3/3 TOP-Selling US Fish Oils Exceed Maximal Peroxide and Total Oxidation Levels - Levels Roughly 4000% Higher Than in Medical Grade N3 Supplements, Harvard Study Shows

The US' favorite fish oil supplements: Dirt cheap and still not worth the money. Better buy fish - fresh fish.

"I told you so!" That's how someone else in my position would probably start today's blogpost. In view of the fact that "smartassing" is not exactly an effective means of education, I will yet refuse from reminding you that I've been reporting about unwanted side effects of the gold-ish pills that claim to have "fish oil" in them on various occasions.

And guess what!? The publication of a recent study by scientists from the Cardiovascular Division, Brigham and Women's Hospital at the venerable Harvard Medical School, gives me yet another reason to rant against the evermore popular fish oil supplements.

You can learn more about omega-3 & co at the SuppVersity

Fish Oil Makes You Rancid?

POPs in Fish Oils are Toxic!

N3/N6 Ratio Doesn't Matter

MUFA & Fish Oil Don't Match

Fish Oil Doesn't Help Lose Weight

Rancid Fish Bad 4 Health

In their study, the scientists analyzed 3 commonly available fish oil dietary supplements and found that (a) their level of omega-3 fatty acids varied significantly, that (b) they contained tons of other fats that you would ask to be paid for to consume if you knew about them and, that (c) the caps were so full of oxidized fats that they exceeded international standards and may (d) may harm, rather than help with your health.

No, we're not talking about cheap Chinese internet purchases, bro!

The Harvard scientists bought the "three top-selling fish oil DS [dietary supplements] in the United States and to examine the extent of oxidative damage in the DS as compared with chemically characterized standards with respect to purity and ability to prevent human sdLDL oxidation in vitro" (Mason. 2016). The commonly heard excuse that this is "just a problem with the cheap Chinese stuff" is thus as useless as it is ridiculous in view of the data from the study at hand.

Figure 1: The TOP3 US fish oil products are rancid... well, mostly (right hand side) and they have almost no ability to prevent human LDL particles from oxidation, as the results of the MDA test on the left indicates (Mason. 2016).

Compared to the medical grade control, the US top-sellers look as if they had been tainted with motor oil from a fishing cutter. Speaking of which: I would not guarantee that the 34%, 21% and 24% of "other oils" in this so-called dietary supplements do not include at least tiny amounts of mineral oils.

Your fish oil contains 4000% more oxidized fats than prescription fish oil! That's a huge problem, because many of the studies you're so fond of, because they seem to prove how healthy fish oil is, have been done with medicinal grade fish oils. Accordingly, the results of these studies have ZERO predictive power with respect to what your "machine oil" fish oil will do to your health. Speaking of "your" - it is not impossible that the oxidative damage occured during storage, which reminds me to remind you NEVER to use fish oil in a bottle that's constantly exposed to pro-oxidative oxygen, whence you've opened the bottle. Note: If stored in the fridge (4°C) the shelf life of the fish oil in fresh fish is, as Boran et al. show in their 2006 paper in Food Chemistry ~ 90 days.

In fact, the scientists measured not just primary oxidation products, as the highly elevated peroxide levels, an indicator of high levels of primary oxidation and hydroperoxides, confirm, but also secondary products of the decomposition of the primary oxidation products during continued exposure to oxidative conditions, as they ar detected in the p-anisidine test.

Figure 2: Indeed, there was also some "fish oil" in the caps - emphasis on "also" and "some" (Mason. 2016)!

The total oxidation levels in Figure 1 were then derived from the peroxide and anisidine values indicate without fail that "[a]ll three DS exceeded the recommended maxima for peroxide and total oxidation values (5 meq/kg and 26, respectively) when normalized to 1 g OM3FA (based on the number of capsules needed to achieve 1 g of OM3FA)" (Mason. 2016). The latter is particularly shocking in view of the fact that the prescription product of pure OM3FA did not contain significant levels of these oxidation products under identical test conditions. Any studies on the health effects of fish oil - mostly conducted with medical grade capsules - is thus meaningless for the average consumer who shies away from the exorbitant costs of LOVAZA and co. - a bad mistake, as it turns out, now, that the Harvard scientists' study shows that EPA and DHA containing oxidized trash fats from the dietary fish oil supplements have a >77% reduced ability to protect your LDL oxidation from (>90% protection for pure products, a meager 21 ± 4% for the "fish oil" you have probably been buying for years).

