Yohimbine & Berberine Protect From Death Due to LPS Intoxication; BCAAs Inhibit Serotonin Metabolism & Cause Anxiety, Tryptophan but not SSRIs Help; Sweet Tea Leaves Are PPAR-G Antagonists & Battle High Lipid + Leptin Levels

Skip the fireworks invest the money in some quality ingredients for a fondue or whatever you like and invest the (often non-negligible) rest of the money in a gym membership for the next year.

Actually my figure of the week is 115,000,000 EUR (~152,000,000 US Dollar), which is the sum my fellow country men and women are about to waste on pyrotechnics this year. And a scientifically unconfirmed addition based on my personal observation: 90% of the worst offenders as far as spending money for fireworks goes are at least overweight. Would be interesting to see, if the use of pyrotechnics on New Years Eve is directly associated with fat mass...

I mean, it could be that they spent so much money on their fireworks that they feel they can only afford the junkfood of which everybody and his/her mama still tend to believe that it would be cheaper than buying fresh products and preparing your own food from those.

Ah, I am ranting. That's usually Carl Lanore's task, so I will better go on with the items I have compiled for the today's last installment of On Short Notice in the year 2012:
 

• Berberine + yohimbine - a synergistic duo to prevent LPS toxicity (Li. 2012) -- With all the recent hoopla about the gut microbiome, I suppose that I don't have to tell you what the acronym LPS stands for, right? Hmm... just to make sure it stands for lipopolysaccharide endotoxins which are produced by gram negative bacteria in your gut and are so "toxic" (in fact they cause profound inflammation) that they can be lethal at higher doses.
  
  

  

  Figure 1: Survival rates (%) after ALB/c mice LPS injection (Li. 2012)

  A group of Chinese scientists have now found that aside from berberine the anti-inflammatory effects of which have been known for quite some time now, yohimbine administered in a daily dose of 2mg/kg (human equivalent 0.16mg/kg) does add to the survival rate of berberine treated rodents (human equivalent 4mg/kg) that were injected intragastrically (so not directly into the blood) with a potentially lethal dosage of 20mg/kg LPS. What's more, taken on its own yohimbine is even more potent than the alkaloid that's found in such plants as Berberis aquifolium, Oregon grape, Berberis vulgaris, Berberis aristata, Hydrastis canadensis (goldenseal), Phellodendron amurense, Coptis chinensis and Tinospora cordifolia.
  
  The mechanism is mediated by the prevention of liver injury, an upregulating of IL-10 production (an anti-inflammatory cytokine), and related anti-inflammatory effects resulting from the suppression of phosphorylation of IkBa, JNK, ERK and IRF3 in macrophages.

• Chronic 9-week high BCAA diet impairs brain tryptophan levels and causes anxiety (Coppola. 2012) -- Scientists from the Duke University took another look at the BCAA-tryptophan depression connection, you may have read about in the context of my "Sugar Addicted or Just Stressed Out?" post from January 3, 2012.
  
  According to the results Anna Coppola and her colleagues are about to publish in the American Journal of Physiology  - Endocrinololgy and Metabolism the provision of a BCAA-enriched diet for 9 weeks leads to both reductions in brain tryptophan levels and an increased turnover of serotonin (5-HT) in rodent brains:
  

  

  Figure 2: Composition of low fat  (LF) and high fat (HF) diets with or without added BCAAs (left); effects on the ratio of tryptophan  to the molar sum of large neutral amino acids with and without supplemental  tryptophan in the drinking water and 5HT turnover in the brain (no supplemental trp, right; Coppola. 2012)

  Both groups (BCAA and non-BCAA) consumed about identical amounts of food as the rodents in the complementary (LF or HF) groups, which confirms that the BCAA content did not modify the taste of the chow or rendered it unpalatable (cannot have been cheap bulk powder then ;-). The reduction in both the availability of tryptophan as well as the increase in serotonin (5-HT) turnover in the brain must in fact have been a consequence of the added BCAAs and are most likely the root of the disrupted transport of tryptophan across the BBB in rats, leading to reduced exploratory behavior of rats in EPM testing, a sign of increased anxiety.

  "Recent studies demonstrating a strong  association between BCAA levels, obesity, and obesity-related metabolic disorders, when linked to the findings reported here, may help to explain the strong association between obesity and behavioral abnormalities, including depression and anxiety." (Coppola. 2012)

  

  As the slight differences between the high an low carb diets show, other nutrients can influence serotonin as well (read more)

  In this regard it is important to point out that these negative side effects were mostly reversible by the provision of 15 mg/100 ml tryptophan in the drinking water of the rodents, but were not alleviated by  the administration of the common serotonine reuptake inhibitor fluoxetine (at 10 mg/kg/day for four weeks).
  
  Bottom line: Isolation is not what you want if what your body has been build for is complex food. And while the single serving of BCAAs you may gulp down during or right before a workout, on the other hand, probably isn't going to harm you. The "I need BCAAs every 30min" approach to gaining muscle mass, may well turn you into a psychotic wrack if you follow it day in and day out for months or years - at least without chronically adding some l-tryptophan to the equation.

