Caffeine By Afrida: 6x Bananas a Day!? Meta-Analysis: Lower Glucose, Insulin and HbA1c Levels From 'Catalytic' Dose of 36g Fructose

Figure 1: At least according to the USDA data, the average US citizen did never in the last 40 years get even close to the "catalytic" dose of fructose - at least not if we go by his / her daily HFCS consumption.

I usually don't start these articles with a disclaimer, but in this case I want to make sure that this post is not misinterpreted as a corn-refiners advertisement (and contrary to one of the authors of the Sievenpiper study, Coca Cola has unfortunately as of yet never covered my travel expenses ;-)... anyways, whenever the word "fructose" is used in the following lines it to the simple monosaccharide found as part of a complex nutrient matrix in many plants and their fruits (who would have expected that?). It is not used to denote the controversial results of a three-step enzymatic isolation process (Cornstarch → alpha-amylase → oligosaccharides + glucoamylase → glucose + xylose isomerase → 42% fructose + 50–52% glucose + other sugar; cf. Wikipedia. "High Fructose Corn Syrup") that's at the heart of a very emotional debate about who would be to blame for the current obesity epidemic, now that the bad fats are no longer bad enough to be the scapegoat and ultima ratio for why we get fat.

Junk food is more than HFCS and fruit is more than fructose!

Fortunately, you, as a "whole food eating" SuppVersity reader, don't really have to care about the whole HFCS business. With your minimal intake of processed foods, your exposure to high fructose corn syrup should ideally be identical to the one of the parents and grandparents of America's obese children in the flower power seventies (~0.1-1g, see figure 1); a time, when your parents would not tell you to "beware of high fructose corn syrup", but to stay away from "those hairy, drug-addicted, reprobate hippies next door". Against that background, today's SuppVersity article is to be understood as an incentive to rethink, whether or not it is really necessary, let alone beneficial to deprive yourself of a whole class of vitamin and micronutrient-laden foods, simply because they contain a small number of molecules of which you are told that they "must not to be eaten, if you want to stay lean & healthy".

To help your thought process along, I have compiled the data from a recently published meta-analysis (that's a study, the results of which are based on data from multiple previous trials, which was weighed and compiled to come up with "new" data with a larger empirical foundation and thus greater significance). And I am honestly curious whether or not the evidence Sievenpiper and his colleagues presented in favor of the existence of a"catalytic dose" of ≤36g/day of fructose that's been shown to improve, not compromise, blood glucose, insulin and HBA1C, when it is consumed instead of 36g of carbs from other sources (the studies in the review used either starches or simple sugars with almost identical beneficial results, by the way) will have catalytic effects on your opinion making process ;-)

Figure 2: Effect of isoenergetic exchange of "catalytic" fructose doses (≤36g/d) for other carbohydrates (starches or simple sugars) on glycaemic endpoints: HbA1c, fasting blood glucose and fasting blood insulin, data calculated based on analysis of the scarce literature that is currently available (adapted from Sievenpiper. 2012)

The improvements in HbA1C, which is still the gold standard for evaluating long-term blood sugar level, in fasting blood glucose and insulin levels were across the board statistically significant, regardless of whether or not you apply the quality criteria, Sievenpiper and his colleagues used to weigh the results of the individual studies (cf. figure 2). Accordingly, the authors are right, when they point out that

[...] this small meta-analysis of controlled feeding trials supports earlier13C NMR spectroscopy investigations and acute feeding studies showing that ‘catalytic’ doses (≤36g/d) of fructose may improve glycaemic control [and that this] benefit is seen without the adverse cardiometabolic effects reported when fructose is fed at high doses or as excessenergy. (Sievenpiper. 2012)

Based on the data in figure 1, which clearly shows that the "average American" does not and never did pass this "catalytic threshold level" it may - at first sight appear odd that 42% of your countrymen and -women are supposed to be obese by the year 2030 (Hellmich. 2012)... at least for so long until you realize that for every American who follows your lead and consumes virtually no HFCS, there must be another one who consumes this person's 43.3g of HFCS on top of his own 43.3g of HFCS on a daily basis and would thus easily surpass the "scientifically proven" catalytic threshold levels which was (and I leave it up to you to decide whether this is coincidence or not) in none of the studies achieved from HFCS intake, by the way (I guess I don't have to tell you that my calculation is of mere illustrative nature, despite the fact that the 43.3g /day HFCS intake are actually from the USDA dataset for 2010).

Bad news for the guy who eats / drinks your daily share of 43.3g of high fructose corn syrup, ...

