Your MUFA + PUFA Intakes Determine Your True Vitamin E Requirements - N-3s are the Worst Offenders + Even MUFAs Need Buffering | Tool to Calculate Your Individual Needs

Nature knows best: Oils and other high PUFA foods come with a naturally high amount of vitamin E (see Fig 1).

As a SuppVersity reader you shouldn't be surprised to hear that there's a link between the amount of highly oxidizeable polyunsaturated fatty acids (omega-3 and omega-6) you consume and the amount of vitamin E you "need" to protect them from being oxidized by free radicals.

The reason we usually speak about vitamin E in this context is that vitamin E (mostly alpha-tocopherol) is recognized as a if not the key essential lipophilic antioxidant in humans. It protects lipoproteins (cholesterol), PUFA, cellular and intra-cellular membranes from damage.

Learn more about hormesis and potential neg. effects of antioxidants at the SuppVersity

Is Vitamin E Good for the Sedentary Slob, Only?

NAC Impairs Anabolic Effects of Exercise

If Vitamin C is Low, Taking More is Good

C+E Useless or Detrimental for Healthy People

Vitamin C and Glucose Management?

Antiox. & Health Benefits Don't Correlate

For a recent review, scientists from DSM Nutraceuticals in Brussels and the Human Development and Health Academic Unit at the Faculty of Medicine of the University of Southampton partnered up in order to "evaluate the relevant published data about vitamin E requirements in relation to dietary PUFA intake" (Raederstorff. 2015).

Table 1: Overview of the currently recommended daily intakes for vitamin E (Monsen. 2000).

For their 10-page review, which does not take into account the interactions between tocopherols, the 'classic' vitamin E, and tocotrienols (this is not really negligent, because only the tocopherols are essential and the interactions between the different forms of vitamin E are not fully elucidated, yet), the scientists considered both evidence from animal and human studies; evidence that indicates that our basal requirement of vitamin E, namely 4–5 mg/d of RRR-α-tocopherol when the diet is very low in PUFA, are way below the RDA of 15mg/day. Now obviously, most Westerners do not fall into the category of people with a "minimal intake of PUFA". Accordingly, their vitamin E requirements are higher, and thus probably in the range of the recommended daily allowance.

You don't even have to consume exuberant amounts of anti-oxidants like vitamin E to ruin your gains. A recent study shows: Icebaths will do the same. By soothing the inflammatory response to exercise, they will also shut down the adaptational processes | learn more

I am healthy, I don't have to care! If you really believe that, you may be healthy but stupid. Even the healthiest person on earth will produce free radical specimen. In fact, ROS are essential for the adaptational processes that occur in response to exercise and involved in normal glucose regulation. On the other hand, very recent scientific evidence highlights that adequate cellular vitamin E levels are necesssary for muscle membrane repair and the rescue of myocytes from necrosis (Howard. 2011; Labazi. 2015). Scientists believe that these benefits are the result of an increased speed and efficacy of membrane repair mechanisms like membrane fusion events. It should thus be obvious that managing, not worshipping or annihilating ROS with adequate amounts of vitamin E and other anti-oxidants should be your primary goal (one you can achieve w/out supps).

Still, the fact that our basal vitamin E requirements, i.e. the amount of vitamin E we would need if we didn't stuff ourselves with tons of PUFAs, amounts to only ~30% of today's RDA (see Table 1) for adult men and women should make us reconsider the necessity and usefulness of vitamin E supplements. I mean, who of you is actually consuming 30g of MUFA, and 22g of PUFA from sources that do not come with adequate amounts of vitamin E?

Figure 1: All suggested oils from the "Quest for the Optimal Cooking Oil"-Article from December 2014 contain way more vitamin E than they'd need to buffer their own PUFA / MUFA content (learn more about the best cooking oils).

If you look at the data in Figure 1, which is a comparison of the actual content of vitamin E in mg and the amount of vitamin E that would be necessary to buffer the "unstable" fats in the three oils you will remember from the "Quest for the Optimal Cooking Oil", the answer to the previously raised question is probably going to be "very few". After all, most of the largely unprocessed we consume contain way more than 100% of the amount of vitamin E they would have to provide to protect the inherent MUFAs and PUFAs from oxidation.

Each unsaturated fatty acid has its specific effect on your vitamin E requirements

Against that background it is no wonder that vitamin E deficiency is a more of less unheard of thing in the Western world. No one here consumes less than the absolute minimum of 4-5mg/day (Harris. 1963; Valk. 2000) for months or longer. The only way to still develop relative vitamin E deficiency is thus to consume processed foods or supplements that do not contain enough vitamin E to satisfy the increase in vitamin E demands due to the specific unsaturation of their fat content.

Table 2: Vitamin E requirements - in mg of vitamin E per gram intake of the respective fatty acid - for different unsaturated fatty acids found in human diets (Raederstorff. 2015)

Since the latter increases almost linearly with the degree of unsaturation of the PUFA in the relative ratios of 0·3, 2, 3, 4, 5 and 6 for mono-, di-, tri-, tetra-, penta- and hexaenoic fatty acids, respectively, Harris' & Norris' (1963), as well as Horwitt's (1986) equations, which do not take into account that omega-3 fatty acids, for example, have a much more pronounced impact on your vitamin E requirements than omega-6s or MUFAs, are now obsolete.

Equation 1: Use this equation or the SV Calculator to determine your personal requirements based on your intakes of  different forms of mono- (M1 and polyunsaturated (M2-6) fatty acids (Equ. from Raederstorff. 2015).

Today, Equation 1 has taken their place. In Equ. 1 Mn is the amount of dietary MUFA/PUFA with n double bonds in grams (see Table 2). If you know how much of the individual unsaturated fats you consume you can thus easily calculate your personal vitamin E requirements - requirement, of which I bet that you will cover them with the vitamin E from cooking and salad oils, alone (compare Figure 1).

Chicken legs, old man? Must have been too much antioxidants - Learn how too much vitamin C + E can blunt the increases in total lean body mass, and leg mass in elderly men after 12 weeks of highly standardized, intense strength training: No wonder, the vitamins virtually suffocated the necessary stressors | read more.

Bottom line: I guess you are already waiting for the link to the calculator I promised, right? Let's just briefly put the result that even the average westerner needs "only" 12-20 mg of natural vitamin E per day into perspective. On the one hand, that's more than you'd find in a few really trashy foods people like to eat. On the other hand, that's only 17-30IU/day and thus 13-24x the amount of vitamin E you will find in many multi-vitamin, and vitamin E pills (many contain 400IU or 269mg), which appaers hilarious considering the fact that whole foods that are high in unsaturated fats will always come with the required amount of vitamin E.

If that does not sooth your mind and you want to know exactly how much your need, here's the spreadsheet I promised. I am sure it's significantly less than the >120mg/day that impaired the size gains of the elderly subjects in the recently discussed study by Bjornsson. It's much less, right? Comment on Facebook!

