High-fructose Corn Syrup: Obesogenic Evil or Dietary Scapegoat, Part 2

Opening Comments

Welcome back for part 2 of the great HFCS debate. Before I begin, I’d like to briefly recap last week’s arguments (for those who may have missed it) by simply copying and pasting my concluding remarks:

In summary, energy from added sugars, namely HFCS, is higher now than it was in 1970, but it increased at a slower rate than that of other macronutrients in proportion to our total caloric intake. Also, availability of HFCS has also been on the decline since 1999 yet obesity prevalence still continued to rise. Finally, total energy has not been driven up disproportionally by HFCS, but rather the diet as a whole. Simply stated; we’re eating more of EVERYTHING. 

So, now that we’re all caught up, we can all agree that increased consumption of HFCS doesn’t prove a thing and we can now move on to today’s focus, which I’m just going to jump right into. Basically there needs to be a compelling and convincing argument that HFCS is indeed different from sucrose (which we’ve already seen really isn’t the case, at least not compositionally) and is uniquely obesogenic, meaning that it causes you to gain weight more so than sucrose could. In lieu of this theory there has been a surge of studies within the past couple of decades on fructose and HFCS. These studies help to provide a biological rationale (mechanism) for why our increased consumption is potentially causing obesity. Much of these studies, however, are based on rodent data and/or studies which involve HUGE doses of fructose (some without accompanying glucose) that are irrelevant to normal human consumption patterns. Although these types of studies provide insight to certain, albeit rarely used, biochemical pathways, and in doing so show us the harms of massive quantities of fructose, my retort is that what nutrient in massive excess WON’T cause adverse effects? Abuse anything well enough and of course you’re going to see detrimental outcomes. That being said, let us begin.

Fructose Metabolism

A common argument when talking about HFCS and obesity is that fructose metabolism is markedly different from that of glucose, and fructose strongly favors fat synthesis, otherwise known as de novo lipogenesis (DNL), a topic I covered in depth a couple of weeks ago. Although the metabolism of fructose is indeed different than that of glucose metabolism, this argument holds PLENTY of water.

First off, upon fructose consumption (which I will say right now, almost NEVER happens devoid of glucose consumption) most of it (~50%) is either oxidized in the liver [1] or is converted to glucose and is then oxidized by other tissues in the body [2]. Either way you look at it, almost half of what you consume is immediately oxidized to CO2 (i.e. not stored as fat). The rest of the fructose is either; 1) converted and stored as liver glycogen (~17%) [3]; 2) converted and released as lactate (~25%) [4-6]; or 3) converted into fatty acids by way of DNL (~8%). However, as you can see, DNL is not a major pathway, as shown by various studies [7-9], and most likely does not contribute to any appreciable gain in body fat (see previous article on DNL).

This, however, is not to say that studies don’t exist where appreciable levels of plasma triglycerides (fat floating around in the blood stream) were made from fructose. There are two that I know of: one was in a hamster study, which is irrelevant because the pathway that was seen in hamsters hasn’t been found in humans yet, and the other was done in humans about 12 years ago. Here a group of researchers saw that a group of healthy males who were fed diets containing fructose increased their plasma triglycerides by 32% [10]. The diet, however, contained 17% of total calories as fructose. Even looking at estimated fructose intake from 1999, when fructose and HFCS consumption were THE HIGHEST THEY HAD EVER BEEN, fructose only accounted for ~8% of total kcals. And it can easily be assumed that this number is lower today due to reduced consumption since that time (see previous HFCS article). Therefore this study is irrelevant to what normal people usually eat. And just to stress the point, if you do the calculations, 17% of today’s kcal intake (which is ~2,700kcals) is about 460kcals. That equates to ~115g of fructose alone. You would have to consume nearly 2 liters of soda a day in order to get that much fructose. Which brings me to the point I will continue to stress within everything I write on this site; and that is context.

Context!!!

Without context, research means nothing. The fact of the matter is that we’re talking about the effects of HFCS within NORMAL consumption patterns. No one in their right mind consumes almost a fifth of their calories as fructose (be it from HFCS or any other sources). And sure, maybe you do know someone who drinks a 2-liter bottle of Coke a day, but my guess is that they’ve probably got a whole host of other things going on rather than JUST fructose consumption (i.e. sedentary behavior, other poor dietary habits, poor sleep/wake cycle, etc.). Moving on.