• Sweet tea leaves protect against obesity: Once more via PPAR-gamma blockade (Zhou. 2012) -- Actually this is probably not news to anyone out there with a degree in Traditional Chinese medicine. After all, Lithocarpus polystachyus Rehd.(Sweet Tea) is Chinese folkloric medicine that has always been used to treat obesity, diabetes, and hypertension in South China:
  

  "Previous experiments revealed that it contains plentiful bioactive flavonoids and polyphenolic compounds, e.g. phlorizin, trilobatin, 3-hydroxy-phlorizin, etc. These components have extensive pharmacological activities, such as anti-diabetes, memory improvement, anti-aging, inhibition of lipid peroxidation and the growth of human colon cancer cells, and so on." (Zhang. 2012)

  From a "scientific" perspective, however, the efficacy of this herbal medicine as an obesity treatment had still to be elucidated.

  

  Figure 4: Effects of oral gavage of 75 mg, 150 mg and 300 mg/kg of body weight/day of sweet tea extract or placebo (DIO) in conjunction with the 8 weeks on a obesogenic diet (Zhang. 2012)

  In this context it is yet worth mentioning that this study demonstrated for the first time that the aqueous dry leaves extract of Lithocarpus polystachyus Rehd. can potently reduce the worst metabolic side effects of obesity, such as the hypolipidemia, hypoleptinaemia and the degree of insulin resistance (FINS, HOMA-IR, cf. figure 3) what it does not answer, however, is whether the decline in PPAR-gamma is tissue specific, what exactly is behind the profound decline in leptin levels and whether or not lean rodents, let alone humans, who don't consume an obesogenic diet will see anywhere similar benefits.
  
  In other words, this is research in progress, but I suppose something you are going to hear more about at the Supppversity in 2013.

* * * * * *

Apropos hearing or rather reading more, I guess you will realize that you have reached the end of today's installment of On Short Notice which means that you will have to progress to the SuppVersity Facebook Wall if you want a second serving of news on...

• The history of vitamin A as a light sensor and beyond - actually a free full-text I guess those of you who like to "think paleo" may enjoy (read more)
• A paper on "good" and "bad" inflammation, where the author points out that soothing inflammation too much can lead to a reduction in energy expenditure and may therefore not be the king's road to getting rid of the last blubber (read more)
• The food-hitlist of young Americans - Featuring sugar, sugary drinks, sugary bakery, sugary ... as their main energy and carbohydrate sources... (read more)
• Problems with synthroid and generics that have surfaced in a recent study on their efficacy in the treatment of congenital hypothyrodism (read more)

as well as a handful of other news, which are already there or are going to be posted within the next hours. Have a great weekend, everyone! 

References

• Coppola A, Wenner BR, Ilkayeva O, Stevens RD, Maggioni M, Slotkin TA, Levin ED, Newgard CB. Branched-chain amino acids alter neurobehavioral function in rats. Am J Physiol Endocrinol Metab. 2012 Dec 18.
• Li H, Wang Y, Zhang H, Jia B, Wang D, et al. Yohimbine Enhances Protection of Berberine against LPS-Induced Mouse Lethality through Multiple Mechanisms. PLoS ONE. 2012; 7(12): e52863. 
• Zhou CJ, Huang S, Liu JQ, Qiu SQ, Xie FY, Song HP, Li YS, Hou SZ, Lai XP. Sweet tea leaves extract improves leptin resistance in diet-induced obese rats. J Ethnopharmacol. 2013 Jan 9;145(1):386-92.

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 "12/21/2012", 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. 2012) -- 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. 2012)

  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. 2012) 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. 2012).
  
  

  

  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. 2012) -- 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. 2012)

  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. 2012)

  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. 2012) -- 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. 2012)

  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. 2012) -- 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. 2012 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. 2012 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 12/21/2012. 
• 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. 2012 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. 2012 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.

Pimp My Olive Oil! When Virgin is not Phenol-Rich Enough: The Pharmacokinetics of Phenol-Enriched Virgin Olive Oil.

Image 1:  "If we have not somehow pimped it, it can never be good enough!" appears to be one of the credos with which mankind approaches almost every health-remedy nature has provided for us. In the past this approach was not particularly healthy, though... is phenol-enriched olive oil going to be the exception to the rule?

Being the health-conscious person you obviously are (why else would you visit the SuppVersity ;-), chances are that olive oil, or, to be specific, extra virgin olive oil is one if not primary source of of mono- and polyunsaturated fats in your diet. But do you actually know why? I mean why olive oil? And why extra virgin? What? "Mediterranean diet", "high MUFA content", "lower incidence of coronary heart disease and cancer"? All right, you have done your homework on olive oil, but what about the "extra virgin"? The polyphenols, right. The phenolic content is in fact what distinguishes a "good" olive oil. The phenolic alcohols, the secoiridoid derivatives, the phenolic acids, the lignans and the flavonoids in concert have been reported to have anti-oxidant, anti-inflammatory, anti-atherogenic and anti-carcineogenic properties and are probably as, if not more important for the beneficial health effects of the Mediterranean gold than its fatty acid profile (Covas. 2007; Covas. 2008).

So, if those polyphenols are the "active ingredients" in olive oil, wouldn't it be nice if we had an oil that had even more of these beneficial healthy secondary plant metabolits in our oils, right?

Now we have tons of polyphenols, but does that make a difference?