References:

• Monsen, Elaine R. "Dietary reference intakes for the antioxidant nutrients: vitamin C, vitamin E, selenium, and carotenoids." Journal of the American Dietetic Association 100.6 (2000): 637-640.
• Harris, Philip L., and Norris D. Embree. "Quantitative consideration of the effect of polyunsaturated fatty acid content of the diet upon the requirements for vitamin E." The American journal of clinical nutrition 13.6 (1963): 385-392.
• Howard, Amber C., Anna K. McNeil, and Paul L. McNeil. "Promotion of plasma membrane repair by vitamin E." Nature communications 2 (2011): 597.
• Horwitt, M. K. "Interpretations of requirements for thiamin, riboflavin, niacin-tryptophan, and vitamin E plus comments on balance studies and vitamin B-6." The American journal of clinical nutrition 44.6 (1986): 973-985.
• Labazi, Mohamed, et al. "The antioxidant requirement for plasma membrane repair in skeletal muscle." Free Radical Biology and Medicine 84 (2015): 246-253.
• Raederstorff, Daniel, et al. "Vitamin E function and requirements in relation to PUFA." British Journal of Nutrition (2015): 1-10.
• Valk, and Gerard Hornstra. "Relationship between vitamin E requirement and polyunsaturated fatty acid intake in man: a review." International Journal for Vitamin and Nutrition Research 70.2 (2000): 31-42.

Supplemental NAFLD (Non-Alcoholic Fatty Liver Disease) Protection for Everyone! Regular Alpha Lipoic Acid (300mg) & Vitamin E (700IU) For Less Than $20 Do the Trick!

You don't have to look at the liver of this person to know that he / she is suffering from NAFLD - just like an ever-increasing minority (soon majority) of US citizens

You may asking yourselves what "looking good naked" has to do with obesity and diabetes right now, but if you think about it, the things you have to achieve the one (don't tell me you don't care if you look good naked, liar!) and avoid the others are actually not too different and what's commonly overlooked: The liver is of pivotal importance for both! Looking healthy and being healthy.

In spite of the fact that I am going to get back to the "liver <> diabetes" connection later in the article, I would like to invite you to take a closer look at a previous article on that topic "Liver Enzymes the #1 Marker of Insulin Resistance!? Plus: What Does the Correlation Bettwen HbA1C & ALT, AST and GPT Tell Us About Diabesity?" to catch up!

You can learn more about NAFLD at the SuppVersity

6 Bananas A Day = No Problem For the Liver!

Can We Blame NALFD on Fructose?

Insulin Sensitivity is Determined in the Liver

Saturated Fat & NAFLD - Is there a Link?

Snack Your Way to a Non-Alholic Fatty Liver

No Choline, No Healthy Liver, But Heart Attacks

Now that we are on common grounds in regards to the importance of liver health, it's about time to drop the bomb. Believe it or not, you can help your liver along tremendously with commonly available dietary supplements - and if I am not totally mistaken that will cost you - at most - 20 bucks a month. Certainly not bad in view of the fact that the stack of alpha lipoic acid (regular, not R-ALA) and - you won't believe it - regular vitamin E has just been shown to A

• 

  CLA always with DHA | learn why

  improve inflammatory cytokine levels, 
• reduce steatosis scores, 
• improve homeostasis model assessment scores, and 
• lower triglyceride levels 

withing only 6 months significantly in comparison to the baseline levels of the to 155(!) patients that were enrolled in the study.

ALA & Vitamin E work - both in conjunction and on their own

In pairs of m=40, the subjects had been randomly allocated to receive either ALA 300 mg, vitamin E 700 IU, or ALA 300 mg plus vitamin E 700 IU, the poor 35 patients who were left were randomized to treatment with placebo.

Figure 1: Changes in selectet parameters of metabolic health over the 6-months study period (Basu. 2014)

As the data in Figure 1 clearly indicates, this was ill fate. Compared to their peers who were treated with alpha lipoic acid and / or vitamin E, they saw significantly less pronounced health improvements in spite of similar lifestyle changes (participants were allowed to consume 1600 calories per day and to participate in moderate exercise, consisting of walking 150 minutes per week at the rate of 100 steps per minute).

No, I would not be scared of vitamin E! If you have NAFLD, there is no doubt that you can benefit from additional antioxidants. Things may look different, for lean athletes like yourself, who tend to fall for the false promises of "nutrient repartitioners" | learn more.

Bottom Line: They are cheap, they can be bought all over the Internet and at every supplement store round the corner and they are effective. Alpha lipoic acid (regular) and vitamin E will boost your efforts to reverse the damage you've inflicted on your liver over the past couple of years and this will have pronounced effects on your overall metabolic health, your lipid and glucose metabolism, your heart disease and cancer risk ("Liver Cancer Kills US Citizens" | learn more) and - of course - the way you look and feel. Not too bad for 100% sage supplements that are worth less than $20 per months, right? Just make sure you don't overdo it. If 300mg + 700IU work, this does not mean that 1,200mg + 2400IU will work better ;-)

Reference

• Basu, Patrick P., et al. "Effect of Vitamin E and Alpha Lipoic Acid in Nonalcoholic Fatty Liver Disease: A Randomized, Placebo-Controlled, Open-Label, Prospective Clinical Trial (VAIN Trial)." Open Journal of Gastroenterology 4.05 (2014): 199.

Antioxidants For Lazy Rodents: Alpha Lipoic Acid + CoQ10 + Vitamin E Work Mitochondrial Wonders On Untrained Female Mice... And ONLY On Untrained Female Mice!

ACE!? Are alpha lipoic acid, coQ10 and vitamin E good for them or not?

With all the bad press on anti-oxidants, you could actually get the impression that performance and longevity should be a function of the amount of oxidative stress you're exposed to.

Despite the fact that this hypothesis may have it's merit, the "True or False" item on the negative side effects of eccentric training should probably have reminded you that keeping a balance between the constant oxidative assault from our environment (in the broadest sense) on the one hand and our bodies' continuously evolving defense system is what we should actually be aiming for.

Whether or not we will benefit from an increase in exogenous anti-oxidants like vitamins, will therefore always depend on both the stressor and the state and performance of our anti-oxidant defense system. A recent paper that has just been published in the peer-reviewed online journal PLOS-ONE does actually appear to confirm this notion of "stress management". In other words:

Adaptation occurs, when you expose yourself to stressors which are taxing, but won't obliterate your defense system = the "i + 1" / hormesis principle

We know from previous human studies that vitamin C and vitamin E (1g Vit C, 400IU Vit E; about as much as you will find in any of the useless "high performance multis") can blunt the hormetic effects of exercise-induced oxidative stress on insulin sensitivity and the concomitant adaptive response of the endogenous antioxidant defense system (Ristow. 2009).

Figure 1: TBARS in the supplemented (no improve in insulin sensitivity) and non-supplemented trainees (Ristow. 2009)

A quick note on how to interpret study results: Whenever you take a look at one of the "pro-antioxidant studies", you got to make sure the scientists don't base their assessment that the use of the respective molecule was beneficial on the observation of a reduction in exercise induced stress.

If the (mito-)hormesis theory holds, the amelioration of the latter in the 2009 study by Ristow (see figure 1) is in fact to blame for the absence of increases in insulin sensitivity, adiponectin, etc.

The results of the Ristow study have caused quite an upset within the scientific community and the world of physical culture. Especially within the latter the results of the researchers from the University of Jena were often misinterpreted as "all anti-oxidants are bad for you" and then prematurely dismissed on the basis of studies in which the researchers were able to observe mostly marginal and in terms of the explanations in the red info box above, highly questionable "beneficial" effects of anti-oxidant supplements.

Not all "antioxidants" are created equal

Suggested read: In a 2012 letter to the proponents of the mitohormesis hypothesis pick the results of a paper by Higishada et al. that's often cited in support of vitamin C + E supplementation to pieces and conclude "The vast majority of experimental evidence clearly advises against this supplementation. Thus, we unreservedly confirm the conclusions derived from our previous research and disagree with Higashida et al. In our opinion, antioxidant supplements are, at the least, useless" (Gomez-Cabrera. 2012). The letter should be accessible for all of you, so feel free to read up on the evidence they provide to support this conclusion... keep in mind, though no honest scientist will claim he would tell you the one and only truth. What they will give you is their assessment of the facts and the conclusion they believe should be drawn based on these facts.

