1.3g of Grape-Seed Extract Could Protect You From Oxidative Damage, Viral Infections, Obesity and Insulin Resistance, Reduce Your Heart Rate and Blood Pressure and Increase Your Nitric Oxide Production by >25%

Image 1: Bought in bulk, grape-seed extract is actually reasonably cheap... and it does not even taste as awful as some other herb / seed extracts ;-)

After initially being hailed as the yet another anti-oxidant panaceum, grape-seed extract (GSE) has been displaced by newer, fancier "superfoods" from the headlines of the major health and wellness newscasters. Therefore, even you, as a highly self-educated student of the SuppVersity could have missed out on a handful of recently released studies which reported antiviral effects of GSE (Su. 2011) and confirmed its ameliorative effect on diet-induced obesity (Ohyama. 2011) and (high) fructose-induced insulin resistance (Meeprom. 2011). Moreover, a meta-analysis of nine controlled with more than 300 human subjects and daily doses ranging from 250mg to 2,000mg of GSE, which was published in the Journal of the American Dietetic Association (Feringa. 2011), found that ...

[b]ased on the currently available literature, grape seed extract appears to significantly lower systolic blood pressure and heart rate, with no effect on lipid or CRP levels.

These results suggest that we (at least some of) the beneficial health effects that have been observed in rodent studies actually translate to human beings - something  we cannot (yet?) say for some of the next generation "panacea" ;-) This is also important in view of the significance of the results GSE-administration had on exercise-induced oxidative stress in a more recent study by scientists from the universities of Konya and Dicle in Turkey (Belviranli. 2011), which was published in the latest issue of the British Journal of Nutrition.

The experiments were carried out with 64 adult male Sprague Dawley rats who were randomly assigned to one of the following six groups:

• sedentary control (C, n=10), 
• chronic exercise control (CEC, n=11), 
• acute exercise control (AEC, n=11), 
• GSE-supplemented control (GC, n=10), 
• GSE-supplemented chronic exercise (GCE, n=11), and 
• GSE-supplemented acute exercise (GAE, n=11)

The rats in the treatment groups received a standardized GSE extract containing 54% dimeric, 13% trimeric, 7% tetrameric and <5% monomeric proanthocyanidines and undisclosed amounts of cathechines and oligomeric proanthocyanidines, at a daily dose of 100mg/kg body weight in their drinking water for 6 weeks.

Image 2: Click here to learn how to calculate human equivalent doses (HED)

Rat to human equivalent dosage calculation: If you have already read my dissertation on how to calculate the so-called human-equivalent-dose (HED), you will probably already have whipped out your calculator and are just about to type "100mg times the K-value for rats, which is 6; divided by the K-value for humans, which is 37" ... and what does your calculator tell you? Correct! The HED of 100mg/kg GSE in rats is 16.33mg/kg - in other words, if you weigh 80kg you will have to take roughly 1,300mg of grape-seed extract per day to mimic the dosage that was used in the study.

The dosage, according to the scientists, was chosen because it had elicited beneficial anti-oxidant effects in previous studies on alloxan induced diabetes (El-Alfy. 2005) and age-related oxidative damage (Balu. 2006). And, as Belviranli et al. had suspected, it exhibited similar protective effects against the oxidative stress triggered by both chronic, 5x a week treadmill exercise at 25m/min for 45 minutes, as well as, acute running on the treadmill at 30m/min until exhaustion.

Figure 1: Effects of acute or chronic exercise and grape seed extract (GSE) supplementation on plasma malondialdehyde (MDA) levels (data calculated based on Belviranli. 2011).

As you can see in figure 1, administration of 100mg/kg grape-seed extract per day augmented the beneficial effect of 6 weeks of chronic exercise on muscle MDA levels (-37% vs. -18% in the control group) and ameliorated the acute +22% increase in MDA levels due to increased lipid peroxidation during exhaustive treadmill running.

Figure 2: Effects of acute or chronic exercise and grape seed extract (GSE) supplementation on plasma nitric oxide (NO) levels (data calculated based on Belviranli. 2011).

GSE supplementation also increased the expression of nitric oxide (NO in  plasma; on average +25%) in all animals (cf. figure 2). Moreover, GSE ameliorated the increase in xanthine oxidase and adenosine deaminase activities due to acute exercise and triggered an overall increase in antioxidant enzyme activities.

So, even if your favorite anti-aging and health (onilne-)magazine or vendor appears to have forgotten about grape-seed extract. For a physical culturist like you and me, it may yet well be worth to (re-)include the extract from the seeds of the fruits of Vitis vinifera, which are a particularly rich source of vitamin E, linoleic acid and, most importantly, oligomeric proanthocyanidins, into our supplement regimen. And if the current study does not convince you, it may help, if I remind you of the 2006 study by Kijima et al. who were able to show that GSE due to its anti-aromatase activity can suppress tumor growth in a breast cancer model (Kijima. 2006) ... ah, and before I forget: don't be stupid and buy over-priced caps. Use google and find yourself a source of bulk grape-seed extract - don't worry the taste is not all too bad ;-)

CoQ10 for Ultra-Endurance Athletes: 150mg of Ubiquinone Reduce Stress & Inflammation and Stabilize Cell Membranes in 52.4 Mile Torture from 640m to 3,393m!

Image 1: Susan Kokesh, blogger and the Crazy Running Mum at the Sierra Nevada ultra-endurance run a 52.4 miles "double marathon"
  in September 2010; I probably would not even have survived this torture - respect!

As a health conscious physcial culturist, you are probably aware that the vitaminesque nutrient CoQ10, which, due to its ubiquitous presence in all living beings, is also known as ubiqinone, plays a fundamental role in cellular bioenergetics. It is a necessary cofactor in the mitochondrial electron transport chain (i.e. your cell's way of "breathing", its respiratory chain) and is therefore essential for the production of ATP, the fundamental energy unit your cells are operating on. In that, CoQ10 works as a mobile redox agent that shuttles electrons and, interestingly, also protons (those little blue and red balls from Bohr's atom model ;-) in the electron transport chain. Within the health and fitness community, it is however better known for its antioxidant value, as in its reduced form, ubiquinol, it is a potent lipophilic (which means that it does not combine with fats) antioxidant, which is able to recycle and regenerate other antioxidants, such as vitamin E and vitamin C (Ernster. 1995). Moreover, CoQ10 participates in cell signaling and gene expression and has been used as a dietary supplement (among others) for the treatment of neurodegenerative diseases and statin-induced myopathies.

In view of its pluripotent influence on mammalian metabolism (on a side note: the "-10" in CoQ10 indicates the length of the isoprenoid sidechain that is attached to the common benzoquinone ring structure; the latter is unique and can be found in humans and a few other mammals only), it should thus not surprise you that Chavier Díaz-Castro and his collegues from the University of Granada report that the intake of 150mg of the natural version of CoQ10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone; natural = has trans configuration), profoundly modulated "the undesirable effects of the evoked oxidative stress and inflammation signaling during high-intensity" (Díaz-Castro. 2011).

Illustration 1: Supplementational protocol used in the study; CoQ10 was administered as 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone in powder form in 30mg capsules.

As you can see in illustration 1, the 20 highly trained male amateur athletes (all had run The Sierra Nevada ultra-endurance race in the previous 2 years), who participated in the study were not given the whole dose of 150mg of CoQ10 at once, but followed what I would like to call a "loading protocol" in the two days before the event. The placebo group received an identically looking product containing beer yeast, cellulose,
acacia, silica stearic acid, magnesium stearate, cellulose gum, and maltodextrin.