The thought, that a souped up version of the already phenol-rich virgin olive oil would be an even more potent health promoter must have occurred to a group of researcher from Spain, as well. Back in 2010 already, Manual Suárez and his coworkers published a paper in the Journal of Argiculture and Food Chemistry in which they describe the development of a "phenol-enriched olive oil with phenolic compounds from olive cake" (Suárez. 2010). In essence, the scientists just put back some of the pulp (an extract to be precise) that is produced when the oil is squeezed from the olives into the end-product. In a more recent study the scientists did now try to evaluate how much of these (additional) health promoters in 30ml of regular virgin olive oil (VO) and the enhanced virgin olive oil (EVOO) actually make it into the blood of 16 (8 men, 8 women) healthy subjects in a randomized, controlled, cross-over trial (Suárez. 2011).

Figure 1: Compositional differences (phenol-enriched vs. standard virgin olive oil) in polyphenol content (data calculated based on Suárez. 2011)

If you take a look at the compositional differences between the regular and the "phenol-enriched" virgin olive oil, it is quite obvious that, from a mere quantitative point of view, Suárez' product with on average 3.3x more secondary plant metabolits should be the more potent health promoter. After all, numerous previous studies have shown that those olive oils with (naturally!) particularly high phenol-content exhibit the most pronounced beneficial health effects (Samanego Sanchéz. 2007). This would yet require adequate absorption of the respective compounds from a now obviously more dense solution, which, according to the results of this study, does not seem to be the case for all compounds - and more importantly, all subjects:

The in vivo study showed that the concentration of fourteen of twenty-four compounds detected was higher in the plasma samples from the EVOO than after ingestion of VOO. Among these, two of them, hydroxytyrosol sulphate and vanil-lin sulphate, were statistically significant in attending their pharmacokinetic parameters, demonstrating the suitability of enrichment. In general, a displacement of the time to reach the maximum concentration is observed in the samples, which indicates that more time is needed to absorb the higher phenolic content. However, inter-individual variabilityin the concentration of the plasma phenol metabolites shows that it is difficult to show statistically significant differences between the VOO and the EVOO.

The scientists thusly conclude that the "metabolism of phenols is affected first by the individual". So until we actually know which influence these are, the label "phenol-enriched" on olive oils and other products has little meaning for you as an individual. And even if you belong to the "lucky" high-absorbers, only two, namely vanillin sulphate and hydroxytyrosol sulphate will reach what the scientists call "pharmocokinetic" levels, if you ingest two tablespoons of the super-potent "phenol-enriched" virgin (and still relatively natural) olive oil.

Figure 2: Changes in total antioxidant activity (TAA) of experimental oils subsequent to heat treatment (from Pellegrini. 2001)

Note: Common Internet wisdom would suggest that you have to be particularly cautious with those "phenol-enriched virgin olive oils", when respective products hit the market (and I bet this won't take long). After all, you will all have heard how heating those oils damages the healthy polyphenols - and while that may to some extend be the case, a 2001 study by Nicoletta Pellegrini et al. found that the total antioxidant value of olive oil does not only increase with increased polyphenol content, but that those polyphenols are also "stabilizers of R-tocopherol during olive oil heating, thus contributing to the nutritional value of cooked foods" and "the prevention of antioxidant activity decay in olive oil during realistic heating conditions" (Pellegrini. 2001), which ranged from 30min at 160°C to 120min at 190°C. The latter happens to be at the upper end of the regular deep-frying temperature and would thus suggest that the commonly heard recommendation not to use extra virgin olive oil for frying is not valid, at least when we focus exclusively on its total antioxidant capacity as measured by Trolox essays (cf. figure 2). In that it should be mentioned that, with its relatively high content of highly oxidizable omega-6 fats, olive oil still isn't the "ideal" frying oil - notwithstanding that frying does not constitute the healthiest way of preparing your food anyways ;-)

And though a recent study has shown that the latter conjugates with LDL and thusly protects it from oxidative damage (González-Santiago. 2010), it remains to be verified whether the consumer variety of the olive oil in this study will actually provide any health benefits. And this is particularly true in view of the fact that the food giants will, as they already do it in the case of "normal" virgin olive oil, minuscule amounts this probably expensive ingredient into their otherwise unhealthy convenient products, just to be able to put the highly marketable "contains phenol-enriched virgin olive oil" on the label... but, hey! I guess, this is just the never-ending story of complete nutritional idiocy ;-)

LDL-P Drops by 27nmol/L With Every 1% Reduction in Trans Fat Intake. Plus: "Trans-Fat Free" Does Not Mean Risk Free!

In contrast to the message "trans fats = bad". The information that cookies and bakery, not cooking oil, margarine, chips & co are the main trans fat offenders in our diet has reached only a very small group of people.

There are only few 'nutritional wisdoms' out there that are actually 'wise'. One of them is the notion that "trans-fats are bad for you". By now that's something every fifthgrader knows. What most people don't know, though, is how bad "bad" actually is and whether the small amounts of trans fatty acids, the industry is cleverly hiding in their products by downsizing them in a way that "one serving"contains less than 0.5g of transfats - that's the magic loophole in the FDA regulations according to which transfats don't have to appear on the label, as long as the total amount per serving is less than 0.5g.

The question I would like you to remember, when you read more about the most recent strudy from the Preventive Cardiology Program at the Columbia University Medical Center/New York-Presbyterian Hospital in 2013 is: 

Do those 0.5g/serving the FDA is turning a blind eye on matter?