Fructose and its Effects on Insulin, Leptin and Subsequent Food Intake

The next huge argument surrounding HFCS and obesity is fructose’s effects (or lack thereof) on insulin and subsequently, leptin. Insulin, as many of you may know, is a storage hormone released by the pancreas in response to a rise in glucose concentration in the bloodstream. As I suspect, most of you don’t know what leptin is, so long story short, leptin is a hormone, stimulated by insulin, which tells the brain to stop eating and increase metabolism (double awesome!). Based on this principle, many researchers believe that, because fructose has such a minimal effect on insulin release, there is no leptin response and therefore no satiety signals on which the brain can act. Simply put; fructose may have no effect on appetite suppression.

No insulin = no leptin = keep on eating. But is this true?

Well, indeed the glycemic index, and therefore the insulin response, of fructose is much (about fivefold) less than that of glucose [11], but this isn’t to say that fructose doesn’t have any insulin response when consumed. If you remember, I mentioned earlier that fructose is converted into glucose in the body. This conversion requires the use of insulin in order to take up the newly formed glucose. So, in fact, there is a small amount of insulin released in response to actual fructose consumption.

But when do you EVER eat fructose by itself? Probably never. It’s nearly impossible to do unless you go to a health food store and buy a bag of fructose powder… and then only eat that. So yea, probably not likely. And let’s not forget, we’re talking about HFCS and not just fructose. If you remember the nice little table I provided last week, you should know that HFCS is nearly HALF glucose! Glucose DOES stimulate insulin, glucose DOES affect leptin. How easily we forget. So the better question would be; is HFCS any different from sucrose at stimulating insulin and leptin?

It just so happens that there is a couple of studies which show just that. A number of then show that not only do sucrose and HFCS BOTH elicit a leptin response, but they also have appetite suppressing effects [12-16]. Let me say that again. They were shown to actually SUPRESS participant’s appetites. How’s that for throwing a wrench into the gears?

And, if we want to take the original argument and pin fructose against glucose, it was shown that when looking at fructose solutions and glucose solutions given before a meal, studies show either NO DIFFERENCE in caloric intake between the two solutions, or a LESSER intake for people who consumed pure fructose before eating a meal [17-21]. There is one study which does show a greater consumption of food after consuming a fructose solution, however, this study had participants consume roughly 30% of their calories as pure fructose [5]. Now remember, just above we talked about how much 17% of total kcals is… now double that! These people were drinking almost 4-liters worth of soda a day. Now I ask you again, how relevant is that to NORMAL human consumption?

Fructose and Thermogenesis

Just to drive the point home, there happen to be a handful of human studies that saw higher levels of thermogenesis (energy expenditure, not fat storage) in men and women, as well as in obese women, after a mixed meal with 75g of carbs coming SOLELY from a fructose solution compared to another meal with 75g of glucose. In other words, there was higher carbohydrate OXIDATION (burning) and higher thermic effect of food (TEF) when fructose is given as the only carbohydrate source [1, 22-25]. This again shows that even high amounts of fructose might not get deposited as triglyceride, at least not in the short term.

Conclusions

Now I know I sound like a soda company’s wet dream right now, but it is my firm belief that, as a future dietitian and advocate for nutrition, we must not succumb to misinformation. We must learn how to accurately and effectively discern the relevant from the irrelevant. My goal over the past two weeks has been to show you all that certain views persist even in the face of solid research saying the exact opposite. HFCS doesn’t make people fat, food does, along with physical inactivity and a whole host of other factors. Trying to use HFCS as a scapegoat isn’t justified as far as I’m concerned. So with that being said, I will leave you all with some key points, taken directly from a paper written by metabolic researcher Dr. Geoffrey Livesey [26], who in my mind is the voice of reason needed within a world of fructose (mainly HFCS) hysteria. If you have never heard of him, I suggest you look him up; he is a world renowned metabolism expert. A few of his Key Points from said paper (not in any particular order) are as follows:

  1. Moderate doses of fructose have neutral or diametrically opposite effects to those expected for very high or excessive fructose intakes and show evidence of improved glycemic control.
  2. There is reason to believe that modest fructose ingestion could be beneficial for public health, whereas excess intake would be a risk to health. Practical application will depend on future research.
  3. Epidemiological studies are difficult to interpret. The roles of [glycemic load] and other factors collinear with fructose intake need to be examined.
  4. Intervention studies using humans use fructose at doses that are excessive compared with amounts generally eaten by adults; such are not interpretable for purposed of public health policy in adult nutrition.
  5. Animal studies often use doses of fructose in excess of what humans would normally consume and so have a high potential to mislead about the public health aspects of fructose.

