Natural Sildenafil & Testosterone Alternatives: Pedalium Murex & Paederia Foetida +150% Testosterone and +200% Erectile Function. Plus: Icariin, Aromatase & Stronger Bones. Probiotics, Phytosterols & Thyroid Activity.

If the Aliens have seen these Bugarash apocalypse pilgrims, they have probably turned tail and fled ;-)

I guess the SuppVersity figure of the week was a date "12/21/2013", I mean this is a once in a life-time event! Or do you really believe there will be another chance for mankind to be snatched from the jaws of extinction?

Ok, enough of the sarcasm, the world is still there and the SuppVersity is still operating, so let's get to the not so short On Short Notice items for today.

If there had been more room in the headline I would probably have labeled it "Endocrine Special" and I guess once you have gone through the posts, you will agree that this would certainly have made sense.

• Traditional treatment of osteopenia with Epimedium brevicornum works, 'cause it's a potent aromatase promoter (Yang. 2013) -- When a group of researchers from the Chengdu Institute of Biology, Chinese Academy of Sciences and the School of Chinese Pharmacy, Chengdu University of Traditional Chinese Medicine in Chengdu, China, set out to investigate the mechanism behind the anti-osteoporotic effects of the dried leave extract from Epimedium brevicornum, they already suspected that it would probably be related to some sort of endocrine modulation.
  
  

  

  Figure 1: In vitro effect of Forskolin and Icariin on aromatase expression in KGN cells (Yang. 2013)

  With estrogen deficiency being the major cause of osteoporosis, a disease which does by the way affect over 200 million people worldwide (Riggs. 1998), being their the most likely mechanism behind the bone building and bone mineral density (BMD) protective effects, it was obvious to study, whether there was some sort of interaction between the extract and the data in figure 1 shows that Yang et al. were right to do so (note: the cell line used in the study was a KGN granulosa cell that's closely associated with the developing female oocyte, so effects could vary from one tissue to the other)
  
  Now all that certainly sounds as if this was bad stuff no sane male human being should be taking. Luckily, for many of you, my fellow men, who may have been exposed to Epimidium / Icariin from various supplements, this is not the case. Why? Simply because estrogen is not the enemy and Epimidium has not only been found to have anti-aging effects (whole extracts; Yan. 2009), it also prevents neurotoxicity from beta-amyloid plague the key feature of Alzheimer's and similar diseases (Zeng. 2010; listen to Thursday's Science Round-Up for other amyloid beta inhibitors / protectant's) and the neurotoxic effects of excess corticosteroids (Liu. 2011). In addition, Epimidium pubescen flavenoids have been shown to reverse the negative effects even passive exposure to cigarette smoke may have on the bone mineral density of male rats (Gao. 2013) and Icariin the common denominator in all of the members of the Epimidium family exerts direct proliferative and thus pro-fertility effects on the sertoli cells in male rodents (Nan. 2013).
  
  

  

  Table 1: Analysis of Chinese Epimidium species (MDida. 2010)

  Ah, and last but not least the beneficial effect Horny Goat Weed (likewise one of the members of the Epimidium family) has on male libido are likely partly a result of the increased aromatase activity, as well. If it works for you, your estrogen levels are probably pretty low to begin with (this reasoning is based on the profound beneficial effects of estrogen on male libido in men expressing little to no aromatase enzyme; Carani. 1999).

• Pedalium murex Linn. fruits may not be as potent acute libido and erectile performance enhancers as sildenafil, but the effects accumulate and persist just as its unique testosterone boosting effects (Sharma. 2013) -- In case taking a potential proestrogenic compound like Horny Goat is nothing you feel would do anything good for your libido, you may want to use some Pedalium murex Linn. in traditional Indian medicinea herb that has been used in traditional Indian medicine for centuries to treat male sexual dysfunction and impotency.
  

  

  Figure 2: Effects of different doses of an ethanolic extract from Pedalium murex (P.m.) and Sildenafil citrate (5mgkg) on penile erection scores and post ejaculatory interval (time it takes to be able to have sex again) exrpessed relative to saline treated control (based on Sharma. 2013)

  As the data in figure 2 shows, its effects on erectile performance are slightly less pronounced than those of sildenafil citrate, but at an appropriate dosage and after some time, it will probably do its job sufficiently for most men with respective problems. What's really exiting though, is that the data in figure 3 clearly shows that it does so not by simple nitric oxide effects (P. murex at 10 mg/
  ml exhibited a relative nitric oxide release of 15.3 mM as compared to a nitric oxide release of 39.3472.7 mM with sildenafil citrate), but probably (also) by boosting testosterone levels. 
  
  

  

  Figure 3: Serum testosterone levels during and after Pedalium murex or Sildenafil citrate administration expressed relative to saline control (Sharma. 2013)

  Since the testosterone levels remained elevated for 14 days after the treatment was seized these observations make P. murex a potential candidate for the next best natty test booster.to be powered by advertisement lines like "up to 125% increase in testosterone that last for more than 2 weeks" even when you take some time off. I guess, the only serious downside here is the close relation of P. murex to the notoriously useless Tribulus, which does also contain furostanol glycosides. Luckily Magnle and Jolley found another potentially active ingredient in P. murex fruit. The compound goes by the name diosgenin and appears to be a direct precursor for the synthesis of sex hormones including testosterone (Mangle. 1998).
  
  Since I don't think you will have to wait very long until the first major players in the supplement business will jump on this bandwagon - you know that a single rodent study is enough to make fortune until people realize that this stuff does not work, at all - you will probably soon be able to test it on yourself. In case you intend to do that, you should certainly look for a standardized ethanolic extract with ~20%+ of diosgenin (that was the content of the extract Sharma et al. used) and a serving size of 16.2mg/kg per body weight, the HED of the 100mg/kg group (that would be 1,300mg /day of the extract for an 80kg adult).

• Paederia foetida Linn. (P. foetida) yet another Indian libido and testosterone boosting herb (Soni. 2013) -- If you like the appeal of exclusiveness a climbing plant found in the Central and Eastern Himalayas, at elevations of up to 5000 ft, you may prefer the an ethanol extract of Paederia foetida Linn. (P. foetida) leaves over the previously discussed Pedalium murex fruit extract.
  
  

  

  Figure 4: Penile erection index and testosterone levels of rats after 15 and 28 days on P. foetida, data expressed relative to saline control (Soni. 2013)

  According to a recent study from the same group of Indian scientists (yet a different lead author), the effects of P. foetida and P. murex are in fact virtually identical. While the general protocol was very similar (in this done on rat, not mice) the positive control was not Sildenafil citrate, as in the previously mentioned experiment, but an intramuscular injection of 0.5 mg/kg body weight of testosterone suspension in arachis oil twice a week. It's actually a pity the scientists didn't measure the actual testosterone levels in the animals in the testosterone group. I would be curious how the 2.5x increase in the high dose group (200mg/kg, human equivalent ~2,600mg/day) would compare. When it comes to the erection quality, it did at least easily top the results of injectable testosterone (see figure 4), which is yet allegedly not the best erection booster, anyway. And if we went by the data on body weight and the weight of the testes, seminal vesicles, prostate glands and epididymis, it even appears to be more anabolic than testosterone; after all the body weight gain in the PF groups were 15%. 23% and 34% higher than in the control group and comparable if not higher to those that were induced by testosterone (+29%).
  
