Pistachio Phenols 90% Bioavailable. Phe, Leu, Glu & Trp - Four Satiating Aminos. Artificial Sweeteners Act as Anti- Convulsants. Dendrobium for Glucose, Lipids & Kidneys

Since I am a little pressed in time, I won't beat around the bush, but rather get to the meat of the matter of this Nutrition Quickie, right away... well, actually today's nutrition quickie has no item on meats, but is has one Dendrobium, which is actually rather a supplement - be that as it may, here you go:

• 

  Since you (hopefully ;-) haven't swallowed a bomb colorimeter, it's actually no wonder that your body can only access 75% and 95% of the energy this little oven can squeeze out of almonds and pistachios. If you went with the Atwood factor (which says fat = 9kcal/g) and simply added fats, proteins and carbs the discrepancy for almonds would even increase to ~35% (Nowotny. 2013)

  Almonds deliver 25% less calories that the nutritional label will tell you (Gebauer. 2013) -- At the FASEB meeting in April 2013, already, scientists from nowhere else than the mighty USDA, respectively the Beltsville Human Nutrition Research Center of the USDA presented the results of a human study that clearly shows that our tummies cannot squeeze out more than 75% of the nutrients a bomb calorimeter does. Nutrition Quickie: 25% Less Kcal in Almonds Than Label Says.
  
  The caloric value on both food labels and respective nutrient tables is thus off 25% too high. And the corrected energy content per 100g of almonds is 456kcal/100g not 575kcal/100g (nutritiondata.com), or even higher values you will find when you google  "almonds kcal" - I am curious if at least the nutrition labes will ever be updated.
  
  A similar but less pronounced mismatch has been found for pistachios by the same researchers earlier this year, already. According to a paper published in the January edition of the British Journal of Nutrition (Bear. 2013), the actual energy content of these heart healthy nuts 565kcal/100g, which is ~5% less than the currently established value. 

• Bioavailability of pistachio polyphenols, xanthophylls, and tocopherols is very high - until you put them into a muffin (Mandalari. 2013) -- Bioavailability, i.e. the ratio of the total amount of a certain molecule that's in the food we eat in intact or at least active form in our bloodstream, can be a real issue for many of the good things the spectral analyzer of brainy scientists detects in our foodstuff.
  
  

  

  Table 1: Phenol, lutein and tocopherol content of the raw, roasted and salted pistacchios and regular and pistaccio (17g/100g) muffins (Madalari. 2013)

  In the upcoming January issue of Nutrition a group of researchers from the UK and Italy report the results of an investigation into the bioavailability of polyphenols, xanthophylls (lutein), and tocopherols (among them the rare gamma-variety) from raw pistachios, roasted salted pistachios, and muffins made with raw pistachios. You can see the original polyphenol, xanthophyll and tocopherol (mind the 90% gamma-tocopherol content, which has better chemoprotective effects than alpha-tocopherol; see "Vitamin(S!) E" post from 2011) content in table 1.
  
  Interestingly enough the availability of the tocopherols was almost identical for all three tested forms (raw, roasted, in muffins) and even the muffin reduced only the bioaccessability of protocatechuic acid (78%) and luteolin (36%), the rest of the phenols achieved the same ~90% Madalari et al. observed for the raw and roasted + salted pistachios in their million dollar model of the human digestive tract (click here for an article about this "artificial gut")

• When the gut "tastes" phenylalanine (PHE), leucine (LEU), glutamate (GLUT) and tryptophane (TRP), satiety ensues (Daly. 2013) -- In their most recent paper Christin Daly et al. report on the cholecystokinin (CCK) release in the gut. According to the scientists from the University of Liverpool (UK) and the Kyushu University (Japan), the effect is mediated by interactions with the gastrointestinal bitter taste receptors. Since CCK inhibits food intake and reduces appetite, this provides another mechanistic explanation for the satiety promoting effects of high protein intakes. The effects was observed only for the L- and not the D-amino acids.
  
  Interestingly, the beneficial effects of  PHE, LEU and GLUT on CCK (but not the TRP-stimulated CCK secretion) were blunted in the presence of gurmarin. "Gurmarin?" Yeah, that's the rodent specific  sweet taste inhibitor in Gymnema sylvestre (note gurmarin does not work in humans; cf. Sigoillot. 2013), which is sold as an anti-diabetes supplement. Inosine, on the other hand increased the CCK release n response to all of the amino acids.
  
  How significant that is specifically for those who have a problem keeping their ravenous appetite in check is however questionable. After all the satiety response to CCK has been shown to be disturbed (at least in rodents; cf. Balaskó. 2013)

• 

  Table 2: Number of mice protected by the administered drug in the MES test (Talevi. 2013)

  Acesulfame potassium, cyclamate and saccharin are potential anti-convulsants (Talevi. 2013) -- It may sound counter-intuitive in view of all the bad stuff you have probably heard about artificial sweeteners, but it is their particular molecular structure and similarities between the T1R3 sweet taste receptor they are supposed to bind to ant several metabotropic glutamate receptors from different species that is probably behind the anticonvulsant effects a group of researchers from the Department of Biological Sciences at the Faculty of Exact Sciences of the National University of La Plata (UNLP) in Buenos Aires, Argentina.
  
  The overall effect size the scientists observed in their rodent model (see table 2) is yet far from earth shattering and generally more pronounced if the sweeteners had been ingested 4h instead of just 20 min before a Maximal Electroshock Seizure (MES) test. Whether this makes them worth "supplementing" is however more than questionable.
  
  Suggested additional reads:
• Stevia - More Than Super Sweet: More Scientific Evidence, More Potential Implications for Weight Loss & -Maintenance, Anti-Diabetic & -Autoimmune and Even Pro-Anabolic Effects
• Fructose Epimer D-Psicose First Sweetener to Actively Promote Weight Loss? Reduced Weight Gain and Direct Inhibitory Effect on Adipocyte Maturation in Rodent + Reduced Postprandial Glucose & Insulin in Human Trial
• The Unsatiating Truth About Aspartame, Acesulfam K, Sucralose & Co: They Don't Induce Glucose or Insulin Spikes, But Do They Make You Hungry?
• other posts with the tag "artificial sweetener"

• Putting things into perspective: While the DPPH radical scavenging activity is not a really good measure of the in-vivo anti-oxidant potency of a given molecule it may yet still be worth mentioning that the one of Dendrobium (IC₅₀ = 29.6 μg/mL) is more than 80% lower than that Areca catechuvar. Cinnamon cassia, Paeonia suffruticosa and Alpinia officinarum extracts which share IC₅₀ values <6µg/mL (Lee. 2003). In other words, you need 80% more Dendrobium than cinnamon, for example, to neutralize the same amount H2O2 radicals.
  Dendrobium extract ameliorates renal fat accumulation, hyperglycemia and hyperlipidemia in rodents on "high fat" diet (Lee. 20012) -- While I cannot say if this is the same Dendrobium extract that's used in a pre-workout supplement that's "all the craze", these days, I can tell you that a group of researchers just published a paper on the renoprotective, hypoglycemic and hypolipidemic effects of an extract from Dendrobium moniliforme (a cursory search revealed that even within this genus of orchids there are at least 90 sub-types ranging from Aochidori to Yuten).
  