In fact, the actual number of exercise interventions in which scientists observed real-world benefits from vitamin C and vitamin E, in particular, is often overestimated. Therefore neither of these most prominent members of a very broad class of molecules that carries the label "antioxidant" can be considered a "proven ergogenic" and it is therefore not very surprising that Nikolaidis et al. conclude their 2012 review of the literature on the words:

"Based on the contradictory evidence regarding the effects of higher intakes of vitamin C and/or E on exercise performance and redox homeostasis, a permanent intake of non-physiological dosages of vitamin C and/or E cannot be recommended to healthy, exercising individuals." (Nikolaidis. 2012)

Now, despite the fact that the acronym may be the same (ACE usually stands for beta carotene, vitamin C and vitamin E), the "antioxidant" supplement in the study at hand has a different makeup. While it does contain vitamin E, it does not contain the additional "kamikaze vitamin" ascorbic acid, which cannot distinguish between "good" and "bad" ROS formation and will - much like a fire extinguisher - quench both "smoke signal" that's telling your boy "the mitochondrial engine is running at full speed, it may be time for an upgrade", as well as the not so beneficial "sparking" that occurs when the engines are overheating.

Does the mix make the difference?

CoQ10 on the other hand, is more or less specialized on protecting the mitochondria. It is not a "fire extinguisher", but rather a fire-proof coating that protects the mitochondria from "leaking" reactive oxygen specimen into the circulation. In conjunction with the cell-membrane protecting effects of vitamin E and the "vitamin recycler" alpha lipoic acid, we get a highly specialized antioxidant stack of which the results of the study at hand show that it is beneficial in those situations, where the baseline protection against an imposed stressor is insufficient.

Figure 2: Differential effect of anti-oxidant supplementation on trained (8 wks treadmill running) (n = 12/group) and untrained (n = 24/group) male and female rodents' endurance performance; data presented in meters (Abadi. 2013)

If you do now take a peak at the data in figure 2 you will realize that the latter was the case in the female rodents who were not exposed to the chronic exercise regimen. Correspondingly the provision of the ALA + CoQ10 + vitamin E stack did improve the exercise performance and mitochondrial respiratory chain protein capacity. The same data plot does yet also reveal that these effects were sex and training specific and generally absent in the trained rodents.

Figure 3: Questionable (female) and non-existant (male) "benefits" of antioxidant supplementation on the relative expression of the mitochondrial builder PGC-1a, the satellite cell recruiting "stress" kinase p-38 MAPK and the well known glucose sensitizing AMPK (Abadi. 2013)

One of the many things, Abadi et al. don't mention, though, is the fact that the "reduced the activation of the stress kinase p38-MAPK following acute exercise in untrained" (Abadi. 2013, cf. figure 3) could also decrease the "repair" and supercompensation process that will take place after the unaccustomed (remember the data in figure 3 is from untrained animals after the 2nd exercise test). After all, the "stress kinase" is at the same time "a molecular switch for satellite cell activation" (Jones. 2005) and thus heavily involved in the recruitement of satellite cells.

"Voilà it works.... ahm, ok only in one out of four groups, but it works!"

Similarly, Arkan Abadi and his colleagues unfortunately forgot to mention is that they did not measure "THE" training-induced adaptations in the sense of "all training induced adaptations", but only a couple of mitrochondrial protein expressions. Against that background we cannot exclude that the insulin sensitizing effects of exercise Ristow et al. have been missing in their human subjects was not blunted in Abadi's C57Bl/J6 mice, as well.

Remember the case is not yet settled: This is an analysis of a single study and the fact that this suggests that CoQ10, ALA and vitamin E are worthless for the majority of trainees does neither negate that the provision of only on of them, e.g. 200mg/day CoQ10 in athletes taking statins (Deichmann. 2012), or the provision of respective supplements during specifically stressful training periods can have ergogenic effects.

The absence of more comprehensive data on the actual metabolic effects of the supplement regimen, as well as the unexplained confounding effects of gender and training status, specifically the non-significant, yet paradoxically opposed effects the scientist observed in the male rodents certainly warrant the question, why the abstract focuses almost exclusively on the already moderate benefits they observed in the untrained females. After all, the scientists declare that the

"study was undertaken to investigate the effects of dietary supplementation with vitamin E, a-lipoic acid, and CoQ10 in combination on basal and training-induced mitochondrial adaptations in mice." (Abadi. 2013)

In other words, their interest was in the effectiveness in mice in general and not in untrained female mice. Against that background, the most significant finding of the study would actually have been that there are confounding factors rendering the combination of these three mitochondrial antioxidants useless.

---

Figure 4: 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 and was first published in a previous SuppVersity article from May 2011)

Bottom line: I bet you will soon see the results, or rather excerpts of the results of this study referenced on the bottles and shiny adverts of the supplement industry. "Most recent studies show that the combination of alpha lipoic acid, CoQ10 and vitamin E in RippYouOffSupplements (ROS) newest product increases ..." You know the whole spiel and are probably not fooled by pseudo-scientific nonsense like that anyway.

Take a look at the data and use your gray matter: Are you rather an untrained female mouse? Or would you rather describe yourself as a devoted physical culturist?  If choose the 2nd option, you don't have to rack your brain any longer about the what ifs and maybes pertaining to potential reductions in the exercise induced increase in insulin sensitivity, because the "scientific evidence" ROS presents in favor of the efficacy of their newest "blockbuster product" is not relevant for you, anyway.

Now that I am done ranting, I should maybe add that I sill like this study. Not just as an educative example of how easily scientifically valid data can be abused to provide proof for whatever you want, by simply skipping on parts of the results, but also because it adds sex as a new confounding factor you have to keep in mind, when you compare studies on the useful an uselessness of antioxidant supplements. And that's not just in an exercise, but also in any other scenario (e.g. longevity, metabolic syndrome, etc.) - after all, the gender-difference was present only in the non-exercised rodents.

References:

• Abadi A, Crane JD, Ogborn D, Hettinga B, Akhtar M, Stokl A, MacNeil L, Safdar A, Tarnopolsky, M. Supplementation with a-Lipoic Acid, CoQ10, and Vitamin E Augments Running Performance and Mitochondrial Function in Female Mice.
• Deichmann RE, Lavie CJ, Dornelles AC. Impact of coenzyme Q-10 on parameters of cardiorespiratory fitness and muscle performance in older athletes taking statins. Phys Sportsmed. 2012 Nov;40(4):88-95.
• Gomez-Cabrera MC, Ristow M, Viña J. Antioxidant supplements in exercise: worse than useless? Am J Physiol Endocrinol Metab. 2012 Feb 15;302(4):E476-7; author reply E478-9.
• Higashida K, Kim SH, Higuchi M, Holloszy JO, Han DH. Normal adaptations to exercise despite protection against oxidative stress. Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E779-84.
• Jones NC, Tyner KJ, Nibarger L, Stanley HM, Cornelison DD, Fedorov YV, Olwin BB. The p38alpha/beta MAPK functions as a molecular switch to activate the quiescent satellite cell. J Cell Biol. 2005 Apr 11;169(1):105-16.
• Nikolaidis MG, Kerksick CM, Lamprecht M, McAnulty SR. Does vitamin C and E supplementation impair the favorable adaptations of regular exercise? Oxid Med Cell Longev. 2012;2012:707941.
• Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Blüher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009 May 26;106(21):8665-70.