Speaking of "for years": Is it possible that you've done more harm than good in the past years of consuming copious amounts of fish oil to your health? Yes, it is, but in view of the fact that even the "motor oil" version of fish oil in the average US dietary fish oil supplement (the brand names are obviously undisclosed = not mentioned in the paper) was still anti- and not pro-oxidative, it's more likely that you have only wasted time and money.

Only three brands, but unfortunately in line with previous research: The scientists make no secret of the fact that a major limitation of their study "is that, although [they] evaluated the top-selling DS in the United States, [they] only assessed three products given the scope of this initial investigation" (Mason. 2016). Bad luck for fish oil fans: e results of this study are consistent with previously published analyses of DS with respect to content and oxidative damage" (ibid.) - studies that didn't just find oxidized fatty acids, but also heavymetals and cholesterol in the pills.

So what do we make of these results? Well, I guess it depends on how indoctrinated you've already been about fish oil being an essential supplement (the word "supplement" already implies that it cannot be essential). If you actually believe in the magic of fish oil (imho bogus for healthy individuals), you should go and buy pharma grade fish oil spending your whole monthly supplement budged on fish. If, on the other hand, you've any sanity left, you simply do what I've been recommending for years: eat your fatty fish once or twice per week (doesn't have to be wild-caught | Farmed Fish is Less Poluted and Has More Omega-3) | Comment!

References:

• Boran, Gökhan, Hikmet Karaçam, and Muhammet Boran. "Changes in the quality of fish oils due to storage temperature and time." Food chemistry 98.4 (2006): 693-698.
• Mason, PR and Sherrat SCR. "Omega-3 fatty acid fish oil dietary supplements contain saturated fats and oxidized lipids that may interfere with their intended biological benefits." Biochemical and Biophysical Research Communications - Available online 21 December 2016 | In Press, Corrected Proof

Eating 75-100g Fat (M-/PUFA) in the AM Improves Glucose (7-8%), Insulin (40-60%), Trigs (4-16%), GSH & MDA (40-75%)

If we assume that the protein fried eggs with its comparatively low insulinogenicity is not a problem (unlike your whey, for example), avocado and eggs fried in olive oil is the perfect breakfast to replace the liquid test meal used in the study.

There's no debating that increased amounts of free fatty acids in the blood will impair your insulin sensitivity, as they should be there only, when your supply of carbohydrate is running out, AMPK and with it the expression of lypolytic enzymes increase and the triglycerides from your fat stores are broken down into free fatty acids and released into your bloodstream where they can be used by liver, muscle and other organs as an alternative energy source.

Now, the word "alternative" is of paramount importance, here, because you'll find yourself being in (diabetic) trouble if those FFAs pile up on top of high glucose levels. This is what happens with the SAD diet and its high carbohydrate and fat content (and energy!) content.

You can learn more about fat at the SuppVersity

Are Men Fat- & Women Sugar-Cravers?

Fat, not Fructose Cons. Increased in the US

Adding Fats to Carbs Does not Reduce Insulin

The Forgotten Pro-Insulinogenic Effects of SFAs

Margarine Not Butter Incr. EU Waists

Low Fat to Blame for Low Vitamin D Epidemic?

It's a vicious circle: When the levels FFAs are up, insulin sensitivity goes down (after all, with a normal diet you'd have to burn the fat and spare the precious glucose | Bodne. 1997; Koves. 2008). Since there's more and more glucose spilling in over the portal-vein, though, insulin will keep increasing to a point where it does no longer simply impair, but almost block the oxidation of free fatty acids. Now, without insulin working its glucose shuttling magic, however, the cells begin to starve for glucose and... right, more FFAs are being released, the insulin resistance increases, still hardly more glucose is being shuttled into the cells to restore AMP to ATP and the process continues.