The total distance of The Sierra Nevada run is >50km. It is considered one of the hardest trials worldwide, mainly because the run, in the course of which the participants "climb" from 640m to a final altitude of  3,393m is almost on a continuous incline! A 5.5 hour torture, for which the CoQ10 supplemented athletes needed on average ~25min less than the subjects in the placebo group. In this study, the exercise performance was yet of negligible importance. What the scientists were really interested were the markers of oxidative damage and inflammation and as the following data shows, those were markedly influenced by the ingestion of this rather "mediocre" (compared to what you see some "health-gurus" advocate) amount of CoQ10.

Figure 1: Effects of CoQ10 supplementation of total bilirubin, triglycerides and urinary creatinine in 20 ultra-endurance runners (data calculated based on Díaz-Castro. 2011)

As you can see in figure 1, CoQ10 induced a significant reduction in urinary creatinine even before the race started (figure 1, left column). Moreover, there were significant differences in the bilirubin (indicates heme catabolism), triglycerides and (again) creatinine (indicates net protein catabolism):

Intense physical exercise resulted in an increase in net protein catabolism and an increase in
creatinine excretion in the PG after the physical test (p < 0.001); however, the urinary levels of creatinine were lower (p < 0.05 before and p < 0.001 after the physical test) in the CoQ10 treated group. Other interesting result was that although there was an increase in urinary creatinine in the CG, it was lower than in PG (38.77 ± 10.20 vs. 88.23 ± 11.21, p < 0.05). We also observed a decrease in the bilirubin concentrations in the CG after the run (p < 0.001) with lower values compared to PG group.

There were also significant differences in the inflammatory response, with (statistically significant, p<0.05) lower values of interleukin 6 (IL-6; -32%) and TNF-alpha (-23%) before the start of the race, and -22% lower TNF-alpha values after the "torture". Moreover, the basal hydroper-oxide content in the erythrocyte membranes, the scientists measured as an indicator of the degree of oxidative stress were lower before and after the exercise test, as the scientists call it.

Taken together, these results suggest that the addition of a small dose of CoQ10 to your supplemental regimen could induce unexpectedly profound cell-stabilizing benefits, of which it would yet be interesting to see how those translate into performance benefits, health and longevity, in the long run.

New Results From the "Test Tubers": Paleolithic Men Could Have Been Healthier Had They Microwaved Their Potatoes.

Image 1: Potato roasting caveman-style - probably not the best way to "cook" your potatoes

As a non-native-speaker, I must admit that the first time I heard someone talk about "tubers" was on Robb Wolf's famous podcast, back in the day, when I was "listener #6" (or seven ;-). Contrary to common (foreign) belief, not all Germans subsist on potatoes and sauerkraut and, what's more, even those who do, don't really care that a potato is a "tuber", i.e. a "Knolle" in German - I suppose the idea that it grows in the dirt is not too appealing to some, while the large majority probably just doesn't care as long as those "tubers" make a good addition to their Schweinebraten... yet, whatever the reasons may be, my first encounter with "tubers" has ingrained the link of these "underground structure[s] consisting of a solid thickened portion or outgrowth of a stem or rhizome, of a more or less rounded form, and bearing ‘eyes’ or buds from which new plants may arise" (OED.com), as the venerable Oxford English Dictionary would have it, to the paleo style of eating so deeply into my brain that I have been seeing cavemen with roasted sweet potatoes on their sticks in front of a fireplace in my mind's eye, ever since. Now, if that really was the way life went, back in the paleolithic days, our ancestors did probably miss about 32% of the antioxidant magic of the tuberous roots - at least this is what the results of a recent study on the effects of different cooking methods on polyphenols, pigments, and antioxidant activity in potato tubers from the San Luis Research Center at the Colorado State University  would suggest (Perla. 2011).

In their experiment, Venu Perla, David G. Holm, and Sastry S. Jayanty

• boiled - 1h in a sieved double-boiler,
• microwaved + cooked - 10min in a commercial microwave oven at max. highest level +10min boiling, and
• baked  - 1h at 204°C in a commercial pre-heated oven

six months old stored potato tubers of 5 cultivars and 9 advanced selections of Colorado state (skin-color: 4x russet; 6x red; 1x white; 3x purple) and analyzed the samples for total phenolics, total flavonoids, total flavonols, and DPPH (2,2-Diphenyl-1-pikryl-hydrazyl) radical scavenging activity.

Figure 1: Loss in total polyphenol content of 5 cultivars and 9 advanced selections of Colorado state potato tubers due to cooking, microwaving, and baking (data calculated based on Perla. 2011).

As the data in figure 1 shows, all three preparation methods led to profound reductions of the potatos' total polyphenol counts. With Purple Majesty being most and Russet Nugget being least perceptible to the heat induced reduction in total polyphenol count. The cultivars CO97222-IR/R and CO97226-2R/R exhibited the highest total polyphenol counts (+77% and +137% above average in the raw state), with the former being particularly resistant to cooking (+119% above average) and the latter being particularly resistant to microwaving and baking (+154% and +169% above average, respectively).

Figure 1: Loss in polyphenol, flavenoid and flavenol content of 5 cultivars and 9 advanced selections of Colorado state potato tubers due to cooking, microwaving, and baking (data calculated based on Perla. 2011).

The superior resistance of these red-fleshed potato cultivars to cooking treatments is yet relative polyphenol-specific, due to their extraordinary high flavenoid and flavenol content in the raw state, CO97222-IR/R and CO97226-2R/R do yet retain a 241%, 155%, 199% and 243%, 331%, 395% higher flavenoid and 78%, 34%, 17% and 80%, 98%, 181% higher flavenol content  than the average potato (in the study) even after cooking, microwaving and baking, respectively.

The scientists also observed that, contrary to the white and yellow fleshed tubers, where the major pigment was lutein, the "dominant pigments in the red and purple fleshed tubers were anthocyanins", the antioxidant activity of which has been implicated in the prevention (by some even the treatment) of obesity, cardiovascular disease, diabetes, hyperlipidemia and even cancer. Unfortunately, these pigments are just as susceptible to cooking, microwaving and baking as the polyphenols, flavenoids and flavenols, so that the total anti-oxidant activity (as measured by DPPH free radical scavenging assays) of the tubers that were tested in this study was reduced by -26%, -32% and -38% by boiling, microwaving and baking, respectively.

Please note: While it is unlikely that you will die from eating a single raw potato. The solanine that can be found in all parts of the plant, including the leaves, fruit, and tubers, is a natural fungicide and pesticide the plant produces to protect itself from insects, the ingestion of which can potentially be fatal!

Now, despite the fact that microwaving is only slightly less damaging that baking, I assume that putting the potatos directly into the fire, like the paloelithic men and women in my daydreams use to do it, probably is the worst way to prepare your tubers. Yet while even microwaving would have been a healthier option, the best and, from an evolutionary perspective, more natural solution would be to boil your potatoes.

Mitohormesis - Suffocated Mitochondria Live Longer: Scientists Probe Longevity-Effect of Low-Level Stressors.

Image 1: Walter Breuning died in April 2011at the biblical age of 114! And you bet that a man who has seen two world wars has had his share of mitohormetic stress in his life.

As a diligent reader of the SuppVersity you will be familiar with the work of S. Schmeisser and M. Ristow from the Department of Human Nutrition at the University of Jena, here in good old Germany (where not everyone eats Sauerkraut und Weisswurst, even now that the Oktoberfest is in full swing). In previous publications, the scientists have (at least in my mind conclusively) argued against the publicly accepted free-radical hypothesis of aging, which implies that the presence of free radicals is one of the fundamental mechanisms of aging. Now, a few month after the publication of their last review back in May 2011, they are presenting the latest results from their own lab in a paper that is going to be published in the October issue of Hormone and Metabolic Research (Schmeisser. 2011).