Reishi Protects Against Cancer & Contains Anti-Androgen; Adrenalin Rejuvenates Brown Fat; Mild Stress Normalizes Cortisol / DHEA Ratio in Elderly; DHEA, Aromatase Inhibitors & BPA vs. Joint & Brain Health; Vitamin E Battles Lymphoma

I am not happy with how the short news on Facebook simply disappear into oblivion.

The SuppVersity figure of the week is "920"! "920" as in "920 published posts" here at the SuppVersity. The reason that's the figure of the week is that I have been thinking about ways to reorganize the archive, but am a bit lost on how to structure things in a better way using blogger. This beast simply isn't made for anything that goes beyond a weekly classic blogpost a la "last week I did this and that, read about..." *yawn*

What's yet even more enervating is that despite having the huge advantage of being easily posted and directly accessible for all of you, the tons of short news items I post on a daily basis on the SuppVersity Facebook Wall simply disappear into the 'Facebook nirvana'. I currently cannot spend any time on those technical / organizational matters, but in the course of 2013 things are going to change.

In the mean time, follow the SuppVersity on Facebook and read the news, right when I post them + use google to find articles you are looking for. You will be laughing, but that's the way I dig through those 920 posts, as well ;-) Simply type whatever you look for and add a "+site:suppversity.blogspot.com" to it.

Chinese fungi are laden with cancer-protective molecules and 5a-reductase (DHT) inhibitors

In view of a recent paper from the Universitat de Valencia (Rios. 2012) it appears that it would actually be hard not to decrease your risk of developing cancer if you include extracts from Ganoderma lucidum and other related fungi, such as Poria cocos, Laetiporus sulphureus, Inonotus obliquus, Antrodia camphorata, Daedalea dickinsii, and Elfvingia applanata in your supplement regimen. With a total of 81 compounds from Ganoderma lucidum and other species from this genus, as well as 96 compounds isolated from other fungi, principally Poria cocos. It appears that these creatures (fungi are no plants, neither are they animals, but still sort of living beings) could hold the key to hundreds o natural anti-cancer agents.

Ganoderma lucidum better known as Rheishi mushroom may have cancer protective effects, but does not taste so bitter that no sane human being would eat it for a reason (photo by Eric Steinert)

I guess, I don't have to tell you that Chinese Medicine, of course, knew about the powerful anti-inflammatory and anti-proliferative effects of the lanostanes in these fungi, all along. Intuitively and probably by trial and error, the Chinese have found the tetracyclic triterpenoids that are derived from lanosterols in these fungi to be effective in the treatment of various diseases including different types of cancer. As of late the mostly anecdotal effects are backed by more and more research. A preliminary study by Sliva et al. (Sliva. 2002), for example, found that a hot water extract of both spores and the dried fruiting body of G. lucidum inhibited the progression of cancerous growth by reducing the expression of constitutively active growth and inflammation promoting transcription factors AP-1 and NF-κB: 

"The extracts also inhibited the secretion of uPA, thereby suppressing the migration of breast cancer MDA-MB-231 and prostate PC-3 cells. [...] High levels of both uPA and uPAR are associated with advanced tumors and decreased survival time in different malignant human cancers." (Rios. 2012)

These benefits do however come with a downside. At least in vitro, some of the fungi, particularly G. lucidum, obviously exert their effects via anti-androgenic pathways (Liu. 2007). A compound in Reishi that goes by the name ganoderol B, for example, does not just have inhibitory activity against 5α-reductase, but can also bind to the androgen receptor directly (if you will you could say it acts like an anti-anabolic SARM). Now, this was good news in a study that has been conducted by Liu et al., because it inhibited androgen-induced cell growth in an LNCaP cell line while suppressing testosterone-induced regrowth of the ventral prostate in rats. If those effects are however non-selective, you are about to run into problems once the molecules bind to receptors outside the prostate -- epression for example, if they block the androgen effects in the brain, etc.

That reminds me: What did Carl say on Thursday's installment of the SuppVersity Science Round Up? "The good thing about supplements is that they work, the bad thing about them is that they work!" I guess you can basically say the same about Reishi. Good that you as a SuppVersity reader always know about both, the good and the bad sides of supplements!

More short news

With me posting stuff on the fly on facebook, I am actally 'wasting' many of the very short news items, but nevertheless, here are a couple of relatively short news to round things up.

• 

  If you missed Monday's new on the quasi non-existent thermogenic effects of ephedrine, this would be a good time to read that post.

  Stress-induced browning of the fat? Chronic overexpression of noradrenaline (re-)generates wasted brown fat! In a way this is a follow up on the ephedrine post "Fat Burners Don't Work" as well as an addendum to a news on the role of GABA and brown fat in obesity, I just posted on facebook. According to an allegedly old study in the International Jornal of Obesity (Lee. 1986),  the chronic overexpression of noradrenaline as it is observed in humans with a certain form of adrenal tumor known as phaeochromocytoma can actually reactivate the intra-abdominal fat of human adults, including the omental fat, which is brown adipose tissue in infancy.
  
  Lee et al. see this as one of the main contributing factors to the weight loss which is typically seen with phaeochromocytoma. Sounds, logical, since the same stimulus that rejuvenates the Brown fat will also have it burn energy continuously - the overexpression of noradrenaline.
  
  
  Symptoms of overtly high noradrenaline levels include abdominal pain, chest pain, irritability, nervousness, pallor, palpitations, rapid heart rate, severe headache, sweating, hand tremor, high blood pressure, sleeping difficulties, and also weight loss.
  Even patients with Cushing's syndrome (hypercortisolemia) there is an increase in brown fat compared to healthy individuals. That the latter is not as profound is probably due to the ameliorative effect of cortisol on nor-adrenaline. After all, cortisol comes into play, when the stress becomes chronic and the acute nor-adrenaline response to stress, when it was prlonged any further would actually pose a direct threat to your health (just as phaeochromocytoma does, by the way; see red box on the right)
• Repeated moderate stress exposure increases DHEA production and normalizes corticosteriod levels in old apes (Goncharova. 2012). Yep, you are reading right we are not just talking about no rodent studies (although macacs are not exactly very human either ;-), but also about the role of repeated moderate stress in the normalization of aged induced abnormalities in the expression of adrenal hormones.
  

  

  Figure 2: Cortisol/DHEA ratio before and after 2h/day of immobilization stress.

  "In old monkeys the basal DHEAS levels were lower, while the [cortisol]/DHEAS ratio was higher than in young animals. Repeated immobilizations inhibited [cortisol] elevation on day 3, caused no changes in DHEAS reaction, led to increase of basal DHEAS levels and to a reduction of [cortisol]/DHEAS ratio on days 2, 3, 4, 10, 11." (Goncharova. 2012)

  In figure 2 you can see how profound the differences between acute, subchronic (3-day) and chronic responses actually are and that after 10 days of daily stress exposure in the form of daily 2-h immobilization stress actually are. Since I assume you don't want to be bound or enchained (well, maybe you want?), I suppose a viable alternative could be a shorter not too intense workout, although the acute responses to the latter vary with age as well (cf. Lennartsson. 2007).
• Monitor your DHEA levels closely, if you are concerned about joint degeneration According to a study that's about to be published in the next issue of the Journal of Steroid Biochemistry and Molecular Biology, DHEA, or the estradiol your body generates from it via local aromatization, exerts major protective effects against osteoarthritis (Li. 2012).
  