  And for all the supplement producers and fans of stacks it may be important to know that the leaves of P. foetida, which is also used as carminative, antiinflammatory, astringent, spasmolytic, antidiarrhoeal, diuretic and antilithic do contain a whole host of well- and lesser known compounds, e.g. iridoid glycosides, sitosterol, stigmasterol, campesterol, ursolic acid, hentriacontane, hentriacontanol, ceryl alcohol, palmitic acid and methyl mercaptan, but no diosgenin. So Ayurvedabol (TM) or whatever name ending on -bol, -drol or -ripp-off has not been used by the creepy competition, already, could benefit from having both Paederia foetida and Pedalium murex in it ;-)

• Combination of probiotics and phytosterols ramps up thyroid function and (re-)establishes a healthy lipid profile (Awaisheh. 2013) -- While I could offer you a minimum of two additional libido enhancing, potentially pro-anabolic testosterone booster, I know that not all of you are into these products (am I right ladies?), so I thought it prudent to close this installment of On Short Notice with a study on thyroid metabolism, which could be is of interested for all of you.
  
  
  Which phytosterols are there and where can I find them? The major phytosterols in the human diet are sitosterol (high in nuts, amaranth, avocados, grape leaves), stigmasterol (high in coriander, chocolate and soy), campesterol (high in various vegetable oils, spec. conola / rapeseed) and brassicasterol (high in cabbage, broccoli, other brassica, but also coriander, seafood and rapeseed oil).
  Contrary to some previous studies and anecdotal reports on the Internet, a recent paper by scientists from the Department of Food Science at the Al-Balqa Applied University, in Salt, Jordan, suggest that phytosterols don't have thyroid inhibiting, but promoting effects.
  
  In their latest study Awaisheh et al. investigated the effects of a probiotic stack containing two strains of each of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus gasseri, and Lactobacillus reuteri and a phytosterol supplement on the lipid metabolism in rodents. Their results show that the addition of the phytosterol supplement promoted the already pronounced effects the probiotics had on the hypercholesterolemia of the rodents who were fed with a high-fat-high-cholesterol basal diet for 8 weeks. In addition, the phytosterols, yet not the probiotics alone, elevated the levels of serum total thyroxine (TT4), total triiodothyronine (TT3), and free triiodothyronin (fT3), which could have exerted additional benefits on the non-measured triglyceride levels.
  
  These results do actually come as a surprise and I would like to see more research - specifically in human trials - before I would buy products from producers who seize the scientists suggestion that this renders probiotics and phytosterols potential candidates for "functional foods" - I mean, let's be honest ever since the first "functional foods" hit the market people have been getting sicker: Do you really believe that's because they don't eat the "good" cholesterol lowering margarine instead of their beloved Kerrygold butter? I don't think so.

That's it for today.. well, aside from the promise to include the other testosterone and libido boosting herb studies in another SuppVersity post and a selection of the latest  SuppVersity Facebook News, of course:

• Iron deficiency makes H Pylori go on a rampage - Iron deficiency enhances H. pylori virulence and increases risk of gastric cancer (read more)
• Danish folk medicine for depression? Not really, but there are a couple of promising natural MAO-A inhibitors the Danes have been using for centuries (read more)
• Strength training equally heart healthy as aerobics - 6-weeks of strength training show particular beneficial effects in African American men (read more)

Since I it's still pretty early and I am certainly not going to the city, before the shops close and all the people who believed they wouldn't need Christmas presents this year, since the world would *put whatever apocalyptic catastrophe you like here*, have gone home, I may be adding some more news later. Until then, I hope you have some fun with what's already there and are looking forward for the 2nd installment of the "Making HIIT a Hit" series that will be published tomorrow.

References:

• Awaisheh SS, Khalifeh MS, Al-Ruwaili MA, Khalil OM, Al-Ameri OH, Al-Groom R. Effect of supplementation of probiotics and phytosterols alone or in combination on serum and hepatic lipid profiles and thyroid hormones of hypercholesterolemic rats. J Dairy Sci. 2013 Nov 22.
• Carani C, Rochira V, Faustini-Fustini M, Balestrieri A, Granata AR. Role of oestrogen in male sexual behaviour: insights from the natural model of aromatase deficiency. Clin Endocrinol (Oxf). 1999 Oct;51(4):517-24.
• Gao SG, Liu H, Li KH, Liu WH, Xu M, Jiang W, Wei LC, Zhang FJ, Tian J, Xiao WF, Yang Y, Song Y, Lei GH. Effect of Epimedium pubescen flavonoid on bone mineral density and biomechanical properties of femoral distal end and femoral diaphysis of passively smoking male rats. J Orthop Sci. 2013 May;17(3):281-8.
• Liu B, Zhang H, Xu C, Yang G, Tao J, Huang J, Wu J, Duan X, Cao Y, Dong J. Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary cultured rat hippocampal neurons. Brain Res. 2011 Feb 23;1375:59-67. 
• Mangle MS, Jolley CI. HPTLC studies on Tribulus terrestris (Chota ghokru) and Pedalium murex (Bada ghokru). Indian Drugs. 1998; 35:189–194.
• MDidea Extracts Professional. Horny Goat Weed or Epimedium Herb: Botanical Origin, Archeology, Traditional and Pharmacological findings of Epimedium species, fractions and isolated components. 08th, Oct. 2010. < http://www.mdidea.net/products/herbextract/icariin/data10.html > retrieved on 12/21/2013. 
• Nan Y, Zhang X, Yang G, Xie J, Lu Z, Wang W, Ni X, Cao X, Ma J, Wang Z. Icariin stimulates the proliferation of rat Sertoli cells in an ERK1/2-dependent manner in vitro. Andrologia. 2013 Nov 7.
• Riggs BL, Khosla S, Melton LJ 3rd. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res. 1998 May;13(5):763-73. 
• Sharma V, Thakur M, Dixit VK. A comparative study of ethanolic extracts of Pedalium murex Linn. fruits and sildenafil citrate on sexual behaviors and serum testosterone level in male rats during and after treatment. J Ethnopharmacol. 2013 Aug 30;143(1):201-6.
• Soni DK, Sharma V, Chauhan NS, Dixit VK. Effect of ethanolic extract of Paederia foetida Linn. leaves on sexual behavior and spermatogenesis in male rats
• Yan S, Wu B, Lin Z, Jin H, Huang J, Yang Y, Zhang X, Shen Z, Zhang W. Metabonomic characterization of aging and investigation on the anti-aging effects of total flavones of Epimedium. Mol Biosyst. 2009 Oct;5(10):1204-13.
• Zeng KW, Ko H, Yang HO, Wang XM. Icariin attenuates β-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells. Neuropharmacology. 2010 Nov;59(6):542-50.