What does all of that have to do with eating more MUFAs and PUFAs to control your glycemia? Well, nothing and everything. First- and most importantly, it should remind you that this is not about eating fat with your carbohydrates. That's exactly not what the latest study from the Hospital Clínico Universitario Valencia in Spain would suggest, even though I bet you will have some idiot already have misinterpret the study in this way "for your" online. Rather than that the study was, as the abstract already tells you, conducted to ...

"[...] evaluate the changes in glycemia, insulinemia, and oxidative stress markers during an oral fat load test in nondiabetic subjects with abdominal obesity and to analyze the association between postprandial oxidative stress markers and postprandial glucose and insulin responses" (Martinez-Hervaz. 2016)

This quote also contains another important information you will have people with an agenda forget to mention: the subjects in whom the fats worked their magic were abdominally obese! Later on we will see why this is relevant and why the same rules won't apply to lean individuals, but for the time being let's firstly take a look at the exact characteristics of the N = 40 (total) subjects in the study in Table 1.

Table 1. General characteristics, fasting lipids and lipoproteins, glucose, insulin and HOMA index values in the studied groups (Martinez-Hervas. 2016); ^a control vs abdominal obesity group (p<0.01).

Even though the discriminating feature, i.e. the characteristic the scientists used to find subjects for the two groups was their waist circumference (>102/88 cm for men and women, respectively vs. <102/88 in the control group), it shouldn't surprise you that the scientists have also observed sign. differences in other anthropometric and metabolic markers such as the BMI, the level of triglycerides, blood lipids and postprandial glucose levels after an oral glucose tolerance test (OGTT | see Table 1).

Is it a problem that the male / female ratio differed? That is difficult to tell. We do know that men and women handle nutrients, esp. fat and carbs slightly differently, but I doubt that the difference between an 11/9 ratio in the control group and a 7/13 ratio in the abdominal obesity group will ruin the results of the study at hand. Nevertheless, this should be addressed in future studies.

After initial testing, the subjects from both groups ingested the same commercial liquid preparation of high-fat meal of long chain triglycerides. The product is called SuperCal and must not be confused with a vitamin D + calcium product with the same name that is being sold on the US market. From a previous European study, I've got some extra-information about its composition, namely that

"[...] 125 ml contains 60 g fat, of which 12 g are saturated, 35.35 g are monounsaturated, and 12.75 g are polyunsaturated. Each 100 ml contains <1 g lauric acid, <1 g myristic acid, 4.8 g palmitic acid, 1.4 g stearic acid, 27.7 g oleic acid, 9.6 g linoleic acid, 1.4 g behenic acid, and 0.5 g lignoceric acid" (Fernández‐Real). 

The detailed fatty acid composition of the SFAs, MUFAs and PUFAs emulsion that was administered at a dosage of 50 g fat per m² of body surface (calculate your body surface if you want to know your individual equivalent dose = result of your calculation in m² x 50g g/m²; e.g. 1.78 m² x 50 g/m² = 89 g of fat) at 8:30 after an overnight fast is not mentioned in the Martinez-Hervas study. What the authors of the study at hand tell us, however is that the likewise relevant ratio ω6/ω3 is > 20/1 - similar to the average diet, by the way; a fact that excludes that this is an omega-3 effect we are seeing, here. Similarly, exercise or previous meals, shouldn't have messed with the results, either. After all, in both groups, only water was permitted during the "eating" or rather "drinking" process, and no physical exercise was undertaken before or during the "fasted" fat loading test in the AM.

Figure 1: Overview of the rel. levels of glucose, insulin, HOMA-index, trigs, the GSSG/GSH ratio and MDA, a byproducs of lipid oxidation (Martinez-Heras. 2016); levels expressed relative to control at baseline (T = 0), see explanation below

In order to make the data more accessible (compared to the tabular overview of absolute values in thee FT) for you, I've standardized each of the measurable variables to match 100%. This means that all the fasting bars at T = 0h will be at the 100% mark, because they are what the effects of fat loading are compared to. Let's take a look at two examples:

• 

  PUFA Increases Postprandial Thermo-genesis in Women & Beyond - 14% Increase Over MUFA & SFA Sounds Huge, But Does it Matter?

