High Fructose Consumption, Inflammation Up (Bad), LDL-to-HDL Ratio Down (Good) - Is That Good or Bad for the Heart?

Remember: If anything fructose from beverages (including juices), yet not fructose from whole fruit is a problem. In fact eating whole fruits will decrease your blood lipids and high sensitivity C reactive protein (hs-CRP) inflammation markers.

Fructose is bad for you, right? Right. According to the latest study from the University of Newcastle, the consumption of only one drink containing containing 50 g of either fructose or glucose or sucrose dissolved in water will have detrimental effects on the #1 indicator of whole body inflammation, which is high sensitivity C-reactive protein (hs-CRP).

Much to the researchers surprise, though, the same amount of fructose had significant beneficial effects on the plasma lipid levels of the healthy male and female adults (n = 14) between the ages of 18-60 years who were recruited by advertisement and underwent study procedures at the Nutraceuticals Research Group Clinic rooms at the University of Newcastle in Australia.

Learn more about fructose at the SuppVersity

Bad Fructose not so Bad, After All! Learn its Benefits.

Fructose From Fruit is NOT the Problem

Americans Don't Eat More Fructose These Days!

An Apple A Day, Keeps... & More (Guestpost)

Fructose is Not Worse Than Sugar

The Obesogenic Fructose Fat Connection

Since the exclusion criteria were: diagnosed hyperlipidaemia, diabetes, gastrointestinal disorders, currently on fructose/sugar restricted diet, vegan diet or weight loss program, undergone any surgical procedure for obesity, pregnant or lactating mother, taking lipid-lowering or anti-inflammatory drugs and BMI >30kg/m², the results may well be different in "sicker" individuals, but for the guys and gals who drank the three 50g "sugar" solutions on three different occasions after an overnight fast, the "negative effects" of fructose were far from being conclusive.

Figure 1: Changes in hs-CRP, HDL and LDL in response to the ingestion of the test drinks (Jameel. 2014).

Even if you belong to the ever-increasing numbers of brainwashed fructose haters who believe that fructose and not a general overconsumption of energy was to blame for the obesity epidemic, you will have to admit that the data in Figure 1 leaves the significance of concomitant increases in hs-CRP and significant improvements in the HDL/LDL ratio, as the scientists phrase it, "to be delineated when considering health effects of feeding fructose-rich diets" (Jameel. 2014).

Apples reduce, apple juice increases hs-CRP in healthy volunteers (Ravn-Haren. 2013).

Don't mistake fruits for pure fructose: Studies indicate that a high fruit consumption is associated with reduced hs-CRP scores and a lower mRNA expression in peripheral blood mononuclear cells of some relevant proinflammatory gene markers (Oliveira. 2009; Hermsdorff. 2010). This is yet not the case for fruit juices, as you may remember from a previous SuppVersity post discussing the results of Gitte Ravn-Haren's 2013 study which showed that the intake of whole apples had beneficial, the consumption of apple juice, however, detrimental effects on plasma lipids and - as you can see in the figure to the left - hs-CRP levels of the healthy volunteers (Gitte Ravn-Haren 2013).

Well, yes, but (a) it's only an acute response and (b) while increased levels of hs-CRP have been found to be associated with heart disease (Rifai. 2001; Danesh. 2004), the same can be said for a high LDL/HDL ratio (Fernandez. 2008).

Figure 2: CRP-dependent risk levels for cardiovascular disease according to the American Hear Association.

If we also take into consideration that the baseline hs-CRP level of the subjects was 1.5mg/L and thus low to mid-range for the average Westerner (depending on his or her ethnicity | Albert. 2004), an increase of 10% to a maximal value of 1.65mg/L would not bring them to critical heights of which the Farmingham study says that they start at 3mg/L for Westerners (Wilson. 2005). That's not ana optimal level, but considering the fact that we are talking about "average Joes and Janes" who probably don't work out, eat whatever they like and give a damn about their sleep hygiene (all three factors have previously been linked to elevated hs-CRP levels) that's not astonishing and has absolutely nothing to do with the ingestion of 50g of fructose.