Probiotics + Green Tea - Synergistic Superstack or Sciency Non-Sense? Green Tea Alone Totally Blunts HFD Induced Weight Gain, L. Plantarum Does Not Add to Its Effects

L. plantarum may metabolize green tea phenols, but don't add to their anti-diabesity effects 

Green tea has actually never seized being all the rage and probiotics are the sexy new kid on the block right around the corner of the supplement shops and and science laboratories of the western hemisphere. Against that background I guess that the title of a paper that's been published ahead of print on Monday will probably suffice to catch your interest: "Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice." (Axling. 2013) - and that despite the fact that "mice are no little men" ;-)

'1 + 1 =4' the synergism of green tea and probiotics could make it possible

I guess, the idea sounds logic: Take one thing that has been proven to ameliorate diet induced obesity, namely green tea, and combine that with another one, of which it appears as if it would also exhibit beneficial effects into an even more potent stack. In fact, the scientists' rationale was yet slightly different:

"The species Lactobacillus plantarum (L. plantarum) has the ability to metabolize phenolic acids  and to split up tannins. The metabolites are presumably more easily absorbed and distributed into the tissues where they can act as antioxidants and electron scavengers. Phenolic compounds can also have antimicrobial effects that may affect the composition of the gut microbiota, in favour of polyphenol-metabolizing components of the microbiota. Also, green tea extracts have been shown to selectively inhibit the growth of pathogenic bacteria while either enhancing or not affecting the growth of beneficial bacteria like lactic acid bacteria. To the best of our knowledge, the impact of green tea powder as a prebiotic compound to promote lactobacilli or other health promoting components of the microbiota has not previously been evaluated."

In other words, the expected benefits of providing both green tea and probiotics in conjunction were (1) an increased bioavailability of the phenols and tannins from the green tea that would be induced by the probiotics and (2) an increase in the probiotics' survival and ability to modify the gut microbiome that would be brought about by the addition of the green tea.

What looks good on paper does not necessarily work out in a complex organism

Figure 1: Ingredient total amount of Flavan-3-ol, Phenolic acid and Flavenol in water and methanol extracts from the green tea leaves that have been used in the study (Axling. 2013); as you can see the total quantity and the ratios of the bioactive ingredients of the extract actually depend on the extraction method.

Apropos green tea, you can see the exact ingredient profile of the green tea supplement that has been used in the study at hand in figure 1. In view of the fact that the C57BL/6J mice received no extract, but simply powdered green tea leaves, it may not be important in this context, but could be relevant for your future purchases that methanol and water extracts differ not only in terms of the total amount of Flavan-3-ol, Phenolic acid and Flavenol they contain, but also with respect to the ratio of the respective phytochemicals. I guess, those of you who have been around in September 2011, already, will remember that I have discussed the impact these ostensibly negligible differences can have more than a year ago in "-20% Reduction in Serum Testosterone by 5 Cups of Green Tea. Endocrine Effects Depend on Catechin Composition". In case you are one of the many newcomers or have simply forgotten (let alone missed ;-) this post, I suggest you go back and read that up, as it may help you get a better understanding of the underlying reasons due to which quality and quantity of the health effects of green tea (supplements) wary from study to study... but let's now get back to the experimental setup of the Axling study.

Green tea alone already blunts HFD induced weight gain

As mentioned before the extracts were simply mixed with the high fat diet, the mice were consuming in the course of the 22 week study period. With the probiotic supplement that was administered with the drinking water (L. plantarum at 1.5% (v/v) or roughly 3 × 10^9 cfu/ml) we are thus dealing with four different groups:

• Control: High fat chow + no supplement
• LP: High fat chow + L. plantarum
• GT: High fat chow + green tea
• GT + LP: High fat chow + green tea + L. plantarum

If you focus solely on the initially quoted hypothesis about the synergistic effects of green tea + L. plantarum, the actual study outcomes - at least as far as the blood markers in figure 2 are concerned  - are certainly disappointing.

Figure 2: Glucose insulin, fructosamine, cholesterol, triacylglycerol, non-esterified fatty acids and adiponectin levels in the blood of the mice in week 11 and week 22 of the study (Axling. 2013)

It's not like '1+1 would equal 4', but rather like '1 + 1' would just be sufficient to yield '1' not just '0.9' or even less. The in fact, the addition of the probiotics, alone, did very little within the first 11 weeks as far as it's ability to th reduce the diet-induced insulin resistance is concerned and it's addition to the green tea supplement did not improve blood glucose and lipid management, but did in fact diminish the impressive effects the green tea supplement brought about.

Figure 3: Relative change (compared to control) in bacterial diversity and lactobacilli count in response to the supplement regimen (Axling. 2013)

That the probiotic was basically useless, is actually no wonder if you take a closer look at the changes of gut microbiome in figure 3. Aside from an intermediate increase in lactobacilli, it could not boost the amount of these supposedly healthy bacteria in the long term. Rather than that it did induce an allegedly statistically non-significant decrease in the overall diversity (figure 3, left).

Minor differences with quasi-nonexistent real-world effects

At the mRNA level, the addition of L. planatrum counter-acted the anti-obesity effects of green tea, as evidenced by

Figure 4: Body weight and fat levels of the mice (Axling. 2013)

• 20% higher fatty acid synthase levels, an enzyme that's responsible for the synthesis of fatty acid
• the reversal of the statistically significant reduction in acetyl-CoA caroxylase (ACC), an enzyme that's one step ahead of FAS in the cascade of which you could say that it supplies the raw material for fatty acid synthesis, and
• minimally higher PPAR-gamma levels (responsible for fat storage) 

in the LP + GT vs. GT group, respectively. The net effects on body weight and fat mass, on the other hand were negligible. In essence the bulk of the beneficial effects of the green tea extract remained intact. Moreover, the addition of L. plantarum did have two distinct effects, that were not observed in the GT only group:

Figure 5: Liver cholesterol and HMG-CoA-R after 11 (top) and 12 (bottom) weeks (Axling. 2013)

1. a statistically non-significant -20% reduction in the mRNA expression of the inflammatory marker TNF-alpha, and
2. a whopping and surprising increase in HMG-CoA reductase of +50% and +70% increase in HMG-CoA reductase mRNA compared to the green tee only and the control group, respectively

And while there is nothing in the study that would suggest that there were any beneficial effects from the TNF-alpha reduction, the increase in HMG-CoA reductase is in fact an oddity. After all, despite statistically significant increases in the enzyme that's responsible for the synthesis of cholesterol and the main target of statin drugs (Stancu. 2001), the cholesterol levels dropped by 64% and 39% compared to the control group, in weeks 11 and 22, respectively.