  Lee et al. administered the methanolic extract at dosages of 200mg/kg (HED ~16mg/kg) for nine weeks and reduced the elevated serum glucose, total cholesterol concentration and renal lipid accumulation in the HFD-fed mice. It also ameliorated renal dysfunction biomarkers including serum creatinine and renal collagen IV deposition. So that the scientists conclude that methanolic extracts from Dendrobium moniliforme exhibit pleiotropic effects on obesity induced parameters and exert renoprotective effect in HFD-fed mice.

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That's it for today, unless you are are interested in one of the following facebook news:

• Crape ginger (Costus speciosus Koen) has significant anti-arthritic properties - at least in a rodent model (read more)
• Ayurvedic polyherbal Unani formulation shows promising results in Acne vulgaris patients - 45 days, 45 subjects, significant improvements on Cook's acne scale (read more)
• Endocannabinoids increase, leptin decreases a "sweet tooth" - And you can take this almost literally, since they do actually modulate sweet taste receptor sensitivity (read more)

There are actually a couple more and they will "proliferate" *rofl* even before the next official SuppVersity  post will be published. Reason enough to check by from time to time, or simply "like" the SuppVersity on Facebook in order to keep up with the news.


References:

• Baer DJ, Gebauer SK, Novotny JA. Measured energy value of pistachios in the human diet. Br J Nutr. 2013 Jan;107(1):120-5.
• Balaskó M, Soós S, Párniczky A, Koncsecskó-Gáspár M, Székely M, Pétervári E. Anorexic effect of peripheral cholecystokinin (CCK) varies with age and body composition (short communication). Acta Physiol Hung. 2013 Jun;99(2):166-72.
• Gebauer SK, Novotny JA, Baer DJ. Macronutrient absorption from almonds: the measured energy value of almonds in the human diet. FASEB Journal. 2013;26:820.25.
• Lee SE, Hwang HJ, Ha JS, Jeong HS, Kim JH. Screening of medicinal plant extracts for antioxidant activity. Life Sci. 2003 May 30;73(2):167-79.
• Lee W, Eom DW, Jung Y, Yamabe N, Lee S, Jeon Y, Hwang YR, Lee JH, Kim YK, Kang KS, Kim SN. Dendrobium moniliforme Attenuates High-Fat Diet-Induced Renal Damage in Mice through the Regulation of Lipid-Induced Oxidative Stress. Am J Chin Med. 2013;40(6):1217-28.
• Mandalari G, Bisignano C, Filocamo A, Chessa S, Sarò M, Torre G, Faulks RM, Dugo P. Bioaccessibility of pistachio polyphenols, xanthophylls, and tocopherols during simulated human digestion. Nutrition. 2013 Jan;29(1):338-44.
• Novotny JA, Gebauer SK, Baer DJ. Discrepancy between the Atwater factor predicted and empirically measured energy values of almonds in human diets. Am J Clin Nutr. 2013 Aug;96(2):296-301. 
• Sigoillot M, Brockhoff A, Meyerhof W, Briand L. Sweet-taste-suppressing compounds: current knowledge and perspectives of application. Appl Microbiol Biotechnol. 2013 Nov;96(3):619-30.
• Talevi A, Enrique AV, Bruno-Blanch LE. Anticonvulsant activity of artificial sweeteners: a structural link between sweet-taste receptor T1R3 and brain glutamate receptors. Bioorg Med Chem Lett. 2013 Jun 15;22(12):4072-4.

Chromium Picolinate Worsens Insulin Sensitivity in Healthy, Non-Diabetic, Non-Obese Individuals by Up to 25%

The more supplements you take the more likely you are to get way more than the 200mcg of chromium of which previous studies have shown that they are useless for healthy people, but at least not detrimental (cf. Lukaski 1996 & 2007; Vincent. 2007). Especially people who like the  'poly-supplementary' approach are yet at risk of getting so much of a this trace mineral that it will hamper not improve their insulin sensitivity.

I don't have to tell you that you would already be dead if you were following all the bro-scientific advice that's out there on the Internet and still I usually recognize a certain reluctance to give up on what X suggests and Y has tried an what has worked so well for Z. One of the instances, where I have hitherto been missing a 100% convincing argument to argue that this is just another instance where common wisdom would in fact be better called "common stupidity" is the "insulin mimetic" or "insulin sensitizer" (or whatever your favorite bro-expert may call it) chromium picolinate. With the recent publication of the result of a study on the effects of chromium supplementation in healthy individuals there is now finally a human study that confirms that chromium, which has never been an "insulin sensitizer", but rather an "insulin release amplifier" that reduced blood glucose in diabetics by simply having them produce even more insulin is not a supplement any healthy man or woman, let alone athlete should consider a staple of his or her regimen.

The long and short: Chromium hampers insulin sensitivity in normoglycemic individuals

For their experiment lead author Umesh Masharani and his colleagues from the UCSA recruited a group of 27 non-obese, non-diabetic, healthy subjects between the ages of 20 and 50 with a body mass index of less than 27 kg/m² and <24 kg/m² for subjects with Asian heritage (the cut-off limits were set so that they would be below a BMI that has not yet been shown to be an independent risk factor for insulin resistance; cf. Clausen. 1996; Newell-Morris. 1998).

To evaluate whether chromium picolinate (ChrPic) supplements, which contributed with $150,000,000 to the revenue of the supplement industry in 1996 (Nielsen. 1996), could come up to the claims that they would exert beneficial effects on glucose tolerance and insulin sensitivity, the study participants were randomized to take either a placebo or a high dose 500µg CrPic supplement twice daily for 4 months (the dosage was selected in view of previews studies reporting greater benefits of 1,000 vs. 200mcg of CrPic in - you already guessed it - diabetic subjects; cf. Morris. 2000).

Figure 1: Insulin sensitivity measured by euglycemic clamp before and after the 16 week intervention (left); change in insulin sensitivity of the individual subjects plotted against serum chromium levels at the end of the study (Masharani. 2013)

As the data in figure 1 goes to show, the results of the CrPic intervention were more or less the exact opposite of what the ~10 million US consumers of respective supplements probably expect from the pills many of them are taking almost religiously. Despite the fact that all subjects had very low chromium levels at the beginning of the study, the previously non-significant minimally benificial relation between both serum and urinary chromium, on the one hand, and insulin sensitivity (r = 0.24, p=0.1; r=0.08, p=0.79 respectively), on the other hand, had turned into a very significant negative correlation between high(er) urinary and serum chromium concentrations and lower insulin sensitivity at the end of the 16 week intervention period (figure 1, right).