References

1. Tappy L, Randin JP, Felber JP, Chiolero R, Simonson DC, Jequier E, DeFronzo RA. Comparison of thermogenic effect of fructose and glucose in humans. Am J Physiol Endocrinol Metab 1986;250:E718-E724.

2. Delarue J, Normand S, Pachiaudi C, Beylot M, Lamisse F, Riou JP. The contribution of naturally labeled 13C fructose to glucose appearance in humans. Diabetologia 1993;36:338-345.

3. Nilsson LH, Hultman E. Liver and muscle glycogen in man after glucose and fructose infusion. Scan J Clin Lab Invest 1974;33:5-10.

4. Burns SP, Murphy HC, Iles RA, Bailey RA, Cohen RD. Hepatic intralobular mapping of fructose metabolism in the rat liver. Biochem J 2000;349:539-545.

5. Teff KL, Elliot SS, Tschop M, Kieffer TJ, Rader D, Heinman M, Townsend RR, Keim NL, D’Alessio DA, Havel PJ. Dietary fructose reduces circulating insulin and leptin, attenuated postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab 2004;2963-2972

6. Tounian P, Schneiter P, Henry S, Jequier E, Tappy L. Effects of infused fructose on endogenous glucose production. Am J Physiol Endocrinol Metab 1994;267:E710-E717.

7. Chong MF, Fielding BA, Frayn KN. Mechanisms for the acute effect of fructose on postprandial lipemia. Arthritis Rheum 2008;59:109-118.

8. McDevitt RM, Bott SJ, Harding M, Coward WA, Bluck LJ, Prentice AM. De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women. Am J Clin Nutri 2001;74:369-377.

9. Parks EJ, Skokan LE, Timlin MT, Dingfelder CS. Dietary sugars stimulate fatty acid synthesis in adults. J Nutr 2008;138:1039-1046.

10. Bantle JP, Raatz SK, Thomas W, Georgopolous A. Effects of dietary fructose on plasma lipids in healthy subjects. Am J Clin Nutr 2000;72:1128-34.

11. Foster-Powell K, Miller JB. International tables of glycemic index. Am J Clin Nutr 1995;62:871S-890S.

12. Stanhope KL, Griffen SC, Bair BR, Swarbrick MM, Keim NL, Havel PJ. Twenty-four-hour endocrine and metabolic profiles following consumption of high fructose corn sysrup-, corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals. Am J Clin Nutr 2008; 87:1194-203.

13. Soenen S, Westerterp-Plantenga MS. No differences in satiety or energy intake after high-fructose corn syrup, sucrose, or milk preloads. Am J Clin Nutr 2007; 86:1586-94.

14. Melanson KJ, Zukley L, Lowndes J, Nguyen V, Angelopoulos TJ, Rippe JM. Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on apetite in normal-weight women. Nutrition 2007; 23: 103-112.

15. Monsivais P, Perrigue MM, Drewnowski A. Sugars and satiety: does the type of sweetener make a difference? Am J Clin Nutr 2007; 86: 116-23.

16. Melanson KJ, Angelopoulos TJ, Nguyen V, Zukley L, Lowndes J, Rippe A. High-fructose corn syrup, energy intake, and appetite regulation. Am J Clin Nutr 2008; 88(suppl): 1738S-44S.

17. Spitzer L, Rodin J. Effects of fructose and glucose preloads on subsequent food intake. Appetite 1987 Apr;8(2):135-45.

18. Rodin J, Reed D, Jamner L. Metabolic effects of fructose and glucose: implications for food intake. Am J Clin Nutr 1988 Apr;47(4):683–9.

19. Rodin J. Comparative effects of fructose, aspartame, glucose and water preloads on calorie and macronutrient intake. Am J Clin Nutr 1990;51:428–35.

20. Rodin J. Effects of pure sugar versus mixed starch fructose loads on food intake. Appetite 1991;17:213–9.

21. Moran TH. Fructose and satiety. J Nutr. 2009 Jun;139(6):1253S-1256S. Epub 2009 Apr 29.

22. Schwarz JM, Schutz Y, Piolino V, Schneider H, Felber JP, Jequier E. Thermogenesis in obese women: effect of fructose vs. glucose added to a meal. Am J Physiol. 1992; 262: 394-401.

23. Schwarz JM, Schutz Y, Froidevaux F, Acheson KJ, Jeanprêtre N, Schneider H, Felber JP, Jéquier E. Thermogenesis in men and women induced by fructose vs. glucose added to a meal. Am J Clin Nutr ; 49(4): 667-74.