What do these Jerusalem artichokes, agave, bananas, burdock, camas, chicory, coneflower, costus, dandelion, elecampane, garlic,jicama, Leopard's-bane, mugwort, onion, wild yams, yacon and a whole host of other foods have in common? Right! They contain inulin. which has only recently been shown to have the ability to ameliorate body weight gains by up to 50%! Intriguing? Go back to my previous post and learn more about inulin, beta-glucans and their anti-diabesity effects.

Bottom line: A non-statistically significant reduction in TNF-alpha and an elevation of cholesterol synthesis in the presence of lower liver cholesterol levels, which would be suggestive of an increased excretion of cholesterol (thus the increased synthesis to come up for the loss), are in my humble opinion nothing that would render the combination of green tea + L. plantarum superior to the provision of green tea alone. The latter on the other hand, appears to be a great tool to keep the damage of the energy-dense Western diet in check - with no added, let alone synergistic benefit of these particular probiotic.

Maybe the provision of another probiotic or even another strain of L. plantaris would yield at least '1 + 1' results. This would yet be a research question for another study (one I would by the way not be willing to finance ;-) and does not change the fact that the original research hypothesis that there would be a potentiating effect due to the synergism of the two supplements is - even if the scientists don't openly acknowledge that - debunked for L. plantaris DSM 15313 and green tea.

References:

• Axling U, Olsson C, Xu J, Fernandez C, Larsson S, Ström K, Ahrné S, Holm C, Molin G, Berger K. Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice. Nutr Metab (Lond). 2013 Nov 26;9(1):105.
• Stancu C, Sima A. Statins: mechanism of action and effects. J Cell Mol Med. 2001 Oct-Dec;5(4):378-87.

Standard American Diet Has 'Optimal' Fatty Acid Ratio to Induce Diabesity. Plus: Study Shows Doubling Saturated Fats Would Yield More Benefits Than Halving Them

Study confirms: The SAD diet yields 'optimal' results (img. forbes.com)

Since this post is already lengthy enough, I will spare you how saturated fatty acids have long falsely been accused as the sole driving force of the western obesity epidemic and how the tides appear to be slowly yet steadily appear to be turning, as scientists delve deeper and deeper into the interactions of the total fat content in the diet, its fatty acid composition and the interaction of both with the two other macronutrients and their specific forms and get right to the study at hand. A study that appears in the current issue of the Journal of Lipid Science and deals with the first of the aforementioned interactions. The one that focuses on the total fat content and the individual fatty acid make-up of the diet (Enos. 2013).

Fat shoot out: Saturated vs. mono vs. PUFA

As Enos et al. point out, the main purpose of their study was to examine the effects of three high fat diets differing only with respect to the percentage of total calories from saturated fats.

• SFA-6% - contained 6% saturated fats,
• SFA-12% - contained 12% saturated fats, and
• SFA-24% - contained 24% of saturated fats

While the the high fat diets were set to have an identical fat (40% of the energy), carbohydrate (45% of the energy) and protein content, the two control diets were low in total fat (12%/68%/20% of the energy from fat/carbs/protein). They did however likewise differ as far as their fatty acid composition is concerned, with the modified chow mirroring the ratios (!) not the amounts of mono- and polyunsaturated fatty acids of the high fat chow (see figure 1).

Figure 1: Fatty acid composition (left) and their sources (right) that were used in the different diets the rodents were fed for 16 weeks (based on Enos. 2013)

The diets were administered for 16 weeks. Body composition and metabolism (glucose, insulin, triglycerides, LDL-C, HDL-C, total cholesterol) were examined monthly.  Adipose tissue (AT) expression of marker genes for M1 and M2 macrophages and inflammatory mediators (TLR-2, TLR-4, MCP-1, TNF-α, IL-6, IL-10, SOCS1, IFN-γ) was measured and so on and so forth... and the results were... well, not exactly as you may have expected (the latter statement assumes that you expected the SFA to be either the savior or the doom of the human race, depending on which side of the LC/LF divide you are stading).

Figure 2: Body composition (left), adipocyte size (right) and fat pad weight (inset) of the rodents at the end of the study period (Enos. 2013) Values not sharing a common letter (abc) differ significantly over time within the given diet treatment (P≤.05)

If you take closer look at the data in figure 2, there are two things that will probably catch your eye right away. The first 'eye catcher' pertains to the influence of replacing a large amount of the omega-6 fatty acids by monounsaturared fatty acids, as you will find them in olive oil, for example.

• The rodents who received the modified standard chow, with a fatty acid composition identical to the high fat diets (SFA-6%, SFA-12%, SFA-24%) had the exact same body composition as their mates who received the standard chow with its 3.7x higher n6:n3 ratio. The removal of omega-6 fatty did thus not have any beneficial effects on adiposity in the low fat groups.

The second 'eye catcher' is the non-linear increase in adiposity with increasing amounts of saturated fatty acids in the diets. This does not mean that the expected increase in obesity and adipocyte size was totally absent (read the latest "Get Lean & Stay Lean" item for more information about the association of large fat cells and metabolic syndrome), though:

• The mice in the SF-6-24% did all gain significantly more body weight and body fat than their peers on the low fat diets, but there appears to be a turning point, when the saturated fat content exceeds 12%. After all the mice in the SFA-24% group had almost the same body composition as their peers on the SFA-6% diet.

So, what do we make of these 'eye catchers'? The first one, you could argue, shows that "omega 6 overload" is not a problem, as long as you are consuming a low fat diet, in the first place. Even with the major part of those 12.2% of energy your diet provides in form of various fatty acids belonging to the potentially inflammatory omega-6 fatty acids, that's still way too low to do any harm. It does, by the way, yet explain why low fat diets work so well in a society, where most high fat foods the public consumes are laden with omega-6 fatty acids - not an insignificant result, I would say.

The 12%-SF diet, most closely mimics the standard American diet

Apropos public, the second 'eye catcher' is even more telling in term of public health,... wait, I should write sickness. Why? Well, the 12%SFA high fat diet, which supplies ...

• 47% of energy in form of carbohydrates (380g sucrose, 100g maltodextrin, 50g cornstarch per 1kg of diet; identical for all SFA groups),
• 40% of energy in form of fats (of which 12% were saturated fats), and
• 13% of energy in form of protein (from casein),

... mimics, as the researchers point out, "most closely" (Enos. 2013) the standard American diet (SAD). And the result is obvious: Diabesity!

It's a fat balancing act of macro and micro ratios  - complex and far from being understood 

What's intriguing though, is that the adipogenic effects of the diet were ameliorated, when the SFA content was further increased and the diet contained 68.6g of lard per kg chow instead of just 35.4g and 96.7g of coconut oil instead of just 30g. Since this increase in SFA was at the expense of both mono- and omega-6 fatty acids, you could of course also argue that replacing at least the latter of the two with SFAs must be healthy. Unfortunately, even a brief glance back at figure 2 reveals that this is not necessarily correct. After all, the SFA-6% group was still better off than the SFA-24% group, although they had the highest amounts of oleic and omega-6 fatty acids in the diet.