Within the past decades, the ill health effects of transfats have been addressed by countless studies. The study at hand, however, is the first one to directly assess and quantify the influence of transfats on LDL particle number (LDL-P = particle number, not LDL-C = LDL content!).

This is not about CLA & Co: Most of you will be aware that the "bad" trans-fat this article is not about CLA, but about the trans-fats from partially hydrogenated vegetable oils and other industrially processed fats and oils. If you want to know how much trans-fats (in % of total fat) the french fries and chicken nuggets at "your" Mc Donald's or KFC contain, just take a look at the table on the left (data from Stender. 2006)

As Garshik et al. point out, compared to the standard measure LDL-C the exact number of LDL particles, i.e. LDL-P, has been found to be a superior indicator of heart disease risk compared.

"Studies have suggested that increased LDL-P leads to progression of CVD and that the predictive value of LDL-P for future CVD events is equal to or greater than more traditional lipid measurements such as LDL-C." (Garshik. 2013)

That alone is a huge plus, but guess what: M. Garshick, H. Mochari-Greenberger and L. Mosca have been working with real patients - no rodents.. ah pardon, strings attached ;-)

This is not just another rodent study

Having the advantage of actually working in a hospital, not a sterile lab setting, the researchers picked participants from the Family Intervention Trial for Heart Health (FIT Heart), a National Heart Lung and Blood Institute (NHLBI) sponsored randomized controlled clinical trial that enrolled 501 family members of patients who were admitted to the cardiovascular service of the New York Presbyterian/Columbia University Medical Center, as their subjects. In the course of a previous study, the subjects had been assigned to two different groups:

• 

  Table 1: Subject characteristics at baseline (Garshik. 2013)

  An intervention group, the members of which were invormed about the CVD risk factor screening results and education about diet and physicalactivity to prevent CVD, with regular contact and feedback by a health educator for up to 1-year, and
• A control group, that did not receive the information about their own CVD risk factor and was not part of the organized education program that did obviously include the advise to reduce your trans-fat intake as much as possible

In the course of this study the control group made similar lifestyle changes as the intervention group - despite a lack of formal information / education (Moska. 2008). The reduction in trans-fat intake, in particular, was virtually identical. Therefore, the scientists could pick any of the men and women from the original cohort, as long as there was no lack of information or implausible dietary data for the 1 year study period.

Is it bad, if you get 2.5% of your daily energy intake from trans-fats?

When all was said and done, M. Garshick, H. Mochari-Greenberger and L. Mosca ended up with a "participant pool" the characteristics of which you I've summarized in Table 1. If you stop gazing at Table 1 and take a look that the data in Table 2, you will see that the average subject consumed approximately 2.5% of his or her daily energy intake from trans-fats.

Table 2: Dietary intake (% of kcal/day) and corresponding serum lipid measures in the subjects of the Garshick study.

"Is 2.5% much?" I guess it depends on what you take as a reference. If your reference is the "average" European in the TRANSFAIR study from 1999, this is much. Only the Icelanders, who have the highest trans-fat consumption of all Europeans (2.1% of total calories) come remotely close.

The Greeks on the other hand, live up to their reputation as the fathers of the often-hailed Mediterranean Diet: With a mean trans-fat intake of 0.5% and 0.8% in men and women, respectively, they are compliant with the recommended maximal daily allowance (RDA) of 2.2g trans-fats per day (this statement is based on the assumption that their average caloric intake was 2,000kcal).

You don't have to move to Greece though, to reduce your personal trans-fat intake even further. It is, after all, another flawed urban nutrition myth that you could produce trans-fatty acids in your kitchen by heating whatever type of oil / fat you use to cook (if you never change the oil you use to fry at very high temperatures, things look different, though). Industrially produced junk... ah, pardon "food" - specifically cakes, cookies, etc. - is thus your most if not only significant source of dietary trans-fats. Eliminate those and you are good to go.

Remember: Higher baseline intake = greater relative effect size!

Figure 1: Linear associations between baseline dietary composition and LDL particle number (top) and between change in dietary trans-fat intake and LDL particle number in the course of 1-year (bottom); data based on Garshik, 2013.

Assuming that you are not the cookie monster and consume mostly fresh foods, your transfat exposure is probably much lower than 2.5% of your total calorie intake. The average reduction in LDL particle count per for each 1% of trans-fats you cut from your diet is thus most likely less pronounced than it was in the study at hand.

If we discard the effect size and focus on the general trend, the results of the Garshik study are still highly relevant for all of us; and what's more, most of us will have friends or relatives with similar transfat intakes, a low activity level, a low MUFA and omega-3 intake and way too little protein in their diets - and as Figure 1 can tell you, MUFAs, n-3s, protein and obviously exercise / physical activity are all factors that have been found to be associated with low(er) LDL particle counts and a correspondingly increased risk of arteriosclerosis and heart disease in the Garshik study (see Rosenson. 2002 & 2010; Prado. 2011 for the link between LDL-P and heart health).

Eggs are trans-fat free and heart-healthy | learn why.