  
  An additional note of caution with respect to the abuse of aromatase inhibitors, natural or not. Since they have the potential to reduce the expression of estrogen at the neuronal level in the brain they can precipitate  Alzheimer's dementia. While estrogen appears to decrease the MMP-3 & 13 expression in the cartilage reasearch by Merlo et al. suggests that it will increase others, namely namely MMP-2 and MMP-9  in the brain and thus facilitate the clearance of the ameloid beta plague that's rendering the brains of AD patients more and more dysfunctional (Merlo. 2012). You see, it's no chance that pre-menopausal women are protected from Alzheimer's yet more susceptible to multiple sclerosis (MS). After all, high MMPs 7 & 9 have only been observed in kids with MS, as well (Unsal. 2012).
  In their experiments on a rabbit model of osteoarthritis the scientists from the Zheejiang University in China tried to nail down the beneficial effects of DHEA on chrondocites and cartilage to estrogen by co-administering DHEA with the aromatase inhibitor letrozole, and/or the estrogen receptor inhibitor fulvestrant and observed that the
  

  "[e]xpression of MMP-3 and MMP-13 increased in both DHEA-treated chondrocytes and cartilage in the presence of letrozole and/or fulvestrant, while the expression of TIMP-1 and collagen type II (Col-II) decreased." (Li. 2012)

  With the former metalloproteinases (MMPs) being proteolytic enzymes, which break down cartilage and the latter, i.e. the tissue inhibitors of metalloproteinases (TIMPs), acting as their antagonists, it appears clear why both patients on testosterone replacement therapy who use too high of a dose of aromatase inhibitors and athletes who abuse respective products on cycle or during PCT often suffer from severe cartilage degeneration - I mean, combine the endogenous cartilage destruction due to high MMPs and low TIMP levels with the wear and tear of weight lifting... what good could come out of that?
  
  Note: A very similar effect has been reported for bisphenol A by Wang et al. in 2010, already (Wang. 2010). No wonder, after all BPA decreases the local expression of aromatization in joints and cartilage so that less estrogen will be floating around to keep the MMP levels in check and TIMP up (Watanabe. 2012).
• Alpha tocopherol to prevent lymphoma Regular vitamin E, i.e. the alpha-version of the tocopherols is no longer the star at the supplement sky it has once been hailed to be. A recent study by Renu Sharma Manjula Vinaya that's been published ahead of print in the journal Molecular Biology Reports shows however that this does not mean that it's outdated and useless (ask Ray Peat about it ;-).
  
  

  

  Figure 3: Lifespan (top) and ascite volume (=water accumulation in the abdominal area) of lymphoma carrying mice treated with what would be in human terms ~325, 650 and 975 IU/day of an alpha tocopherol only supplement  (Sharma. 2012)

  In order to test the hypothesis that the ROS scavenging abilities of vitamin E should help with cancer prevention (as a student of the SuppVersity you know that respective data from epidemiological studies are equivocal, some suggesting the exact opposite; read more), the researchers initially induced the growth of lymphomas in 10-15 week old male mice and subsequently treated them with either 1.5 mg (50 mg/kg bw), 3 mg (100 mg/kg bw) or 4.5 mg (150 mg/kg bw) of alpha-tocopherol for 14 days.
  
  As the data in figure 1 goes to show you, the treatment increased the lifespan of the rodents by 25% and reduced the ascite fluid volme (see image in figure 1) by ~46%. This was accompanied by reductions in protein carbonylation and increases in the "master anti-oxidant" GSH, as well as several other markers showing that vitamin E exerted profound anti-inflammatory effects in this rodent model of lymphoma.
  
  At least in my humble opinion that does not change the fact that your best sources of vitamin E are natural and that's smart to stay away from alpha-tocopherol only supplements and prefer a whole spectrum tocopherol + tocotrienol supplement. Remember: More is not better, when the one thing that counts are the ratios (read more about vitamin E)!
  

That's it for this week's installment of On Short Notice. As mentioned in the introduction, there are more and even shorter news on the SuppVersity Facebook Wall, which usually gets updated 3+ times per day with I would guess 9-12 items total - depending on whether it's a slow news day or not and the time I have to skim studies and popular science mags and repost summaries and links of and to the latter. Let's see what did we have today, already? Ah, yeah: "Review concludes: Just being patented makes Kinesio® no better than conventional taping" (more), "Interesting stupid science finds that GABA directly mediates energy expenditure." (more), or maybe you are interested in "If rapamycin blocks seizures in model of epilepsy. Is mTOR to blame for both?" (more)?

References:

• Goncharova ND, Vengerin AA, Chigarova OA. Repeated Moderate Stress Stimulates the Production of Dehydroepiandrosterone Sulfate (DHEAS) and Reduces Corticosteroid Imbalance in Old Macaca Mulatta.  Bulletin of Experimental Biology and Medicine Volume 153, Number 5 (2012), 750-753. 
• Lean ME, James WP, Jennings G, Trayhurn P. Brown adipose tissue in patients with phaeochromocytoma. Int J Obes. 1986;10(3):219-27. 
• Lennartsson AK, Kushnir MM, Bergquist J, Jonsdottir IH. DHEA and DHEA-S response to acute psychosocial stress in healthy men and women. Biol Psychol. 2012 May;90(2):143-9.  
• Li WJ, Tang LP, Xiong Y, Zhou XD, Wu LD. The chondroprotective effects of dehydroepiandrosterone probably exerted by its conversion to estradiol. J Steroid Biochem Mol Biol. 2012 Oct 18. 
• Liu J, Shimizu K, Konishi F, Kumamoto S, Kondo R. The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum. Bioorg Med Chem. 2007 Jul 15;15(14):4966-72. 
• Merlo S, Sortino MA. Estrogen activates matrix metalloproteinases-2 and -9 to increase beta amyloid degradation. Mol Cell Neurosci. 2012 Apr;49(4):423-9.
• Ríos JL, Andújar I, Recio MC, Giner RM. Lanostanoids from Fungi: A Group of Potential Anticancer Compounds. J Nat Prod. 2012 Oct 23.
• Sharma R, Vinayak M. α-Tocopherol prevents lymphoma by improving antioxidant defence system of mice. Mol Biol Rep. 2012 Oct 14.
• Sliva, D.; Labarrere, C.; Slivova, V.; Sedlak, M.; Lloyd, F. P., Jr.; Ho, N. W. Biochem. Biophys. Res. Commun. 2002, 298, 603– 612.
• Unsal Y, Kıvılcım G, Ayşegül A, Arzu A, Esra G, Ercan D, Ayşe S. Matrix metalloproteinase-7 and matrix metalloproteinase-9 in pediatric multiple sclerosis. Pediatr Neurol. 2012 Sep;47(3):171-6.
• Wang KC, Lin YF, Qin CH, Chen TL, Chen CH. Bisphenol-A interferes with estradiol-mediated protection in osteoarthritic chondrocytes. Toxicol Lett. 2010 Oct 5;198(2):127-33. 
• Watanabe M, Ohno S, Nakajin S. Effects of bisphenol A on the expression of cytochrome P450 aromatase (CYP19) in human fetal osteoblastic and granulosa cell-like cell lines. Toxicol Lett. 2012 Apr 5;210(1):95-9.

Tocotrienols: What They Are, What They Do & How They Work + Why the RDA of Palm Olein is NOT 1xCup Per Day

Image 1: If you wanted to get the tocotrienol levels a producer of respective supplements says are  "required", you would have to eat at least 200g palm fruits a day. Alternatively, you can resort to 4kg of oats, if you like those better... What? you are wondering that you are not dead by now? After so many years of tocotrienol deficiency from not getting your 4kg of oats?

