Glucose vs. Fructose and Their Effects on Glucose, Insulin & Fat Oxidation in Men on Both Ends of the BMI Spectrum

"Fructose handles"? "Glucose handles"? "Saturated fat handles"? No, just the net result of a trashy diet.

I don't have to tell you that I don't buy into the "fructose is the devil" hysteria that's rampant in the blogosphere and certain parts of the scientific community. It's a matter of quantity and quality that determines the toxicity of a poison and in most of the "convincing" evidence on the detrimental effects fructose. I mean let's be honest, you don't have to be a rocket scientists to figure out that 5+ cans of Coke a day cannot be good for you (cf. "Fat Content Per Energy Drink 0g, Body Fat Gain Per Energy Drink 18g!"; read more) "194 Bananas in Three Weeks", on the other hand, are nothing to be afraid of (learn why).Have we been fooled again or is it just a high fructose corn syrup producer conspiracy?

Enough of the rants, let's get to the facts!

I guess that's enough for the "ranty" introduction. Let's now have a look at what a group of researchers from the School of Medicine in Portland has in stock for us: It's a paper titled "Change in postprandial substrate oxidation after a highfructose meal is related to body mass index in healthy men" that's about to be published in one of the future installments of Nutrition Research. As you will by now probably have figured out, the Anne C. Smeraglio and her colleagues had two things in mind, when they came up with the protocol that involved

• What did the subjects eat? Participants were fed an egg omelet, bagel with cream cheese, and sweetened beverage breakfast consisting of one-third of their estimated daily caloric. The meal consisted of 30% fat, 15% protein, and 55% CHO (as % of energy). The CHO energy was further divided into complex and simple CHOs; 25% of the total calories were from complex CHOs and 30% of the calories were from either glucose or fructose added to the beverage.
  12 healthy men without diabetes, with a mean age of 25 (23-31) years and a BMI less than 30 kg/m²,
• 2 visits at their labs that were separated by at least 1 week, but less than 1 month,
• two meals that were high in glucose or fructose which were served in random order as a breakfast after an overnight fast, and
• fasting for 7h after the ingestion of the standardized breakfast (sitting around watching TV or performing other, non-exciting quiet activities without the propensity to produce a catecholamine response)

During the experiment, the oxygen consumption and CO2 production were measured by indirect calorimetry to calculate resting energy expenditure and respiratory quotient (RQ; high RQ = burning predominantly glucose, low burning predominantly fat). The scientists also took blood samples at pre-defined intervals and collected the urine of their participants.

Figure 1: Insulin and glucose levels, as well as non protein respiratory quotient (high = carb oxidation; low = fat oxidation) 0-7h after the fructose and glucose breakfasts (Smeraglio. 2013)

The data in figure 1 is a summary of the the most "significant" results. In that the "quotation marks" enclosing the word "significant" is in my humble opinion the most significant information here - one that's encoded with irony, because after all, the only statistically significant effect the scientists observed were the ~2.5x higher insulin levels in the glucose group 60min after the ingestion of the test meal... yep, that's in the glucose group.

"There must be a mistake here!? Fructose is bad for you!"

The scientists have really done their homework as they did even take into account whether or not the amount of protein in the meals would have been responsible for differences in the respiratory quotient. The latter was not the case, the "baseline RQs between the fructose and glucose study visits were equivalent (0.82 ± 0.08 and 0.81 ± 0.10, respectively) and the p-value, indicating that there was a difference even rose from 0.72 to 0.75, when "when protein use was accounted for by evaluating NPRQ [non-protein respiratory quotient]" (Smeraglio. 2013)

Surprised? Well, I guess over all the lustig (=German for "funny") and unwarranted hoopla about how bad even small amounts of fructose are, you must have forgotten why scientists believed not too long ago that fructose could be the solution to, not the cause of the diabesity epidemic. After all, the paradigm of the mid to late 20th century was: Fructose does not spike glucose, so it should be the ideal sweetener for diabetics, because it is not necessary that your pancreas produces insulin to get rid of it.