By now you should actually have realized that this is once more a difficult balancing act. Where different baseline intakes of dietary fat and carbohydrates (total) are pair of setscrews and the individiual fatty acid composition of the diet is another one. And the way these setscrews are set will not just influence the body composition:

Figure 3: Serum IL-6, MCP-1, adiponectin and leptin levels, TNF-alpha mRNA expression in the adipose tissue (left), adipose tissue sample form the rodents receiving standard chow, the SFA-12% and the SFA-24% diet (Enos. 2013). The fat cells of the SFA-6% animals looked similar to those on the SFA-6% diets.

Based on the body composition data presented in figure 2 the marked increases in serum leptin and TNF-alpha mRNA expression in the adipose tissue of the rodents in figure 3 (left) should be about as unsurprising as the fact that the adipocytes of the SFA-12% group show the greatest macrophage infiltration and subsequent necrotic tissue.

If anything is surprising, it is the non-significance of the peak in IL-6 in the SFA-24% group (this was due to a very high standard deviation) and the fact that the serum level of MCP-1 a marker of increased macrophage activity was not elevated, while the adipose tissue mRNA expression was significantly higher (5-8x) in all SFA groups compared to both of the control diets. In the end this is yet only another clear sign that far more processes than we have previously thought happen locally and do not depend on circulating and thus endocrine signaling molecules.

Figure 4: Blood glucose and insulin levels of the mice over the course of the study period (Enos. 2013)

If you take the data from figure 4 into account as well, you will certainly agree with the statement Enos. et al. make pertaining to the negative effects of the SFA-12% diet, which is - just to remind you - the mirror image of the standard American diet:

"The 12%-SF diet, most closely mimicking the standard American diet, led to the greatest adiposity (absolute fat mass), macrophage infiltration, and IR [insulin resistance]." (Enos. 2013)

Figure 5: Total  cholesterol (TC, top) and LDL-C to HDL-C (bottom) ratios (Enos. 2013)

And I guess it would actually be about time to get to the bottom line, here, if it was not for the sentence that follows this assertion:

"Although the 24%-SF diet increased adiposity and produced IR, it did not significantly increase macrophage infiltration, it led to a lesser degree of AT inflammation, and it did not raise the TC/HDL-C ratio." (Enos. 2013)

Yep, you are reading right, as the data in figure 5 shows the total to HDL ratio of the SFA-24% group, which were those rodents who consumed the largest amount of "bad" saturated fat, was virtually identical to the one of the rodents on the standard and the modified standard chow and significantly lower than in those rodents who 'lived the American way of life' (SFA-12%). A similar trend was seen in the LDL:HDL radio and the triglyceride levels.

Bottom line: So, does that mean that we would just have to fry our potato chips in lard and all will be good? Not really, no. If we keep munching tons of plain sugar, even a saturated fat only diet is not going to save us from doom (I suspect there will be another inflection point at levels which exceed 50% SFA, anyway). What the study results do yet clearly implicate is that the macronutritent and fatty acid composition of the standard American diet is downright conspicuously obesogenic, pro-diabetic, inflammatory.

While the macronutrient ratio (high carb + high fat) appears to set the body into fat storage mode, the individual ratios of the fatty acids determine the efficacy of body fat storage, the negative effects on blood glucose management, and the degree of adipose tissue inflammation - and the standard American diet excels in all these disciplines.

As far as the saturated fats go (I wonder if it also plays a role that one of the main sources was coconut oil), the study suggests that you can achieve ameliorations of adiposity on both sides of the 'obesogenic optimum' of 12% saturated fats. If you take a last look at the data in figure 4, you will yet have to concede (or triumph?) that eating more not less saturated fat and thus frying your potatoes in lard, appears to be the more promising modification you could make, if the saturated fat content of the diet was your only set screw. Feels good to know it isn't right?

References:

• Enos RT, Davis JM, Velazquez KT, McClellan JL, Day SD, Carnevale KA, Murphy EA. Influence of Dietary Saturated Fat Content on Adiposity, Macrophage Behavior, Inflammation, and Metabolism: Composition Matters. J Lipid Res. 2013 Oct 28.

Particle Size & LCAT Analysis Shows: Three Whole Eggs per Day Improve Lipid Profile in Men & Women W/ MetSyn. Plus: Up to 700% Increased Lipid Oxidation in Hardboiled vs. Fresh Omega-3 Eggs From Hens on Fish Oil Enriched Diet

"Not the yellow part of the egg!", is the literal translation of "Nicht das Gelbe vom Ei!", which is German and means "not exactly brilliant" - telling isn't it?

As a regular here at the SuppVersity you will probably have come across a line like "make sure to get at least 20g of quality protein (meats, poultry, eggs, fish, dairy) with every meal!" at least once. If we discard the fish, which is, outside of the occasional discussions about mercury and other heavy metals in our food chain, about the only of these highly nourishing foods, the various experts appear to agree is healthy for you, all of them are to be consumed only "on occasion", "in moderation" and preferably in their "lean" or "low-fat" varieties. And while you (should ;-) have read about the beneficial effects of full-fat dairy, yesterday, and about the actually not so bad "bad meats" in the "Meat-O-Logy" post from August 17, 2013, I thought I'd take the forthcoming publication of a paper by Christopher N. Blesso, Jeff Volek et al. as incentive to remind you not to make the mistake and flush the yolk, the best part of the egg, down the toilette.

Recipe for disaster? Take 20 men and women with metabolic syndrome, 5040 whole eggs...

With 40 men and women aged 30–70 years who had been classified with metabolic syndrome the researchers from the University of Connecticut and University of Antioquia in Medellin, Columbia, intentionally picked a representative sample from the ever-increasing number of people with metabolic syndrome for their 12-week dietary intervention trial. I mean, who if not the men and women in this high risk group should suffer from the negative side effects of the cholesterol-laden yellowy, orange-yellow heart killers in disguise?

AHA Definition of Metabolic syndrome

according to Grundy. 2004

Abdominal obesity (waist)
Men	>102 cm
Women	>88 cm
Triglycerides	≥150 mg/dL
HDL cholesterol
Men	40 mg/dL
Women	50 mg/dL
Blood pressure	≥130/≥85
Fasting glucose	≥110 mg/dL

The assumption that subjects with established metabolic syndrome (for the "official" criteria check out the table on the right) is however one of the very few things the study at hand and studies like the one that triggered such an upheaval in August (see Sciencedaily. 2013) have in common. Instead of relying on total, low density and high density lipoprotein levels in the sera of their study participants, Blesso et al. conducted a differential analysis that included paricle number, size (measured by nuclear magnetic resonance spectroscopy), apolipoproteins (apos), oxidized LDL (oxLDL), cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) activities at baseline and after 12-weeks on a carbohydrate-restricted diet (25%–30% energy) that contained either  3 regular whole eggs/day (EGG, n = 20) or the volume equivalent in form of a yolk-free egg substitute (manufactured by Sysco Corporation, Houston, TX).

