The Oiling of the Liver: The Good & Bad Short- & Long-Term Effects of Tocotrienol + Carotenoid Laden Red Palm Olein, Regular Palm-, Corn- and Refined Coconut Oil

I would not expect "red palm olein wonders", but more RPO and less corn oil in the American diet may at least buffer the liver disease burden in the US (the figure is based on data provided by the American Liver Foundation)

On Turesday, November 19, 2013, you've learned from a study by Subermaniam et al. about the "anti-rust" effects of coconut oil (if you missed that, you can catch up here), today, we are going back to Malaysia and the Universiti Kebangsaan Malaysia and the results of another team of researchers to learn about the effects the various oils have on the "oiling of the liver" (Dauqan. 2013).

I guess most of you will remember my previous comments about the critical role of the liver (and its health or disease) in the development of the metabolic syndrome (read it up). It is thus by no means irrelevant, whether the chronic ingestion of a certain type of oil will result in MDA levels of 92µmol/g or  27.3µmol/g.

Boring!? No, rather surprising!

If you think this sounds boring and are by no means surprised that the malondialdehyde levels of the liver samples the researchers harvested after 4 weeks were 27.3µmol/g, 92µmol/g, 54µmol/g, 47.4µmol/g and 72.6µmol/g for the control diet with mixed fats, red palm oloein (RPO), regular palm oil (PO), corn oil (CO) and the previously celebrated coconut oil (COC), respectively, I would suggest you have a closer look at the the "magic" that happened over the following 4 weeks of on 15% RPO, PO, CO and COC diets.

Figure 1: MDA levels (µmol/g) of liver tissue as a marker of lipid oxidation after four and eight weeks on control diet or control diet with 15% of red palm olein, palm oil, corn oil or coconout oil (Dauqan. 2013)

Well, you see, the way the effects of red palm olein came full circle after another months on the 15% RPO diet is hardly "boring", is it? The MDA levels, a relatively reliable indicator of local lipid oxidation, of the rodents on the 15% red palm olein diet is now, 4 weeks after peaking at 92µmol/g down to 25.2µmol/g, indicating that the level of lipid peroxidation in the livers of the RPO group is now significantly lower than that of any other group (43.4µmol/g, 50.1µmol/g and 48.3µmol/g for control, palm oil, corn oil and coconut oil).

Short term detriments, long term benefits!

I know it sounds more than awkward, but eventually every SuppVersity student should be aware of the fact that the extrapolation of long-term effects from short-term data is a 'risky' business. Unfortunately, even 'experts' often disregard this fundamental rule, when they formulate their recommendations on nutrition, supplementation and exercise.

Table 1: Carotenoid  and vitamin E composition (in %) of crude palm oil and red palm olein; the data is from a different study by Bonni & Choo who tested commercially available products (Bonni. 2000)

The statement, "Prefer coconut oil and avoid red palm olein!", for example would have been a reasonable dietary if we did not know about the turn-around in the second part of the study, when the beneficial effects of the saturated fat content of the coconut oil begin to fade and the absence of natural anti-oxidants in refined coconut oil begins to show its ugly face. At this point, the moderate amount of unsaturated fats in red palm olein (13% omega-6, 0% omega-3; see Bonnie. 2000), of which I am honestly not sure if it is the actual reason of the initial increase in lipid peroxidation (remember: corn oil has more PUFAs!), or whatever other underlying cause of the initial rise in inflammation is overriden by the accumulating amounts of vitamins E and carotenoids from the red palm olein, which rendered the liver of the oxidation-proof, or "rustless" if you will - similarly rustless as the hearts of the rogents in the previously cited study by Subermaniam et al. (learn more).

200g of palm fruits have the same amount of tocotrienols as 4kg of oats. Learn more "tocotrienol" and red palm oil facts in "Tocotrienols: What They Are, What They Do & How They Work + Why the RDA of Palm Olein is NOT 1xCup Per Day " | more

Bottom line: I would like to formulate two take home messages for today's SuppVersity article. Firstly, a theoretical one, which shall remind you of the fact that you can do more harm than good, if you (accidentally) terminate a study in a transitional state and formulate long-term dietary recommendations based on short-term observations, because the study at hand clearly indicates that some effects - in this case the antioxidant effects of the tocopherols, -trienols and carotenoids - take their time to become measurable. And seconfly a very practical one, which is eventually only a reminder of the existence of red palm oil (see article referenced on the right) - an excellent source of dietary antioxidants and probably your only chance to get your tocotrienols and high(er) amounts of some of the rarer carotenoids from regular foods.

References: 

• Bonnie, T. Y. P., & Choo, Y. M. (2000). Valuable minor constituents of commercial red palm olein: carotenoids, vitamin E, ubiquinones and sterols. Journal of Oil Palm Research, 12(1), 14-24.
• Dauqan, E., Abdullah, A., & Sani, H. A. (2013). LIPID PEROXIDATION IN RAT LIVER USING DIFFERENT VEGETABLE OILS. Malaysian Journal of Analytical Sciences, 17(1), 300-309.
• Valls, V., Goicoechea, M., Muniz, P., Saez, G. T., & Cabo, J. R. (2003). Effect of corn oil and vitamin E on the oxidative status of adipose tissues and liver in rat. Food Chemistry, 81(2), 281-286.

Rustless Hearts: Adding 15-20ml of Virgin Coconut Oil to Your Diet May Counter the Oxidative Stress From Partially Oxidized Fats and Keep Your Heart Rust-Free

Could a daily dose of virgin coconut oil really be all it takes to escape the #1 leading cause of death (CDC data) - despite French fries and co?

Originally I wanted to post the results of this study from the Universiti Kebangsaan Malaysia as a short news item in the Facebook News. Then I decided that it may actually be worth to allow you to have a look a the surprisingly pronounced effects the addition (not replacement!) of 3-4 tablespoons of virgin coconut oil had on the in vivo lipid oxidation levels of rodent hearts in the course of this 4 months study at the end of which the researchers did not simply measure the systemic, but the more significant local malondialdehyde (MDA) levels. With the direct analysis of the presence of lipid oxidation production in the heart being a more reliable indicator of whether or not the changes the researchers observed in the study at hand are physically relevant...

Ah, I don't want to give it all away. So let's rather take a look at Subermaniam et al.'s attempt to "to investigate the influence of virgin coconut oil on the malondialdehyde level in the heart tissue of rats fed with heated palm oil." (Subermaniam. 2013)

Palm oil is ubiquitous

I am not sure if you are aware of that, but the regular palm oil (not the red PO with the high carotene and tocotrienol content), with its saturated - unsaturated fatty acid ratio close to one, has become the most widely used "vegetable oil" worldwide. In fact, if the product label says "vegetable oil" and there is a significant amount of saturated fats in a product, it's likely that what you are about to eat contains palm oil, which is easy to process and, with its 1:1 ratio of saturated to unsaturated fats relatively stable.