Want to live longer? Then you better put another log on the fire

Schmeisser, Zarse, and Ristow used lonidamine (LND), a indazole-3-carboxylic acid derivate, to inhibit cellular respiration in the infamous round-worm (Caenorhabditis elegans) model for aging processes (for a review on the pharmacology, biochemistry and toxicology of lonidamine see Silvestrini. 2008). In essence, they thusly made it more difficult for the cells to "breath", which as you may probably imagine, is a major stressor, which will inevitably increase the formation of purportedly dangerous free radicals (ROS) and should thus increase the aging process, if... yes, if there was any truth to the nonsensical idea that you better sit there, don't eat, don't drink, don't move - in essence - don't live to avoid any potential ROS formation, if you want to extend your lifespan... I guess, you as a self-educated SuppVersity reader won't be surprised that the roundworms did not only survive the "torture" (of life), but - after an initial mitohormetic response, i.e. an adaptational response to the the scientists' effort to suffocate their mitochondria (the initial reduction in oxygen consumption was -37 %!) - thrived on the purportedly life-shortening inhibitor of mitochondrial respiration!

Figure 1: Lifespan of C. elegans treated with 5µM lonidamine, n-acetyl-L-cysteine (NAC) or both (data calculated based on (Schmeisser. 2011)

As you can see in figure 1, the "pro-oxidant" treatment with lonidamine, of which Schmeisser's, Zarse's and Ristow's data shows that it increased respiration and thus mitochodrial ROS formation, increased both median as well as maximal life-expectancy of the nematodes (roundworms) by ~8% - an increase with statistical significance, as the p-value of p<0.001 (= chances that the increased lifespan observed in the study is just coincidence are <0.1%). The latter cannot be said of either the slight increase in maximal lifespan nor the slight decrease in median lifespan in the group of nematodes that was treaded with n-acetyl-L-cysteine (p=0.17; non-significant) or a combination of the anti-oxidant sulfur-amino acid and lonidamine (p=0.95; absolutely non-significant; cf. figure 1).

These observations may be considered further experimental "evidence" for Schmeisser's and Ristow's previously formulated mitohormesis theory ("evidence" in the sense that the results do not falsify their hypothesis - they do yet falsify the ROS hypothesis of aging). A theory that refutes the idea that the aging process is driven by reactive oxygen species and emphasizes (mitochondrial) adaptation processes to (external) stressors that strengthen, not weaken the organism in the long-run - or as the scientists phrase it:

[...] the induction of endogenous defense mechanisms as a secondary response to a stressful condition is assumed to contribute to longevity [...] a lifetime low dose oxidative stress with a subsequent secondary induction of defense mechanisms could delay the aging process

It is thus the interplay of manageable stress and metabolic adaptation which extends life and not an overall reduction of reactive oxygen species, as the vendors of some "super-potent" anti-oxidants would have you believe. What is still missing though, is a tool which would help us to identify the critical point, where the endogenous adaptation processes cannot keep pace with ever-increasing (mainly) exogenous stressors... in case any scientist finds an answer, I guess you will soon be able to download the respective app on your shiny new iPhone - I just hope that this app will account for the significantly (!) decreased glucose metabolism the iPhone itself will induce in the temporoparietal junction and anterior temporal lobe of the right hemisphere of your brain within less than 30 minutes (Kwon. 2011), as well.

The Pistachio Manifesto: Antioxidant, Metal Chelator, DNA Protector, Anti-Cancer Agent, Bug Killer (incl. H. Pylori & Herpes Simplex) & More. Have You Been Missing Out?

This is not exactly what I was talking about, when I said "going nuts", but in this case it would actually qualify as "going pistachios" ;-)

Walnuts, almonds and Brazil nuts, these are the stars among the hard-shelled fruits people tend to go nuts about (all puns intended ;-). Pistachios, on the other hand, get very little love. I have in fact written about their surprisingly low effective energy content and their highly bioavailable phenolic content before (learn more), but what the myriad of phenols in these small nutritional powerhouses the ancient Egyptians used as incense, preservative and breath sweetener, while their Iranian neighbors in the North East already knew about their beneficial effects on digestive, hepatic and kidney health (Avicenna. 2008) can do for our health has not been covered here at the SuppVersity.

So what is it pistachios can do for you?

With their traditional use as a remedy for digestive, liver and kidney issues, you already have an idea where this could be heading. The shelled fruits of which we know that they have been part of the human diet for at least 9,000 years and that's cultivated in the Middle East, United States and Mediterranean can however do more for you:

• 

  Histidine happens to be an excellent chelator and potential weight loss adjuvant, as well (learn more)

  Potent antioxidants: Different parts and constituents from P. lentiscus  have been shown in vitro radical scavenging properties They protect your LDL molecules from being oxidized and will thus have direct beneficial effects on your atherosclerosis and overall heart disease risk (Holvoet. 2004).
• Metal chelators: A 2011 study by Orhan et al reports that pistachios (P. terebinthus fruits) are potent metal chelators (on par with EDTA) and have an impressive radical scavenging activity. Interestingly engough, the Antioxidant activity of the fruits actually seems to increase, when they are roasted (Orhan. 2012).
• DNA protection: More or less a downstream effect from the high content of antioxidant compounds, specifically gallic acid, digallic acid and 1,2,3,4,6-pentagalloylglucose, and polyphenols have direct protective effects on cellular DNA and pro-carcinogenic mutations.
• Antimicrobial activity (incl. anti H. Pylori): Certainly among the most interesting effects are the anti H.Pylori effects of α- pinene, a compound from the essential oils in pastachios (speficifally P.atlantica var. kurdica). Other ingredients, like verbenone, rterpineol, and linalool showed high antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis (Koutsoudak. 2005).
  
  

  

  You can battle H. pylori with probiotics, as well. If you want to learn more about this, I'd suggest you go back a couple of months and read the full story in the SuppVersity Short News from October 2012 (go for it)

  Sakami et al. report similar beneficial effects against pathologic bacteria (Porphyromonas gingivalis and Prevotella melaninogenica) antiplauqe activity on teeth by inhibiting bacterial growth in saliva (Sakagami. 2009). Özçelik et al. add noticeable anti-viral effects to the list of anti-microbial activities of pistachio species (Özçelik. 2005). The viruses tested in the study were Herpes simplex (DNA) and Parainfluenza viruses (RNA). The effects were significant for both Kernel and seed extracts.
• Anti-inflammatory activity: Extract of the resin of P. lentiscus var. Chia and its isolated phytosterol tirucallol exert direct anti-inflammatory effects on human aortic endothelial cells and inhibit the activity of adhesion molecules that express the inflammatory cytokine TNF-α (Tzakou. 2007). Tzakou et al. ascribe the effects to phytosterol that goes by the name if tirucallol - never heard of it? Me neither, but who knows on which supplement label you may find it in the future ;-)
• Digestive health: I already mentioned this in the introduction. One of the most important traditional uses of gums from Pistacio species is the management of gastrointestinal disorders; and that has been confirmed by several studies (Rahimi. 2009 & 2010; Farzaei. 2013). Resin of P. lentiscus has been shown to significantly reduced the intensity of gastric mucosal damage induced by pyloric ligation, aspirin, phenylbutazone, reserpine and restraint with cold stress  via its  antisecretory and cytoprotective activities (Al-Said. 1986)
  

  

  Figure 1: Improvements of acid regurgitation and heartburn in forty eight patients fulfilling Rome II criteria for functional dyspepsia were randomly assigned to receive either Pistachio var chia mastic gum 350 mg three times daily or placebo after three weeks (Dabos. 2009)

  A double- blind  placebo controlled trial, P. lentiscus gum lead to significant improvement of the symptoms of patients with functional dyspepsia  (Dabos. 2009). Extracts have been successfully tested in experimental models of acute colitis and IBS (Rahimi. 2013), and there is supporting evidence for beneficial effects of P. lentiscus var. chia resin in patients with established mild to moderate active crohn’s disease (CD) after 4 weeks of supplementation (Kaliora. 2007a,b).