  Insulin: In contrast to what you will see if you co-administer fat and carbohydrates (learn more), the administration of the high MUFA + PUFA fat supplement in the absence of carbohydrates lead to a sign. reduction of the initially 3.8-fold increased insulin levels. Not to normal levels, but at least to 158% (i.e. 1.6-fold elevated) of the fasted value of the lean subjects. Ah, but remember: All that happened with the fat load, alone, and in the absence of CHOs. In the presence of carbs the results would have been much different.
• GSSG/GSH ratio: The effects on the ratio of 'used' glutathione (GSSG) to the amount of the 'fresh' master anti-oxidant (GSH) were quasi the opposite of what the scientists observed for insulin. Here, the abdominally obese group had 2.4x elevated levels to begin with. This tells you that, compared to the normal controls, their anti-oxidant status was a mess. After only 8h, however, their GSSG/GSH ratio had not just declined, it was actually lower than the fasted value of the control group.
  
  And again, likewise similar to the effects on insulin, the control group saw benefits as well, with a 64% decrease in the GSSG/GSH ratio their antioxidant defenses did also benefit from the MUFA + PUFA load in the AM.

For other parameters you will see similar, for many of you probably surprising benefits. Things to keep in mind, though, is that we are talking non diabetic subjects in both groups, even if the abdominally obese subjects had fasting HOMA index values fourth fold higher than controls, higher fasting triglyceridemia and higher fasting oxidative stress markers. If that sounds like you, then the acute ingestion of ~75-120g (depending on your body surface) of fat on empty in the AM, when hyperlipidemia is not that much of an issue, you can benefit from a high MUFA + PUFA fat load as you would find it in an avocado + egg fried in olive oil, for example... or, as the authors of the study at hand have it:

"[O]ur study has demonstrated a significant reduction of postprandial glycemia, insulinemia, c-peptide and oxidative stress markers using an acute oral overload of unsaturated fat. We have found a significant correlation between oxidative stress markers and postprandial lipemia. There is an increase of TG achieving the maximum peak four hours after the beginning of the test. However, although postprandial lipemia has been implicated in the development of insulin resistance and oxidative stress, and despite the increase of TG, there are significant reductions of the HOMA index and oxidative stress markers" (Martinez-Hervas).

Even though you may think otherwise, the authors are also right, when they point out that "[t]he influence of dietary macronutrients in insulin sensitivity is not well known" (ibid.) This is especially true, when we begin mixing proteins, carbohydrates and fats and start to take into consideration that we can have a dozen of types of the three in a single meal.

What about me? I am not abdominally obese, will I benefit, too? If we assume that you deprive yourself of any carbohydrates (and proteins?), you should see the same benefits as the subjects in the control group - those are lower than what we see in the big belly group and may simply be a result of the moderate energy intake (that's < 900kcal before an 8h fast even for many bigger guys), it would appear as if the answer to your rightly asked question would be "Yes, you can benefit, as well." Whether this will also require you to abstain from all, not just insulinogenic dairy proteins, however, will have to be tested in future studies.

It may thus depend on the food-matrix whether the results of previous studies, most of which clearly indicate that saturated fat will increase in fasting and postprandial insulin resistance would have yielded different results if the meals were administered in the absence of carbohydrates, for example - even though, additional evidence traced these effects back to increased levels of saturated fat in the cells' phospholipids that can alter their phyco-chemical properties and decrease the glucose transporters (while MUFA and PUFA have been shown to do the opposite | Borkman. 1993). Martinez et al. who have not actually tested the effect of SFAs in their studies provide additional evidence in their discussion:

Will the additional butter on top of the potatoes reduce the insulin response? You can find the answer to this and the other questions in today's episode of "True or False?" | Learn the answer

"Iggman et al demonstrated in elderly men that palmitic acid, the major saturated fatty acid found in adipose tissue, inversely correlates to insulin sensitivity measured by euglucemic-hyperinsulinemic clamp. However, they also found a positive relation of insulin sensitivity with the content of linoleic acid in adipose tissue (Iggman. 2010). It is in accordance with our results because our commercial liquid preparation of high-fat meal of long chain triglycerides is composed in the majority by linoleic acid (59%). Furthermore, in line with our findings, the replacements of dietary saturated fat by unsaturated fat also improved fasting insulin sensitivity (Vessby. 2001).