Rejection points of various oils (Marikkar. 2007; Berger. 2005; Casai. 2010)

Cooking with Virgin Coconut Oil (VCO) - good or bad idea? The answer to this question is not as straight forward as you may think. On the one hand frying the "virgin" oil, will have it lose it's virginity, i.e. most of those molecules that are responsible for the beneficial health effects. On the other hand, a study by Marikkar et al. (2007) shows that these molecules act as a buffer, due to which VCO has a 30% higher rejection point (13h vs. 10h of frying at "only" 180°C; compare to the other oils in the table to the right) than regular coconut oil (CNO) and refined corn oil (CO). After those 13h the concentration of newly formed compounds (TPCs) that have higher polarity such as oxidized triglycerides, diacylglycerides and fatty acids is >25% and downright unhealthy.

Despite being less prone to oxidation, the way the oil is reheated and (ab-)used for deep frying by the food industry can cause changes in the fatty acids composition of palm oil that may have significant health consequences.

"Repeatedly heated oil undergoes changes in physical appearance and a series of chemical reactions such as oxidation, hydrolysis and polymerization that eventually alter the fatty acid composition . Therefore, when the degree of unsaturation in fatty acid is greater, it is more vulnerable to lipid peroxidation (Choe. 2007)." (Subermanian. 2013)

In mouse and man, the ingestion of this chemically altered oil has been found to increase the levels of ,alondialdehyde  (MDA), one of the major end products of lipid peroxidation which causes endothelial damage, vascular inflammation and cell membrane injury (USDA. 2007).

Virgin coconut oil to the rescue?

Studies by Harrison and Ng have shown that the increases in MDA levels in response to the ingestion of oxidated palm oil causes "oxidative stress" and increases in blood pressure that cannot be countered by the ingestion of common antioxidants such as vitamin C and E (Harrison. 2007). Now, Subermaniam et al. were interested, whether the same would be true for the sunsaponifiable components in virgin coconut oil.

SuppVersity Suggested Read: True or false - Eating tons of medium chain triglycerides (MCTs) will make you lean | learn the truth!

In previous studies, these molecules, which are lost when the milk is not extracted under controlled temperature, have been linked to a host of beneficial health effects, e.g.

• anti-inflammatory and anti-thrombotic properties,
• the ability to reduce the oxidation of LDL cholesterol, or
• beneficial effects on the immune factor and cytokine response to endotoxins,

of the increasingly popular medium-chain-triglyceride rich oil from Cocos Nucifera Linn - an oil of which Figure 1 tells you that it has a lower peroxide value than freshly extracted palm oil even after processing and storage.

In view of its already established health benefits, the assumption that virgin coconut oil can ameliorate the pro-oxidative effect of diets that were fortified with 15% pre-heated palm oil, when it is administered to rodents at a daily dose of 1.43 ml/kg of body weight/day by oral gavage does not appear to be too far-fetched.

Figure 1: Left - MDA level in heart tissue after 4 months of feeding with basal diet (control), five times heated palm oil (HPO), basal diet and VCO supplementation (VCO) and five times heated palm oil with VCO supplementation (HPO+VCO; left); right - baseline peroxide value (in mEQO2/kg) of the oils used in the study (Subermaniam. 2013)

The rats stayed on these regular palm oil, pre-heated palm oil, regular palm oil + VCO, pre-heated palm oil + VCO and an unmodified control diet for 4 months. Thereafter, the thirty two rats were sacrificed and their heart tissues were harvested in order to measure the level of lipid oxidation. The results? Well, you just have to look at Figure 1 to see that there was a significant (p < 0.05) decrease in MDA (and peroxide / data not shown) values in the rodents which received the supplemental coconut oil on top of their heated palm oil diets.

Bottom line: It is unquestionably impressive that the effects of what would have been ca. 15-20ml commercially available virgin coconut oil for a human being were so pronounced that the oxidative stability of the lipids in the cells of the rodents on the HPO + VCO ended up being virtually identical to that of the rodents which received the regular chow. I must still warn you not to expect any of the meanwhile literal "Coconut Miracles".

In view of the fact that the benefits of the 'VCO supplement' did not depend on the presence of a "junk food" diet, it is still obvious that the addition of one or another tablespoon of virgin coconut oil may be one of the 1001 pieces of your personal "healthy lifestyle" puzzle - along with a protein- and vegetable-rich whole foods diet, exercise and more than just an occasional night of good night's sleep, of course ;-)

References

• Berger KG. The use of palm oil in frying. Malaysian Palm Oil Promotion Council. 2005.
• Casal S, Malheiro R, Sendas A, Oliveira BP, Pereira JA. Olive oil stability under deep-frying conditions. Food Chem Toxicol. 2010 Oct;48(10):2972-9.
• Choe E, Min DB. Chemistry and reactions of deep-fat frying oils. Journal of Food Science. 2007; 72(5):R77-R86.
• Harrison DG, Gongora MC, Guzik TJ, Widder J. Oxidative stress and hypertension. Journal of the American Society of Hypertension. 2007; 1(1):30-44.
• Marikkar et al. Assessment of the stability ofvirgin coconut oil during deep-frying. Cord 2007; 23(1).
• Ng CY, Kamisah Y, Faizah O, Jubri Z, Qodriyah HM, Jaarin K. Involvement of inflammation and adverse vascular remodelling in the blood pressure raising effect of repeatedly heated palm oil in rats. Int J Vasc Med. 2012;2012:404025.
• Subermaniam K, et al. Virgin Coconut Oil (VCO) Decreases the Level of Malondialdehyde (MDA) in the Cardiac Tissue of Experimental Sprague-Dawley Rats Fed with Heated Palm Oil. Journal of Medical and Bioengineering. 2014; 3(2).
• World  Vegetable  &  Marine  oil  Consumption,  World  Statistics, USDA, 2007, pp. 10

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

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

Since this post is already lengthy enough, I will spare you how saturated fatty acids have long falsely been accused as the sole driving force of the western obesity epidemic and how the tides appear to be slowly yet steadily appear to be turning, as scientists delve deeper and deeper into the interactions of the total fat content in the diet, its fatty acid composition and the interaction of both with the two other macronutrients and their specific forms and get right to the study at hand. A study that appears in the current issue of the Journal of Lipid Science and deals with the first of the aforementioned interactions. The one that focuses on the total fat content and the individual fatty acid make-up of the diet (Enos. 2012).