"Due to the apparent variation in the degree of chromium absorption between subjects, we examined the relationship between serum chromium and change in insulin resistance. After controlling for baseline patient characteristics, results of a multiple regression analysis showed a strong association between serum chromium and worsening of insulin–mediated glucose disposal (β= -0.83, p<0.01), where subjects with the highest serum chromium had a decline in their insulin sensitivity. To further explore the association between chromium absorption and insulin resistance, patients within the chromium group were divided (based on  a medial split at 3.10 µg/L) into a high (n=6) and low (n=8) serum chromium group [...] There were no group differences at baseline; however, at post-assessment participants in the high serum chromium group (> 3.1  µg/L) were more insulin resistant than participants in the low serum chromium group (≤3.1  µg/L) or the placebo group (p=0.02, p=0.05 respectively) (Figure 3)." (my emphases in Masharani. 2013)

Due to the fact that the scientists did not observe any differences between the placebo and low serum  chromium groups (on a side note, contrary to many other studies insulin Masharani et al. measured the insulin sensitivity in a very reliable way with an euglycemic hyperinsulinemic clamp; cf. Defronzo. 1979), the scientists also conducted a post-hoc analysis to identify potential confounding factors that may have influenced the outcome of the trial. Neither changes in triglycerides levels LDL, BMI, or truncal fat were yet associated with the differences they observed between the supplemented and non-supplemented participants. Interactions that would reduce the significance of the observed correlations were likewise absent:

"Furthermore, when changes in triglycerides, LDL, BMI, and truncal fat were individually added to the model, none were independent significant predictors of change in insulin sensitivity, and chromium absorption remained a significant predictor of reduced insulin sensitivity in each model." (Masharani. 2013)

Against that background the scientists conclude that there must be a "direct effect of chromium on changes in insulin action". A mechanism, by the way, which is totally independent of classic markers of insulin resistance such as high serum lipids and abdominal / truncal adiposity .

Being healthy is a good predictor of increased chromium absorption and more pronounced negative effects, so if you are healthy and want to stay this way don't even think of taking high dose chromium supplements.

Despite the fact that the changes in insulin resistance did not depend on changes in serum lipids and other markers of metabolic health, Masharani and his colleagues were able to show that the increase in chromium levels in response to supplementation did. With the already mentioned statistically significant correlation between increases in serum chromium levels (higher response to supplementation = higher increase), on the one hand, and the worsening of insulin sensitivity, on the other hand, this means that the healthiest subjects, namely ...

"[...] subjects with lower triglycerides, and those with lower levels of homocysteine [who had] a greater likelihood of being in the high absorption group" (Masharani. 2013)

... were at the same time those who were at the greatest risk of the ill side-effects high dose chromium supplements exert on the insulin tolerance of healthy, non-diabetic, normal-weight individuals.

No matter if it may have helped you produce insulin back in your obese days, once you have accomplished this you better avoid high dose or multiple (hidden) sources of supplemental chromium like a plague - unless you can't afford new jeans, of course ;-)

Bottom line: Unless you are not a type II diabetic or feel the urgent desire to become one, you better steer clear of exuberant amounts of supplemental chromium the RDA is enough. This is particularly true, if you are already taking a multi (which is almost guaranteed to have 200mcg in it), or any BB-style supplements. After all, "broscience" wants it that chromium is in everything that's even remotely related to insulin / nutrient uptake or whatever. With the use of only one of these products and 200mcg of supplemental dietary chromium per day, you may still argue that it probably won't do much harm. When you add another 200mcg from your "nutrient partitioner" on top of the 200mcg you get from your multi and the 200mcg of which you probably did not even realize yet that they are part of your pre-workout supplement, however, you can hardly complain about simply not being able to tolerate carbohydrates - I mean, what's your body supposed to do if you are dumb enough to believe in the promises of fat loss and lean mass increases that have been debunked in the late 1990s, already (cf. Lukaski 1996 & 2007; Vincent. 2007), and simply chose to ignore the latest scientific evidence that chromium picolinate supplements are not just useless, but actually detrimental to your health?


References:

• Clausen JO, Borch-Johnsen K, Ibsen H, Bergman RN, Hougaard P, Winther K, Pedersen O. Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of  the impact of gender, body fat, physical fitness, and life-style factors.  J Clin Invest. 1996;  98(5):1195– 1209.
• Defronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979; 237:E214–E223. 
• Lukaski HC, Bolonchuk WW, Siders WA, Milne DB. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr. 1996 Jun;63(6):954-65.
• Lukaski HC, Siders WA, Penland JG.  Chromium picolinate supplementation in women: effects on body weight, composition, and iron status. Nutrition. 2007; 23(3):187– 195.
• Masharani U, Gjerde C, McCoy S, Maddux BA, Hessler D, Goldfine ID, Youngren JF. Chromium supplementation in non-obese non-diabetic subjects is associated with a decline in insulin sensitivity. BMC Endocr Disord. 2013 Nov 30;12(1):31.
• Morris BW, Kouta S, Robinson R, MacNeil S, Heller S. Chromium supplementation improves insulin resistance in patients with Type 2 diabetes mellitus.  DiabetMed. 2000; 17(9):684–685.
• Newell-Morris LL, Treder RP, Shuman WP, Fujimoto WY. Fatness, fat distribution, and glucose tolerance in second-generation Japanese-American (Nisei) men. Am J Clin Nutr. 1989; 50(1):9–18.
• Nielsen FH. Controversial Chromium: Does the superstar minearal of the mountebanks receive appropriate attention from clinicians and nutritionists?  Nutr Today. 1996; 31(6):226–233.
• Vincent JB: The nutritional biochemistry of chromium (III). Amsterdam, Boston: Elsevier. 2007.

The Counterintuitive Catabolic & Pro-Diabetic Effects of Leucine Supplementation in Rodents on Corticosteroids

Not the mice from this study, but still a nice example of the effects of dexamethasone on skeletal muscle (right; Quin. 2013)

"Leucine-laced water + stress = insulin resistance" - This simple equation is the net result of a recent study by Nelo Eidy Zanchi and his colleagues from the Laboratory of Applied Nutrition and Metabolism at the School of Physical Education and Sports of the University of Sao Paulo in Brazil. Inspired by previous research which clearly indicated that leucine does not only have pro-anabolic, but also insulin sensitizing effects, Zanchi et al. speculated that the provision of adequate amounts of leucine would blunt the catabolic and pro-diabetic effects of 7 days of intraperitoneally injections of  dexamethasone, an artificial corticosteroid that's used to treat all sorts of inflammatory diseases.

Remember SuppVersity Rule of Smart Supplementation No. 2? Right. Specificity!

In order to test their hypothesis that leucine supplementation either in low doses in the drinking water or as higher dosed oral gavage would ameliorate the negative side effects of DEXA treatment, the scientists randomized groups of 10 male Wistar rats to six groups receiving either low dose or high dose leucine supplements with and without dexmethasone.

"During  the duration of the experiment, which lasted  seven  days,  DEXA (a synthetic glucocorticoid analogue that does not bind to plasma binding proteins) was given daily (at 9:00 a.m.) through intraperitoneal injection (5 mg/kg/day); control groups received  an equivalent volume of saline (0.9% NaCl). As DEXA was reported to decrease food intake, all groups were  fed the same amount of food (in terms of caloric intake) equal to the DEX group. Thus, differences among groups did not originate from different food intakes. We measured the caloric content of our standard chow (16.32 kJ/g) as well as leucine (25 kJ/g) in a calorimetric bomb (FTT Oxygen Bomb Calorimeter) in  order to avoid differences in the caloric ingestion between experimental groups and observed that the total caloric consumption was not statistically different among groups." (Zanchi. 2013)

The leucine was administered either in dosages of 0.068g/kg body weight per day (low dose) or 1.35 g/kg per day (high-dose) twice daily at 8:00  a.m. and  2:00  p.m. through gavage over seven days. And while the scientists had selected the high dose (LH) "to induce a maximal increase in muscle protein synthesis and insulin plasmatic levels", the dosage in the LL (=low leucine) group was too low to increase either muscle protein synthesis or plasma insulin levels. The third, non-supplemented control group received an NaCl (sodium) placebo, the volume of which was identical to the supplement to make sure that any possible volume-induced effects of oral gavage that could for example be induced by gastric expansion would not skew the study results.