The long lists of pathologies related to vitamin E deficiency include, among others, all sorts of degenerative diseases from ataxia over general muscle degeneration to degeneration of sperm and subsequent infertility. But despite the fact that there is a pretty substantial amount of evidence that would suggest that a diet rich in vitamin E could not just prevent the aforementioned pathologies, but would also protect us from many of the currently prevalent ailments of western society such as obesity and coronary vascular disease (Mishra. 2003; Rimm. 1993), respective trials with dietary supplements usually show no, or even negative effects. I have already addressed a couple of  reasons why the benefits of dietary vitamin E intake often cannot be replicated with supplements in previous posts. The most significant one, probably is the absence of the "right" mixture and ratio of alpha-, beta-, gamma- and delta-tocopherols and, as an emerging contributer, the total absence of tocotrienols in the vast majority of vitamin E supplements and almost 99.9% of the pertinent trials.

What are tocotrienols? And what do they do?

I could now rant about the structural differences between the two, with the tocotrienols being an unsaturated variety of the tocopherols with a isoprenoid side chain, but I guess it is enough to know that due to  differences in their molecular structure, they also differ in their effects on the human body, of which you may already have apprehended that their cholesterol lowering effects were the first to attract the attention from researchers (Qureshi. 1986). Within the last 26 years researchers from all around the world have identified additional health benefits, the most prominent of which are...

• Anti-cancer effects (Kato. 1985; Sundram. 1989; Weng. 2009),
• General antioxidant effects (Newaz. 1999),
• Brain specific antioxidant effects (Khanna. 2003),
• Exercise-specific antioxidant effects (Lee. 2009),
• Cardiovascular disease (Shibata 2009)
• Diabetic neuropathy (Kuhad. 2009)
• Bone health (Ahmad. 2005)
• Metabolic syndrome (Weng. 2011)
• Antithrombotic effects (Qureshi. 2011)
• Endocrine health (Yu. 2005)
• Liver health (Patel. 2012)

The purpose of today's SuppVersity article is yet not so much to compile the most extensive list of potential, purported or demonstrated benefits of tocotrienols, the major dietary sources of which are (Kobayashi. 1975; Tan. 2011)

• rice bran oil (50:50 tocopherol:tocotrienol ratio), 
• palm oil (25:75 tocopherol:tocotrienol ratio), and 
• annatto (0.1:99.9 tocopherol:tocotrienol ratio) oil
• human breast milk (!) [though this is probably no major source for you ;-]

but rather to take a look at an intriguing chart of the various molecular targets (Aggarwal. 2010) and discuss the implications:

Figure 1: Molecular targets (left) and proteins that directly interact with tocotrienols (right; adapted from Aggarwal. 2010)

As you can see  without even looking really close at the above graphic, the number of those targets is vast. Another thing you should see right away is that the effect of the tocotrienols is mostly inhibitory (red ovals in the left) and include a couple of old foes, such as:

• the inflammatory cytokines & transcription factors: IL-1, IL-6, TNF-alpha, nf-kappabeta, IL-8 (probably involved in auto-immune reactions), PF-A4 (increases platelet aggregation and thus thrombosis risk)
• factors involved in angiogenesis and cardiocascular disease: VEGF (vascular growth factor, involved in CVD) and its receptor VEGF-r, VCAM-1 (increases adhesion of immune cells to the endothelial wall)
• kinases involved in the cell cycle and apoptotic regulators: CDK's, PKC, pERK, etc. & survivin, IAP-1 & 2 etc., but also telomerase, which are all involved in the proliferation of cancer
• enzymes involved in inflammatory processes: eNOS, iNOS, COX-2, etc.

On the upregulatory side of things, we have

• enzymes from the CYP cascade, which are among other involved in the clearance of estrogen, and other hormone like substances and the metabolism of drugs,
• MAPK and JNK, which exert anti-catabolic effects on muscle tissue, or 
• GPX and SOD, two of the major enzymes involved in the antioxidant defenses

Now, if we take a look at all these, you may remember that low COX-2 levels have only recently been identified with profound overtraining (cf. "Overtraining inflammation insufficient repair"), that AKT (not mentioned above, but in figure 1) is one of the driving forces of skeletal muscle anabolism and telomerase, extends cell life in general, not just in cancer cells. Which brings us back to the issue of ...

...how much anti-oxidants do we actually need?

Figure 2: Total tocopherol and tocotrienol content of high vitamin E foods / oils (top) and tocopherol ratios (bottom) , data based on Whittle. 1967 and Slover. 1971

Or, in this particular case, how much tocotrienols are still beneficial? Neither I, nor anybody else knows the exact answer to this question. And against this fact, the recommendations I came across on the website of a major producer of respective supplements, which state that you would need

• 80g of palm oilen (cooking oil),
• 160g of rice bran oil,
• 3kg of barley,
• 1.5kg of wheatgerm, or 
• 4kg of oats

to (I quote) "achieve the required [my emphasis] level of tocotrienols" should tell any reasonable person that those "required" levels (~150mg) are probably required to generate the target revenue of the said company, yet probably not required for you or any other human being to thrive.

Do not stack one more, but take one out!

Instead of adding another overpriced (and probably overdosed) tocotrienol supplement to your regimen, it is thus probably wiser to simply drop any superflous and potentially harmful alpha-tocopherol only supplements which do would offset the alpha- to gamma- and delta- tocopherol ratio (this could potentially be ameliorated by taking a natural blend) and limit the total tocopherol intake to reasonable levels, as the latter has also been shown to hamper the absorption and retention of tocotrienols (Ikeda. 2003). In this context it is also noteworthy that Ping Tou Gee writes in a 2011 paper with the aptly chosen title "Unleashing the untold and misunderstood observations on vitamin E" that this fact alone would suggest that "there is a need to review critically on the dietary reference intakes recommendations" for alpha tocopherol (α-T). His bold statement that

[i]t is not known whether α-T is still essential to humans in long terms, α-T₃ [alpha tocotrienol] diet appeared to produce healthy rats over five generations.

is yet probably an attribution to Palm Nutraceuticals Sdn. Bhd. (which is not the aforementioned company which wants to force-feed you either their supplements or 2 cups of rice bran oil), of which he states in the acknowledgments that he thanks them "for permission to publish this paper" and further evidence for how pathetic parts of the research in the medical field is - awful this science business, isn't it?