Furthermore, a comparison of the predictive value of different risk markers for cardiovascular disease by Folsom, et al. (2006) indicates that the hs-CRP values did not add to the prognostic value of the standard risk factors which are age, race, sex, systolic blood pressure, smoking status, diabetes and - you guessed it - total and high density lipoprotein cholesterol, which increased by almost 7% while the amount of LDL dropped by maximally 6%. Thus the LDL/HDL ratio decreased from 1.84 to 1.62. That's a 12% decrease that would be health relevant if the subjects' LDL/HDL ratio was not far away from the danger-zone (>5 | see Manninen. 1992), already. Similarly, the total cholesterol to HDL ratio dropped by -1.97 but wasn't in the danger zone before, either.

Incremental area under the curve for glucose and insulin 0-120min after consuming the test beverages (Jameel. 2014).

So what? Overall the results provide no evidence that the occasional consumption of a larg(er) bolus of fructose was unhealthier than the same amount of glucose or sucrose. If you take a parting look at the glucose and insulin response you will also see why fructose has long been haled as the "healthier" alternative to sugar for type II diabetics: there is no increase in glucose or insulin in response to the ingestion of 50g of fructose. And even the dreaded increase in triglycerides that occurs when the liver converts the fructose to fat did not occur (in fact, the levels dropped by ~4%, while they increased when the subjects consumed glucose (+11%) or sucrose (+4%).

So, if you've been drinking your first real coke of 2015 last night, don't worry. It probably didn't hurt your heart. If you plan to continue drinking 1l of the brown sugar-liquid everyday, this year, though, I would not guarantee that the extra pounds you may be gaining and the diabetes you may be developing won't have negative consequences for your heart and maybe liver health  | Comment on Facebook.

References:

• Danesh, John, et al. "C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease." New England Journal of Medicine 350.14 (2004): 1387-1397. 
• Fernandez, Maria Luz, and Densie Webb. "The LDL to HDL cholesterol ratio as a valuable tool to evaluate coronary heart disease risk." Journal of the American College of Nutrition 27.1 (2008): 1-5.
• Folsom, Aaron R., et al. "An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study." Archives of internal medicine 166.13 (2006): 1368-1373. 
• Hermsdorff, Helen Hermana M., et al. "Research Fruit and vegetable consumption and proinflammatory gene expression from peripheral blood mononuclear cells in young adults: a translational study." (2010).
• Jameel, Faizan, et al. "Acute effects of feeding fructose, glucose and sucrose on blood lipid levels and systemic inflammation." Lipids in Health and Disease 13.1 (2014): 195.
• Manninen, Vesa, et al. "Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment." Circulation 85.1 (1992): 37-45.
• Oliveira, A., F. Rodriguez-Artalejo, and C. Lopes. "The association of fruits, vegetables, antioxidant vitamins and fibre intake with high-sensitivity C-reactive protein: sex and body mass index interactions." European journal of clinical nutrition 63.11 (2009): 1345-1352. 
• Ravn-Haren, Gitte, et al. "Intake of whole apples or clear apple juice has contrasting effects on plasma lipids in healthy volunteers." European journal of nutrition 52.8 (2013): 1875-1889.
• Rifai, Nader, and Paul M. Ridker. "High-sensitivity C-reactive protein: a novel and promising marker of coronary heart disease." Clinical chemistry 47.3 (2001): 403-411.
• Wilson, Peter WF, et al. "C-reactive protein and risk of cardiovascular disease in men and women from the Framingham Heart Study." Archives of internal medicine 165.21 (2005): 2473-2478.

It's in the Peel - The Protective Hull of These 61 Super Fruits Can Ward Off Cancer: Prunes, Plums, Jujube, Kiwi, Pitaya, Apple, Banana, Lemon, Cherry, Kumquat, Pomelo,...

Peru Ground Cherries could be among the most potent fruity anti-cancer agents nature has to offer.

In all the hoopla around "anti-nutrients", people tend to forget that the majority of the hailed phenols, flavenoids etc. serve the very same purpose, they protect the fruit of certain plants. For a recent study from the School of Public Health and the Chinese Academy of Sciences in Guangzhou, as well as the Peking Univerity Fang Li et al. have now compiled an extensive list of fruits, their peels, pulp and seeds and the corresponding anti-proliferative activity, you may want to use as an anti-cancer shopping guide, when you are grocery shopping... and if you do so, don't peel them: the protective peel is where nature stores most of the stuff that kills cancer cells by having them suffocate in their own reactive oxygen species!

Keep in mind, while the fruits can kill cancer in the petri dish you would be asking too much if you expect to cure existing cancer by just eating one or to servings of the top items on the list below per day. In conjunction with the nutrition & exercise tips you receive on the SuppVersity every day, they may yet contribute their share to render you "cancer proof".