"But leucine has been shown to be anabolic! So it must help."

Aside from the usual basal fasting glucose, insulin, tryacilglycerol (TAG) and HOMA-IR values, the scientists did also assess the motor performance of the animals by the means of two standardized strength and ambulation tests (Kennel. 1996; Anderson. 2004; Viera. 2008).

Figure 1: Effect of 7 days of low (LL) and high (LH) dose leucine supplementation with and with out dexamethasone on total body mass, soleus (slow twitch) and EDL (fast twitch) muscle mass in male Wistar rats (left; values expressed relative to non-supplemented control) and corresponding changes in mean ambulation and grip strength (right; Zanchi. 2013)

As you can see in figure 1 the supplemental leucine failed to reduce the negative side effects of dexamethasone. As far as the total body weight and the fast-twitch muscle mass (EDL) are concerned, you could even argue that the high dose treatment (DEX-LH) did even amplify the catabolic effects of the synthetic corticosteroid:

"Thus, leucine supplementation at both low and high doses did not counteract body weight loss in both food restricted (control groups) and DEXA-treated animals. Soleus muscle mass did not differ among groups. Leucine supplementation at  high doses  attenuated food  restriction-induced EDL muscle loss (CON-LH group) when compared with the CON-NS group  (p < 0.05). All DEXA-treated animals presented reduced EDL muscle mass when compared with the CON-NS group (p < 0.05), and leucine supplementation at both low and high doses of amino acid did not attenuate it." (Zanchi. 2013)

Now, you may well argue that the mere fact that the muscle weight was "statistically significant" reduced, this does not mean that these reductions would be physiologically significant and that the minimal differences between the DEX groups would not matter, anyway. If you just go by the data on the left side of figure 1, this is certainly right, if you do yet also consider the significant reductions in muscle function (figure 1, right) and the fact that all that happened within no more than 7 days, the overall result should actually remind you of the "Three Simple Rules of Smart Supplementation" - and here specifically the 2nd one: Specificity!

Figure 2: Time course of the dexamethasone-induced detoriations in fed serum glucose levels and ameliorative effect of low and high dose leucine supplementation (left) and effects of the treatment on fasting insulin levels and HOMA-IR (index of insulin resistance) at the end of the study (Zanchi. 2013)

In fact, the data in figure 2 only confirms the notion that things that you cannot define "good and bad", "black and white" and "beneficial or detrimental" without a context and the outcome you are expecting. If you are trying to keep the postprandial blood sugar in check, for example he addition of an effective (high dose) of leucine to the diet would appear to be a good idea. If, on the other hand, you are more concerned about insulin resistance, you would be better advised to use minimal amounts of leucine or simply refrain from supplementation altogether.

Figure 3: If the ingestion of bolus amounts of leucine is not helpful, lacing the water of the rodents DEXA treated rodents with leucine turned them into full-blown diabetics (Zanchi. 2013)

As these results clearly demonstrate the provision of additional leucine is not useful to counter the negative side-effects of synthetic corticosteroids. On the contrary, the negative effects on insulin resistance are apparently even augmented and the muscle function is further compromised by the purpotedly anabolic high dose leucine supplement.

And while the overall effects of the bolus administration may still be negligible, the scientists ingenious idea that the provision of similar amounts of leucine in the drinking water in a second follow-up experiment turned out to be "capable of inducing a massive diabetic state" (Zanchi. 2013; see figure 3 for the ensuing surge in fasting blood glucose levels) while decreasing the mass of the fast-twich EDL muscles even further.

Bottom line: Overall these results only confirm the simple, but often neglected truth that inductive reasoning is a futile undertaking in the realms of exercise and nutrition sciences: What is good for an athlete is rarely optimal for an obese person, the same diet that helps the obese lose weight, will make the athlete feel miserable, and lacing the drinking water of rodents on corticosteroids with the exact same amount of leucine that has had highly beneficial effects on the insulin sensitivity of diabetic rodents in previous studies (Guo. 2010) will not only fail to ameliorate the glucocorticoid-induced detoriations in blood glucose, it will even exasperate them.

So, does that mean you should not take your whey protein or BCAAs any longer? No, if you did that you would make the exact same mistake as someone who laces his water with leucine in order to avoid the catabolic effects of the synthetic corticosteroid he is taking for medical reasons. On the other hand, the results of the study at hand should make you re-evaluate the necessity and even benefits of guzzling BCAAs all-day long, at least if the reason for doing so is that you believe that you are so stressed that you would otherwise fall into a catabolic black hole.

That said, there may even be implications for the average pre-diabetic inhabitant of the Western hemisphere who is eating his hamburger and French fries on the parking lot of the local fast food restaurant, because he cannot make room to prepare and consume a real meal somewhere in his busy and stressful schedule. I mean, despite the fact that the aforementioned specificity principle does not allow for anything but a still to be verified hypothesis, it does at least appear not to far-fetched that this chronic endogenous stress, despite being very different from the "stress" that's induced by the administration of a synthetic corticosteroid that does not bind to serum proteins, could have similar negative modulatory effects on the purported benefits of chronic leucine supplementation ... but as I've said before, this would be something to investigate in another study. So unless you are actually taking dexamethasone for medical reasons, you are probably not at risk of developing diabetes due to a high amount of leucine in your diet.

In the unfortunate case that you are actually on synthetic corticosteroids, a previous study by the same group of scientists, in the same rodent model does suggests that three workouts with three sets of squats (10 reps each) per week may offer the protection against corticosteroid induced muscle loss decreased skeletal muscle GLUT-4 expression and insulin resistance, leucine does not have to offer.... well, at least as long as you abstain from leucine supplementation, because the latter had the exact same detrimental effects in the 2011 study where it was administered to one of the experimental groups in conjunction with resistance training as it had in these more recent experiments in the absence of any type of workout (Nicastro. 2011). 

References:

• Anderson,  K.D.; Abdul, M.; Steward, O. Quantitative assessment of deficits and recovery of
  forelimb motor function after cervical spinal cord injury in mice.  Exp. Neurol.  2004,  190,
  184–191.
• Kennel,  P.F.; Fonteneau, P.; Martin, E.;  Schmidt,  J.M.; Azzouz, M.; Borg, J.; Guenet,  J.L.;
  Schmalbruch, H.; Warter, J.M.; Poindron, P. Electromyographical and motor performance studies
  in the pmn mouse model of neurodegenerative disease. Neurobiol. Dis. 1996, 3, 137–147.
• Nicastro H, Zanchi NE, da Luz CR, de Moraes WM, Ramona P, de Siqueira Filho MA, Chaves DF, Medeiros A, Brum PC, Dardevet D, Lancha AH Jr. Effects of leucine supplementation and resistance exercise on dexamethasone-induced muscle atrophy and insulin resistance in rats. Nutrition. 2013 Apr;28(4):465-71. Epub 2011 Nov 12.
• Qin J, Du R, Yang YQ, Zhang HQ, Li Q, Liu L, Guan H, Hou J, An XR. Dexamethasone-induced skeletal muscle atrophy was associated with upregulation of myostatin promoter activity. Res Vet Sci. 2013 Aug 29.
• Vieira, N.M.; Bueno,  C.R., Jr.; Brandalise, V.; Moraes,  L.V.; Zucconi, E.; Secco, M.; Suzuki, M.F.; Camargo, M.M.; Bartolini, P.; Brum, P.C.; Vainzof, M.; Zatz, M. SJL dystrophic mice express a significant amount of human muscle proteins following systemic delivery of human adipose-derived stromal cells without immunosuppression.  Stem Cells  2008,  26, 2391–2398.  
• Zanchi NE, Guimarães-Ferreira L, de Siqueira-Filho MA, Felitti V, Nicastro H, Bueno C, Jr, Lira FS, Naimo MA, Campos-Ferraz P, Nunes MT, Seelaender M, de Oliveira Carvalho CR, Blachier F, Lancha AH, Jr. Dose and Latency Effects of Leucine Supplementation in Modulating Glucose Homeostasis: Opposite Effects in Healthy and Glucocorticoid-Induced Insulin-Resistance States. Nutrients. 2013; 4(12):1851-1867.