Fat shoot out: Saturated vs. mono vs. PUFA

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

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

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

Figure 1: Fatty acid composition (left) and their sources (right) that were used in the different diets the rodents were fed for 16 weeks (based on Enos. 2012)

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

Figure 2: Body composition (left), adipocyte size (right) and fat pad weight (inset) of the rodents at the end of the study period (Enos. 2012) Values not sharing a common letter (abc) differ significantly over time within the given diet treatment (P≤.05)

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

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

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

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

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

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

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

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

... mimics, as the researchers point out, "most closely" (Enos. 2012) the standard American diet (SAD). And the result is obvious: Diabesity!

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

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

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

Figure 3: Serum IL-6, MCP-1, adiponectin and leptin levels, TNF-alpha mRNA expression in the adipose tissue (left), adipose tissue sample form the rodents receiving standard chow, the SFA-12% and the SFA-24% diet (Enos. 2012). The fat cells of the SFA-6% animals looked similar to those on the SFA-6% diets.

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

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

Figure 4: Blood glucose and insulin levels of the mice over the course of the study period (Enos. 2012)

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

"The 12%-SF diet, most closely mimicking the standard American diet, led to the greatest adiposity (absolute fat mass), macrophage infiltration, and IR [insulin resistance]." (Enos. 2012)

Figure 5: Total  cholesterol (TC, top) and LDL-C to HDL-C (bottom) ratios (Enos. 2012)

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

"Although the 24%-SF diet increased adiposity and produced IR, it did not significantly increase macrophage infiltration, it led to a lesser degree of AT inflammation, and it did not raise the TC/HDL-C ratio." (Enos. 2012)

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

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

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

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

References:

• Enos RT, Davis JM, Velazquez KT, McClellan JL, Day SD, Carnevale KA, Murphy EA. Influence of Dietary Saturated Fat Content on Adiposity, Macrophage Behavior, Inflammation, and Metabolism: Composition Matters. J Lipid Res. 2012 Oct 28.

Sesame Powered High Omega-6 Diet Boosts Endurance Performance in Rodents - High Omega-3 Diet Sucks: Intra-Muscular Lipid Ratios Determine Exercise Performance

At least in rodents omega-6s appear to make abetter match with exercise than in human beings.

I actually referenced this study several times in the past. It came up in a Facebook conversation I had with Roy Nelson who pointed me to a press release telling me that (I quote) "Certain Fat Could Help Humans Lose Weight". Interestingly, the "certain fat" in this particular study is (brace yourselves) linolic acid, better known as "omega-6" (obviously a misnomer, since omega-6 is actually referring to a whole class of fatty acids).

In view of the fact that the corresponding study in which Rogowski et al. observed a significant correlation between the omega-6 fatty acid content in the muscle and mitochondrial uncoupling and fat oxidation. The problem with the study is however that it was conducted not just with mice, but with genetically modified mice.

The results of the said study by Rogoswki, Patin et al. may thus form the basis for further investigations, but should not be taken as "hard evidence" that a high intake of omega-6 fatty acids will have similar effects. The accumulation of linolic acid in the mouse muscles was after all a result of the genetic modification and not the consequence of high n-6 chow.

So what's the effect of dietary linolic acid, then?

Unlike Rogowski et al., Kerry J. Ayre and A.J. Hulbert from the University of Wollongong did not just use normal male Wistar rats as their test objects, they also did what the scientists from Texas Tech didn't do: They supplied their rodents with diets with different fatty acid profiles.

Table 1: If you have ever wondered about the "evolution" of the omega-3 vs. omega-6 ratio in our (=the human) diet, I suggest you take a closer look at the table to the right. According to this overview from a 2004 paper by Artemsis Simopoulus in Food Reviews International. As you will see, it has more than just reversed ever since the paleolithic era.

All diets contained the exact same macronutrient composition with 22%, 56% and 22% of the total energy being derived from fat, carbohydrates, and protein, respectively. The amount of essential fatty acids and their ratios in the 22% fat content of the diet did however differ significantly:

• 

  Irrespective of the fact that it sucks for rodent endurance, coconut oil could help you approach a flat tummy like the one above| learn more

  Coconut diet: Designed as (almost) "essentially fatty acid free", the coconut oil based diet had a saturated fatty acid / mono-unsaturated fatty acid / N-6 / N-3 ratio of 95:4:1:0
• High N-6: Being based on sesame oil, the high N-6 diet had a SFA / MUFA / N-6 / N-3 ratio of 16:30:50:4 that translates to an N-3:N-6 Ratio of 0.08 (1:12.5); now that sounds crazily low, but the average Westerner consumes a diet with a N-3:N-6 ratio of 0.0625 (1:16; cf. Simpopoulos. 2004) in other words - that was not even "as bad" (?) as the Western diet
• High N-3: By adding both sesame and a commercially available omega-3 supplement to the diet, the scientists hit a 21:25:35:16 ratio for SFA / MUFA / N-6 / N-3 - that's still far from "N-3 exclusive" but much more like what current expert advice tells us we should strive for, i.e. 1g of omega-3 for every 2g of omega-6

If we go by the contemporarily popular dietary paradigms, it should be obvious that the health of the rodents in the N-6 diet will take a beating. Against that background it is all the more surprising that it were the rodents in the high N-6 group that outdistanced their hairy competition in an endurance test at the end of the 9 week study period.

Figure 1: Fatty acid composition of the diets and corresponding endurance performance of male Wistar rats after 9-weeks on coconut, high n-6 and high n-3 diet (Ayre. 1997)

What's more, it's not as if the omega-6 mice had simply been running slower and were thus able to run for a longer time, they did also have higher workloads (=product of body mass, distance traveled, and percentage grade of the incline).

"So where is the connection to the new study from Texas Tech, then?"

If we look back at the initially mentioned results from the Texas Tech study, it appears logical to assume that the beneficial effects on the endurance capacity could be another downstream effects of an increased ability to oxidize dietary fats (which is basically what the Rogowski, Paton et al. argued). Compared to the minimal amount of blood glucose and the highly limited glycogen stores in the muscle and liver, the fat stores of mice (and man) do after all hold an almost inexhaustible amount of energy - they just have to be accessed.