...but what does that mean for you? As long as your only significant fructose source are whole fruits and the few vegetables that contain more than trace amounts of fructose, you can answer this question by taking a look at the data in figure 3. The small figures on top of the bars will tell you how many 100g servings of apples, dates, pears or tomatoes you can consume until you hit the catalytic limit*uhuhhh...*: 3.9x 100g servings, of apples, for examples, or 5x 100g servings of bananas, or a whopping 32.7x 100g servings of lemons... sounds plenty? Well, I don't know, but certainly plenty enough to finally stop worrying when Adelfo Cerame would not ruin his health, let alone his physique, when he eats a banana along with his postworkout shake, wouldn't you agree?

Figure 3: Number of 100g servings of various common fruits to get to the more or less arbitrary ≤36g/day threshold.

Notwithstanding, this ≤36g/day limit does certainly appears more or less arbitrary. This is all the more true in face of previous results by Livesey & Taylor, who could not find evidence that such a thing as a "threshold dosage" for the Hb1AC improving effects of fructose even exists (Livesey. 2008) or the fact that a "low-GI fruit intake [and not the number of servings of fiber-laden cereals!] was the strongest independent predictor of [lowered] HbA1c" in a 2011 6-months low-GI diet experiment by Jenkins et al. who compared Kellog's... ah, pardon me, I meant the medical orthodoxy's gold standard, the high-cereal fiber diet in 152 participants with type 2 diabetes with a simple low-GI diet (Jenkins. 2011).

Can ≤35g of fructose per day really be the answer to everything?

Though the main reason for the arbitrariness of the 36g limit certainly is the scarcity of valid experimental data from well-controlled human trials, Sievenpieper et al. claim that their reference for the "catalytic range" was in accordance with "an emerging literature" that "has shown that low-dose fructose (≤10g/meal) may benefit glycaemic control".

Now, those of you who have read my "Carbohydrate Shortage in Paleo Land" post from back in June 2011, will probably remember that from a mere physiological point of view every healthy (=nondiabetic and with an intact liver) human being, including the tiniest woman, should be able to handle a minimum of ~100g of carbohydrates on a daily basis. If we now take the 2:1 glucose to fructose ratio, of which Walliset al. found that it is just as effective in repleting muscle gylcogen stores after a workout as the same amount (90g) of pure glucose, and apply it to the 36g fructose threshold this yields a "total carbohydrate threshold" of 108g - coincidence or physiological necessity?

And even when you didn't replace some of the starches or other simple sugars for your daily dose of 2kg of apples (another example of exclusively illustrative nature), you would maybe get fatter, but according to the results of Silbernagel et al. not a single gram fatter than from the same amounts of calories from glucose from fructose or glucose conducted with healthy young men; cf. Silbernagel. 2011).

You can have another apple today and will still (or rather hence?) live tomorrow ;-)

Image 3 (edited in response to anon & JP, thx!): Certainly impressive what lifelong caloric restriction did to the 27.6 year-old ape on the right, if you take a look at his wrinkled age-mate on the left, no? Suggested read: "Health and Longevity Effects of Intermittent Fasting"

Overall it does therefore seem more than unlikely that a healthy, non-sedentary or even athletic individual has to worry about eating another apple, when he or she already reached their purported catalytic limit of 36g with the pound of blackberries, two bananas and a huge grapefruit this person could have eaten earlier in the day.

Moreover, skipping on the apple would also mean that you would miss out on its recently confirmed life-extending effects (+130% in yeast; Palermo. 2012), of which Vanessa Palermo and her colleagues from the Dept. of Biology and Biotechnology “Charles Darwin” have shown that they are the prerogative of the whole fruit and not a result of the high antioxidant or polyphenol content of apples, as they occurred only, when the yeast is treated with a handcrafted extract that had approximately 26.7 g/100ml of fresh apple in it... and guess what, that apple, Golden Delicicious, happens to be one of my personal favorites, taste-wise, or course ;-)

Bottom line: I know it is more than questionable to which extend (1:20, 1:100, not at all?) the lastly cited life-prolonging effects of whole apples can be extrapolated to human beings, but that does neither diminish the perplexing results of Sivenpiper's meta-analysis nor long-established cancer protective effects of fruits in general and apples in particular (eg. Veeriah. 2006; McCann. 2007; Yoon, 2007; Gerhauser. 2008; Zessner. 2008; Jedrychowsk. 2009; Liu. 2010; Reagan-Shaw. 2010) and should therefore suffice to put more than a non-legible font-size "1" questionmark behind any previously taken decision of yours that it would be better to deprive yourself of these delicious superfoods (=fruits) than trust on your livers ability to to what she has evolved to do and turn the slow influx of relatively low amounts of fructose and glucose into energy and deliver the rest of the vitamins, polyphenols, and other micronutrients via the bloodstream to other organs.