References:

1. Aggarwal BB, Sundaram C, Prasad S, Kannappan R. Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. Biochem Pharmacol. 2010 Dec 1;80(11):1613-31. Epub 2010 Aug 7.
2. Ahmad NS, Khalid BA, Luke DA, Ima Nirwana S. Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone. Clin Exp Pharmacol Physiol 2005;32:761–770 
3. Gee PT. Unleashing the untold and misunderstood observations on vitamin E. Genes Nutr. 2011 Feb;6(1):5-16. Epub 2010 Jul 20.
4. Ikeda S, Tohyama T, Yoshimura H, Hamamura K, Abe K, Yamashita K. Dietary alpha-tocopherol decreases alpha-tocotrienol but not gamma-tocotrienol concentration in rats. J Nutr. 2003 Feb;133(2):428-34.
5. Kato A, Yamaoka M, Tanaka A, Komiyama Ka, Umezawa I. Physiological effect of tocotrienol. J
   Japan Oil Chem Soc (Yukugaku) 1985;34:375–376.
6. Khanna S, Roy S, Ryu H, Bahadduri P, Swaan PW, Ratan RR, et al. Molecular basis of vitamin E
   action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced
   neurodegeneration. J Biol Chem 2003;278:43508–43515.
7. Kobayashi H, Kanno C, Yamauchi K, Tsugo T. Identification of alpha-, beta-, gamma-, and delta-
   tocopherols and their contents in human milk. Biochim Biophys Acta 1975;380:282–290.
8. Kuhad A, Chopra K. Attenuation of diabetic nephropathy by tocotrienol: involvement of NFkB
   signaling pathway. Life Sci 2009;84:296–301.
9. Lee SP, Mar GY, Ng LT. Effects of tocotrienol-rich fraction on exercise endurance capacity and
   oxidative stress in forced swimming rats. Eur J Appl Physiol 2009;107:587–595.
10. Mishra GD, Malik NS, Paul AA, Wadsworth ME, Bolton-Smith C. Childhood and adult dietary vitamin E intake and cardiovascular risk factors in mid-life in the 1946 British Birth Cohort. Eur J Clin Nutr. 2003 Nov;57(11):1418-25.
11. Newaz MA, Nawal NN. Effect of gamma-tocotrienol on blood pressure, lipid peroxidation and total antioxidant status in spontaneously hypertensive rats (SHR). Clin Exp Hypertens 1999;21:1297–1313.
12. Patel V, Rink C, Gordillo GM, Khanna S, Gnyawali U, Roy S, Shneker B, Ganesh K, Phillips G, More JL, Sarkar A, Kirkpatrick R, Elkhammas EA, Klatte E, Miller M, Firstenberg MS, Chiocca EA, Nesaretnam K, Sen CK. Oral tocotrienols are transported to human tissues and delay the progression of the model for end-stage liver disease score in patients. J Nutr. 2012 Mar;142(3):513-9. Epub 2012 Feb 1. 
13. Qureshi AA, Burger WC, Peterson DM, Elson CE. The structure of an inhibitor of cholesterol biosynthesis isolated from barley. J Biol Chem. 1986 Aug 15;261(23):10544-50.
14. Qureshi AA, Karpen CW, Qureshi N, Papasian CJ, Morrison DC, Folts JD. Tocotrienols-induced inhibition of platelet thrombus formation and platelet aggregation in stenosed canine coronary arteries. Lipids Health Dis. 2011 Apr 14;10:58.
15. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993 May 20;328(20):1450-6.
16. Slover HT. Tocopherols in foods and fats. Lipids. 1971 May;6(5):291-6.
17. Sundram K, Khor HT, Ong AS, Pathmanathan R. Effect of dietary palm oils on mammary
    carcinogenesis in female rats induced by 7,12-dimethylbenz(a)anthracene. Cancer Res 1989;49:1447–1451
18. Shibata A, Nakagawa K, Sookwong P, Tsuduki T, Oikawa S, Miyazawa T. delta-Tocotrienol
    suppresses VEGF induced angiogenesis whereas alpha-tocopherol does not. J Agric Food Chem
    2009;57:8696–8704.
19. Tan B. Tocotrienols: The New Vitamin E. Spacedoc.net. http://www.spacedoc.com/tocotrienols
20. Weng-Yew W, Selvaduray KR, Ming CH, Nesaretnam K. Suppression of tumor growth by palm
    tocotrienols via the attenuation of angiogenesis. Nutr Cancer 2009;61:367–373.
21. Weng-Yew W, Brown L. Nutrapharmacology of tocotrienols for metabolic syndrome.
    Curr Pharm Des. 2011;17(21):2206-14. 
22. Whittle KJ, Pennock JF. The examination of tocopherols by two-dimensional thin-layer chromatography and subsequent colorimetric determination. Analyst.1967 Jul;92(96):423-30.
23. Yoshikawa S, Morinobu T, Hamamura K, Hirahara F, Iwamoto T, Tamai H. The effect of gamma-tocopherol administration on alpha-tocopherol levels and metabolism in humans. Eur J Clin Nutr. 2005 Aug;59(8):900-5.
24. Yu FL, Gapor A, Bender W. Evidence for the preventive effect of the polyunsaturated phytolside chain in tocotrienols on 17beta-estradiol epoxidation. Cancer Detect Prev. 2005;29(4):383-8.

Does the Usefulness of Vitamin E Supplementation Depend on Your Activity Level? Profound Decreases in Baseline and Peak Exercise Induced DNA Damage Would Suggest So

If you are an athlete, let's say a competitive rower who trains 3+h per day, it appears as if 400IU of vitamin E would be nothing, but beneficial. If you are a couch potato, though, even that may hamper the small hormetic response you get from taking the stairs once a week ;-)

I don't know if you do remember, but it is actually not all too long ago that vitamin E was what vitamin D is known: The highly celebrated non-pharmacological savior of the ailing human race. Cancer? Heart disease? Diabetes? Alpha-tocopherol, which proved to be the most potent anti-oxidant in the tocopherol family, would solve all your problems and with its ability to "scavenge" the bad "free radicals" (sounds like a story from the Brother's Grimm, doesn't it?) it would also prolong your life expectancy. After all, those mischievous reactive oxygen species were the primary drivers of the aging process... well, today we know better. Supplemental vitamin E alone does neither prevent nor cure any of the diseases of the civilization. And the "free radical theory of aging" has come under fire, as of late (cf. previous blog posts on hormesis).

Vitamin E - fallen angel or an angelic demon!?

After being disregarded by the disappointed lay-press for years, vitamin E has gotten quite a bad rep, as of late. "Journalists" claimed that scientists had found that instead of offering protection, supplemental vitamin E (+selenium) would actually increase the risk of developing cancer. Those of you who have been following my posts for more than the last two weeks, will yet probably remember that this was a similarly single-sided presentation of intrinsically questionable epidemiological data, as the latest upheaval about the life-shortening effects of multi-vitamin pills (cf. "Vitamin E & Cancer?" & "Is Your Multi Killing You?").

In view of the emerging image of the critical role of "inflammation" in the highly beneficial adaptive response to exercise, it may yet still be worth to re-evaluate the cost-benefit ratio of vitamin E supplementation. If we temporarily disregard the discussion that revolves around the use of natural vs. synthetic and isolated vs. complex forms (I would always recommend using a natural supplement with alpha-, gamma- and delta-tocopherol), and focus on the athletic or at least physically active population who is leading an otherwise relatively healthy lifestyle (whatever that may be ;-), we could probably narrow this complex issue down to the question whether or not, and in which contexts, the use of vitamin E to sooth down overall inflammation could turn out to be advantageous.

Sedentary or trained. Does it make a difference?

The first of two pertinent studies, which resurrected my personal interest into this topic has been conducted at the Warsaw University of Life Sciences in Poland (Debski. 2012). It is a 10-day rodent study in which 27 of the 54 vitamin-E deprived young male Wistar rats that were maintained on diets with 0, 0.5, 1.0 and 4.0 mg of alpha-tocopherol (as alpha-tocopherol acetate) per day, had to run on one of those funky rodent treadmills for 15 minutes a day, while the rest of the rats led their usual "sedentary" lives. The intention of the study was to elicit the effect of physical exercise on the vitamin E status and requirements of mammals and its downstream effects on insulin levels - both are issues which would obviously be important for any aspiring physical culturist, as well, since previous research has shown that low alpha-tocopherol levels impair the beneficial effects of physical activity on blood glucose management. On the other hand, you will probably remember my previous blogposts on the research of two German scientists, which suggests that very high doses of anti-oxidants could be similarly detrimental, as they could potentially impair the hormetic response to exercise / stress (cf. "Are You Stressed Enough?" and "Update on Antioxidants and Exercise").