Figure 2: Skeletal muscle fatty acid composition after 9 weeks (Ayre. 1997)

As you can see, in figure 2 the fatty acid composition of the skeletal muscle of the rodents in the Ayre study did reflect the fatty acid composition of the diets (remember: the changes in the Rogowski study occured on the same chow, simply due to a genetic mutation) and the significantly increased omega-6 content in the N-6 group mirrors the effect Rogowski et al. observed in response to their neat GMO tricks. It does therefore appear logical to assume that the rodents in the Ayre study experienced a similar upregulation of PPAR-delta (unfortunately back in the day scientists did not measure that). The latter would increase the oxidation of fatty acid and thus the energy availability during aerobic activity.

"Making the Right Fish Choices" is important for your healths, so I suggest you learn how in the same-titled SuppVersity article.

What should not go unmentioned is that the performance discrepancies were very long-lived. Even after 5 weeks on a regular diet, the rodents in the N-6 diet easily outperformed their coconut and omega-3 competition - probably because it takes months (in rodents and years in men) to restore a "normal" muscular fatty acid profile. Now this is an interesting thought, because it will eventually lead us to the hypothesis that the huge benefits we are currently seeing (at least in some individuals) from the consumption of supplemental omega-3 fatty acids would be a direct result of the their effect on a cellular fatty acid ratio that has been messed up over years!

In view of the profundity of the omega-6 overshoot in the SAD diet and considering the fact that many of us have been consuming diets containing 15x more omega-6 fatty acids than omega-3s for decades, this does not appear unlikely. From a scientific perspective it would yet reaffirm that the "optimal n3:n:6 ratio" for someone with a well-balanced cellular level of the latter could be very different from the 1:1 optimum some experts currently recommend as target in the battle against diabesity - right?

Swine study says 1:5 ratio of N3:N6 or higher = optimal health | more

Let's ground ourselves: Don't take this post as an incentive to guzzle vegetable oil all day.

As a strength athlete you may actually harm yourself as it appears that the high omega-6 intake favors the oxidative over the glycolytic pathway. As an endurance athlete, however you may reconsider how important it really is for you to avoid all omega-6 fatty acids as a plague.

On a more general note, it may in fact be worth to take another look at "optimal ratios". While some of the effects of the polyunsaturated fatty acids are in fact acute, their major effects appear to be brought about by their accumulation in our bodies.

The "optimal intake" will thus necessarily depend on the status quo, i.e. the current tissue level of n-3 and n-6 fatty acids and their respective ratios. Against that background we should not be surprised that you can counter the negative effects of an imbalanced diet by administering another imbalanced diet. In our case this is a correction of a profound omega-6 overshoot that can be achieved by increasing our consumption of omega-3 rich foods and limiting our use of omega-6 laden vegetable oils and the products of which the "food" industry tells us they were good for us, because they contain only healthy vegetable oils... this is a practice I have recommended in the past and something I still recommend today.

What I would hope we could agree on, though is the idea that the study at hand, despite being conducted in rodents should remind us that simply switching from one scapegoat to another did not help us, when that scapegoat was saturated fat. Do you really believe the outcomes will be better, when we simply glue the "avoid like a plague" sticker to the omega-6s? Yes? Well, I guess the first thing you should do then, is take your beloved extra-virgin olive oil and pour it away! Why? Well, 10% omega-6 and basically no omega-3 - that's a no go ;-)

References:

• Ayre KJ, Hulbert AJ. Dietary fatty acid profile affects endurance in rats. Lipids. 1997 Dec;32(12):1265-70. 
• Pella D, Dubnov G, Singh RB, Sharma R, Berry EM, Manor O. Effects of an Indo-Mediterranean diet on the omega-6/omega-3 ratio in patients at high risk of coronary artery disease: the Indian paradox. World Rev Nutr Diet. 2003;92:74-80.
• Rogowski MP, Flowers MT, Stamatikos AD, Ntambi JM, Paton CM. SCD1 activity in muscle increases triglyceride PUFA content, exercise capacity, and PPARδ expression in mice. J Lipid Res. 2013 Oct;54(10):2636-46.
• Simopoulos, AP. Omega-6/omega-3 essential fatty acid ratio and chronic diseases. Food Reviews International. 2004; 20(1).

Fighting Body Fat W/ Green Tomatoes; Fasting, Exercise & Cognitive Performance; Potassium Citrate & Coconut Oil Strengthen the Bone; 25mg Clomid Double Testosterone

Image of the week: Golf-ball sized tumors from GMO corn and a >100% increase in mortality in female rodents are the results of the (at least in Europe) much debated study by Gilles-Eric Séralini et al. (Séralini. 2012)

I must admit that I got somewhat bored with writing the same, or at least very similar introductions time and again. So I decided to start each and every installment of On Short Notice with either a picture or a figure that impressed, amused, enraged or, as in this case, shocked me, when I hit on it. The image you see on the right shows the rodents from the French GMO corn study that made the news earlier this week. Females, to be precise. With golf-ball sized mammary gland tumors. Nasty and the result of a life on a 22% GMO or 22% GMO + Round-Up diet ... yeah, you read me right: 22% was enough. In fact, "the rate of mortality [...] reach[ed] a threshold at the lowest (11%) or intermediate (22%) amounts of GM maize" (Séralini. 2012), already, and that irrespective of whether the corn was or wasn't treated with round-up.

Quite a difference to the previous 13 week rodent study, which was obviously enough for the officials to allow the Frankenfood to be sold as "save for human consumption". But enough of those nasty tumors and pre-mature deaths and on to a short collection of recent science news from the world of health, nutrition, supplementation and medication (exercise news will follow in a couple of days, don't worry ;-)

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Red Tomatoes Are Good, But Green Ones Could Be Even Better - For weight Loss, At Least That's the simple message the results from a soon-to-be-published study on the AMPK- and PPAR-gamma mediated anti-obesity effects of 20 g/kg diet of red vs. green tomato water extracts (extraction took place at room temperature for 1h; Choi. 2012).

Figure 1: Significant benefits on weight gain, epididimal (=visceral) and liver fat were observed only with the dehydrotomatine, α-tomatine, trigonelline rich green tomato extract (based on Choi. 2012).

While both, the red (RTE) and green tomato extracts (GTE) did ameliorate the weight gain and fat accumulation of male C57BL/6 mice who received the RTE and GTE enriched chow after they had been pre-fattened on a "high fat diet" for 4-weeks, only the green tomato extract with its higher dehydrotomatine, α-tomatine and trigonelline extract had statistically significant effects on total body weight and visceral fat gain (see figure 1).