• 

  Suggested read: Supplements to Preserve and Restore Insulin Resistance (read more)

  Antidiabetic activity: This is not about the nuts, but about a leaf extract, which has demonstrated significant acute postprandial  antihyperglycemic activity comparable to metformin and glipizide in starch-fed rats, in which it also lead to significant overall improvements in glucose tolerance (Kasabri. 2011). Unfortunately, a study by Kasibri et al. does not support these results - at least not for normoglycemic and streptozocin-induced hyperglycemic rats (Kasibri. 2004) on a regular diet.
  
  This would suggest that there is a direct correlation with carbohydrate intake, and voilá a 2007 human study confirmed that the gum, not the leaf extract can effectively, lower blood serum glucose levels in men... however, there is another "on the other hand attached here": this did not work for the female study participants (Triantafyllou. 2007).

• 

  The Protective Hull of These 61 Super Fruits Can Ward Off Cancer (more)

  Anti-cancer effects: In a relatively recent review of the literature, Giaginis & Theocharis call pistachio mastic gum a "conglomeration of effective anticancer drugs" (Giaginis. 2011) - probably not without reason, after all they cite a plethora of scientific data from peer-reviewed studies to support the anticancer activities of mastic gum and its major constituents and highlighting the various molecular mechanisms through which the triterpenoids work their anti-cancer magic.
  
  Rezaei et al., for example were able to show that the fruit extract of P. atlantica sub. kurdica exerts direct inhibitory effects on human colon carcinoma cells that was comparable to the drug Doxorubicin (Rezaei. 2012). Another example? Well what about the anti-breast cancer, anti liver-, anti cervical and anti skin-cancer effects of oleoresin (Almehdar. 2012)
• Hypolipidemic effects (=lowering high blood lipids): Extracts from P. vera  fruits have shown beneficial effects on HDL and LDL level in rabbit model of atherosclerosis, they exert positive effects on the lipid levels of patients with moderate hypercholesterolemia (Edwards. 1999). And have several animal studies to support their anti-artherogenic effects (e.g. Bakirel. 2003) 

Impressed? Well I'd hope so, after all this turned out to be more work than I initially thought, when I started to "just write a brief overview of the health effects of pistachios" ;-)

---

Brazil nuts & selenium: "How much is too much?" A weighty question I addressed in a July 2013 SuppVersity article: "Brazil Nuts & Selenium: Are You Nuts If You Have More Than One Per Day?" (more)

Bottom line: Ok, I have to admit there is no scientific evidence that all the good things mentioned above are going to happen to you, if you have a handful of pistchios every other day, but you know what? It may still be a piece in the puzzle people often refer to as "healthy diet" - so if you are into nuts and can "afford" their relatively high energy content, go for it! After all, the above are only the "confirmed" effects.

Note: Actually everybody can "afford" eating nuts, it's more a question of being able to stop before the whole 500g family pack is annihilated... and trust me, if you love nuts, this can happen pretty fast, even if you have to shell them as it is the case with pistachios.  

Last but not least, in traditional Iranian medicine, certain ingredients in pistachios are known to exhibit various additional pharmacological activities incuding diuretic, lithontripic, anti-tussive, anti-rheumatic, anti-asthmatic, anti-hypertensive, and aphrodisiac effects of which Bozorgi et al. point out that the "are not [yet] supported by any current scientific documents and so, they could be considered  for investigating by researchers." (Bozorgi. 2013)

References:

• Almehdar H, Abdallah HM, Osman AM, Abdel-Sattar EA. In vitro cytotoxic screening of selected Saudi medicinal plants. J Nat Med. 2012 Apr;66(2):406-12.
• Al-Said MS, Ageel AM, Parmar NS, Tariq M. Evaluation of mastic, a crude drug obtained from Pistacia lentiscus for gastric and duodenal anti-ulcer activity. J Ethnopharmacol. 1986 Mar;15(3):271-8.
• Avicenna.The canon. Translated by: A . Shrafkandi. Soroush Press, Tehran. 2008.
• Bakirel T. The Investigation of the Effects of Pistacia terebinthus L. Upon Experimentally
  Induced Hypercholesterolemia and Atherosclerosis in Rabbits. Turk. J. Vet. Anim. Sci. 2003; 27: 1283- 1292.
• Bozorgi M, et al. Five Pistacia  species (P. vera, P. atlantica, P. terebinthus, P. khinjuk and P. Lentiscus): A review of their traditional uses, phytoche mistry and pharmacology. The Scientific World Journal. 2013.
• Dabos KJ, Sfika E, Vlatta LJ, Frantzi D, Amygdalos GI, Giannikopoulos G. Is Chios mastic gum effective in the treatment of functional dyspepsia? A prospective randomised double-blind placebo controlled trial. J Ethnopharmacol. 2010 Feb 3;127(2):205-9.
• Edwards K, Kwaw I, Matud J, Kurtz I. Effect of pistachio nuts on serum lipid levels in patients with moderate hypercholesterolemia. J Am Coll Nutr. 1999 Jun;18(3):229-32.
• Farzaei R et al. An evidence-based review on medicinal plants used for the treatment of peptic ulcer in traditional Iranian medicine, Int J Pharmacol. 2013 [ahead of print]
• Giaginis C, Theocharis S. Current evidence on the anticancer potential of Chios mastic gum. Nutr Cancer. 2011 Nov;63(8):1174-84.
• Holvoet P. Oxidized LDL and coronary heart disease. Acta Cardiol. 2004 Oct;59(5):479-84. Review.
• Orhan IE et al. Neuroprotective potential of some terebinth coffee brands and the unprocessed fruits of Pistacia terebinthus L. and their fatty and essential oil analyses. Food Chemistry. 15 February 2012; 130(4):882–888.
• Özçelik B, Aslan M, Orhan I, Karaoglu T. Antibacterial, antifungal, and antiviral activities of the lipophylic extracts of Pistacia vera. Microbiol Res. 2005;160(2):159-64. 
• Kaliora AC, Stathopoulou MG, Triantafillidis JK, Dedoussis GV, Andrikopoulos NK. Chios mastic treatment of patients with active Crohn's disease. World J Gastroenterol. 2007a Feb 7;13(5):748-53.
• Kaliora AC, Stathopoulou MG, Triantafillidis JK, Dedoussis GV, Andrikopoulos NK. Alterations in the function of circulating mononuclear cells derived from patients with Crohn's disease treated with mastic. World J Gastroenterol. 2007b Dec 7;13(45):6031-6.
• Kasabri V, Afifi FU, Hamdan I. In vitro and in vivo acute antihyperglycemic effects of five selected indigenous plants from Jordan used in traditional medicine. J Ethnopharmacol. 2011 Jan 27;133(2):888-96.
• Koutsoudaki C, Krsek M, Rodger A. Chemical composition and antibacterial activity of the essential oil and the gum of Pistacia lentiscus Var. chia. J Agric Food Chem. 2005 Oct 5;53(20):7681-5.
• Rahimi R, Mozaffari S, Abdollahi M. On the use of herbal medicines in management of inflammatory bowel diseases: a systematic review of animal and human studies. Dig Dis Sci. 2009 Mar;54(3):471-80.
• Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of traditional Iranian medicine for inflammatory bowel disease. World J Gastroenterol. 2010 Sep 28;16(36):4504-14. Review. 
• Rahimi R, Baghaei A, Baeeri M, Amin G, Shams-Ardekani MR, Khanavi M, Abdollahi M. Promising effect of Magliasa, a traditional Iranian formula, on experimental colitis on the basis of biochemical and cellular findings. World J Gastroenterol. 2013 Mar 28;19(12):1901-11. 
• Rezaei PF, Fouladdel S, Hassani S, Yousefbeyk F, Ghaffari SM, Amin G, Azizi E. Induction of apoptosis and cell cycle arrest by pericarp polyphenol-rich extract of Baneh in human colon carcinoma HT29 cells. Food Chem Toxicol. 2012 Mar;50(3-4):1054-9.
• Sakagami H, Kishino K, Kobayashi M, Hashimoto K, Iida S, Shimetani A, Nakamura Y, Takahashi K, Ikarashi T, Fukamachi H, Satoh K, Nakashima H, Shimizu T, Takeda K, Watanabe S, Nakamura W. Selective antibacterial and apoptosis-modulating activities of mastic. In Vivo. 2009 Mar-Apr;23(2):215-23. 
• Triantafyllou A, Chaviaras N, Sergentanis TN, Protopapa E, Tsaknis J. Chios mastic gum modulates serum biochemical parameters in a human population. J Ethnopharmacol. 2007 Apr 20;111(1):43-9.
• Tzakou, O., Bazos, I. and Yannitsaros, A. (2007), Volatile metabolites of Pistacia atlantica Desf. from Greece. Flavour Fragr. J., 22: 358–362.