Asparagus Extract Tops Anti-Diabetes Drug Glibenclamide. Plus: Dozens of Add. Health Benefits - From Aphrodisiac to Anti-Hangover & from Neuroprotection to Anti-Aging

Coho salmon, shrimp and asparagus with melted butter - better than any diabetes drug ;-)

Within the last couple of weeks, I have been moving news-items like this one into the "On Short Notice"  category, or simply totally discarded the dozen or so "herb XYZ" or "extract ABC ameliorates hypoglycemia in rodent model of type II diabetes" papers that are published on a weekly basis. The mere number of studies on whatever exotic, herb, spice or isolated polyphenol from the most remote areas (usually in Asia) the names of which I often even have heard about before, is simply too large to cover them all... and let's be honest: In the end, it's also downright boring to read about stuff that decreases blood glucose in a rodent model to a miniscule extend, when you already know that chances that you ever get your hands on a significant amount of that are zero, right?

There are however, two good reasons, why Rahman Md. Hafizur, Nurul Kabir and Sidra Chishti most recent paper, which has been published on November 24 in the latest issue of the British Journal of Nutrition, has still made it not just into the short, but actually the 'official' SuppVersity news are twofold: Firstly, the effects of the Asparagus officinalis extract they administered at two different dosages to their rodents were just mediocre, but - as you are about to see - right on par with the diabetes drug glibenclamide, a sulfonylurea based medication that is often sold in combination with metformin (the respective drugs are called Glucovance and Glibomet). And secondly, briefly summarizing the main results of the study provided a nice incentive to dig somewhat deeper into the already established beneficial health effects of asparagus - and I can tell you, those are about as numerous as the aformentioned boring "herb XYZ"-studies ;-)

From the scientists' petri dishes to the rodent cage and... onto your dishes?

Asparagus officinalis L. is probably what the average Westerner would call "common asparagus". It's native to most European, African and Asian countries and its medicinal usage has been reported in the British and Indian Pharmacopoeias and in traditional systems of medicine such as Ayurveda, Unani and Siddha. Most of you will probably be aware of its mild diuretic effects and the distinct smell of your urine which will betray that you are someone who loves its delicate flavor in salads, vegetable dishes, soups and (if you are like me) poundwise with melted Kerrygold butter, some potatoes a decent amount of ham or some grilled meat during the asparagus season... but I am digressing here, let's get back to the facts.

To get to the bottom of previously reported beneficial effects of asparagus in various inflammatory (metabolic) diseases, the initially conducted an in-vitro study, to test the radical scavenging ability of their Asparagus extract and found that ...

"[...] A. officinalis at a concentration of 0·5 mg/ml exhibited 86·8 % radical-scavenging activity, as shown by a significant decrease in the absorbance of DPPH radicals. These results suggest that A. officinalis has potent antioxidant activity, as the positive control propyl gallate exhibited 91·4 % radical-scavenging activity. (Hafizur. 2013)

Afterwards they injected a group of male and female Wistar rats with streptozotocin to induce diabetes. Subsequently, the rodents received either 250 or 500mg/kg body weight of an Asparagus officinalis (AO) extract or 5mg/kg body weight of glibenclamide (GIB) once daily via an oral syringe - the dosage was adapted once weekly according to changes in body weight.

Figure 1: Fasting blood glucose and insulin levels, total antioxidant status (TAS was measured using the ABTS) and beta cell area / islet expressed relative to control at the end of the 29 day study period (based on Hafizur. 2013)

A cursory glance at the data in figure 1 reveals: The initially betrayed anti-hypoglycemic effects (hypo[...] = ability to lower [blood sugar]) the high dose of Asparagus officinalis extract (AO500, figure 1) had on the fasting glucose levels of the animals were as potent as those of the diabetes drug glibenclamide.  Moreover, the treatment with AO500 had a slightly, but statistically significanty higher impact on the total antioxidant capacity and the same benificial effect on the morphology and function of the pancreas. Nevertheless, neither the A. officinalis extract, nor the glibenclamide treatment were able to restore the compromised insulin producton to more than ~70% of the value the non-streptozotocin-intoxicated animals.

There is much more to asparagus than it's antidiabetic effects

As impressive as these results may be, if we simply rely on the findings Hafizur, Kabir and Chishtiit present in this recent paper, we will actually miss not just half, but rather 95% of the potential health benefits the different genus and parts of asparagus have to offer.

Figure 2: A. racemosis administered at a dose of 200mg/kg per day makes male rats about as horny (and able to perform) as bi-weekly injections of testosterone (Thakur. 2009) - not that you would need that, but it's nice to know anyways.

Despite the fact that asparagus is a highly nutritious source of vitamin B6, calcium, magnesium and zinc, and a very good source of dietary fiber, protein (in at least in view of the fact that it's an almost zero calorie veggie ;-), vitamin A, vitamin C, vitamin E, vitamin K, thiamin, riboflavin, rutin, niacin, folic acid, iron, phosphorus, potassium, copper, manganese, selenium, highly bioavailable chromium, and even small quantities omega-3 fatty acids (Morales. 2013), so that the regular incorporation of asparagus alone into your diet will supposedly be beneficial for you, some of the more intricate health effects may in fact require the extraction of and supplementation with specific phytonutrients from Asparagus officinalis, A. racemosus, A. cochinensis and its various cousins.