So! How dangerous are those 0.5g of trans-fat in "trans-fat free" foods? If we consult the results of a 2011 study by Prado et al., symptom-free individuals with LDL-P levels in the 1953–3560 nmol/L tertile are 3.7x more likely to exhibit coronary artery calcification than those in the 620-1530 nmol/L tertile and take into consideration that the RDA for trans-fats is < 2.2g/day, it should be obvious that those 0.5g of trans-fats, i.e. ~25% of the your maximal daily allowance, are a problem we must not ignore.

If we assume that there is a linear relationship between LDL-P and trans-fat intake (obviously this is a gross simplification) and make a rough and scientifically highly questionable estimate of the consequences, we will find that those unlabeled 0.5g of transfats could boost your LDL levels from the first into the third tertile of LDL-P values in the Prado study (+by 675nmol/L).... that this would also mean that a daily dose of only 0.5g of hidden trans-fats could triple your likelihood of arteriosclerotic plaque should be obvious, right?

References: 

• Cromwell WC, Otvos JD, Keyes MJ, Pencina MJ, Sullivan L, Vasan RS, et al. LDL particle number and risk of future cardiovascular disease in the Framingham offspring study-implications for LDL management. J Clin Lipidol 2007 Dec;1(6):583-92. 
• Cromwell WC, Otvos JD. Low-density lipoprotein particle number and risk for cardiovascular disease. Curr Atheroscler. Rep 2004 Sep;6(5):381-7.
• Garshick M, Mochari-Greenberger H, Mosca L. Reduction in dietary trans fat intake is associated with decreased LDL particle number in a primary prevention population. Nutr Metab Cardiovasc Dis. 2013 Oct 4.
• Hulshof KF, van Erp-Baart MA, Anttolainen M, Becker W, Church SM, Couet C, Hermann-Kunz E, Kesteloot H, Leth T, Martins I, Moreiras O, Moschandreas J, Pizzoferrato L, Rimestad AH, Thorgeirsdottir H, van Amelsvoort JM, Aro A, Kafatos AG, Lanzmann-Petithory D, van Poppel G. Intake of fatty acids in western Europe with emphasis on trans fatty acids: the TRANSFAIR Study. Eur J Clin Nutr. 1999 Feb;53(2):143-57. Review.
• Mora S. Advanced lipoprotein testing and subfractionation are not (yet) ready for routine clinical use. Circulation 2009 May 5; 119(17):2396-404. 
• Mosca L, Mochari H, Liao M, Christian AH, Edelman DJ, Aggarwal B, et al. A novel family-based intervention trial to improve heart health: FIT Heart: results of a randomized
  controlled trial. Circ Cardiovasc Qual Outcomes 2008 Nov; 1(2):98-106.
• Prado KB, Shugg S, Backstrand JR. Low-density lipoprotein particle number predicts coronary artery calcification in asymptomatic adults at intermediate risk of cardiovascular disease. J Clin Lipidol 2011 SepeOct;5(5):408-13.
• Rosenson RS, Otvos JD, Freedman DS. Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) trial. Am J Cardiol 2002 Jul 15;90(2):89.94.
• Rosenson RS, Davidson MH, Pourfarzib R. Underappreciated opportunities for low-density lipoprotein management in patients with cardiometabolic residual risk. Atherosclerosis 2010 Nov; 213(1):1-7. 
• Stender S, Dyerberg J, Astrup A. High levels of industrially produced trans fat in popular fast foods. N Engl J Med. 2006 Apr 13;354(15):1650-2.

Gene-ial or Dan-Gene-rous? Better Make Sure You Are Made For Every Other Day Fasting, If You Don't Want to Ruin Your Glucose + Lipid Metabolism and Become Viscerally Obese

Yes! I freely admit that I do have a problem with the subliminal "binge and starve" of the popular every other day fast, because it paves the not so royal road to binge eating disorders.

Only 2 years ago, there was hardly anyone but the followers of Martin Berkhan's "Lean Gains" regimen who knew what intermittent fasting would be. Ironically, now that mainstream is catching on, the hype within the fitness community is slowly abating  - maybe part of the reason is that it's no longer "cool" enough now that your fat neighbor does it ;-).

It goes without saying that the mainstream version comes without an obligatory exercise component and - what's probably even worse - in the absence of macronutrient, let alone food prescriptions that would make sure that the every other day fasts that are becoming increasingly popular these days become "binge and starve" protocols.

The every other day fast, a gateway to eating disorders?

I could probably write a whole article about the potential of feast and fast strategies to function as a gateway to binge-eating disorders, but I know that most of you will discard that by stating: "Pah, that's happening only to the psychologically labile person who can't control his-/herself"... I will argue against that in another article, but I want to let you know here and now, that you could hardly be more off.

Did you know that eggs can improve the lipid profile of most of us?

Stay calm! In view of the fact that rodents in the wild-type control group, who had fully functional LDL receptors did not show a similar negative response to the well-meant dietary intervention, the results of the study at hand are hopefully irrelevant for most of you. If you do have friends and relatives with inexplicably high cholesterol levels, you would however be ill-advised to encourage them to battle their problems with every other day fasting.

Anyway... What this article is actually about is a paper from the British Journal of Nutrition. It was written by Dorighello et al. and has been published online ahead of print. The corresponding study was designed to test the hypothesis that alternate day fasting, which has previously been shown ... 