Accordingly, the subjects in the "real egg group" (EGG) consumed approximately 534 mg cholesterol, 0 g carbohydrate, 16 g protein, 12 g fat per day (186 kcal) from hole eggs, while a single serving of the cholesterol and fat-free substitute (SUB) contained approximately 2 g carbohydrate, 14 g protein, no fat, no cholesterol and only 60 kcal.

To minimize possible confounding factors and allow for "blinding" (you can't tell me you don't taste the difference between egg whites and whole eggs, but alas...), the eggs / egg supplements were prepared in advance.

"Compliance was monitored by use of weekly questionnaires and collection of empty product containers. Participants were asked to maintain their normal physical activity, medications, and dietary supplement usage upon starting the 12-week study." (Blesso. 2013)

To be able to track the dietary intake of the subjects, all participants had to fill out 5-day dietary intake records (3 weekdays + 2 weekend days) at baseline, week 6 and week 12 of the study period. Based on the analysis of the respective data, the scientists determined that

• increased relative protein intake from 17.3%± 3.0% to 23.9%± 4.1%
• increased relative fat intake from 38.6%± 6.4% to 45.7%± 7.4%

• reduced total energy intake of -24% for all participants
• reduced relative CHO intake from 40.9 ± 7.4 to 28.3 ± 9.5% of total energy 
• reduced absolute CHO intake from 211.9 ± 51.8 to 114.5 ± 55.0 g/d 

Moreover, there were "significant differences between groups for dietary cholesterol intake (EGG vs. SUB, P < 0.0001) and dietary choline intake (EGG vs. SUB, P < 0.0001)"

• Δ cholesterol intake +106% in EGG vs. -38% in SUB
• Δ choline intake +52% in EGG vs. -12% in SUB

In that, it is important to point out that these changes and their metabolic effect should not be seen in isolation, because choline plays a major role in the metabolism, transport and incorporation of cholesterol into the cell membrane (read more about choline in "Old School Supplements - Choline: Stronger, Faster, Leaner & More Muscular, or Just Another Dumb-and-Barbell Story?").

"So, the men and women in the egg-group did not die?"

Not exactly, no. Rather than being as bad as cigarettes (as the aforementioned "study" that was published roughly 2 months ago would make us believe; Spence. 2013), the consumption of three eggs per day lead to rather favorable changes in the lipoprofile of the EGG consumers:

Figure 1: Lipoprotein serum levels (left), particle size and ratio of LDL to HDL count (right) of the 37 participants who completed the 12-week trial (data expressed relative to baseline; calculated based on Blesso. 2013)

Contrary to the lipoprotein metabolism, which showed differential (and general positive) effects in response to whole egg consumption, the reductions in circulating insulin, HOMA-IR and triglycerides did not show statistical significant inter-group differences:

triglycerides: -29% vs. -18%
• insulin: -21% vs. -14%
• HOMA-IR: -22% vs. -18%

The existing changes were yet on average still somewhat more pronounced in the EGG group, which is an observation you could interpret as joint effect of low carb dieting + egg eating.

The same goes for the increase in LCAT activity the researchers observed only in the EGG group. Since LCAT is critically important in facilitating HDL particle stability and HDL maturation, its elevation in the EGG group

"[...] could be indicative of an enhanced capacity for HDL maturation and may help explain the shift towards larger HDL particles seen with egg feeding" (Blesso. 2013; my emphasis)

and would thus favor enhanced HDL-mediated reverse cholesterol transport from (e.g. the endothelium of your coronary heart arteries) back to the liver.

What about the lipid oxidation?

If we assume that part of the negative effects that have been ascribed to the consumption of egg(-yolks) are brought about by oxidized fatty acids and respective byproducts, it appears wise not to hard-boil your eggs, because the prolonged heat exposure during hard-boiling increases the oxidation of fatty acids. Aside from temperature and duration of the heat exposure, Cortinas et al. also identified the fatty acid composition of the eggs and their vitamin E content as crucial factors that will influence the formation of oxidized lipids. Since the fatty acid composition of the eggs depends on the diet the hens are fed, you would be particularly ill-advised to hard-boil eggs from hens who were fed a diet enriched in fish oil.

As you can see in the figure above the "fish oil eggs" with their readily oxidized long-chain PUFAs had by far the highest  TBA values (expressed as ng MDA/g dry matter) - specifically, if the hens did not receive additional vitamin E that would be transfered to the eggs and reduce the heat-induced oxidation of the long-chain PUFAs in the "omega-3 eggs" during cooking.

So what's the verdict? In conjunction with the aforementioned additive effects on glucose management and the slightly more pronounced decrease in oxidized LDL (both are probably rather a result of the -12% reduction in carbohydrate content of the participants' diets than the effect of the eggs), the statistically significant improvements in LCAT activity in the EGG eater group speak in favor of the notion that three whole eggs a day will still help you keep the doctor away. Whether they will suffice to throw his statins away, as well (see "Eat Whole Eggs All Day and Throw Your Statins Away?"), will yet have to be elucidated and appears overall questionable - and this goes regardless of whether you belong or don't belong to the relatively small subgroup of people who actually benefit from taking a statin, or not.

What stands out of question, however, is that the "side effects" of three egg yolks per day are quite distinct from those of cigarettes, the consumption of which the headline of the aforementioned ScienceDaily.com article implicitly equates with "egg yolk consumption". And just like smoking and eating eggs are two very different pairs of shoes, there is a huge difference between this well-controlled trial, on the one hand, and the undifferentiated observational hokum that got Spence et al. so much media attention back in August, when they concluded "Our findings suggest that regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease." (Spence. 2013), on the other hand.

References:

• Blesso CN, Andersen CJ, Barona J, Volek JS, Fernandez ML. Whole egg consumption improves lipoprotein profiles and insulin sensitivity to a greater extent than yolk-free egg substitute in individuals with metabolic syndrome. Metabolism. 2013 Sep 26.
• Cortinas L, Galobart J, Barroeta AC, Baucells MD, Grashorn MA. Change in α-tocopherol contents, lipid oxidation and fatty acid profile in eggs enriched with linolenic acid or very long-chain ω3 polyunsaturated fatty acids after different processing methods. J. Sci. Food Agric. 2003; 83: 820–829.
• Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C; American Heart Association; National Heart, Lung, and Blood Institute. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004 Jan 27;109(3):433-8.
• ScienceDaily. Egg yolk consumption almost as bad as smoking when it comes to atherosclerosis, study suggests. August 13, 2013 < http://www.sciencedaily.com­ /releases/2013/08/120813155640.htm > accessed on October 03, 2013.
• Spence JD, Jenkins DJ, Davignon J. Egg yolk consumption and carotid plaque. Atherosclerosis. 2013 Oct;224(2):469-73.

Aspartame's Anti-Insulinogenic Effects During a Workout; Optimal Protein Intake on a Diet is Relative. Plus: Folate Fortification, Spirulia, Succinate, Sucrose, Pork Brain & the Low Cholesterol-Suicide Connection Reviewed!