I will not have to tell you, though that this assumption and the corresponding notion that totally replacing glucose with fructose would be a great idea is about as unwarranted, as the current fear of the "toxicity" of the small amounts fructose contained you'll be exposed to from a couple of pieces of fruit. I mean, let's take a peek at the data again.

Compared to the same amount of glucose, the consumption of the fructose equivalent of 5-6 medium sized (185g) apples (50-70g fructose, which is the amount of fructose the subjects in the study consumed) produces lower insulin levels and does not change either the leptin, triglyceride or glucose concentration in the blood or the ratio of glucose to fatty acid oxidation in healthy non-obese volunteers...

...apropos, non-obese, there was another thing to the headline wasn't there?

You are absolutely right, the research question involved (a) finding out what happens if you ingest a realistic breakfast where the carbohydrate content comes from (i) glucose or (ii) fructose and (b) determining whether the reaction would depend on the body weight / height² (BMI) ratio of the participants. So what about that, then? Let's see...

Did you know that there is a catalytic dose of ~40g of fructose per day (=6 normal size bananas) that will improve your glucose metabolism? (learn more)

"Although the absolute values for fat and CHO oxidation were not different between the fructose and glucose study visits, we did find a correlation between BMI and change in fat oxidation as a result of consuming the high-fructose meal compared with the high-glucose meal. The difference in fat oxidation (fat oxidation after the fructose meal minus fat oxidation after the glucose meal) was negatively correlated with BMI at the 4- and 7-hour time-points (Fig. 3; r =−0.59 [P= .04] andr=−0.59 [P= .04] for 4- and 7-hour time points, respectively) but not the 1-hour time point (Fig. 3; r=−0.52, P< .09). Nonprotein RQ displayed these same trends but did not reach significance." (Smeraglio. 2013)

As the scientists rightly point out, this suggests that the postprandial fat oxidation after the fructose meal was less than the fat oxidation after the glucose meal only among subjects with a higher BMI, and that the correlation with body weight, but not the difference itself was statistical significant.

Figure 2: Correlation of BMI with change in fat oxidation pearson correlation with linear regression trend lines between BMI and change in fat oxidation (fat oxidation after the fructose study visit minus fat oxidation after the glucose study visit; Smeraglio. 2013)

What's more, if you take a peek at the linear regression in the graph on the right hand side (figure 2) you will realize that that this does also mean that the fatty acid oxidation in lean individuals is actually increased after the ingestion of fructose. If I intended to drive my message "fructose from real foods is not your problem, folks!" home at all costs (which is what the "fructose is the devil" advocates like to do), I could seize on this observation and tell you: "Look folks, as long as you are already lean fructose will help, not impair your effort to get ridiculously shredded." I would yet hope that you are clever enough to see through this tactics and realize that neither the effect on the left hand side (=more fatty acid oxidation in the leaner folks with fructose vs. glucose), nor the one on the right hand side of figure 2 is physiologically relevant.

And that's not just because it's simply too small, but also because the ratio of glucose to fatty acid oxidation, i.e. the respiratory quotient (RQ) is not determining whether you store or lose body fat - if it were, you'd better be training in the "fat burning zone" for the rest of your (in that case) miserable lives.

---

Figure 3: Adding 7.5g of fructose ( to a 75g glucose load will improve not detoriate the glucose metabolism and that without increasing the amount of insulin that's released in response to the glucose load (Moore. 2000)

Bottom line: I am confident that that even without resorting to extreme interpretations of cherry picked data, the main message of today's article is clear. The comparatively small amounts of fructose you'll get right with the appropriate polyphenols & other cofactors from fruit and other fructose containing whole foods in your diet is not your enemy (Other items? Yeah, you know that even onions have 2g fructose, right?).