If you take a closer look at the photos of the rodents (small picture in figure 1), you will probably agree that judged by their physique the mice in the HFD + GTE appear to be the leanest. Now, it given the fact that "high" amounts of dietary fat and fatty livers are not exactly conducive to rodent health, the image may be misleading; and still, the fact that the purported "high fat" diet, had 4g more protein, 17g more fat and 23g less carbs per 100g, than the regular chow and thus a macronutrient composition of 24g / 41g / 24g makes me wonder if the control mice on the "healthy" low fat rodent chow would not have seen similar benefits from a few mg of GTE per day ;-)

As far as the underlying mechanisms are concerned the additional in-vitro experiments, Choi et al. conducted revealed that the anti-obesity effects were probably the result of concomitant increases of p-AMPK (to normal = control levels) and a profound suppression of the pro-adipogenic (=fat storage promoting) proteins PPAR-gamma, C/EBP-alpha and perillipin in the adipose tissue of the GTE treated animals. And with tomatine turning out to be the most potent (-80%) inhibitor of fat accumulation (vs. -10% for trigonelline), we eill probably soon see the first stanardized green tomato extracts being sold as dietary supplement. I mean, you all know how it works these days: If there is a single rodent study showing benefits, people will be willing to pay for it and since demand determines supply, it won't take long until you see the first 2xGTE based "fat burner" (featuring GTE as in green tea extract and GTE as in green tomato extract ;-) hit the shelves.

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Regardless of whether you are low-carbing or not, eggs could literally give you a head-start in the morning (click here to learn more about the good "bad" eggs)

Breakfast Counters Mental Fatique, Exercise curbs appetite - Regardless of Whether You "Break the Fast" or Not! That's what a group of researchers from Korea found, when they analyzed the effects of consuming or omitting breakfast on the physical and mental fatique, as well as the cognitive task performance, mood and appetite ratings of twelve healthy male participants during and after four different test conditions:

• no breakfast and rest, 
• breakfast and rest, 
• no breakfast and exercise and
• breakfast and exercise

On each of the four test days the participants went through the 'same' routine that consisted of "breakfast (or continued fast), a 2 h rest, an exercise (treadmill run at 60% VO2max to expend ~710 kcal) or an equivalent rest period, a liquid snack, a 90 min rest period and finally an ad libitum lunch" (Veasey. 2012).

As I already mentioned in the title of this item, the mental fatigue ratings were significantly higher during the fasted compare to the fed trials. Correspondingly consuming breakfast prior to resting increased speed on a Rapid Visual Information Processing task (RVIP) - an effect that was not observed, when the breakfast was supplied after the exercise. The treadmill exercise lead to a significant reduction in hunger ratings during and even temporarily after the exercise, irrespective of whether or not the subjects had had breakfast. The effect was however more pronounced in the fed condition.

Recent UK study says: Children learn better w/ breakfast The findings of a study that used an online questionnaire + test system to establish a connection between breakfast consumption and cognitive performance in 1386 children aged between 6 and 16 years, from schools throughout the UK, appears to confirm previous laboratory studies, suggesting that breakfast can help maintain attention and memory during the morning (Wesnes. 2012).

Now, though all this clearly suggests that skipping breakfast was a very bad idea, I would like to remind you of the "priming" or "programming" effect I have outlined in my recent post on "breaking the fast". Against that background, the scientists' conclusion that "consuming breakfast before exercise decreased mental fatigue ratings following cognitive task completion and exercise reversed the detrimental effects of breakfast consumption on RVIP reaction time" would have to be confirmed in a group of habitual "non-breakfast eaters", whose circadian rhythm is adapted to running on stored fuel in the morning, before we ascribe general validity to it.

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Potassium Citrate: Could the "Best Calcium Supplement" Contain No Calcium, At All? Usually the reason doctors will prescribe or tell people to take calcium supplements is that they are afraid their patients would otherwise pee out their bones - literally! Unfortunately, that does not reduce but will often rather exasperate the urinary excretion of calcium and thus belongs to the realms of counterproductive or at least incomplete text-book knowledge, which stands in contrast to a handful of studies of which the average physician usually has not heard, before (Harrington. 2003; Karp. 2009; Marangella. 2004, Sakhaee 2005; Taylor. 2010).

Figure 2: Changes in urinary calcium and calcium balance (mg/day), as well as serum parathyroid levels (PHT in pg/dl) after 6 months on 650mg calcium citrate (placebo) with or without 60 or 90mmol potassium citrate

The latter probably won't change with the soon-to-be-published paper that deals with the effects of potassium citrate supplementation on calcium balance in older men and women. And that despite the fact that the results could be of relevance for anyone following a high protein, high fat or SAD diet, as well - especially if he is like Adelfo's client Mr. C and "does not like his vegetables" ;-) After all, the main mechanism by which the administration of 60 or 90 mmol of potassium citrate improved the calcium balance of the subjects who had a low baseline calcium intake and a high phosporus load (556/1338 in the female and 618 / 1410 in the male subject) and a potassium intake 10-15% below the RDA of 3,500mg was the "complete neutraliz[ation]" of the dietary acid load, which can be a serious problem with far-reaching metabolic ramifications not just for the elderly (Mosele. 2012).

In the study at hand, the alkalizing effect of the potassium supplement went hand in hand with increases in urinary potassium (42.0 in the low and  67.3 mmol/day in the high dose arm) and profound decreases in urinary calcium loss. In conjunction with the elevated calcium intake from 630mg of supplemental calcium citrate, all subjects (placebo included) received, this induced a shift from a negative into a positive calcium balance and corresponding decreases in PTH, the hormone that will not just leach calcium out of the bones to keep your serum calcium levels steady (see figure 2), but has also been found to be associated with increased body fat levels (interestingly specifically fat and not other anthropometric markers like body weight!) and metabolic syndrome (Snider. 2005; Hjelmesaeth. 2009)

Is the dosage used in the study already dangerously high? No. 90mmol K-citrate are usually tolerated without problems (this assumes that you have healthy kidneys!), but must be spread across the day and are best ingested with food.

In view of what you've learned about the role of phosphorus in calcium and vitamin D metabolism ("Phosphor, Calcium and Vitamin D"), as well as the potential pitfalls of becoming overtly acidic (scroll down to figure 3) and what you can do to stay on the alkaline side of things, it is probably not necessary I remind you of the fact that you can avoid running into problems in the first place by simply eating a balanced whole foods diet without tons of grainy junk (whole or not) and convenience "foods". If you do that, the use of supplements should be unnecessary and could, if consumed in excess, have serious side effects, which range from gastrointestinal distress over low blood pressure, muscular warkness and dehydration (due to a low sodium : potassium ratio), up to cardiac arrhythmias and - in the worst case - sudden cardiac arrest.