In order to give you an idea of what you can expect, I have compiled a comprehensive, yet by no means extensive list of benefits which have been ascribed to root, seed, and even leaf extracts of asparagus over the past decades

• anti-cancer effects: Asparagus contains saponins that have in-vitro anti-(liver-)cancer effects (Ji. 2013); 
• neuroprotective effects: Chinese asparagus contains pregnanes that sooth neuro-inflammation (Jian. 2013; compounds could be present in regular A. officinalis as well) and can protect your liver and brain from aging (Xiong. 2011); 
• antiaging effects: A. contains enzymes that help with protein digestion (Ha. 2013); 
• hypolipidemic effects: n-butanol extracts from A. officinalis exert anti-hyperlipidemic effects (Zhu. 2011); 
• antimicrobial effects: A. has antibacterial activity against Escherichia coli, Shigella dysenteriae, Shigella sonnei, Shigella flexneri, Vibrio cholerae, Salmonella typhi, Salmonella typhimurium, Pseudomonas putida, Bacillus subtilis and Staphylococcus aureus (Mandal. 2000); 
• allows for geno-typing at home ;-) A. allows you to do a personal gene analysis to find out whether you have a single nucleotide polymorphism at rs4481887, which would make it impossible for you to smell the distinct odor the urine acquires after eating asparagus (Pelchat. 2011); 
• anti-hangover effects: A. helps your liver to metabolize alcohol and can even prevent a hangover (Kim. 2009); 
• buttery taste: A. contains phytochemicals which generate the sensation of having butter in the mouth (Dawid. 2013); 
• anti-stress effects: Ethanolic extracts from Asparagus racemosus have anti-stress activity and help your adrenals take a time out (Joshi. 2013)
• carbblocking effects: Asparagus racemosus inhibits the digestion of carbohydrates and enhances insulin action (Hannan. 2011); in this context it is interesting to remark that the in-vitro essay of the the study at hand suggested that A. officinalis, or rather the specific extract the scientists used in their study "has a very little effect on delaying glucose absorption" (Hafizur. 2013)
• immune promoting effects: A. racemosus ramps up natural killer cell activity (Thakur. 2013); AR also enhances memory and prevents amnesia (Ojha. 2013), 
• profound aphrodisiac effects: A dried root extract likewise from A. racemosus more than doubled the 'desire' of male rodents within 29 days (Thakur. 2009; cf. figure 2)
• MAO and acetylcholine breakdown inhibition: A. racemosus competitively inhibits acetylcholine and monoamine metabolizing enzymes (Meena. 2011)

As this highly incomplete list goes to show you, the health benefits are numerous. Unfortunately, this does also apply to the different phytochemicals which trigger all these effects. The probability that the next best extract you may find on the shelves or virtual outlets of a supplement store is actually going to to yield the health benefits you may be looking for are therefore pretty slim.

Although parts of it are edible as well, A. racemosus, is actually better known for its multitude of beneficial health effects that range from Antibacterial activity (some) antisecretory and antiulcer activity over mood enhancing and anti-depressive properties, and immunomodulatory effects to such profane things as libido enhancement or getting rid of superfluous water before a show or photo shoot.

Bottom line: In view of the practical problems associated with spotting appropriate extracts, I guess it would be best you take the fact that a 2003 paper in scientific journal Nutrition (Pellegrini. 2003) ranked asparagus 7th among 34 fruits and vegetables with respect to its free radical scavenging abilities, as an incentive to simply incorporate asparagus into your diets more frequently.

If, on the other hand, you are dealing with any specific health condition, it would certainly make sense to look for an extract that contains the proper genus of asparagus, is made from the right parts of the plant and - if possible - is even standardized for a specific compound: If you were interested in upping your estrogen levels, you would for example have to pick a whole plant extract of A. dumosus that would at best contain a standardized amount of 20-hydroxecysterone (Kaur. 1998). If it's rather the anti-ulcer effects you are after, your 'asparagus product of choice' should be made of the roots of A. racemosus ideally standardized for its Shatavairin content (Bhatnagar. 2005)... 

And now, you tell me eating healthy was complicated and taking supplements was easy ;-)

References

• Bhatnagar M, Sisodia SS, Bhatnagar R. Antiulcer and antioxidant activity of Asparagus racemosus Willd and Withania somnifera Dunal in rats. Ann N Y Acad Sci. 2005 Nov;1056:261-78.
• Dawid C, Hofmann T. Identification of Sensory-Active Phytochemicals in Asparagus (Asparagus officinalis L.). J Agric Food Chem. 2013 Nov 8.
• Ha M, Bekhit Ael-D, Carne A, Hopkins DL. Characterisation of kiwifruit and asparagus enzyme extracts, and their activities toward meat proteins. Food Chem. 2013 Jan 15;136(2):989-98. 
•  Hafizur RM, Kabir N, Chishti S. Asparagus officinalis extract controls blood glucose by improving insulin secretion and β-cell function in streptozotocin-induced type 2 diabetic rats. Br J Nutr. 2013 Nov;108(9):1586-95.
• Hannan JM, Ali L, Khaleque J, Akhter M, Flatt PR, Abdel-Wahab YH. Antihyperglycaemic activity of Asparagus racemosus roots is partly mediated by inhibition of carbohydrate digestion and absorption, and enhancement of cellular insulin action. Br J Nutr. 2011 Sep 8:1-8.
• Ji Y, Ji C, Yue L, Xu H. Saponins isolated from Asparagus induce apoptosis in human hepatoma cell line HepG2 through a mitochondrial-mediated pathway. Curr Oncol. 2013 Jul;19(Suppl 2):eS1-9.
• Jian R, Zeng KW, Li J, Li N, Jiang Y, Tu P. Anti-neuroinflammatory constituents from Asparagus cochinchinensis. Fitoterapia. 2013 Oct 24.
• Joshi T, Sah SP, Singh A. Antistress activity of ethanolic extract of Asparagus racemosus Willd roots in mice. Indian J Exp Biol. 2013 Jun;50(6):419-24. 
• Kaur H. Estrogenic activity of some herbal galactogogue constituents. Ind J Anim Nutr. 1998;5:232–4.
• Kim BY, Cui ZG, Lee SR, Kim SJ, Kang HK, Lee YK, Park DB. Effects of Asparagus officinalis extracts on liver cell toxicity and ethanol metabolism. J Food Sci. 2009 Sep;74(7):H204-8. 
• Meena J, Ojha R, Muruganandam AV, Krishnamurthy S. Asparagus racemosus competitively inhibits in vitro the acetylcholine and monoamine metabolizing enzymes. Neurosci Lett. 2011 Sep 26;503(1):6-9.
• Morales P, Ferreira IC, Carvalho AM, Sánchez-Mata MC, Cámara M, Tardío J. Fatty acids profiles of some Spanish wild vegetables. Food Sci Technol Int. 2013 Jun;18(3):281-90.
• Ojha R, Sahu AN, Muruganandam AV, Singh GK, Krishnamurthy S. Asparagus recemosus enhances memory and protects against amnesia in rodent models. Brain Cogn. 2010 Oct;74(1):1-9.
• Pelchat ML, Bykowski C, Duke FF, Reed DR. Excretion and perception of a characteristic odor in urine after asparagus ingestion: a psychophysical and genetic study. Chem Senses. 2011 Jan;36(1):9-17.
• Pellegrini N, Serafini M, Colombi B, Del Rio D, Salvatore S, Bianchi M, Brighenti F. Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. J Nutr. 2003 Sep;133(9):2812-9. 
• Thakur M, Chauhan NS, Bhargava S, Dixit VK. A comparative study on aphrodisiac activity of some ayurvedic herbs in male albino rats. Arch Sex Behav. 2009 Dec;38(6):1009-15. Epub 2009 Jan 13.
• Thakur M, Connellan P, Deseo MA, Morris C, Praznik W, Loeppert R, Dixit VK. Characterization and in vitro immunomodulatory screening of fructo-oligosaccharides of Asparagus racemosus Willd. Int J Biol Macromol. 2013 Jan 1;50(1):77-81.
• Zhu X, Zhang W, Pang X, Wang J, Zhao J, Qu W. Hypolipidemic effect of n-butanol Extract from Asparagus officinalis L. in mice fed a high-fat diet. Phytother Res. 2011 Aug;25(8):1119-24.

