Some Sugars Worse than Others? The Bittersweet Fructose/Glucose Debate.

Excessive consumption of sugar has been associated with increased incidences of type 2 diabetes, formerly called adult-onset diabetes, obesity and tooth decay.

There are many sugars around. Natural sugars and refined sugars. The refined table sugar and sugar cubes would be called “sucrose” by a chemist. Sucrose consists of two simple sugars (monosaccharides): 1 fructose and 1 glucose molecule (5).

Glucose is a sugar that occurs in the blood. Because of its name, fructose (Latin= fructus, fruit) is often regarded as more “natural” and therefore as a healthier alternative to glucose. However, unlike glucose, that can be metabolized anywhere in the body, fructose has to be metabolized by the liver. Here, fructose is easily converted to fat.

There is an intensive debate whether glucose or fructose is the real culprit for overweight and related health problems. This discussion is  relevant, because of the shift towards use of (cheaper) high fructose corn syrup from sucrose (especially in the US).

Last week a journal article was published in the Journal of Clinical Investigation, written by Stanhope et al (1) that was widely covered in the media. Headlines were for instance “Fructose slechter dan glucose” (NRC, Dutch, 8), “Fructose is the bad sugar, not glucose” (Indo-Asian News Service, i.e. 9) “Fructose-Sweetened Beverages Linked to Heart Risks” (NY-times, 10).

Is this study a breakthrough? What has been done?

This study was a double-blinded parallel arm study that assessed the relative effects of fructose- versus glucose – sweetened beverages in 32 matched, obese individuals, 40 to 72 years old (see 1).

The study consisted of 3 phases:

1. The first 2 weeks the volunteers lived in a clinical research center, consuming an energy- balanced high complex carbohydrate diet. This phase established baseline measurements for the study.
   
2. An 8-week outpatient intervention period during which subjects consumed either fructose- or glucose-sweetened beverages providing 25% of daily energy requirements along with their usual ad libitum diet. The aim was to imitate the ‘normal situation’, where sugar-sweetened beverages are typically consumed as part a normal energy-rich diet.
3. A 2-week inpatient intervention period during which subjects consumed fructose- or glucose-sweetened beverages providing 25% of daily energy requirements with an energy-balanced diet.

Results

Both study groups put on the same amount of weight, but people drinking fructose showed an increase in intra-abdominal fat, an increased hepatic de-novo (new) synthesis of lipids, higher triglyceride, LDL and oxidized LDL (“bad fats”), and higher fasting plasma glucose and insulin levels, but lowered insulin sensitivity. All these parameters are associated with a higher risk for diabetes and cardiovascular disease.

Positive Aspects of the study

• Intervention directly comparing fructose and glucose
• Human study
• Randomized Controlled Trial
• Many variables measured, related to diabetes and cardiovascular disease.

Critique:

• The first thing that came to my mind was: is it ethical to expose obese man and woman (or any healthy volunteer) to 10 weeks of a very unhealthy diet: extra glucose or fructose beverages making up 25% of the calorie intake?
• Because the subjects were obese, the results may not directly apply to lean persons.
• Minor point: It is a rather difficult to read paper, with a plethora of data. I wonder why SEM are given instead of SD and why the statistical significance is only determined versus baseline.
• Only surrogate markers were tested.
• Most important: the doses of sugars used are excessive, not reflecting a real-life diet.
• Nor can results with pure fructose be directly translated to health effects of high-fructose corn syrup, which is not pure fructose, but still contains 45% glucose.
• In addition the abstract and introduction suggests that it is the first human intervention study, which it isn’t.

Quite coincidentally the Journal of Nutrition published a supplement about “the State of the Science on Dietary Sweeteners Containing Fructose” [2-4]. In his paper Geoffrey Livesey [2] stresses the pitfalls of studies on Fructose, not only of animal and epidemiological studies, but also of intervention studies using excessive high fructose (excessive is > 400 kcal/day = >20% of energy intake), that may bear little relevance to the normal situation.

Many hypotheses of disease risk and prevention depend on inferences about the metabolic effects of fructose; however, there is inadequate attention to dose dependency. Fructose is proving to have bidirectional effects. At moderate or high doses, an effect on any one marker may be absent or even the opposite of that observed at very high or excessive doses; examples include fasting plasma triglyceride, insulin sensitivity (..) Among markers, changes can be beneficial for some (..) but adverse for others (e.g., plasma triglycerides at very high or excessive fructose intake). Evidence on body weight indicates no effect of moderate to high fructose intakes, but information is scarce for high or excessive intakes. The overall balance of such beneficial and adverse effects of fructose is difficult to assess but has important implications for the strength and direction of hypotheses about public health, the relevance of some animal studies, and the interpretation of both interventional and epidemiological studies.

References:

1. Stanhope, K., Schwarz, J., Keim, N., Griffen, S., Bremer, A., Graham, J., Hatcher, B., Cox, C., Dyachenko, A., Zhang, W., McGahan, J., Seibert, A., Krauss, R., Chiu, S., Schaefer, E., Ai, M., Otokozawa, S., Nakajima, K., Nakano, T., Beysen, C., Hellerstein, M., Berglund, L., & Havel, P. (2009). Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans Journal of Clinical Investigation DOI: 10.1172/JCI37385
2. Livesey, G. (2009). Fructose Ingestion: Dose-Dependent Responses in Health Research Journal of Nutrition DOI: 10.3945/jn.108.097949
3. White, J. (2009). Misconceptions about High-Fructose Corn Syrup: Is It Uniquely Responsible for Obesity, Reactive Dicarbonyl Compounds, and Advanced Glycation Endproducts? Journal of Nutrition DOI: 10.3945/jn.108.097998
4. Jones, J. (2009). Dietary Sweeteners Containing Fructose: Overview of a Workshop on the State of the Science Journal of Nutrition DOI: 10.3945/jn.108.097972
5. Wikipedia: http://en.wikipedia.org/wiki/Sugar
   
6. Essentially Healthy Food: Sugar, a bittersweet story part 2
7. http://www.askmen.com/sports/foodcourt_250/257_health-benefits-of-sugar.html
8. NRC, April 21, 2009. http://www.nrc.nl/wetenschap/article2219138.ece/Fructose_slechter_dan_glucose
9. The Idian http://www.thaindian.com/newsportal/sci-tech/fructose-is-the-bad-sugar-not-glucose_100184408.html
10. NY Times,  April 2, 2009: Fructose-Sweetened Beverages Linked to Heart Risks

Photo Credits

• Sugarcube: http://www.flickr.com/photos/uwehermann/132244825/ (CC)
• Glucose/Frucose structure: http://www.elmhurst.edu/~chm/vchembook/543fructose.html
• Softdrinks: http://www.flickr.com/photos/tuis_imaging/3198244845/ (CC)