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25mg Clomiphene Citrate Still a Good Choice For Non Testosterone Based TRT (or Restart) ... and as if that was not already enough, it will also maintain your bone health, when your testosterone can't do the job for you, or help you and your significant other if you have problems conceiving (see box "Clomiphene citrate?", below; Da Ros. 2012)

Clomiphene citrate? For those of you who have no idea, what clomiphene citrate aka "clomid" is: It's a SERM = selective estrogen receptor modulator - basically a molecule that looks and behaves similar to estrogen, but has only insignificant estrogenic effects, when it binds to the estrogen receptor. Originally developed for the treatment of breast cancer, SERMs have caught some attention within the bodybuilding community as the goto drug to "restart" the HPTA after the use of androgens. This works simply because estrogen, the last hormone in the steroid cascade has the most pronounced suppressive effect on steroid production. As soon as the respective receptors in the brain are blocked and the brain tricked to believe that there is almost no estrogen floating around it will ramp up the hormonal production again and the sex hormone levels will rise. Obviously, this does not work for former performance enhancing drug users, only, but also for men in whom the HPTA or testosterone production is suppressed for other reasons. And as if that was not astonishing enough, clomid has also been used with some success as a fertility drug for women (Zadehmodares. 2012).

In a prospective study the results of which have been published in the International Brazilian Journal of Urology Carlos Teodósio Da Ros and Márcio Augosto Averbeck were able to show that the (in bodybuilding circles probably laughed at) dosage of 25mg/day clomiphene citrate increased the testosterone levels of 125 men with hypogonadism and low libido (mean age was 62 years) from Serum T levels ranged from 309 ng/dL at baseline to 642 ng/dL within no more than 3 months.

What about the side effects? Well, the only ones the scientists observed were improvements in the
post-treatment Quality of Life (QoL) scores. Total cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose and prolactin did, if anything, improve (!) - statistically significant was yet only the -5% reduction in total cholesterol.

No serious adverse events were recorded. And if it were not for the absence of statistically significant improvements in sexual performance in the 26 men who had already passed the 71y age mark - you could probably say: "It worked like a charm" ;-)

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Curried Carrot Soup w/ coconut oil (DrAxe.com) - I doubt the chef who came up with this recipe was aware of a recent study by Conlon et al. which showed that coconut oil can increase carotenoid accumulation in tissue & serum of gerbils by up to 900%(!) over safflower control

Virgin Coconut Oil For Everything - Including Bone Strength! Sounds hilarious, but is true: Researchers from the Pharmacology Department at the Faculty of Medicine of the Universiti Kebangsaan Malaysia in Lumpur, Malaysia, have found that the addition of 8g /100g virgin coconut oil (VCO) to the diets of the ovariectomized rats (this is the standard rodent model of menopause), was more effective than calcium supplements in preventing the menopausal bone loss.

While calcium only prevented the reduction in trabecular separation but failed to increase the bone volume and trabecular number, the rodents in the VCO group had a significantly greater bone volume and trabecular number than the ovariectomized non-supplemented controls, as well.

The scientists speculate that the beneficial effects the coconut oil had on the bone-structure of the estrogen deficient rodents was most likely due its high amount of saturated fats, particularly the medium chain triglycerides (MCTs). At least in my humble opinion the the additional biologically active components like vitamins and polyphenols, probably played an almost as important role. At least, that's what their antiallergenic, antiatherogenic, anti-inflammatory, antimicrobial, antithrombotic, cardioprotective, and vasodilatory effects would suggest - I mean, why don't we simply add antiosteoperotic to that list ;-)

Hungry for more news? Visit the SuppVersity on Facebook!

That's it for today, but there will be more in the days to come... more short news and an article I have promised to write looooong ago. So stay tuned and don't forget to check out the SuppVersity Facebook page for a couple of even shorter news-items on the bone-obesity connection, the potential downsides to chronic high dose glutamine supplementation, why total LDL cholesterol number and even LDL particle size could be less important than we have thought and much, much more ;-)

References:

• Choi KM, Lee YS, Shin DM, Lee S, Yoo KS, Lee MK, Lee JH, Kim SY, Lee YM, Hong JT, Yun YP, Yoo HS. Green tomato extract attenuates high-fat-diet-induced obesity through activation of the AMPK pathway in C57BL/6 mice. J Nutr Biochem. 2012 Sep 10. pii: S0955-2863(12)00184-2.
• Conlon LE, King RD, Moran NE, Erdman JW Jr. Coconut Oil Enhances Tomato Carotenoid Tissue Accumulation Compared to Safflower Oil in the Mongolian Gerbil ( Meriones unguiculatus ). J Agric Food Chem. 2012 Aug 16.
• Da Ros CT, Averbeck MA. Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency - a prospective study. Int Braz J Urol. 2012 Jul;38(4):512-8.
• Harrington M, Cashman KD. High salt intake appears to increase bone resorption in postmenopausal women but high potassium intake ameliorates this adverse effect. Nutr Rev. 2003 May;61(5 Pt 1):179-83. 
• Hayatullina Z, Muhammad N, Mohamed N, Soelaiman IN. Virgin Coconut Oil Supplementation Prevents Bone Loss in Osteoporosis Rat Model. Evidence-Based Complementary and Alternative Medicine. 2012; 237236: 8 pages.
• Hjelmesaeth J, Hofsø D, Aasheim ET, Jenssen T, Moan J, Hager H, Røislien J, Bollerslev J. Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study. Cardiovasc Diabetol. 2009 Feb 3;8:7.
• Karp HJ, Ketola ME, Lamberg-Allardt CJ. Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women. Br J Nutr. 2009 Nov;102(9):1341-7. 
• Marangella M, Di Stefano M, Casalis S, Berutti S, D'Amelio P, Isaia GC. Effects of potassium citrate supplementation on bone metabolism. Calcif Tissue Int. 2004 Apr;74(4):330-5.
• Moseley K, Weaver C, Appel L, Sebastian A, Sellmeyer DE. Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women. J Bone Miner Res. 2012 Sep 18.
• Sakhaee K, Maalouf NM, Abrams SA, Pak CY. Effects of potassium alkali and calcium supplementation on bone turnover in postmenopausal women. J Clin Endocrinol Metab. 2005 Jun;90(6):3528-33. 
• Séralini GE, Clair E, Mesnage R, Gress S, Defarge N, Malatestab M, Hennequin D, de Vendômois JS. Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food and Chemical Toxicology. 2012. Ahead of print.
• Snijder MB, van Dam RM, Visser M, Deeg DJ, Dekker JM, Bouter LM, Seidell JC, Lips P. Adiposity in relation to vitamin D status and parathyroid hormone levels: a population-based study in older men and women. J Clin Endocrinol Metab. 2005 Jul;90(7):4119-23.
• Taylor EN, Stampfer MJ, Mount DB, Curhan GC. DASH-style diet and 24-hour urine composition. Clin J Am Soc Nephrol. 2010 Dec;5(12):2315-22. 
• Veaseay RC, Gonazalez JT, Kennedy DO, Haskell CF, Stevenson CS. Breakfast consumption and exercise interact to affect appetite, cognitive performance and mood later in the day. Appetite 59 (2012) 618–638.
• Wesnes KA, Pincock C, Scholey A. Breakfast is associated with enhanced cognitive function in schoolchildren. An internet based study. Appetite. 2012 Aug 15;59(3):646-649.
• Zadehmodares S, Niyakan M, Sharafy SA, Yazdi MH, Jahed F. Comparison of treatment outcomes of infertile women by clomiphene citrate and letrozole with gonadotropins underwent intrauterine insemination. Acta Med Iran. 2012;50(1):18-20.

