fructose empties from the stomach more rapidly than other sugars and is more slowly absorbed than glucose. When foods and beverages containing fructose as the dominant sugar are consumed, the capacity for fructose absorption in the small intestine can easily be exceeded. A study by Beyer et al. investigated the frequency of fructose malabsorption and gastrointestinal symptoms in normal healthy individuals using two doses of fructose (25 and 50 g). Fructose absorption was measured using three-hour hydrogen breath tests. Mean peak breath hydrogen, time of peak area under curve for breath hydrogen and gastrointestinal symptoms were measured and differences analysed. More than half of the 15 adults showed evidence of fructose malabsorption after 25 g and more than two-thirds after 50 g, indicating that commonly consumed amounts of fructose may result in mild gastrointestinal distress in normal individuals.

High fructose consumption and liver disease
While the rise in non-alcoholic fatty liver disease parallels the increase in obesity and diabetes, a significant increase in dietary fructose consumption in industrialized countries has also occurred. The increased consumption of high fructose corn syrup, primarily in the form of soft drinks, is linked with complications of the insulin resistance syndrome. Furthermore, the hepatic metabolism of fructose favors de novo lipogenesis and ATP depletion. Increased fructose consumption contributes to the development of non-alcoholic fatty liver disease.

Questions
I came across this article, can you comment on it? "Diets high in fructose - a type of sugar found in most processed foods and beverages - could impair spatial memory, says a study on adult rats. To reach the conclusion, Amy Ross, a graduate student in the lab of Marise Parent, associate professor at Georgia State’s Neuroscience Institute and Department of Psychology, fed a group of Sprague-Dawley rats a diet where fructose represented 60 percent of calories ingested during the day. She placed the rats in a pool of water to test their ability to learn to find a submerged platform, which allowed them to get out of the water. She then returned them to the pool two days later with no platform present to see if the rats could remember to swim to the platform's location. "What we discovered is that the fructose diet doesn’t affect their ability to learn," Marise Parent said. "But they can’t seem to remember as well where the platform was when you take it away. They swam more randomly than rats fed a control diet," the expert added. "
    It is not unusual to have poor brain function when the diet is so unbalanced with any type of sugar, it is rare for most humans to consume a diet that is so high in fructose, but those that do may not have optimal brain function.