Unbelievable: The results of the latest study from the University of Western Sidney appear to suggest that you could keep your insulin levels at bay, if you mixed your sugary intra-workout supplement with aspartame-laden diet coke instead of water! The mechanism that's behind this phenomenon does yet still have to be elucidated.

You may be surprised to see a long headline, a long post and a couple of bullet points: "Looks like On Short Notice, reads like On Short Notice, but is not published on Saturday? What's that?" The answer to this question is easy. Lot's of interesting stuff I have come across as of late! And while some of them, like the study on the marginal utility of higher protein intakes on a diet would actually deserve their own post, I decided to give you the "long(er) version of a short notice" in order not to miss any of them... and yes, this means there is going to be more than today's news on the unexpected anti-insulinogenic effects of aspartame, the only partly expected outcomes of the US folic acid fortification program, the aforementioned protein study, the usefulness of spirulina, succinate and sucrose supplements for athletes and physical culturists and some brainy insights into a possible connection between low cholesterol, depression and suicide risk in men and women... ah, ok I see, you are already reading the aspartame item - well, go for it!

• The astonishing anti-insulin effects of intra-workout aspartame consumption Meanwhile even bodybuilders who are injecting and "supplementing" with all sorts of unquestionably unhealthy stuff are so afraid of the hitherto still rather vaguely established pro-carcinogenic effects of aspartame that supplement companies place huge stickers on the boxes of their products saying "ASPARTAME FREE!" Now, I am pretty sure that a recently published study that was conducted by scientists from the School of Science and Health at the University of Western Sydney in Campbelltown, Australia (Siegler. 2013), won't do much about that, but you will probably have to agree that it is still remarkable, to say the least, that the co-administration of an artificial sweetener which has not produced any glucose, insulin or whatever response in previous trials (cf. "Sweeter than your tongue allows") would do that!?

  

  Figure 1: While the mechanism is still unknown and the results need to be repeated in a second experiment, there is no question that the drop in insulin during the workout (see arrow(s)) which occurred during the carbohydrate + aspartame trial in the presence of identical glucose ingestion and blood glucose levels warrants further investigations (based on Siegler. 2013)

  During the four trials, which were separated by 7-10 days of rest, the 9 healthy, recreationally active males (age: 22±2 years; height: 180±9 cm; weight: 78.6±8.5 kg; participating in regular physical exercise at least twice per week) who had volunteered for this (in the eyes of some aspartame extremists, probably unethical undertaking ;-) cycled fasted for 60 minutes in a climate controlled laboratory. The only difference between the four sessions was the "intra-workout nutrition" the participants were fed, with...
  

  1. carbohydrate - 2% maltodextrin and 5% sucrose (figure 1, C),
  2. carbs + aspartame - 0.04% aspartame with 2% maltodextrin and 5% sucrose (figure 1, CA),
  3. water - plain water, only (figure 1, W), and
  4. aspartame + malto - 0.04% aspartame with 2% maltodextrin (figure 1, A)

  As it is common practice in studies like this, "all participants were instructed to follow the same diet and training schedule for the three days prior to each experimental trial." (Siegler. 2013, my emphasis)
  The respective intra-workout beverages were to be consumed in boluses of 4ml/kg body weight before and at 15-minute intervals throughout the trial. For the CHO groups this summed up to a total carbohydrate intake of 104.4±11.3g per participant and did - probably not to your surprise - cause a corresponding increase in insulin levels... with one exception, however: the intraworkout period in the CHO + Aspartame group (figure 1, red), when the insulin level dropped, during the exercise sessions and bumped back up to the same level as in the carbs only control afterwards (see figure 1).
  As the researchers point out, we do not yet have a mechanistic explanation for this phenomenon... nor can we even be sure that this was not some sort of strange artifact, so that
  

  "the disparity between insulin levels [does not only] warrant further investigation with a larger cohort of clinically relevant subject populations (e.g. metabolic syndrome, diabetes, etc.) [, but must also] be considered when designing nutrition-based, exercise intervention studies [in the future]" (Siegler. 2013

  That this observation could actually have very practical implications, both, in view of its potentially compromising effects on blood glucose levels in diabetics, where any insulin blocking effect of aspartame would probably reduce the already compromised glucose uptake even more, as well as in view of the anti-lipolytic (=blocks the release of fat from the cells) of insulin during a workout, which could actually be blocked with a minuscule amount of aspartame ... but alas, until the results have been confirmed and the mechanism behind this effect has been elucidated, what we are doing here is more or less intellectual masturbation - nothing to feel bad about, but still not the real deal ;-)

• 

  Figure 2: This is what the USDA expected to happen - more folic acid in food = higher intake (here in the elderly) = lower homocysteine levels; the reality looked pretty different, though, at least in adolescents the folic acid intake went up, but the homocysteine levels did not go down; moreover the B12 levels have declined as well... how much of this is related to confounding factors still has to be elucidated, but as of now it does not seem as if the fortification program was the success the USDA wanted it to be (Mc Bride. 2007).

  US adolescents and their "healthy grains" are now folic acid fortified, but are they also healthier? According to a study that has just been published in the Journal of Public Health, the great idea to put another artificial vitamin into our the food chain and fortify "healthy" cereal-grain products with folic acid, was so "successful" that the average US teen (14y at the time the fortification program began, 18y now) does now have 16% higher folate and 14% higher B6 concentrations.
  Instead of the expected decrease in homocysteine levels, of which scientists still believe that it plays in imminently important role in the development of heart disease, its serum levels did likewise increase by 17%, while the serum concentrations of vitamin B₁₂ decreased by 11 % post-fortification. The additional ~118 μg folate/d the subjects ingested from the fortified food products, appeared to be particularly useless (or even detrimental?) for boys / young men whose total homocysteine (tHcy) levels increased by 24%  to a much greater extent than in the girls / young women.
  Honestly, I don't really know what to make of these results at the moment, ... at least nothing better than to shake my head over the hilariousness of trying to turn junk(-food) into (good) food by simply enriching it with artificial vitamins. On the other hand, I am happy that even Daniel A. Enquobahrie and his colleagues feel that it is "warranted to investigate the significance of these improvements in folate status on clinical outcomes, in the post-fortification era." (Enquobahrie. 2013) - and that not just because the fortification program did not produce the desired results, but also because the folic acid intake already started to exceed the RDA in many of the subjects. This, and the alarming decrease in B12 levels of which Katherine L. Tucker had cautioned in the 2007 interview with Judy Mc Bride, already, that "better diagnosis for B12 deficiency should be given high priority"(Mc Bride. 2007) do not "warrant", imho, they rather make it imperative to follow the effect of this "nationwide health program" very closely.

• 

  Figure 3: The principle of relativity for protein based body recompositioning diets - When it comes to weight los, the word "high" in high protein diets must always be seen in the context of habitual protein intake and to whom we are comparing our dieters; or put simply: The average SAD dieter benefits from every gram, the average bodybuilder will hardly benefit from the 7th whey shake.