On a related note, you are aware that small amounts of fructose, like the 7.5g of fructose scientists added to the 75 g of glucose their 11 healthy subjects ingested during an oral glucose tolerance test had an up to 31% lower glucose response (these were the values for the 6 subjects with the highest level on the regular test) in the absence of concomitant increases in insulin response (see figure 3; Moore. 2000)!? You did not know that? Well, I guess it was about time to take a mental note, then ;-)

References:

• Moore MC, Cherrington AD, Mann SL, Davis SN. Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults. J Clin Endocrinol Metab. 2000 Dec;85(12):4515-9. 
• Smeraglio AC, et al. Change in postprandial substrate oxidation after a high-fructose meal is related to body mass index in healthy men. Nutr Res.2013 [epub ahead of print]

30 Min of Exercise Can Avoid Costly & Unhealthy Gestational Diabetes. Carbohydrate Oxydation Determines Appetite After Workouts. Using a Measuring Tape to Judge Visceral Fat Mass. Update: Vitamin D, Age & Obesity.

85 sessions (general fitness class, three times/week, 55-60 min/session from weeks 8-10 to weeks 38-39 of pregnancy are nothing but healthy for mother + child (Barakat. 2013)

Obese mothers with gestational diabetes are more than just a financial burden. That's what the SuppVersity Figures of the Week clearly indicate.

According to a recently published paper from the National University of Ireland Galway woman who develop gestational diabetes during pregnancy (mostly due to pre-existing extra fat-pounds; not BMI), produce 34% higher health-care costs (Gillespie. 2013). Just as the 75% increase in the necessity to have the kids being delivered by cesarean section, this would still be tolerable, though, if their poor offspring did not also have a increased risk of being born with pathological ventricular hypertrophy (Ullmo. 2007) and a 214% higher likelihood of having to be admitted to the neonatal unit, which, in turn, is associated with "increased and/or aberrant adiposity, in addition to postnatal growth retardation" (Gianni. 2012).

Another good reason to (a) get healthy (and contrary to what the soothing news in the mainstream media will tell you this involves having normal body fat levels), before you even think of bringing a baby into this world and (b) not dropping your exercise regimen all-together, when you're pregnant:

 "A supervised program of moderate exercise performed throughout pregnancy is not a risk of preterm delivery for heal thy pregnant women." (Barakat. 2013) 

This, by the way, works not only in type II, but also type I diabetic mothers, whose chance of developing gestational diabetes and/or even more hazardous extreme spikes and troughs in blood glucose can be reduced from 19% to ZERO with only 30 min of light exercise per day (a self-paced walk in the park is enough!) and making the right food choices (Kumareswaran. 2013).

• Related D-News from Japan: Vitamin D deficiency in Japan comes with current smoking, being female, lack of regular walking and low dietary vitamin D intake, study shows (Yoshimura. 2013).
  

  Overall, 81.3% of the subjects in the study from the University of Tokyo were vitamin D insufficient - only 1.2%, though, had a full-blown deficiency, defined as 25OHD levels below 10 ng/ml.
  Being fat is a critical determinant of baseline vitamin D levels and the response to vitamin D supplement in older Irish adults (Forsythe. 2013).

  "In older adults, vitamin D status was inversely associated with BMI (kg/m2), WC (cm), FM (kg and %), FMI (kg/m2) and FM:FFM (%) at baseline (r − 0·33, − 0·36, − 0·33, − 0·30, − 0·33 and − 0·27, respectively, all P values < 0·01). BMI in older adults was also negatively associated with the change in 25(OH)D following supplementation (β − 1·27, CI − 2·37, − 0·16, P = 0·026)."

  What's surprising, though, is the fact that this correlation of which I have previously argued that is is probably based on the pro- and anti-inflammatory effects of obesity and vitamin D and initiated by being fat, not vitamin D deficient, was not present in the younger study participants.
  