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.

Supplemental (!) Coconut Diet Reduces Waist Circumference in Men more Than in Women While Leaving Lipid Profiles Unchanged

I take the recent New York Times Article on coconut oil as clear evidence of the fact that the health benefit of tropical oils is getting more and more public attention. Studies that establish the many anecdotal reports you can find all over the Internet may even speed up this process and thus I am happy to report the findings of a Malasian study (Liau. 2011) that clearly underlines that the "bad" saturated fat cannot be so "bad" after all.

The scientists had a group of 20 healthy, but obese Malay volunteers consume an additional 30 mL of coconut oil (approx 2 tablespoons) per day taken in three divided doses, half an hour before each meal (as far as digestive side effects are concerned, this was the best tolerated dose as assessed before the actual study) and found...

that only waist circumference [WC] was significantly reduced after one month of VCO with a mean reduction of 2.87 +/-4.95 cm.

The high standard deviation of this data may well be attributed to the fact that there was no additional control of the dietary habits of the volunteers. The study says subjects "continued their weight loss efforts", but you probably know these "efforts" often turn out to be hardly comparable. I also feel that the real-world significance of the scientists statistical assessment "WC reduction was only seen in males" must be reevaluated, especially in view of the fact that "the reduction [meaning in cm WC] was larger in females" and the reduction in females with BMI <30 (4.8 +/-6.1 cm), other than in females with BMI >30 2.61 +/-2.17) was statistically significant (for more data cf. figure 1).

Figure 1: Comparison of mean differences in anthropometric measurements and lipid profile values in 7 males and 13 females after VCO consumption. (Liau. 2011)

I refrain from commenting on the reasons and invite readers to come up with their own theories, why someone who has gotten to a BMI of >30 (!!) may have problems losing weight on an uncontrolled intervention. What this should tell you, however, is that you may safely assume that 2 x tablespoons of coconut oil (~30ml) à day may be a worthwhile addition to your well-planned diet & exercise regimen.

On a side note: Who knows how much centimeters the volunteers had lost if the had just replaced some of the "good" seed oils in their diets? Well, I guess in view of the fact that the scientists seemed surprised that the bad saturated fats in coconut oil did not ruin their volunteers fatty acid profiles, they probably considered it unethical to ask their participants to completely replace corn with coconut oil ;-)

Coconut Miracle? Anti-Arthritis Effects of Virgin Coconut Oil Confirmed - Plus: 10 Additional Benefits of "White Gold" From "A" in 'Alzheimer's' to "W" as 'Waist Circumference'

Coconut Wonder, Coconut science or Both?

As a seasoned SuppVersity veteran, you will remember that I have been mocking the incredible hype around (virgin) coconut oil for years; not because there wasn't something "magic" to coconut oil, but rather because of the bazillions of incredible web-reports and recommendations and dozens of e-"books" on which the hype was / is built.

If you turn your head away from hype and hearsay and take a look at the coconut-science that's out there, the wonder begins to appear "wondrous", but does not disappear.

A recent study from the St. Thomas College in Kualalumpur, for example, does confirm the part where coconut oil made a lame person walk again (any similarities to biblical wonders are obviously mere coincidence ;-)

The said study was published in the International Immunopharmacology and its abstract says that the results of the corresponding rodent experiment confirm the "potential beneficiary effect of PV [virgin coconut oil] on adjuvant induced arthritis in rats" (Vysakh. 2014) - an effect, of which you as a SuppVersity reader already suspected that it was a direct results of the antioxidant and anti-inflammatory effects of virgin coconut oil.

The beneficial effects on blood lipids are more or less absent with refined coconut oil (Nevin. 2004)

Refined or not refined, this is not a question: There is a reason the virgin in the last sentence of the previous paragraph is printed in italics. Chances that the (meanwhile similarly glorified) medium chain fatty acids in coconut oil are - in one way or another - involved in the anti-arthritic effects are slim to zero. It's thus unlikely to expect similar benefits from the consumption of industrially "cleaned" zero-polyphenol refined coconut oil and - at least for rodents, a study by Nevin from 2004 did already confirm that (see figure to the left).

Now the obvious question is: What exactly have the scientists done? And how representative are their results for a human being suffering from one of the 100 different forms of this debilitating and painful joint disorder?

Basically, the researchers immunized the right hind paw of animals was immunized by injecting 0.1 mL of complete Freund's adjuvant containing heat killed mycobacteria in paraffin oil. This is a treatment that has been used quite successful for decades (Bendele. 2001) and results from previous trials would suggest that there is a satisfactory match between the effects scientists observe in the rodent model and those that occur in follow up human studies. There were three groups of rodents: The "non-arthritic" (=no injection of Freund's adjuvant) control (NC), the "arthritic" rats (AA), and two groups with arthritic rats who received

• 80mg/kg virgin coconut oil orally (HED: 1-1.25g/day for a human being)
• 3mg/kg indomethacin, a std. NSAID (HED: 35-40mg/day for a human)

over the course of a 30-day experiment, at the end of which the (poor) critters were were sacrificed by euthanasia.

Figure 1: Comparison of histopatho-logies of the paws (Vysakh. 2014)

"For histological analysis, paw tissues were dissected,fixed in 10% buffered formalin and then decalcified for 7 days in 20% EDTA.

The tissues were then processed and embedded in paraffin. Synovialfluid was obtained by injecting 100μL of normal saline into the knee joints followed by gentle aspiration.