• to decrease established metabolic risk factors of CVD and diabetes in human subjects and rodents (Varady. 2007),
• to reduce the production of liver mitochondrial reactive oxygen in mice (Caro. 2008), and 
• to increases the lifespan of rodents (Martin. 2006)

would ameliorate tissue mitochondrial oxidative stress and glucose intolerancr in LDL-receptor knockout mice. The LDL-receptor negative mouse is a common, or rather the scientific model of familial high cholesterol (these are the people who are put on a statin the very moment, they enter their doctor's office).

What the scientists expected and what they found were two pair of shoes

I guess you don't have to be a rocket scientists to see what the data in Figure 1 is telling us: In spite of a 20% reduction in energy intake (over the whole week), the rodents in the Dorighello study did not benefit from their every other day fasting regimen (EODF)

Figure 1: Changes in lipid and blood glucose levels (relative to control on ad libitum diet; left) and carcass composition in % of total weight (right; data based on Dorighello. 2013)

Accordingly, the Brazilian scientists who had expected that the fasting induced energy restriction, (-20%), alone, should ameliorate the metabolic disturbances in LDL-receptor knockout mice, and reduce their susceptibility to atherosclerosis, had to acknowledge that their clever every other day fasting regimen can have unexpected and, in the last consequence, eventually fatal effects on the heart health of the laboratory mice:

• Epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively.
• Pasma levels of leptin were 50 % higher in the EODF mice than in the ad libitum-fed mice.
• EODF mice showed increased plasma levels of cholesterol -  total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). 
• The glucose homeostasis of the "EODF mice" also disturbed. The scientists observed a +40 % increase in glycemia and a +50% increase in insulinaemia. In short, the mice became glucose intolerant and insulin resistant.
• The significant increases in systemic inflammatory markers, TNF-a and C-reactive protein, only topped the list of negative side effects of the every other day fast off.

Overall this lead to a 3-fold increase in spontaneous atherosclerosis development, an effect of which it cannot be said often enough that it was observed exclusively in the LDL-receptor negative mice.

Practically speaking... In spite of the fact that the main take home message of the study at hand may be relevant only for those who harbor a certain genetic disposition, I do not recommend a zero calorie every other day fast to anyone - irrespective of whether he or she does or doesn't have LDL receptors  ;-)

If you are not aware of cases of familiar hyper-cholesteraemia and want to improve your lipid metabolism by fasting and eating clean, I suggest you re-read my previous article about the "Two Day High-Protein, Low-Carb Fast" and try this, or a classic intermittent fasting routine with a 6-8h feeding window to shed some body fat and get in better metabolic shape.

So what does this mean? The results of the study at hand are exemplary of something regular SuppVersity readers have encountered a dozen of times, already. A fact that vindicates the often-heard, but rarely understood notion that "we are all different". As the study at  hand clearly shows, our gene's and their consequences on our physiology determine not just what we should eat, but also when we shoult eat it. 

You got to be wary, though! Contrary to what you may read in some shiny magazines and on banners on the Internet, the often advertized "gene type diet" is not even on the horizon, yet.

Yes, we can (theoretically) identify each and every gene in our bodies, but in contrast to a general LDL receptor dysfunction, many of the more subtle genetic differences are as of yet totally unknown. Any list of foods, or, as this study shows, suggest food frequency rules you may get are up to know about as accurate as the names of the man or woman of your dreams you will get if you follow the friendly advice the music television advertisement gives you and "send an SMS with the keyword 'love' and your name" to a random number. Even for the well-studied APO-E polymorphisms, scientists are time and again surprised to find that their results are not in line with data from previous studies. Contemporary accepted implications, such as "people whose apolipoproteins belong to the APO-E4 class will do more harm than good if they consume larg(er) amounts of fish oil" could thus be as flawed as the idea that only fat can make you fat - likewise the result of premature conclusions that seemed logical in view of the contemporarily available, highly insufficient data, by the way.

References:

• Caro P, Gómez J, López-Torres M, Sánchez I, Naudi A, Portero-Otín M, Pamplona R, Barja G. Effect of every other day feeding on mitochondrial free radical production and oxidative stress in mouse liver. Rejuvenation Res. 2008 Jun;11(3):621-9.
• Martin B, Mattson MP, Maudsley S. Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev. 2006 Aug;5(3):332-53.
• Varady KA, Hellerstein MK. Alternate-day fasting and chronic disease prevention: a review of human and animal trials. Am J Clin Nutr. 2007 Jul;86(1):7-13. Review.

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 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, 2012, 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. 2012) 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. 2012)

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. 2012), 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. 2012)

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. 2012; 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. 2012), 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. 2012 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, 2012 < http://www.sciencedaily.com­ /releases/2012/08/120813155640.htm > accessed on October 03, 2012.
• Spence JD, Jenkins DJ, Davignon J. Egg yolk consumption and carotid plaque. Atherosclerosis. 2012 Oct;224(2):469-73.