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. 2013)

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. 2013)

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. 2013)... 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. 2013), 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, 2013 < http://www.usatoday.com/news/health/story/2013-05-07/obesity-projections-adults/54791430/1 > accessed Aug 07, 2013
• 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. 2013 [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. 2013 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, 2013. 
• 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.

Passionate Diabesity Prevention: Passion Fruit Rind Extract Halves Weight Gain & Quadruples HDL on Regular Diet

Image 1: Looks like color matters! The yellow variety of Passiflora edulis is not just a particularly rich source of low-methoxyl pectin (dietary fiber), it's also packed with other bioactive substances which could keep you lean and healthy!

The title of the paper Sandra Maria Barbalho and colleagues published in the Journal of Diabetes Research & Clinical Metabolism a couple of days ago is quite telling "Yellow passion fruit rind (Passiflora edulis): an industrial waste or an adjuvant in the maintenance of glycemia and prevention of dyslipidemia?", as it does imply that we could once again have missed an important part of the whole picture in our never-ending strive for ever maximal standardization, isolation and convenience: The waste that is generated from Brazil's 35,000 hectare passion fruit industry, more than 317,000 metric tons of fiber-, mineral., vitamin-, phenol- and flavenoid-laden flavedo (colored part of the rind) and albedo (white part of the rind) from Passiflora edulis.

Passion Fruit Rind - Nothing in Nature is Wasted!

If we dig somewhat deeper into the archives of the medical, chemical and even historico-cultural journals, it's not as if we could not have known about the potential health benefits of the putative "natural packaging" that protects the juicy kernel of the fruits of a plant which belongs to the family Passifloracea and originated in the tropical and subtropical regions of the American continent. Previous studies by Deng, Janebro and Ramos, for example, did already hint at the potent anxiolytic, antihyperglycemic and antihyperlipedemic effects of a fruit that has a longstanding tradition in traditional medicine (Ramos. 2007; Janebro. 2008; Deng. 2010). Against that background, it is almost surprising that the existent literature on the use of respective extracts is not exactly comprehensive.

Figure 1: Changes in body weight (in g), absolute serum values (mg/mL) for glucose, triglycerides, cholesterol (total), HDL-C and LDL-C after 30 days of either regular or passion fruit bark powder solution (2x 1ml/kg body weight) supplemented diet in healthy Wistar rats (data adapted from Barbalho. 2013)

Malicious gossip would probably have it that the surprisingly profound effects Barbalho et al. observed in healthy rodents in response to the twice-daily administration of 1ml/kg bodyweight of a quasi-homemade (see infobox on the right of the next paragraph for details), obviously non-patentable passion fruit extracts would hamper the sales of metformin, lipitor and the recently FDA-approved weight loss drug Belviq (a 5-HTC-2 serotonin receptor antagonist). After all, aside from the decrease in LDL, all the diabetes- and  CVD relevant changes in figure 1 were statistically highly significant (p<0.01); and what's more, the necessary raw material is not just looked down upon, as if it was a waste product, it is according to the authors also treated like any other industrial waste by Brazil's passion fruit juice industry who either dumps it on illegal landfills or has to pay money for its proper disposal (Barbalho. 2013).

My GNC Does Not Have Passion Fruit Rind Extracts! Can I Make My Own?

How to home-brew your own PFR extract ;-)

1. dehydrate the rind on trays in a forced air circulation drying oven at 55ºC until a constant dry weight is reached
2. ground 200g into powder in a multiprocessor for 6 minute (turn off the processor at 2 min intervals to stir the product)
3. prepare a solution of 20 g of powdered rind and 500 mL of water
4. beat solution in a blender for 12min 
5. filtered through filter paper
6. divide resulting solution into aliquots and stored in a freezer at -10ºC

Ingest 2x10-14ml servings per day (standard HED calculation)

Ecology and health aside, I bet that for (too) many people the -76% reduction in weight gain would constitute the most convincing argument to buy Passion-o-Lean(TM) or whatever stupid name the first company whose "product designer" reads the study will come up with ;-)

Now, the good news is that we do actually have human data to confirm a statistically significant weight loss effect from passion fruit rind products: The nineteen 30-60 year-old, still normal-weight (BMI 24.8kg/m²) but hyperlipidemic (cholesterol > 200 mg/dL; went down by -18% as a result of supplementation) women in the aforementioned study by Ramos et al. lost 1.7 kg within one month (Ramos. 2007), but they did ingest 30g of passion flower rind flour per day and the weight loss stalled in the second month in the course of which they lost <300g, only - by no means as impressive as the weight loss, or, I should say, the absence of weight gain in the rodents from Barbalho study, right?

Due to the fact that Ramos et al. don't disclose how the co-authoer Sabaasrur, who provided the flour, actually prepared it, we cannot definitely answer the question whether or not these differences could simply be a result of the different preparation methods and consequent yield of bioactive substances in the extract (Barbalho. 2013) and the flour (Ramos. 2007). It is however very unlikely that the production of the floor involved either low temperature drying (1), water extraction (3-5) or refrigeration to maintain the maximal vitamin and phenols content (see figure 2) as they were part of the manual extraction process that was used in the Barbalho study (for details on the preparation see box on the left).

Figure 2: If you are more of a juicer, make sure to drink your juice right away to get the maximum amount of the good phenolic acids and avoid the potentially hazardous HMF (click to enlarge for more info; data based on Talcott. 2003)

Implications: Despite the fact that the data in figure 2, though based on an analysis of passion fruit juice, would support the hypothesis that the handmade passion fruit rind extract in the Barbalho study was more than just one magnitude "stronger" than the flour that's been used with some success in the Ramos and the Janebro study, it is still questionable, whether the profound reductions in blood glucose, the  improvements in the triglyceride (1.3 vs. 4.3) and total cholesterol to HDL ratios (2.5 vs. 10.4) will translate 1:1, or even at all to human beings. After all, it could be partly mediated by the reduced weight gain... apropos, 'not gaining weight' is still very different from 'losing weight' and it is therefore not feasible to compare, the relatively mediocre weight loss in the Ramos study, of which the scientists assume that it was, just as the reduction in cholesterol, mediated by the high content of soluble fiber in the passion fruit flour (73% of the dry matter is fiber, 60% of it insoluble; Yapo. 2008), to the profound 'anti-obesity' effect in the Barbalho study.