Paw tissue and blood were also collected for various biochemical estimations." (Vysakh. 2014)

If you take a look at the results of this process, even you as laymen (and -women ;-) should be able to see the difference between the paw of the AA-rats (B - top right) and the relatively "mild" changes you can see in the histopathologies from the coconut oil treated group (D - bottom right, Figure 1).
If you take a look at the inflammatory markers in Figure 2, as well, it's actually not surprising to see that this relatively low amount of virgin coconut oil ameliorated the tissue damage. And even the fact that it did just that better than the standard NSAID idometacine, which commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling and works by inhibiting the production of prostaglandins, cannot come as a total surprise - the "coconut miracle" did after all do a much better job as a IL-6, TNF-alpha and even COX-2 inhibitor (see Figure 2).

Fat alternatives: It's quite telling that fats, not holy... ah, I mean "hole grains" are the #1 nutritional anti-arthritic agents: Fish and Krill oil (Ierna. 2010; Lopez. 2012)!

Of the former, a group of UK researchers has reported only recently that their proven (albeit nor earthshatteringly potent) anti-arthritis effects are mediated not by DHA and EPA directly, but by so-called resolvins, molecules that enzymatically produced from the LC-N3-PUFAs which are log-orders more potent than their precursors (see figure above; cf. Norling. 2013).

And while the use of resolvins is still being explored by various researchers, we do already know that adding another virgin, in this case virgin olive oil (~10g/day) to the fish oil equation will yield more "precocious and accen-tuated improvement[s]" (Berbert. 2005) than fish oil alone.

And if even this does not work, there is still albeit anecdotal evidence of the usefulness of low-dose naltrexone treatments (Brown. 2009).

So what more can you ask for? Well, aside fro the fact that even the "coconut rodents" suffered significant tissue damage, you could ask for (a) a study to confirm these results in human arthritis sufferers, you could (b) ask for alternatives (see box on the right) and you could (c) ask me about the scientific evidence in favor / against other effects that are said to be brought about by the regular consumption of virgin coconut oil.

I can't offer you (a), i.e. the randomized controlled human study that would confirm these results. In view of the fact that most of you are hopefully still arthritis-free, it may yet be more interesting to hear that Ian Prior reports in his 1981 paper that the higher coconut oil intake of the Pukapuka, inhabitants of one of the atolls near the equator had significantly lower prevalence of arthritis, as well as heart disease, cancer, diabetes than their cousins, the Tokelau from the atoll next door, whose diet contained only 34%, instead of 63% coconut oil (Prior. 1983).

Looking back at our list, the observations Prior made, when he analyzed the diets and health of the inhabitants of Polynesian atoll dwellers, we have actually already breached issue (c) and the question for other 'non-anti-arthritic miracles' - and yes, a reduced heart disease risk, as well as lower cancer and diabetes rates are on the list of scientifically supported (yet not necessarily verified) benefits of virgin coconut oil (Amarasiri. 2006). There are also case reports to support the anti-Alzheimer's (Newport. 2010) and rodent studies to support bone, liver and testes protection, lipid lowering effects (Nevin. 2009, Zakaria. 2011; Abujazia. 2012; Dosumu. 2012), and beneficial effects on blood pressure and wound healing (topical application; Nevin. 2010; Nurul-Iman. 2013) and, last but not least, there are even (methodologically questionable) human trials which support the often-touted fat loss effects (-1% waist circumference in obese men - Assunção. 2009; Liau. 2011).

Miracle or not, the notion that virgin coconut oil is among the healthiest sources of dietary fats you can chose from appears to be more or less undeniable. The same is yet also true for the fact that this does not mean that you have to chose between virgin olive and coconut oil. On the contrary! If you read my recent article on the pro-/anti-diabetic effects of dietary fat, you will be aware that only a balanced mix will provide you with all the good fats and their unique "extras".

Reference:

• Abujazia, Mouna Abdelrahman, et al. "The effects of virgin coconut oil on bone oxidative status in ovariectomised rat." Evidence-Based Complementary and Alternative Medicine 2012 (2012).
• Amarasiri, W. A. D. L. "Coconut fats." Ceylon Medical Journal 51.2 (2006): 47-51.
• Assunção, Monica L., et al. "Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity." Lipids 44.7 (2009): 593-601.
• Bendele, Alison M. "Animal models of rheumatoid arthritis." J Musculoskelet Neuronal Interact 1.4 (2001): 377-385.
• Berbert, Alair Alfredo, et al. "Supplementation of fish oil and olive oil in patients with rheumatoid arthritis." Nutrition 21.2 (2005): 131-136. 
• Brown, Norman, and Jaak Panksepp. "Low-dose naltrexone for disease prevention and quality of life." Medical hypotheses 72.3 (2009): 333-337.
• Ierna, Michelle, et al. "Supplementation of diet with krill oil protects against experimental rheumatoid arthritis." BMC musculoskeletal disorders 11.1 (2010): 136. 
• Liau, Kai Ming, et al. "An open-label pilot study to assess the efficacy and safety of virgin coconut oil in reducing visceral adiposity." ISRN pharmacology 2011 (2011).
• Lopez, Hector L. "Nutritional interventions to prevent and treat osteoarthritis. Part I: focus on fatty acids and macronutrients." PM&R 4.5 (2012): S145-S154. 
• Nevin, K. G., and T. Rajamohan. "Beneficial effects of virgin coconut oil on lipid parameters and in vitro LDL oxidation." Clinical biochemistry 37.9 (2004): 830-835.
• Nevin, K. Govindan, and Thankappan Rajamohan. "Wet and dry extraction of coconut oil: impact on lipid metabolic and antioxidant status in cholesterol coadministered rats." Canadian journal of physiology and pharmacology 87.8 (2009): 610-616.
• Nevin, K. G., and T. Rajamohan. "Effect of topical application of virgin coconut oil on skin components and antioxidant status during dermal wound healing in young rats." Skin pharmacology and physiology 23.6 (2010): 290-297.
• Newport, M. "Case study: dietary intervention using coconut oil to produce mild ketosis in a 58 year old APOE4+ male with early onset Alzheimer’s disease." 25th International Conference of Alzheimer’s Disease International (ADI). 2010.
• Norling, Lucy V., and Mauro Perretti. "The role of omega-3 derived resolvins in arthritis." Current opinion in pharmacology 13.3 (2013): 476-481. 
• Nurul-Iman, Badlishah Sham, et al. "Virgin coconut oil prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil." Evidence-Based Complementary and Alternative Medicine 2013 (2013).
• Prior, Ian A., et al. "Cholesterol, coconuts, and diet on Polynesian atolls: a natural experiment: the Pukapuka and Tokelau island studies." The American journal of clinical nutrition 34.8 (1981): 1552-1561.
• Zakaria, Z. A., et al. "Hepatoprotective activity of dried-and fermented-processed virgin coconut oil." Evidence-Based Complementary and Alternative Medicine 2011 (2011).