References:

Gerhauser C. Cancer chemopreventive potential of apples, apple juice, and apple components. Planta Med. 2008 Oct;74(13):1608-24. Epub 2008 Oct 14. Review.
Hellmich J. Obesity could affect 42% of Americans by 2030. USA TODAY. Aug 05, 2012 < http://www.usatoday.com/news/health/story/2012-05-07/obesity-projections-adults/54791430/1 > accessed Aug 07, 2012
Jandrain BJ, Pallikarakis N, Normand S, Pirnay F, Lacroix M, Mosora F, Pachiaudi C, Gautier JF, Scheen AJ, Riou JP, et al. Fructose utilization during exercise in men: rapid conversion of ingested fructose to circulating glucose. J Appl Physiol. 1993 May;74(5):2146-54.
Jedrychowski W, Maugeri U. An apple a day may hold colorectal cancer at bay: recent evidence from a case-control study. Rev Environ Health. 2009
Jenkins DJ, Srichaikul K, Kendall CW, Sievenpiper JL, Abdulnour S, Mirrahimi A, Meneses C, Nishi S, He X, Lee S, So YT, Esfahani A, Mitchell S, Parker TL, Vidgen E, Josse RG, Leiter LA. The relation of low glycaemic index fruit consumption to glycaemic control and risk factors for coronary heart disease in type 2 diabetes. Diabetologia. 2011 Feb;54(2):271-9.
Livesey G, Taylor R. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am J Clin Nutr. 2008; 88, 1419–1437.
Liu L, Li YH, Niu YB, Sun Y, Guo ZJ, Li Q, Li C, Feng J, Cao SS, Mei QB. An apple oligogalactan prevents against inflammation and carcinogenesis by targeting LPS/TLR4/NF-κB pathway in a mouse model of colitis-associated colon cancer. Carcinogenesis. 2010 Oct;31(10):1822-32.
McCann MJ, Gill CI, O' Brien G, Rao JR, McRoberts WC, Hughes P, McEntee R, Rowland IR. Anti-cancer properties of phenolics from apple waste on colon carcinogenesis in vitro. Food Chem Toxicol. 2007 Jul;45(7):1224-30.
Reagan-Shaw S, Eggert D, Mukhtar H, Ahmad N. Antiproliferative effects of apple peel extract against cancer cells. Nutr Cancer. 2010;62(4):517-24.
Palermo V, Mattiv, F, Silvestri R, La Regina G, Falcone CM. Oxidative Medicine and Cellular Longevity. 2012 [Article in press]
Sievenpiper JL, Chiavaroli L, de Souza RJ, Mirrahimi A, Cozma AI, Ha V, Wang DD, Yu ME, Carleton AJ, Beyene J, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Kendall CW, Jenkins DJ. 'Catalytic' doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials. Br J Nutr. 2012 Aug;108(3):418-23.
Silbernagel G, Machann J, Unmuth S, Schick F, Stefan N, Häring HU, Fritsche A.Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. Br J Nutr. 2011 Jul;106(1):79-86.
Veeriah S, Kautenburger T, Habermann N, Sauer J, Dietrich H, Will F, Pool-Zobel BL. Apple flavonoids inhibit growth of HT29 human colon cancer cells and modulate expression of genes involved in the biotransformation of xenobiotics. Mol Carcinog. 2006 Mar;45(3):164-74.
Wallis GA, Hulston CJ, Mann CH, Roper HP, Tipton KD, Jeukendrup AE. Postexercise muscle glycogen synthesis with combined glucose and fructose ingestion. Med Sci Sports Exerc. 2008 Oct;40(10):1789-94.
Wikipedia contributors, "High-fructose corn syrup," Wikipedia, The Free Encyclopedia, < http://en.wikipedia.org/w/index.php?title=High-fructose_corn_syrup&oldid=505539604 > accessed August 7, 2012.
Yoon H, Liu RH. Effect of selected phytochemicals and apple extracts on NF-kappaB activation in human breast cancer MCF-7 cells. J Agric Food Chem. 2007 Apr 18;55(8):3167-73. Epub 2007 Mar 21.
Zessner H, Pan L, Will F, Klimo K, Knauft J, Niewöhner R, Hümmer W, Owen R, Richling E, Frank N, Schreier P, Becker H, Gerhauser C. Fractionation of polyphenol-enriched apple juice extracts to identify constituents with cancer chemopreventive potential. Mol Nutr Food Res. 2008 Jun;52 Suppl 1:S28-44.