  Just as a review I mentioned only a couple of days ago said: There is still much to learn about vitamin D - in that case D2 & D3 - and how their enzymatic hydroxylation influences both our baseline levels as well as their metabolic downstream effects (read more)

• Exercise does not make you hungry, per se, but the more carbs you burn during your workout the hungrier you're gonna be afterwards (Hopkins. 2013) That's the main finding of a recent study from the Leeds Trinity University in the UK.
  
  

  

  There comes a time, when getting fat and sick is no longer only about making the "wrong" food choices or a non-warranted urge to eat. A time, when neither the apple nor granny's pie will satisfy your hunger, and your cells will be starving within a nutritious cocktail of partially oxidized fatty acids and sticky glucose molecules... yet still, or I should say, exactly for that reason simply "cutting calories" won't solve the problem. Learn more about how this state is creeping up on the obesity generation (read more)

  According to the data the researchers gathered in the course of a bout of cycling individually tailored to expend 400 kcal (EX) or a time-matched no exercise control condition in a randomized, counter-balanced order,
  

  "[...] there was a marked individual variability in compensatory EI. The difference in EI between EX and the control condition ranged from -234.3 to 278.5 kcal. Carbohydrate oxidation during exercise was positively associated with postexercise EI, accounting for 37% of the variance in EI (r=0.57; p=0.02)" (Hopkins. 2013)

  That's particularly interesting, because the average total energy intake did not differ significantly between the exercise and the control condition (666.0±203.9 vs 664.6±174.4 kcal, respectively) in the overweight and obese women with a mean BMI of 29.6±4.0 kg/m².
  
  These observations provide further evidence of the detrimental effects of metabolic inflexibility, a classic characteristic of developing or full-blown metabolic syndrome and a state in which your body is heavily (in the worse cases almost exclusively) reliant on glucose as a substrate - a paradox, in view of the fact that thee aberrant insulin resistance of obese individuals has their cells starve in a state of glucose abundance (learn more)

• Toss your scale and use a measuring tape! Nothing predicts metabolic risk and high risk visceral fat as adequately as the circumference of your midsection (Grundy. 2013)
  
  As a SuppVersity reader you should actually have banned your scale into the depth of your "things I will never need again (!)"-cupboard, once you achieved a normal body weight (on a side note: I don't have a functional scale). From the many questions I receive on a daily basis, I do yet know that some of you are either hesitant to do that or fill inclined to get it back out from time to time to ruin their days and results by stepping on the scale at least thrice a week. If that's you, I suggest you take a peak at the results of a recent study from the Clinical Nutrition and Center for Human Nutrition and the Division of Cardiology of the University of Texas Southwestern Medical Center in Dallas.
  
  To find out whether or not a simple measuring tape by the means of which you would assess the circumference of your waist (WC) would be an adequate measure of total abdominal fat (TAF), abdominal subcutaneous fat (ASF) and intraperitoneal fat (IPF) Scott M. Grundy and his colleagues correlated the measuring tape data with results they had obtained from magnetic resonance imaging (MRI) and found an excellent correlation between WC and total abdominal fat (R² = 0.81 − 0.88) "with progressively lower correlations with ASF (0.65–0.82) and IPF (0.29–0.85)" (Grundy. 2013)
  

  

  Figure 1: Median intra-abdominal fat (median in kg), waist circumferences and corresponding intraperitoneal to total abdominal fat rario (IP/ABS x10) for quintile 1-5 of total abdominal fat in men (left) and women (Gruny. 2013)

  As hinted at in the arrow in figure 1 the accuracy of the waist circumference as a means to quantify the body fat levels and metabolic risk does not only depend on gender, but also on ethnicity, with African American men and women having lower median IPF masses than Whites and Hispanics, in general, but high(er) greater amounts of subcutaneous. In view of the fact that unlike IPF, ASF correlated only with HOMA2-IR, whereas elevated IPF values were also reliable predictor of high triglyceride levels, as well - African Americans may be at a slightly, but probably not significantly lower risk of developing heart disease (high triglycerides are a neat predictor here) than Whites and Hispanics of whom the latter tend to carry the most vicious visceral fat per cm on their waists.