Moreover, in the absence of detailed information about the body composition of the lab animals and their energy intake, we could as well be dealing with the results of micronutrient malabsorption or anorexia as root causes of the reduced body weight in the passion fruit rind extract group of the Barbalho study.... although, with the twice daily bolus administration of only 2x 1ml of the PFR extract, both explanations, i.e. 'failure to thrive due to nutrient malabsorption' and 'anorexia in response to too much fiber', appear pretty unlikely, so that passion fruit rind extract would actually be a good candidate for a home-brew diabesity prevention potion... well, at least if you live next to one of those Brazilian dumping grounds where the passion fruit industry disposes of their hitherto unrecognized treasures ;-)

References:

• Barbalho SA, da Silva Soares de Souza M, de Paula e Silva J, Mendes CG, de Oliveira GA, Costa T, Farinazzi-Machado. Yellow passion fruit rind (Passiflora edulis): an industrial waste or an
  adjuvant in the maintenance of glycemia and prevention of dyslipidemia? FMV. Journal of Diabetes Research and Clinical Metabolism. 2013.
• Deng J, Zhou Y, Bai M, Li H, Li L: Anxiolytic and sedative activities of  Passiflora edulis f. flavicarpa. J Ethnopharmacol  2010; 128;(1.);148-53.
• Janebro D I, Queiroz M S R, Ramos A T, Sabaa-Srur A U O, Cunha MAL,  Diniz M F. Effect of the flour of the yellow passion fruit peel (Passiflora  edulis f. flavicarpa Deg.) in the glycemic and lipid levels of type 2 diabe- tes patients. Rev Bras Farmacog 2008;18: 723-732. 
• Ramos AT, Cunha MAL, Sabaasrur AUO, Pires VCF, Cardoso AA et al. Use of Passiflora edulis f. flavicarpa on cholesterol reduction. Braz J Pharmacog 2007;17: 592-560.
• Talcott ST, Percival SS, Pittet-Moore J, Celoria C. Phytochemical composition and antioxidant stability of fortified yellow passion fruit (Passiflora edulis). J Agric Food Chem. 2003 Feb 12;51(4):935-41.
• Yapo BM, Koffi KL: Dietary fiber components in yellow passion fruit rind - a potential fiber source. J Agric Food Chem  2008; 56;(14.);5880-3. 

Fat Content Per Energy Drink 0g, Body Fat Gain Per Energy Drink 18g! Human Trial Confirms: +1kg of Body Fat in 4 Weeks From Less than 2x Energy Drinks per Day!

Image 1 (NYC Dept. of Health & Mental Hygiene): The words on this poster from a 2009 campaign in the NY subway must be taken literally!

There is a reason for me to always begin my "dietary advice" with the statement "there is NO WAY that you ever again drink any soft, energy drinks or fruit juices on a daily basis". And though I would not have needed a study to confirm skipping, lemonade, coke & co is one of the simplest, for many people yet not easiest steps to a healthier and leaner physique, I must admit that I was pretty surprised how rapid both your health and body composition deteriorate, once you reintroduce this junk into your diet. +1kg of pure body fat in 4 weeks, that was the amount of weight the 11 healthy men and women in a recently published study by scientists from the UK, Italy and the US gained within just 4 weeks in the course of which they drank on average two more or less tasty Lucozade Energy drinks per day (Sartor. 2013).

Fat content of energy drink 0g, body fat gain per energy drink 18g!

Figure 1 (gsk): Nutritional information of the energy drink the subjects drank during the 4-week study period

Sartor et al. about whose study on the "habituation effects" of sweet beverage you may already have read in one of the installments of the Insulin Resistance Saga (cf. "Where Has All the Sweetness Gone? Plus: Bullied to Eat Twinkies") had recruited 11 healthy young men (n=5) and women (n=6) with a mean age of 26 years, who were handed a month's supply of GlaxoSmith Kline's yummy Lucozade Energy of which they had to drink ~2 bottles per day (2x 380ml; in fact the average intake was only 760ml and was matched to deliver 2g carbohydrates per kg body weight; for detailed "nutritional" information based see figure 1) - just to make that clear, I suspect the results would not have been much different if this had not been Lucozade, but plain Coke, if the daily consumption (1.2l) had delivered the same amount of sugary carbs.

Apropos effects, if you take a look at the actual data in figure 2 it is quite obvious that the increase in body fat did not occur in the absence of the rise of other characteristic features of the metabolic syndrome, i.e. changes in blood glucose and lipid metabolism.

Figure 2: Changes in body composition, HOMA markers of insulin resistance, sensitivity and pancreatic function, as well as blood lipids after 4 weeks of sugar-sweetened beverage consumption (based on Sartor. 2013)

A particular reason of concern - at least in my humble opinion - are the rapid (remember these deteriorations occurred within only 4 weeks!) reductions in HOMA measure insulin sensitivity / increases in HOMA based insulin resistance measures. Which would only exponentiate the detrimental effects of the daily glucose overload.

High blood glucose, high RER, high insulin, but no increase in energy intake

Together with the significantly increased fasting glucose (+6%) and fasting insulin levels (+25%) and the accompanying reversal of the fat-to-carbohydrate oxidation rates from 2:1 to 1:3 in the fasted state this does already suggest that this is once more not solely an effect of an increase in energy intake as conventional wisdom would have it!

Figure 3: Changes in macronutrient composition and non-existent changes in total caloric intake over the course of the 4 weeks of sugar-sweetened beverage consumption (based on Sartor. 2013)

If you take a closer look at the data in figure 3 you can even drop the "solely" from the previous sentence and state: "the obesogenic effect of sugary beverages has no relation whatsoever to an increase in overall energy intake!"

Its not so much about how much, its about what and which!

It stands to reason that this increasingly accepted "violation" of the rules of thermodynamics *rofl* did not go unnoticed by Sartor et al., who had also analyzed the expression of several genes in samples of the skeletal muscle tissue of their subjects and found that there were statistically significant

• increases in glyceraldehyde-3-phosphate dehydrogenase (GAPH), acetyl-CoA carboxylase alpha (ACC) and MonodA mRNA expression, which are indicative of increased glycolysis, decreased fatty acid oxidation and an increased cellular awareness of blood sugar abundance, respectively, as well as a significant
• decrease in peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1a), of which you have read in relation to Irisin in "If a High Fat Diet was a Pill, the Lay Press Would Celebrate it as Exercise in a Pill!" that it is responsible for increases in mitochondrial firepower and fatty oxidation capacity

Much more so than the 1kg of body fat, which should be relatively easy to shed by simply pouring energy-, soft-drinks & co down the sink, instead of downing them with a gulp, these transcriptional (epigenetic) changes and the previously reported deteriorations in taste perception in response to the consumption of sugar (not fructose!) sweetened beverages (Sartor. 2011), are the real alarming results of this 4-week trial. After all, they are the ones that predispose to future fat gain, diabetes and hyperlipidemia!

So, what can be done?

Image 2: OTC solution to the problem? Water + Workout

Luckily there is a tried and proven non-pharmacological solution to this problem, an OTC double-whammy, if you will that is not just free, but will actually save you truckloads of money! Initially for all the energy drinks and soft-drinks you are not buying anymore and for all the medication the medical bill's and the XXL coffin for your funeral in the weeks, months, years and decades to come. What? You want to know what this OTC double-whammy is? Plain water and regular exercise! While the former is equally if not more thirst-quenching than the differently colored sugar waters, the latter will help to gradually reverse the epigenitic changes and restore a healthy glucose and fatty acid metabolism.

References:

1. GlaxoSmithKline (gsk). Lucozade Official Shop. Lucozade Energy - Original. 2013 < http://www.lucozadeshop.com/lucozadeenergy/lucozadeenergyoriginal > Received on June 30, 2013.
2. Sartor F, Donaldson LF, Markland DA, Loveday H, Jackson MJ, Kubis HP. Taste perception and implicit attitude toward sweet related to body mass index and soft drink supplementation. Appetite. 2011 Aug;57(1):237-46. 
3. Sartor F, Jackson MJ, Squillace C, Shepherd A, Moore JP, Ayer DE, Kubis HP. Adaptive metabolic response to 4 weeks of sugar-sweetened beverage consumption in healthy, lightly active individuals and chronic high glucose availability in primary human myotubes. Eur J Nutr. 2013 Jun 26.