Table 1: Anti lung-, breast-, liver- and colon-cancer activity of 61 fruits,  or rather their pulp, their peel and their seeds; marked in green are all values that are larger than the mean + 60% of the standard devidation (Li. 2013)

I have been thinking for quite some time about the optimal way to present the data, to pick a TOP10 or to come up with a selection and then realized that I - if I were in your position - would like to take a look at the data myself.

Instead of telling you what I thought were the most remarkable results I did thus decide to simply confront you with the complete data marking every value that is at least 60% above the mean + one standard deviation in green and ordering the data by the mean protective effect against the three different cancer types (lung, breast, liver, colon cancer) the researchers have tested for.

If you just take a cursory look at the data, the most striking observation the scientists made is unquestionably, the overall potency of the fruit polyphenols. What you have to keep in mind though is that we are talking about in-vitro studies and direct exposure to dosages of 50.09–141.79 mg/mL, as they were necessary to actually kill breast cancer cells are probably something you will never achieve no matter how many Peru ground cherries you eat. With the latter being among the most potent fruity anti-cancer "meds" we have, it is obvious that the question we will still have to answer pertains to the effects of actually eating any of these items.

It appears out of question that it's not going to hurt you. It should also be obvious that eating a packed of cherries is not going to rid you of existing cancerous growth. On the other hand, there is already plenty of evidence that

• cherries (in this case tart cherries) administered in an extract form, can reduce the risk of colon cancer in rodent models (Kang. 2003)
• polyphenol-rich cloudy apples juices can protect against gastric diseases associated with cancer formation (Graziani. 2005)

etc. The picture that's emerging though is that the in-vivo effects of the above and other fruit polypenols are more or less locally, namely in the gut, where the individual cell is directly exposed to a high amount of the active ingredients in the respective fruit. To achieve maximal benefits and actually battle cancer in other parts of our body than the gut, it may thus be necessary to isolate the molecules, compound them and inject them locally in the the cancerous tissue...

---

Bottom line: While consuming high amounts of these anti-cancer fruits will have a plethora of health benefits, which will eventually protect you from cancer in all parts of your body, using them as a druglike medicine in our "war against cancer" would warrant extraction and isolation procedures that allow us to apply them in high concentrations to certain parts of our bodies.

I would bet money that all of the "superfruits" in the list above, also help to avoid prostate cancer

Suggested read & podcast: Last weeks' special issue of the SuppVersity Science Round-Up on prostate cancer is certainly something you either have remembered, when you went through the items on the list. And yes, while the scientists did not test for it, you bet that all of the "superfruits" in the list will also be good for your prostate. And just in case you missed the last installment of the Science RoundUp, I'd highly recommend you briefly go back to the corresponding seconds to read and listen to all the details | learn more about prostate cancer...

Although I doubt that isolating the nutrients and developing corresponding delivery systems entails insurmountable technical difficulties (in fact corresponding nano-technology would probably be available, already; cf. Khandelia. 2013), I am pretty sure nobody is going to do this; after all, the compounds themselves would not only be non-patentable, because naturally sourced, they would also compromise the sales of conventional cancer drugs and are thus a red rag to any of the big players in the business public health has become.

References:

• Graziani G, D'Argenio G, Tuccillo C, Loguercio C, Ritieni A, Morisco F, Del Vecchio Blanco C, Fogliano V, Romano M. Apple polyphenol extracts prevent damage to human gastric epithelial cells in vitro and to rat gastric mucosa in vivo. Gut. 2005 Feb;54(2):193-200.
• Kang SY, Seeram NP, Nair MG, Bourquin LD. Tart cherry anthocyanins inhibit tumor development in Apc(Min) mice and reduce proliferation of human colon cancer cells. Cancer Lett. 2003 May 8;194(1):13-9.
• Khandelia R, Jaiswal A, Ghosh SS, Chattopadhyay A. Gold Nanoparticle-Protein Agglomerates as Versatile Nanocarriers for Drug Delivery. Small. 2013 Feb 27. 
• Li F, Li S, Li HB, Deng GF, Ling WH, Wu S, Xu XR, Chen F. Antiproliferative activity of peels, pulps and seeds of 61 fruits. Journal of Functional Foods. 20 May 2013.

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 excess energy. (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.