DHEA Revives Liver of Aged Rats and Improves Antioxidant Reserves and Akt Signaling in Young and Old Rats.

Image 1:  I don't think celebrities realize it, but there is more to anti-aging than an unlined face. New studies show that DHEA could after all help with all sorts of age related diseases (img. antiagingpossible.com)

It's been a while since DHEA was in the news. While I have posted a handfull of mostly beneficial findings related to dehydroepitestosterone (DHEA), the hype that sourrounded its purported anti-aging effect in the late 1990s has completely abated. In view of DHEA's implication  (or rather the lack of the latter) in age-related autoimmune disease, sexual disfunction, osteoporisis, deteroiations of lipid metabolism, type 2 diabetes and cardiovascular and liver disease (Basci. 2007- ignificance of  dehydroepiandrosterone  and  dehydroepiandrosterone  sulfate  in  different  diseases), it is questionable how people beyond the age of 40, when DHEA production declines by 2% per year(!) could not benefit from a carefully planned and monitored DHEA treatment. A group of scientists from Brazil obviously thought the same and decided to take a fresh look at what happens on a molecular level, when 3 (young rats) and 24 months (old rats) old male Wistar-rats are given 10mg/kg deyhdroepitestosterone [human equivalent: 1.62mg/kg; 80kg human: 130mg/day] subcutaneously per day for 5 weeks (Jacob 2011).

Figure 1: Relative changes in total, reduced and oxidized glutathione in young and old rats after 5 weeks on 10mg/kg DHEA (data adapted from Jacob 2011)

As you can see in figure 1, the treatment induced profound increases in total and reduced glutathione and age-dependendly increased (young) or decreased the absolute level of oxidized glutathione (GSSG). Despite the absolute increase in GSSG, usually a marker of oxidative stress, the more important GSH / GSSG ratio, i.e. the ratio of reduced to oxidized glutathion, a more comprehensive marker of the balance of pro- vs. anti-oxidant metabolic processes, improved even more in the twelve young rats, (+6% GSH/GSSG) than in their older companions (+1% GSH/GSSG).

Figure 2: p-Akt levels in young and old rats with and without DHEA supplementation (data adapted from Jacob 2011)

As a faithful student of the SuppVersity, the serine/threonine kinase Akt should not be a stranger to you, after all, mTOR and p706SK (the "muscle builders", you've read about in the context of BCAAs, leucine and exercise-induced protein synthesis), are among its intracellular substrates. In agreement with previous studies, chronic administration of DHEA increased p-Akt-expression in the study at hand (cf. figure 2). The scientists speculate "that the Akt activation in this organ [the liver] is a protective answer" and could, after all, be the underlying reason for the preservation / restauration of hepatic function in the old rats.

Image 2: Oral DHEA supplements are sold for a few bucks over-the-counter (at least in the USA). Yet,
esp. for people under the age of 35, it probably does not make sense to buy and use those. At least, for
as long as it takes for the results of the study at hand to be confirmed in humans. And the allegedly benign 7-Keto DHEA could wreak havoc on your natural corticosteroid metabolism.

So how much DHEA should I take? Given the fact that the name of this blog is SuppVersity, I should have apprehended DeDeRa's question on which form and how much DHEA I would suggest you take. My answer is quite simple: NONE! Why? Well, this is a rodent study done with injectable DHEA. Not only would it be imprudent to extrapolate any dosing suggestions for oral DHEA supplements in humans, without clinical tests, we cannot even be sure that the effects would be identical, even if we hit the right dosage. Thus, while I am convinced that DHEA is probably more benign than many other OTC "supplements", especially people under the age of 30-35 should think twice or better thrice before popping any DHEA supplement - this includes 7-keto, the cortisol-suppressant effects of which can wreak havoc on your natural corticosteroid balance, make you feel tired and sluggish and deprive your body of an important anti-inflammatory pathway.

Most importantly, however, the study does away with the longstanding prejudice that DHEA (at the given dosage) "represent[s] a toxic potential to [the] liver". The isolated finding that endogenous DHEA lead to increased oxidation in the liver (it still does, but the overall pro- vs. anti-oxidant balance still improves!), as well as insufficient funding by the pharmaceutical industry, who obviously is not interested in naturally occuring and thus non-patentable treatment methods, had been one of the primary reasons many scientists decided not to dig deeper into the ameliorative, preventive and restaurative effects of DHEA in the context of age-related diseases. Personally, I hope that the few new studies that have been published, lately, will encourage other researchers to have another look at a hormone with profound yet complex and complicated effects on numerable aspects of the mammalian metabolism.

Meat Science: To Cook or Not to Cook? The Raw Truth About Antioxidants in Raw and Cooked Meat and Fish.

Image 1: Now, that we know that meat is not
bad for you. Let's get to the meat of the matter:
Is raw meat better than cooked meat?

"Eat Raw!" If its referring to peppers, tomatoes and salads, even the Vegan lobby won't disagree with this slogan, yet when it comes to eating raw meat, dairy and eggs, hell breaks lose. "Don't do that you will kill yourself!" is what you will hear even from respected scientists. Strangely, I am eating raw eggs and other raw stuff on a daily basis without noticing any detrimental health effects whatsoever. All bacteria-hysteria aside (this would be the topic for a whole new blogpost, cf. red info-box at the bottom), the idea that meat has to be cooked before it is eaten is actually counterintuitive. I do not want to bring up the "Look at the lion, does he cook his pray before savoring on his bloody prey?"-debate, but didn't you ever ask yourself, why the same people who are scared of a medium steak, order their veggies steamed, or even raw (again see red info box at the bottom of the page), so that the antioxidants in them do not get damaged by the heat. Assuming that these people are aware that raw meat is full of healthy antioxidants (I assume many or them are not, though), common wisdom about the effects of heat on anti-oxidants tells us that they should be eating all our foods raw. As it turns out, though, even that may not be the optimal strategy to boost your antioxidant defenses...