Intermittent Thoughts on Intermittent Fasting - The Fast #2: Health & Longevity Effects of Intermittent Fasting

Image 1: Any roundworms reading this? I hope you know that by not eating enough and feeling miserable you can extend your lifespan ;-)

Thanks Caenorhabditis elegans, or "C. elegans", almost everybody who is able to read a newspaper or online magazine will have heard of the miraculous effects of calorie restriction and fasting on longevity (of this worm!). Since I assume that you possess more gray matter than this transparent nematote, you will probably have asked yourself how, or rather if these results from a worm with an average lifespan of 2-3 weeks translate to human beings,... well, all I can tell you is that leading a miserable life of lifelong dieting appears to work in non-human primates, as well (Kemnitz. 2011). Now, the obvious question is:

How does all that relate to Intermitent Thoughts on Intermittent Fasting? Obviously, none of the roundworms or rhesus monkey's followed Martin Berkhan's intermittent fasting approach, did they?

No, I have not seen pictures of abes on leangains.com, either, so I suppose they did not follow Berkhan's approach, but - and this is the likewise fascinating, as well as surprising, connection - there is scientific evidence that intermittent fasting could reproduce some of the beneficial effects of caloric reduction while avoiding a whole host of its undesirable side-effects. Reason enough for me, to devote this episode of the increasingly popular Intermittent Thoughts on Intermittent Fasting series to the non-cosmetic health effects of intermittent fasting (I know that's not as getting ripped and jacked, guys ;-)

Figure 1: Ramadan fasting leads to profound beneficial changes in inflammatory markers (left) and blood lipids (right) in 20 healthy male non-obese volunteers aged 23-39 (data calculated based on Aksungar. 2006)

We touched on one of this unsexy, yet vitally important health-benefits at the end of the last installment on the metabolic and endocrine effects of fasting, already: the beneficial effect on insulin resistance (as measured by a +44% increase in the inverse of the long-term marker of insulin resistance 1/HOMA-IR and the slight increase in QUICKI) Shariatpanahi et al. had observed in 55 ramadan fasting subjects (Shariatpanahi. 2008) for example constitutes one of these "boring side-effects", of which many dieters fail to realize that improvements in insulin sensitivity or reductions in inflammatory markers and C-reactive protein (cf. figure 1, left), as they were reported by Aksungar et al. in a 2006 study on the effects of religious "intermittent" fasting (Aksungar. 2006) facilitate weight - and more specifically - fat loss.

Image 2: Would the issue of dehydration distort the results of Ramadan studies and thus render them irrelevant for our argumentation? (photo Offline Clinic)

As in almost every episode I want to make a few brief statements regarding the "Ramadan model of intermittent fasting". I have already discussed its advantages over "over-other day" or "alternative day" fasting in the second installment of this series and I have hinted at possible problems related to the restriction of water intake within the fasting period in the third installment of the series. Now, in view of the general recommendation to drink more and more frequently to avoid dehydration (USDA), it seems prudent to verify that potential beneficial health effects of fasting are not masked by detrimental side effects of dehydration, if we - once again - want to rely on the available data on religious fasting as part of our argumentation. In a paper published in the European Journal of Clinical Nutrition in 2003, Leiper, Molla and Molla report that despite the fact that "[d]uring the daylight hours of Ramadan fasting, practising Muslims are undoubtedly dehydrating", it is neither "clear whether they are chronically hypohydrated" nor have there been any "detrimental effects on health [...] directly attribut[able] to negative water balance at the levels that may be produced during Ramadan" observed in any scientifically relevant studies (Leiper. 2003). It is thus relatively safe for us to assume that we can neglect he influence of potential dehydration in our initial analysis of respective studies.

Now, what about the longevity effects?

Image 3: The effects the calorie restriction had on the ape on the right is certainly impressive, when you compare it to his 27.6 year old age-mate on the left - would be interesting to see how an "intermittently fasted version would end up ;-) (img. from the Irish Medical Times)

With or without the beneficial effects on cardiovascular risk markers, the question still remains: "Can intermittent fasting mimic the longevity effect of calorie restriction without the constant cravings, continuous hunger and all sorts of "human" problems that won't show in studies on yeast, worms, rodents or even apes (see image 3)?"

In order to answer this question, we will first have to give a clear cut definition of what our understanding of intermittent fasting is, in this context, because, obviously, if we coupled our (intermittent) fast with a a deliberate and severe calorie restriction we would probably end up like Canto, the ape from the the longevity study in image 3 - old, but miserable. What we want, on the other hand, is an intermittent fast, where - within the feeding window - we are allowed to eat to satiety... similar to what we are seeing in religious fasting: no calorie counting and perceived (when compared to normal meal sizes) overeating.

Now, we do already know from the studies cited above (and in previous installments of this series) that one month on a dietary regimen like that provides considerable benefits as far as weight loss, insulin sensitivity, blood lipid ratios (! this is important, because we are knowledgeable enough to give a f*** about total cholesterol & co) and inflammatory markers, all of which are associated not only with an increased life-expectancy (Danaei. 2010), but, more importantly, with an increased life-quality and neurological health (Bronwen. 2006) up into the old(er) ages. From the same studies, we do yet also know that breaking the fast, and returning to our old dietary habits returns these markers to baseline (cf. post values in figure 1). What we do not know, however, is whether ...