  Effectiveness of high(er) protein diets for weight loss depends on spread / change vs. baseline not on total protein intake That's basically how you could summarize the conclusion of the latest review of the existing data on the influnece of (high) protein intakes on changes in body composition by John D. Bosse and his colleagues from the University of Utah. To find out whether either the protein change (=high protein diets are only effective when the change in protein intake from baseline to intervention is large enough) or the protein spread theory (=those dieters within a cohort with the highest protein intake will see the most beneficial changes in body comosition) could explain the different outcomes of previous studies best, the researches collected an impressive dataset comprising 51 peer-review studies the analysis of which yielded the following two main results (Bosse. 2013):
  1. The 35 successful dietary interventions had on average 58.4% higher average protein intakes than those trials in which the authors had not been able to observe an additional beneficial of going high protein over the standard calorical restriction approach
  2. The 17 successful (=greater anthropomorphic changes than with calorie restriction alone) of the 25 studies, where the baseline protein intake of the subjects was available, the increase in protein intake was 28.6% (if you ate 100g protein per day before, that would mean you would eat 128.6g while you are dieting), minimal increases in 4.7% range, on the other hand, did not provide any additional benefit over energy reduction, alone.
  Overall, the review does therefore support the original hypothesis of the researchers that there are certain thresholds which have to be surpassed before dieters will see any benefits from an increase in protein intake. This does yet also mean, that for someone who is already eating 200g of protein on a daily basis, the addition of a protein shake with 20g of protein is probably not going to make so much of a difference as it would be way below the 28.6% change in protein intake, the protein change theory would prescribe (see [2] in the list above). As a matter of fact going higher and higher (e.g. like eating 300g of protein per day), will, if anything stall, not propel your progress, after all, there will be too little room for other nutrients, when you are already getting the lions share of your daily energy intake from protein... and NO you cannot lose weight without being in a caloric deficit, even if that is not readily calculable by the idiotic "calories-in-vs-calories-out" equation.
• The BMJ Supplement Review says: Thumbs up for sucrose, thumbs down for succinate and undecided  for spirulina In installment #36 of the A-Z of Nutritional Supplement Supplements, a series dedicated to review the pros and cons of purported ergogenic aids, the authors conclude that ...

  

  Figure 4: In view of the fact that the TCA or citric acid cycle is one of the #1 aerobic source of cellular energy (APT) and succinate is one of its intermediates it makes sense that supplementation could improve exercise performance, but hitherto this has not been confirmed.

  • ...the studies on spirulina fail to "study well-trained individuals", to use appropriate standardization regimen with relevance for physical culturists and athletes, identify the active ingredients and their effect on the antioxidant status, of which the respective scientists speculate that it would be the underlying mechanism of the observed ergogenic effects on chronic low-intensity exercise regimen
  • ...the research on succinate (only) supplementation is basically non-existent and claims with respect to its permanence enhancing effects is mostly based on theoretical considerations about its role in the TCA cycle 
  • ...despite the general trend within our society, where the overconsumption of sucrose (table sugar) is one of the major offenders to public health, "there may be value in, or at least room for, its inclusion in sports products targeting the provision of carbohydrate fuel during exercise"
  Nothing exciting, but a realistic and educative analysis, which has all the classic elements you should keep in mind, whenever you try to find out whether a product is worth its money: What research is there? What are the results? Are the positive results significant for me as a person? And... in the case of succrose: Could the use of this ergogenic aid be an obstacle for another goal of mine? I mean, you can benefit from guzzling tons of sugary drinks during your workouts, but if "looking good naked" is your primary goal and your performance only a means to an end - it is probably not wise to do so ;-)

• 

  Figure 5: Suicide risk in psychiatric patients /w (SA) or w/out (PS) prev. suicide attempt and surgical control (SC) in lowest, 2nd and 3rd cmp. to highest quartiles (Olié. 2011)

  Can pork brain in milk tell us something about suicide? Those of you who are on the SuppVersity Facebook news RSS channel will already know the image on the right. I only saw it today, but as Mark mentioned on my Facebook wall, he has used it (the image not the brain) in lectures before... be that as it may, that reminded me of an older study on the highly significant correlation between cholesterol levels and suicide attempts Emilie Olié and her colleagues observed in a 2010 study on the reliability of serum cholesterol levels as a predictor of the suicide risk in 3207 subjects [510 patients with a history of suicidal attempts (SA), 275 patients with no history of suicidal attempts (PC), and 2422 surgical controls (SC); Olié. 2011].
  The exact mechanism for the highly significant increase in suicide risk, esp. among women with previous suicide attempts in the lowest (1st quartile) is still not fully elucidated, Olié et al reference previous studies which suggest that low serum cholesterol levels, a "potentialmarker of central nervous systemcholesterol", impair the serotoninergic activity and" increase impulsivity" and thus precipitate to severe depression and the tendency and ability to pot a premature end to your life.
  In view of the fact that this and similar results were derived exclusively from analysis of psychiatric patients and considering that the cholesterol levels in the SA group were already significantly lower that in the PC and SC control (178±36 mg/dL vs. 217±43 mg/dL and 219±52 mg/dL, respectively) we should be very wary of transferring these results 1:1 to the "normal" people. 

I guess this is enough for today. After all, news are not so different than protein, it's the relative intake that makes all the difference - in other words: If I keep flooding you with those awesome posts, you won't appreciate each and every of them the same way you do now... and we don't want that to happen, do we? 

References:

• Bosse JD, Dixon BM. Dietary protein in weight management: a review proposing protein spread and change theories. Nutr Metab (Lond). 2013 Sep 12;9(1):81.
• Enquobahrie DA, Feldman HA, Hoelscher DH, Steffen LM, Webber LS, Zive MM, Rimm EB, Stampfer MJ, Osganian SK. Serum homocysteine and folate concentrations among a US cohort of adolescents before and after folic acid fortification. Public Health Nutrition. 2013; 15: 1818-1826.
• Mc Bride. Foods To Be Fortified With Folic Acid. USDA ARS. News. February 7, 2007. < http://www.ars.usda.gov/is/ar/archive/jun97/folate0697.htm > retrieved on September 14, 2013.
• Olié E, Picot MC, Guillaume S, Abbar M, Courtet P. Measurement of total serum cholesterol in the evaluation of suicidal risk. J Affect Disord. 2011 Sep;133(1-2):234-8.
• Siegler J, Howell K, Vince R, Bray J, Towlson C, Peart D, Mellor D, Atkin S. Aspartame in conjunction with carbohydrate reduces insulin levels during endurance exercise. J Int Soc Sports Nutr. 2013 Aug 1;9(1):36.
• Zemski AJ, Quinlivan RM, Gibala M, Burke LM, Stear SJ, Castell LM. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance: Part 36. Br J Sports Med. 2013 Sep;46(12):893-4. 

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.