A recently published study by Serpen et al. (Serpen. 2011) showed that the total antioxidant capacity (TAC) of meat and fish actually peaked after brief (<5 min) heating at 180°C - intriguing, no?

The Turkish scientists had bought four samples of your favorite meats and fish - chicken (breast), pork (tenderloin), beef (tenderloin) and fish (Sea bream, fillet) - at a local market, determined the proximate composition (cf. fig 1) of the samples and cut identical cylindrical (5x2cm) slices from the samples.

Figure 1: Composition of raw meat extracts (data adapted from Serpen. 2011)

In the next step, Serpen and his colleagues determined the total antioxidant value of raw and thermally treated meat / fish samples using a process that is called the QUENCHER method. The method was described by the same authors in a previous paper (Gökmen. 2009) and has already become a widely used and generally accepted way of determining the total antioxidant content of foodstuff.

Figure 2: Total antioxidant capacity (calculated average from ADPS and DPPH probes) of meat and fish samples after 0, 5, 10, 15 and 20 minutes of heating at 180°C (data calculated based on Serpen. 2011)

As can be seen in figure 2, where I plotted the mean total antioxidant values of the meat / fish samples as measured by ABTS and DPPH challenges, heating at 180°C does not - as common wisdom would have it - lead to a linear or even exponential decline of the antioxidant capacity of raw meats and fish. The total anti-oxidant capacity rather peaks at around 5 minutes, decreases thereafter, just to rise again at about 20 min. According to the scientists, the highly non-linear effects of heating on the antioxidant value of various meats and the observable variety in heat responses among the different samples can be explained by the interaction of the following processes

1. denaturation and exposure of reactive sites of proteins; 
2. thermoxidation and degradation of endogenous antioxidants; 
3. formation of antioxidant MRPs (Maillard Reaction Products)

While some antioxidants are destroyed in the course of the heating process, others are created. This interplay appears to be most pronounced in the case of chicken (breast) and is the least obvious in fish (Sea bream fillet). Yet, despite the fact that short-fried <5 min meat and fish appears to be the best choice in terms of its overall antioxidant properties, specific anti-oxidants, amino acids and proteins, such as L-cysteine could get damaged even in the course of very brief heating processes. Furthermore it should be mentioned that other than a chef would do it, the scientists removed their probes from the oven and cooled them down immediately, in order to stop the continuing chemical processes. To see the same results as the scientists did for their 5min-steak, you would thus have to fry it for no more than let's say 2 minutes (this is just a very rough estimation) to make up for the ongoing reactions that won't stop if you do not shock-freeze your food before you eat it.

Note for the non-Europeans: Just in case you did not see it on CNN - the EHEC bacteria that killed people in Germany and all over Europe did not come from raw meats, but from sprouts. And it was the prejudice that raw meat, dairy and eggs were the worst (if not only) offenders, when it comes to food poisoning, that significantly hindered the investigations into the roots of an infection that has killed 37 people (according to Bild.de, 07-02-2011) in Germany, alone, when the first patients were hospitalized a few weeks ago.

Bottom line: While heating is obviously less detrimental to the overall antioxidant capacity of meat and fish, as some raw food eaters (and interestingly even the steam cooker faction) would have it, it remains questionable how you can reproduce the optimal fyring time of 5 minutes without immediately deep freezing your meat in a way, which would not leave you with your a steak that would be at least pretty rare. In turn, this means that a steak without a few drips of blood will not provide an optimal level of total antioxidants (TAC). Now, its up to you to decide whether a 2.3% decrease in mean TAC values are worth eating your steak rare - I would say no, but I don not love my steak rare, anyways, but I also read Sean Casey's formidable article on AGE formation, so if you cannot get over your socialized aversion against raw meat, dairy and eggs for what it does contain, i.e. antioxidants, then maybe for what it does not contain, which is advanced glycation end-products ;-)

Are You Stressed Enough for a Longer Life? Reactive Oxygen Specimen and Oxidative Stress May Contribute to Longevity

In June 2010 my fellow countrymen Michael Ristow from the Department of Human Nutrition at the University of Leipzig formed an interesting hypothesis (Ristow. 2010) stating that the dreaded reactive oxygen species [ROS], most scientists associate with accelerated cell-aging and degenerative diseases were in fact "essential signaling molecules which are required to promote health and longevity". In a more recent paper he picks this hypothesis up and, in cooperation with Sebastian Schmeisser from the Department of Clinical Nutrition at the German Institute of Human Nutrition in Nuthetal, Germany, reviews the current literature on selected longevity-promoting intervention.

Figure 1: Health and longevity as a function of mitochondrial reactive oxygen species (ROS) formation.
Both too much and too little ROS are detrimental, due to either insufficient stimulus for or overtaxing of hormetic processes (this graph is a mere illustration and is not based on any existing experimental data)

Ristow and Schmeisser conclude that, as different as they may at first appear, calorie restriction, the reduction of specific macronutrients (esp. low-carb diets), life-extension related to insulin and IGF-1 modulation and physical exercise, have one common denominator, which is

enhanced mitochondrial activity and subsequently increased ROS formation that ultimately induce an adaptive response (increased defense mechanisms and improved stress resistance) which culminates in metabolic health and extended longevity.

For someone, who has been told for years, to avoid the formation of radical oxygen species at all cost, and, for that purpose, to supplement with as much anti-oxidants as possible, this proposition may sound absurd. It also goes against the free radical hypothesis of aging (FRTA) and the hitherto accepted hypothesis that calorie restriction, the one and only relatively established means of life-extension in several animal models (I just want to remind you that the results still await direct confirmation in human beings), would work, because it would reduce the metabolic rate of the fasting critter and thus reduce the amount of potentially harmful reactive oxygen specimen (ROS) which are produced by the down-regulated mitochondria. The authors' response to this hypothesis is that

[...] more recent findings regarding the question whether CR [calorie restriction] actually decreases metabolic rate are, at least in part, inconsistent with FRTA [the free radical theory of aging]. Hence, it has been reported that CR increases metabolic rate (quantified by both oxygen consumption and heat production) in the nematode and well-established model organisms for aging research,  Caenorhabditis elegans. Furthermore, a positive correlation between low metabolic rate and enhanced lifespan could also not be observed in the fruitfly Drosophila melanogaster.

As a diligent student of the SuppVersity you will also be familiar with the lack of effect of antioxidant supplementation in human intervention studies to increase lifespan, promote health or prevent cancer, of which Ristow and Schmeisser write:

[...] in contrast to some of the above-mentioned work in lower organisms, several prospective clinical intervention studies were unable to found a positive association between the supplementation of antioxidants and health beneficial effects. Whereas most studies found a lack of effect in regards to health promotion in humans, other reports even suggest that antioxidants may promote cancer growth. Moreover, supplementation with antioxidants has been linked to increased incidence of a number of diseases to adverse effects of human longevity. 

These observations stand in line with the previously reported findings of Ristow et al. (Ristow. 2009) on the detrimental effect of antioxidant supplementation on exercise induced health promotion, which caused quite a stir in the world of supplement addicted exercise junkies. In all these cases, the German researchers suspect that the inhibition of the formation of an adequate amount of reactive oxygen species (ROS) blocks the initiation of hormetic physiological responses - just like using the 0.5 pound dumbbells for biceps curls to avoid injury would, at the same time, forestall muscular adaptations in form of muscle growth.