Figure 1: Plasma vitamin E levels (in mg/L) in previously vitamin E deprived rats after 10 days on diets containing 0, 0.5, 1.0 and 4.0mg of alpha-tocopherol acetate (left) and relative change vs. baseline (left; data adapted from Debski. 2012)

If you take a closer look at the differential effects the four different amounts of supplemental vitamin E had on the alpha-tocopherol concentration in the plasma of the lab animals, you may be surprised that despite an initially greater response in the sedentary rodents, the exercised rodents exhibited a more favorable response to the highest doses of vitamin E (4mg for a rat ~1200IU for a human). Although the overall effect of exercise on the plasma level was non-significant (the amount of vitamin E in the diet was the critical determinant), the greater "vitamin E capacity" of the exercised rats could in itself be a "hormetic" response to the low grade stress. And - and this is certainly the data you are waiting for - the beneficial effects on insulin levels were present in all groups, including the high as well as the no supplementation group.

So, vitamin E is not harmful, but useless?

In isolation, the results of the Debski study would thusly support the hypothesis that the beneficial, as well as the potential detrimental effects of vitamin E, which were perpetuated by the lay-press, as of late, are largely overblown. That vitamin E was basically useless... well, if you are a rat, running on a treadmill for 15 minutes a day (which I would say is probably less "exercise" than a natural rat is "supposed to have" < attention: paleo reasoning at work ;-) that may well be the case. If you are a competitive athlete who trains 3-3.5h per day, like the rowers in a study which was recently published in the Journal of Clinical Toxicology, things may be different, however (Sardas. 2012).

Semra Sardas and her (?) colleagues obviously had a similar question in mind when they conducted a study to assess the potentially differential and hopefully beneficial effects of two months (note: for this kind of studies this is a very long and thusly meaningful study period!) of 400IU/day of supplemental alpha-tocopherol on the exercise induced DNA-damage in "recreational active" individuals (physical education students; >1h of exercise min. 2x/week) and the aforementioned competitive rowers.

Figure 2: Relative change in DNA-damage in response to 60 days on 400IU/day vitamin E in competitive rowers (highly trained athletes) and physical education students ("active individuals"; data calculated based on Sardas. 2012)

If you take a look at the relative change in DNA-damage (comparing the pre- vs. post-supplementation period) subsequent to a standardized exercise test (high intensity for the rowers, medium intensity for the students) which was performed at the beginning and the end of the 60-day study period, the first thing that will probably catch your eye are the statistically significant decreases in baseline (pre-exercise) and peak (post exercise) DNA damage in both groups. What may appear to as if it was a source of concern, though is that the relative increase in DNA damage to the acute exercise bout in the rowers was more pronounced after, than before the intervention period.

In view of the fact that the total DNA damage was yet still -9% and thusly statistically significantly reduced, it does not appear likely this would be a consequence of an inadequate ability to adapt to stressors... it is rather a consequence of the profoundly (-25%) reduced baseline DNA-damage, which in itself would suggest that especially highly trained athletes should not discard the potential benefits at least moderate doses of vitamin E could have on their overall health - even if there are no noticeable short-term effects in terms of improved body composition and / or performance... always remember: You are in this for a life-time!

Epidemiological Study Shows Correlation Between Anti-Oxidant Intake and C-Reactive Protein & Homocystein

After a sudden onset of discussions around the beneficial or even detrimental effects of vitamin supplements in general and antioxidants in particular in the mid to late 2000s, vitamins and, even more, other anti-oxidants have been put back on the map, lately.

A recent epidemiological study from the University of Connecticut (Floegel. 2011) provides further evidence for the hypothesis that, after all, consumption of adequate amounts of vitamins C and E, beta carotene, flavonoids and selenium would be beneficial to your overall health

Intakes of vitamins C and E and carotene were inversely associated with the probability of having serum CRP concentrations >3 mg/l in multivariate logistic regression models. Flavonoid and Se intakes were not associated with the odds of elevated serum CRP concentrations. The mean plasma Hcy concentration was 8·61 (95 % CI 8·48, 8·74) μmol/l. Intakes of vitamins C, E, carotenes and Se were inversely associated with the odds of plasma Hcy [Homocysteine] concentrations >13 μmol/l after adjusting for covariates

While all these results appear to be quite unambiguous, you still have to keep in mind that they support the interpretation "antioxidants are healthy" only, if we assume that the relation between high C-Reactive Protein [CRP], inflammation and the metabolic syndrome, as well as the relation between homocysteine and heart disease is more than just a correlative one; and, to my best knowledge, no study has yet been able to show that injection of homocysteine caused heart disease or an increase in CRP increases inflammation or causes tissue damage. In this context, for example, the hitherto hardly understood involvement of "positive inflammation", such as an exercise induced rise in IL-6 levels, come to mind. In this context, studies such as Ristow et al. (2009) that found the positive effects of exercise being blocked by antioxidant supplementation would warrant further research into what - irrespective of reductions in purported markers of inflammation and cardiac disease - the actual health outcome of higher antioxidant intakes are.


Note: Don't get me wrong. I do not want to argue against a diet rich in natural antioxidants. I just want YOU to be aware that the proven health benefits from eating healthy, antioxidant-rich foods cannot be extrapolated to high (or even mega-dose) vitamin & flavonoid supplements and that taking megadoses of isolated antioxidants such as alpha-tocopherol (especially in its synthetic form and without the complementary tocopherols and -trienols), which is the most commonly sold form of vitamin E, may in fact do more harm than good.

ALA + Vitamin E Make Up for Fructose Induced Cardiovascular and Metabolic Changes

Alpha Lipoic Acid (ALA) and vitamin E are among the most investigated and best-known natural antioxidants. And, despite the fact that scientists came to realize, that both, ALA as well as alpha-tocopherol, are far from being the saviors of the metabolically deranged, they were once hailed as, a recent study from the University of Queensland (Patel. 2011) demonstrates their therapeutic potential in an animal model that (unfortunately) is not far from the high fructose corn syrup fed morbidly obese man/woman in a western(-ized) society.

Patel et al. found that supplementation with vitamin E (either α-tocopherol or tocotrienol-rich fraction, 0.84 g/kg food) and α-lipoic acid (1.6 g/kg food) could prevent (high fructose diet + Vit E + ALA) and even reverse (Vit E + ALA after high fructose diet for 8 weeks; reversal protocol) "glucose intolerance, hypertension, and increased collagen deposition in the heart together with an increased ventricular stiffness" in rats fed a high fructose diet over a course of 16 (prevention) / 8 + 8 (reversal) weeks.

Figure 1: (a): Plasma glucose concentrations following oral gavage of glucose (2 g/kg) recorded after 16 weeks for rats fed with corn starch (⬤), fructose (⚪), or fructose with α-tocopherol and α-lipoic acid as either prevention (FTPP) (▲) or reversal (FTPR) (▾) protocols. (Patel. 2011)

As a faithful visitor of the SuppVersity, you probably won't be surprised to read that supplementation with a tocotrienol enriched vitamin E source produced even more favorable outcomes in terms of blood glucose (5.0 vs. 6.4mmol/L in the prevention groups) and the other markers of metabolic health. It should not astonish you, anyway. It's no coincidence that nature provides us with certain nutrients in certain ratios and isolated alpha-tocopherol is something you won't find in nature...