1. intermediate improvements in correlates of health and longevity as they can be observed during intermittent periods of Ramadan (intermittent) fasting provide any, or even significant longterm health benefits, and
2. longterm (as in for years and decades) intermittent fasting would not over months or years lose its effect, or even worse, be detrimental to our overall health and thus reduce not extend our life-expectancy and/or life-quality

From rodent studies we already know that a life-long alternate-day feeding protocol increases lifespan in the absence of any caloric reduction (Goodrick. 1990; Mattson. 2000). Evidence that similar beneficial effects, at least as far as mortality from chronic disease is concerned, would occur in human beings comes from a 2007 study by Varaday and Hellerstein (Varaday. 2007), who do yet remark that (as I already pointed out) "more research is required to establish definitively the consequences of ADF [alternate day fasting]".

The circadian clock hypothesis

A finding from alternative day fasting studies that may be of paramount importance in view of the "quality of life"-aspect, is the increase in brain-derived neurotropic factor (BDNF) that has been observed in animal studies. BDNF is involved in brain development and plasticity and its (intermittent) fasting-induced elevation could explain the neuroprotective effect of respective feeding patterns (Duran. 2001). In a review of the literature, Fory and Miskin do yet remark that (Froy. 2010)

[...] BDNF could not be [directly] linked to the neuro-protective effects in the brain of calorically restricted rats, but increased levels of another neurotrophic factor, glial cell line-derived factor (GDNF), were correlated with neuro-protection of a calorically restricted primate model of Parkinson's disease. Interestingly, BDNF is also a component of the hypothalamic melanocortin pathway that controls food intake and body weight in adult mice, and it has been implicated in the regulation of energy metabolism.

After all, the scientists believe that IF exhibits part or even all of its effects by (re-)setting clock genes, a hypothesis which despite having its merits would yet lead us into theoretic considerations with little merit to our "intermittent thoughts" on the real-world outcomes of intermittent fasting, which is why I will, at this point, skip forward to the results of a 1999 study into the relation of adipose tissue size and reductions thereof to longevity.

Is it not about eating less, but just about getting leaner?

Image 4: When we are talking about the benefits of losing body fat, this obviously does not imply you have to get in Phil Heath Mr. Olympia '11 shape to live longer (photo bodybuilding.com)

In the introductory paragraphs of this installment of the Intermittent Thoughts on Intermittent Fasting series I somewhat ridiculed the idea of changing one's whole life to get "ripped and buffed", now, after revisiting some of the studies and observing the close correlation of improvements in metabolic health markers, reductions in body fat and consequent life-extending effects of (intermittent) fasting, the central question of Nir Barzilai's and Gaurav Gupta's 1999 paper Revisiting the Role Fat Mass in the Life Extension Induced by Calorie Restriction seems by no means far fetched: What if ain't inflammation and insulin resistance & co that make us fat and reduce our lives, but being fat that leaves us insulin resistant, inflammed & co and thusly reduces our life-expectancy? The answer, according to Barziilai and Gaurav, is simple (Barzilai. 1999):

In fact, all of the benefits of CR on the neuroendocrine system and those related to the improvement in glucose homeostasis can be attributed to decrease in adipose cells and their products.

Probably too simple and above all difficult to treat with a drug and thus not profitable enough to be accepted by the medical establishment. Now, if this would be the case, intermittent fasting would in fact provide the sought-after silver bullet to leading a leaner, healthier life, as both the anecdotal reports on the Net, as well as the the majority of the studies that have been cited in this, as well as the previous installments show quite conclusively that going without food for periods <24h is capable of reducing body fat stores, while preserving lean muscle (and bone) mass. But why, or better how does that work?

Intermittent fasting, fat reduction, health improvements and the cyclicality of life

Illustration 1: It probably is the magic interplay of AMPK and mTOR that produces such remarkable transformations as Duong Nguyen's. We will delve deeper into the their reciprocal interaction in the next installment of the Intermittent Thoughts on Intermittent Fasting Series

Due to its cyclic nature intermittent fasting seems to temporarily produce similar "reductions in protein synthesis" (Barrows. 1978) as the ones which have been established as the fundamental mechanisms of the life-extending effects of calorie restriction as early as in the late 1970s and of which we know today that they partly mediated by an AMPK-induced downregulation of the mTOR pathway. In that, this transient AMPK response to intermittent fasting, which most intermittent fasters further stimulate by exercising in a (semi-)fasted state, appears to be profound enough to stimulate or, according to some recent research (cf. Canto. 2010), we should probably say "sustain" the SIRT1-pathway to an extent that allows dieters to benefit from its immediate fat-mobilizing effect on white adipocytes (Picard. 2004) and its ability to maintain telomer length (and subsequent longevity, cf. Palacios. 2010) without the unwanted muscle-wasting side-effects of prolonged fasting periods.

The fasting induced AMPK expression is yet only one part of the cycle, of which we have learned in this installment that it is responsible for both, the "cosmetic" effects on body fat, which could, after all, be causative and not just corollary or even subsequent to improvements in insulin sensitivity (cf. What Comes First: Inflammation or Obesity?), lipid profiles, and the whole string of beneficial health effects which irrefutably contribute to the longevity effect of inhumane low-calorie diets. In view of the fact that another valuable Sunday afternoon is drawing to a close, the discussion of the second player in this cycle, the mammalian Target of Rapamycin, or in short mTOR, will yet have to be postponed to the next episode of the Intermittent Thoughts on Intermittent Fasting Series - so stay tuned, keep the questions and comments coming and don't forget to check back on Thursday to see what AMPK and mTOR are doing to our man at the 2012 wheelchair nationals, Adelfo Cerame!