24. Simonson DC, Tappy L, Jequier E, Felber JP, DeFronzo RA. Normalization of carbohydrate-induced thermogenesis by fructose in insulin-resistant states. Am J Physiol 1988; 254: 201-7.

25. Blaak EE, Saris WH. Postprandial thermogenesis and substrate utilization after ingestion of different dietary carbohydrates. Metabolism: clinical and experimental 1996; 45: 1235-42.

26. Livesy G. Fructose ingestion: dose-dependent responses in health research. J Nutr 2009 Jun;139(6):1246S-1252S.

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4 Responses to High-fructose Corn Syrup: Obesogenic Evil or Dietary Scapegoat, Part 2

  1. James says:

    Hi Dylan, great blog. Could you comment on the effect of simple sugars in the diet and the overall link to mortality beyond contributing to obesity, perhaps linked to insulin sensitivity and/or inflammatory pathways? (e.g. the science behind the recent WHO recommendation to cut sugar intake to 5% of calories, and the discussion a few years ago whether Alzheimer’s should be considered type-3 diabetes). The main question I am asking is whether fit, healthy people can still cause themselves harm by “normal” sugar intake, due to innate biochemical mechanisms, and whether we should try to consume as little sugar as possible.

    • decline104 says:

      James,

      Thanks for your thoughtful response. Your question is quite complex, but I will try to answer it as concisely as possible.

      To my knowledge, the upcoming WHO guidelines about sugar consumption are based on a meta-analysis that looked at the effect of dietary sugars on body weight. As I have commented in other posts, there is nothing inherently obesogenic about sugar – a finding that is echoed in the meta-analysis. To quote the article’s conclusion:

      “Among free living people involving ad libitum diets, intake of free sugars or sugar sweetened beverages is a determinant of body weight. The change in body fatness that occurs with modifying intakes seems to be mediated via changes in energy intakes, since isoenergetic exchange of sugars with other carbohydrates was not associated with weight change.”

      Rather, it is the vehicle with which sugar is consumed that is the real problem – e.g. sugar-sweetened beverages like soda, juices and the like. Simply put; it’s easy to down a liter of sugar-laden Cola and not even realize (or physiologically be able to compensate for) the hundreds of excess calories just consumed.

      In response to your questions about sugars and insulin resistance (IR)/inflammation, sugars do not cause these symptoms. Rather, they are products of genetics coupled with excess weight gain (i.e. increased fat mass due to hypercaloric diet) and a sedentary lifestyle. Once IR is established, sugars can only worsen the situation by putting an unnecessary stress on the pancreas to put out more insulin. If this is continued for years on end, by way of a poor diet, the pancreas eventually fails and is unable to keep up with the necessary insulin production. Moreover, peripheral tissues, esp. muscle and liver, become resistant to the insulin that is produced (the causes of which are not yet completely understood). This is where the notion of AD being called T3D came from. There appears to be insulin resistance in the brain, similar to what is seen in muscle and liver, that leads to the progression of AD. I’ll point you to a 2008 review paper on the topic: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/

      Moreover, there is also amyloid build up in the pancreas (due to IR and overproduction of inuslin) which leads to beta-cell death and the need for insulin injections in poorly controlled T2DM. This is similar to the amyloid plaques that form in the brain during AD. This just illustrates the similarities between the two diseases.

      To answer your final question, I don’t think there is anything intrinsically harmful about sugar at reasonable intakes for a healthy, active population. However, once you throw bad genetics, weight gain and inactivity into the mix, you set the stage for a whole host of health maladies. That is to say, unhealthy people should be more concerned with added sugars than healthy, insulin sensitive persons.

      I hope this answered your questions!

      • James says:

        Thanks for the quick and thorough response. To clarify and expand on one point, is there anything to the widely asserted ‘fact’ that ‘sugar causes inflammation’, which is usually stated alongside ‘chronic inflammation contributes to everything from cancer to CHD’? I understand that sugars can contribute to obesity and affect insulin resistance, but there is a belief that there is an additional unspecified pro-inflammatory mechanism by which they cause harm. Is ‘diet-induced chronic inflammation’ a medically-accepted phenomenon outside the internet? Thanks again!

  2. decline104 says:

    James,
    As far as sugar causing inflammation etc. I wouldn’t worry too much. Here is a recent review on the topic.
    http://ajcn.nutrition.org/content/99/4/813.abstract

    A lot of people get caught up in thinking that inflammation ’causes’ disease, but in reality it’s really hard to say – does it truly ’cause’ disease or is it accompanying and/or a product of the disease itself? Things aren’t so black and white.

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