Believe it or not, but that's it for today! I know that was fast and therefore I'll provide you with a couple of additional facebook news, you may be interested in.

• 

  The fact that simply dropping the weight and lying around for weeks could lead to fat gains is actually not that surprising right? So what can be done to make constant progress without overtaxing the system? One of the answers certainly is P-E-R-I-O-D-I-Z-A-T-I-O-N and the Step By Step Guide to Your Own Workout Routine is the series, where you can learn about planning your training schedule in the long and short run to maximize your results and accommodate it to your personal goals (read more)

  Is giving up physical culture worse for your health than being a sedentary slob in the first place Rodent study suggests there is propensity for increases in visceral fat gain during 4-week detraining that surpasses in previously trained rats that of the sedentary controlled (read more)
• Fooled again 2.0: By one way or another Subway bamboozles customers to believe their junkfood was less junky than that of the competition. According to a recent Harvard study, adolescents dining at Subway underestimate the caloric value of their nutrient deficient junk food by more than 500kcal! That's... (read more)
• The "starve yourself to live longer"-bubble is bursting! Now scientists realize that even in yeast, what you eat is more important than how much you eat and that the simple addition of a pH buffer can go a long way (read more)
   
• SuppVersity Suggested Read: Prolotheraphy? Can you actually HEAL those chronically painful tendons, ligaments and cartilage without having to resort to a butcher's... ah, I mean a surgeon's knife? My buddy Sean Casey just posted part II of his scientifically grounded answer (read more).

Now that you're through with these as well, all that's left to be said is: "Have a nice weekend, everyone, and don't forget that the SuppVersity is open on Sundays, as well!"

References:

• Barakat R, Pelaez M, Montejo R, Refoyo I, Coteron J. Exercise Throughout Pregnancy Does Not Cause Preterm Delivery. A Randomized, Controlled Trial. J Phys Act Health. 2013 May 10.
• Forsythe LK, Livingstone MB, Barnes MS, Horigan G, McSorley EM, Bonham MP, Magee PJ, Hill TR, Lucey AJ, Cashman KD, Kiely M, Strain JJ, Wallace JM. Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults. Br J Nutr. 2012 Jan;107(1):126-34. 
• Giannì ML, Roggero P, Piemontese P, Orsi A, Amato O, Taroni F, Liotto N, Morlacchi L, Mosca F. Body composition in newborn infants: 5-year experience in an Italian neonatal intensive care unit. Early Hum Dev. 2012 Mar;88 Suppl 1:S13-7.
• Gillespie P, Cullinan J, O'Neill C, Dunne F; ATLANTIC DIP Collaborators. Modeling the independent effects of gestational diabetes mellitus on maternity care and costs. Diabetes Care. 2013 May;36(5):1111-6. 
• Kumareswaran K, Elleri D, Allen JM, Caldwell K, Westgate K, Brage S, Raymond-Barker P, Nodale M, Wilinska ME, Amiel SA, Hovorka R, Murphy HR. Physical Activity Energy Expenditure and Glucose Control in Pregnant Women With Type 1 Diabetes: Is 30 minutes of daily exercise enough? Diabetes Care. 2013 May;36(5):1095-101. 
• Ullmo S, Vial Y, Di Bernardo S, Roth-Kleiner M, Mivelaz Y, Sekarski N, Ruiz J, Meijboom EJ. Pathologic ventricular hypertrophy in the offspring of diabetic mothers: a retrospective study. Eur Heart J. 2007 Jun;28(11):1319-25.
• Yoshimura N, Muraki S, Oka H, Morita M, Yamada H, Tanaka S, Kawaguchi H, Nakamura K, Akune T. Profiles of vitamin D insufficiency and deficiency in Japanese men and women: association with biological, environmental, and nutritional factors and coexisting disorders: the ROAD study. Osteoporos Int. 2013 May 15.