Ristow and Schmeisser also point out that, just as it is the case for resistance training, where using too heavy weights may easily lead to injury, the same "so-called adaptive response processes [which] may explain how increased ROS formation culminates in promotion of health and lifespan" may eventually turn against you, if the rate of ROS formation exceeds certain limits:

Interestingly, low doses of ROS seem to exert such effects [promotion of health and lifespan], while higher doses are unquestionably detrimental. Such biphasic responses to a potentially harmful compound are commonly named hormesis, a concept which was initially postulated in 1943 by Southam and Ehrlich and which was shown to have significant impact on aging with a variety of stressors described.

It is this concept of "mitochondrial hormesis or mitohormesis" you should thus keep in mind, when you read about the latest and greatest antioxidant supplement that just hit the market. As an athlete on a two-a-day intensive training regimen, you may well find yourself deep within the red zone on the right of the "optimal health" window in my little graph in figure 1 and thus need additional antioxidants to reduce the amount of ROS and return into the 'hormetic window' of optimal health and longevity. As a couch potato lounging in the red zone to the left of the hormetic window, you better get your metabolism going in order to produce some reactive oxygen specimen and to reap the health and longevity benefits of ROS-triggered hormetic adaptations.

Study Puts "?" Behind Beneficial Health Effects of Veggies! Is There No Correlation Between Antioxidant Content & Beneficial Health Effects of Cucumber, Lotus & Rape!?

Don't obsess about "optimal" antioxidant contents, just eat your veggies!

Over the past couple of weeks, ... no actually over the past years I have repeatedly written about the concept of (mito-)hormesis and its consequences for the well-established, but not necessarily accurate free radical theory of aging (and for some people everything else). ROS, i.e. reactive oxygen species, have been established as an important signalling molecule that is - among other things - heavily involved in the insulin sensitizing effects of exercise. "Inflammation" makes muscles grow and burns body fat and the "what doesn't kill me makes me strong" principle appears to reign everywhere you look.

You can learn more about the secrets of longevity at the SuppVersity

Are You Stressed Enough to Live Forever?

Suffocated Mitochondria Live Longer

Get Lean & Live Longer With I. Fasting

Can You add 9 Years to your Life W/ Glucosamine?

5+ Tips To Live To See Your Great Grand Children

Is a Latent Acidosis Killing You Softly?

That being said, the latest study from the Institute of Health and Environmental Medicine in Tianjin, China, opens another "anti-antioxidant" Box of Pandora. One that puts a huge questionmark behind the implications of hundreds of thousands of scientific studies, when it says in it's title, already: "No correlation is found for vegetables between antioxidant capacity and potential benefits in improving antioxidant function in aged rats"

"Skin of Grape Tomatoes Contains Max. Amount of Antioxidants" - You can find this and dozens of other daily updated SuppVersity Science News on www.facebook.com/SuppVersity

This is a title that may in fact change the way we look at study results like those of a recent study by Valdez-Morales, et al. (2014) investigating the "best" = highest antioxidant tomato, the results of which you are about to find among the ~20/day SuppVersity Facebook News @ www.facebook.com/SuppVersity - don't forget to like it, or you'll miss out on the latest science news!

If the results of the study can be confirmed by an independent team for vegetables other than lotus root, rape or cucumber and if there is an identical mismatch between the in-vivo anti-oxidant capacity and the potential benefits in improving antioxidant function in (aged) humans.

This would be big and highly consequential news for nutrition experts, scientists and average Joes and Janes like you and me. Why? Well,...

• any ranking of "superfoods" that was based even partly on in vitro data derived with the good old ferric reducing antioxidant power (FRAP) assay would be invalid, ...
• every scientist who has been following up on "promising" data from FRAP assays would have been wasting his time, ...
• and you may have been eating all the wrong foods for years...

... hell no, as long as you ate your veggies over the past years, I wouldn't worry if you may have made a "suboptimal" selection (which would be different based on whatever new criteria you select).

Figure 1: FRAP value, vitamin C and vitamin E content and total amount phenolics in the powdered vegetables that were added to the rodent diets in the study at hand (Ji. 2014)

Honestly, I'd hope that you didn't select your foods only based on the orthorexic principle of maximal antioxidant content, anyways. 

Never forget the three principles of veggie eating: Variety, seasonality, colorfulness

Against that background I'd recommend you keep eating your lotus roots, if you like them, although, they have a significantly lower beneficial effect on SuperOxide Dismutase (SOD, a group of antioxidant enzymes) than rape and cucumber.

Figure 2: Serum markers of anti-oxidant status / oxidative damage after 6 weeks on the three experimental diets (Ji. 2014)

Moreover, if you look closely at the data in Figure 1+2, you will realize that lotus may suck at SOD and its ability to reduce hemolysis (the destruction of red blood cells), but will have the most profound beneficial effects on the levels of malondealdehyde (MDA), a marker of lipid oxidation, and the amount of plasma carbonyls, which have - just as in cellular regulation, aging, and disease (Levine. 2002). Just like their similarly radical cousins, carbonyls will thus play a dual role so that in the end, their reduction may not be beneficial in each and every case.

Figure 3: Blood mononuclear cell DNA damage expressed as total injury rate (%) and total tails low (% of all) in male Wistar rats on control and experimental diets (Ji. 2014)

The Take Away: Whatever the role of carbonyls, MDA & co may be and no matter what you believe which of the three tested vegetables may be the "best" one, if there is one definite message you can take home from today's SuppVersity article, it's not to overly rely on the abstract data from chemical tests the reliability of which appears to be inversely proportional to their accuracy.

Trust your instincts and go for a broad variety of vegetables. Eat seasonal! Eat colorful! And most importantly eat plenty. Optimal or not, none of the vegetables in the study at hand would harm you - all of them would help you defy diabesity and slow the aging process as best mother nature allows.

Reference: 

• Ji, Linlin, et al. "No correlation is found for vegetables between antioxidant capacity and potential benefits in improving antioxidant function in aged rats." Journal of Clinical Biochemistry and Nutrition 54.3 (2014): 198-203.
• Levine, Rodney L. "Carbonyl modified proteins in cellular regulation, aging, and disease^{2, 3}." Free Radical Biology and Medicine 32.9 (2002): 790-796.
• Valdez-Morales, Maribel, et al. "Phenolic content, and antioxidant and antimutagenic activities in tomato peel and seeds, and tomato by-products." Journal of Agricultural and Food Chemistry (2014). Accepted Manuscript.

TTA + Fish Oil - Fat Burning Superfats or Hepatoxic Pro-Oxidants? Why You Better Avoid Large Amounts of Omega-3 and Tetradecylthioacetic Acid in the Long Run

Image 1: Even if you align them like that, it is at least debatable whether capped fish oil is much more natural than the structurally modified 16 -carbon saturated fatty acid tetradecylthioacetic acid (TTA). As far as their effects on weight loss are concerned, the latter is certainly more potent,... the debate on the side-effects of both is yet still far from being settled. Despite the mainstream hoopla around the former...

At least for those of you who have been around the supplement world for some time, the acronym TTA, which stands for tetradecylthioacetic acid, a structurally modified 16 -carbon saturated fatty acid (SFA), which has been shown to increase fatty acid oxidation and reduce triglyceride levels via interactions with purportedly all PPAR-receptors, should ring a bell. For the rest, it will yet probably be news that, back in the early 2000s, TTA was all the rave as the new star among OTC-fat burners. And in fact, the weight loss people experienced on respective products was non-negligible... yet so were the side-effects which crept up over time (and with ever-increasing dosages): Headaches, cramps, dehydration and water retention specifically in the abdominal area were only the minor complaints. Unbearable fatigue and even palpitations were at the other extreme of the spectrum and probably the actual reason why company after company  altered the formulation of their "effective" and above all commercially successful tetradecylthioacetic acid containing fat burners.

While TTA works well, but has well-known side-effects,...

A recent long-duration rodent study that was conducted by a group of European researchers and which my friend Sean Casey from CasePerformance has brought back up onto my radar (Vigerust. 2012), did now investigate the long term (50 weeks) effects of supplemental tetradecylthioacetic acid and another purportedly saver PPAR-agonist, with similarly beneficial effects on triglycerides yet hardly noticeable effects on weight management - my all-time favorite fish oil! To this extend, the scientist kept their rats on their infamous interpretation of a "high fat" diet, which, as you will probably already have expected, had a moderate fat content of 25% tons of carbs and little protein and had thusly more of the standard American diet than of what people in the bloggosphere usually refer to as a "high fat" diet, i.e. a diet that is really high in fat (>50%) and low in carbohydrates.

Figure 1: Relative body weight (compared to identical baseline) in rats at different time points during 50 weeks on high fat diet (control) with either TTA, fish oil or both (data calculated based on Vigerust. 2012).

It is thusly not surprising that replacing 10% of the fat by fish oil (~11g EPA + 6g DHA for avg. human) had absolutely no effect on the weight gain of the hyperphagic (overeating) rodents. The miniscule amount of 0.365% TTA, which would be equivalent to a daily intake of ~912.4mg of TTA for someone consuming 2000kcal/day, on the other hand, lead to statistically highly significant reduction in weight gain over the whole 50 week feeding period (cf. figure 1).

Figure 2: Relative expression of uncoupling protein 3 (UCP3, primary axis) and enzymes involved in fatty acid metabolism (secondary axis) at the end of the 50-week dietary intervention; expressed relative to high fat control (data calculated based on Vigerust. 2012).

As evidenced by the elevations in carnitine palmitoyltransferase II (CPT II), which is necessary to shuttle the fat into the cell, HMG-CoA, which is one of the key players in ketogenesis, and peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), which initiates the first enzymatic reaction during beta oxidation, the hepatic fatty acids oxidation in the TTA (and TTA + FO) group was profoundly increased, in conjunction with the exorbitant increase in UCP-3 expression (>1500x in the TTA only, and >1300x in the TTA + FO group) and the subsequent "leakage" of energy in the form of protons, this easily explains the -11% / -19% reduction in total body weight in the TTA and the TTA + FO groups at the end of the 50 week study period.

....fish oil hardly works and has less-known side-effects

In that, it is important to note, that only TTA (respectively its addition to FO), not fish oil, was able to reduce the diet-induced elevations in hepatic triacylglycerol (TAG) levels. This leads to scientists to speculate, that despite similar effects on TAG and cholesterol transport in the liver, ...

[...] animals given the FO diet are less able to metabolize the excess hepatic lipid levels [... so that] FO redistributed lipids without affecting the total lipid level and body weight.

This would also explain the detrimental effects the fish oil supplement had on hepatic cholesterol levels and lipid oxidation, which would suggest that, at least under these dietary conditions (relatively high fat + high carb + high energy = typical western diet), one would be better off taking no fish oil at all, or a combination of fish oil and TTA.

Figure 3: Relative mRNA expression of markers of protein and lipid oxidation in liver and liver mitochondrial fraction of the rodents at the end of the 50-week study period (data calculated based on Vigerust. 2012)

The latter is all the more indicated in view of the fact that the use of the highly oxidizable fish oil alone lead to non-negligible increases in protein oxidative damage (cf. GSA, alpha-AASA, figure 3) and an increase in total hepatic glyco- and lipooxidation, as evidenced by the increase in Ne-Carboxymethyl-lysine (NCL, figure 3) in the whole-liver samples and a corresponding increase in Nɛ-Malondialdehyde-lysine (MDAL), a lipid-specific marker of oxidative damage in whole-liver and the mitichondrial homogenate (liver M-fraction) of the animals in the fish oil (only) group (cf. figure 3).

These detrimental oxidative longterm effects of fish oil supplementation, which "showed a significant positive correlation with DHA content" of the liver (meaning more DHA in tissue = more oxidation), were only ameliorated, yet not totally prevented by co-treatment with tetradecylthioacetic acid (TTA), which reduced the amount of oxidizable PUFA in plasma and tissue and reduced the mitochondrial ROS production via the UCP-3 induced energy leakage and the subsequent relative reduction in oxidative energy production (remember the overall energy expenditure was still increased by TTA, yet not by FO treatment).

Bottom line: Avoid the dietary PUFA burden, eat healthy and exercise...

Image 2: "You told me to eat more protein and this burger has both meat and cheese!" - click here for more info on why dietary interventions fail

As far as the amelioration of negative side-effects of the typical Western high carbohydrate, relatively high fat diet are concerned, the results of this study would argue against the longterm use of omega-3 polyunsaturated fatty acids from fish oil (DHA in particular) and for the use of structurally modified 16-carbon saturated fatty acid TTA in order to reduce weight gain, triglyceride and liver cholesterol levels in individuals who are either unwilling or unable to make the necessary life-style-changes that would, instead of just prolonging their suffering, help them finally escape from the maelstrom of the metabolic syndrome (cf. yesterday's blogpost on "High Carb vs. High Fat, When Science Meets Real Life").

Whether the same holds true for athletes, fitness enthusiasts or at least moderately active human beings, who stick to an overall anti-inflammatory low(-er) carb (not "no carb" and not necessarily, but possibly "paleo") diet, would certainly warrant further investigation. It would nevertheless, my previously voiced concerns over the injudicious (over-)use of omega-3 supplements in the futile effort to "balance" the dietary over-indulgence of omega-6s... after all, the most straight-forward explanation for the increase in oxidative damage in the fish oil only group is the increased amount of PUFAs in the liver tissue, which are - across the board, i.e. omega-6 and omega-3 - much more susceptible to oxidative damage due to radical oxygen specimen (ROS). I thusly stick to my previous recommendation to just watch your overall PUFA intake and resort to alternative fat sources, such as coconut oil (which is, by the way, the topic of the first "non-SuppVersity" article of mine in the all-new article-section of the VPX-website; don't worry I won't neglect the SuppVersity and stick to topics without potential "conflicts of interest and objectivity" ;-), butter, dairy and meat products from grass-fed animals, eggs and obviously real fish!

... and you won't need TTA to lose weight or ward off unwanted body fat

Moreover, I strongly caution against a similar injudicious (ab-)use of large amounts of TTA especially over longer periods of time. The latter was probably the underlying reason for the initially mentioned side-effects, due to which most supplement manufacturers either totally removed tetradecylthioacetic acid from their products or reduced the amounts per servings to levels, where the other ingredients would give you palpitations before you would achieve dosages way beyond the 1g range, which, as previous human trials would suggest, appears to be save at least in the short term (<30days, cf. Lovas. 2009). With respect to longer durations and/or higher dosages, you should yet be aware that the very same depletion of plasma and tissue PUFAs which is partly responsible for the overall reduction in oxidative damage in the study at hand, may well backfire and produce exactly those cramps, the water retention, and the profound lethargy reports of which you will find in the archives of various health and fitness boards, all over the web.