Several other studies have demonstrated that unsaturated fat improves fasting and postprandial IR, although the mechanism is largely unknown (Wang. 2015). Moreover the PREDIMED study has recently demonstrated that unsaturated fat can improve fasting insulin sensitivity and prevent the incidence of type 2 diabetes (Salas-Salvadó. 2011).

Another thing the study could not address is the chicken or egg question: After all, you can argue athat the significant reduction in oxidative stress markers the scientists throughout the fat load test could - as a result - have improved the subjects insulin sensitivity, but - at least in theory - it is imaginable that this worked the other way around... by an unknown feedback loop.

Figure 2: Relative in-group reduction in the parameters from Figure 1 from 0h to 8h (Martinez-Hervas); in contrast to the previous figure the one at hand shows the in-group difference, i.e. the change in control at 0 vs 8h, etc.

As you see, there's still lots to be learned about dietary fat out there - including the fact that a "high fat" diet that combines high energy with high fat and high carbohydrate intakes is always detrimental for your health and should no longer be used in studies, unless the goal is to mimic the Western diet (and I beg scientists to then call it what it is, and that's not a "HFD").

Beware of dairy proteins, especially whey, but also casein are highly insolinogenic and may reduce if not reverse the effects of fat loading in the AM on glucose management and inflammation | learn more.

Bottom line: Before you get addicted to the previously suggested avocado + eggs fried in olive oil breakfast, please keep in mind that this is not what the scientists tested. Especially in view of the relatively high protein level in eggs, another study would have to make sure that the latter won't interfere with the benefits... even if that's much less likely for eggs, meat or fish than for the highly insulinogenic dairy proteins.

Furthermore, the study at hand cannot tell us anything about the long-term effects, because it is an acute intervention (not even lasting for 24h, there could have been a rebound at 12h or 24h or with the ingestion of another meal at noon, etc.) that suffers from another methodological problem.

Without a control supplement containing high(er) amounts of saturated fat, the assumption that the results were MUFA + PUFA specific is simply based on the scientists' review of the existing research (see previous elaborations + quotes). And as the scientists add, last- and [f]inally, oxidative stress markers analyzed could be also altered by others players regulating the postprandial state" (Martinez-Hervas. 2016) | Leave a comment, praise or criticism on Facebook!

References:

• Boden, Guenther. "Role of fatty acids in the pathogenesis of insulin resistance and NIDDM." Diabetes 46.1 (1997): 3-10.
• Borkman, Mark, et al. "The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids." New England Journal of Medicine 328.4 (1993): 238-244.
• Fernández‐Real, José M., et al. "Fat overload induces changes in circulating lactoferrin that are associated with postprandial lipemia and oxidative stress in severely obese subjects." Obesity 18.3 (2010): 482-488.
• Iggman, David, et al. "Adipose tissue fatty acids and insulin sensitivity in elderly men." Diabetologia 53.5 (2010): 850-857.
• Koves, Timothy R., et al. "Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance." Cell metabolism 7.1 (2008): 45-56.
• Martinez-Hervas, Sergio, et al. "Unsaturated Oral Fat Load Test Improves Glycemia, Insulinemia and Oxidative Stress Status in Nondiabetic Subjects with Abdominal Obesity." PloS one 11.8 (2016): e0161400.
• Vessby, Bengt, et al. "Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study." Diabetologia 44.3 (2001): 312-319.

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

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

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

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

Are You Stressed Enough to Live Forever?

Suffocated Mitochondria Live Longer

Get Lean & Live Longer With I. Fasting

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

5+ Tips To Live To See Your Great Grand Children

Is a Latent Acidosis Killing You Softly?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Reference: 

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

Artichoke Leaves Diabetes No Chance: Thistle Qualifies as Anti-Oxidant, Carb Blocker, Digestive Help & Diabesity Drug

Boiled Artichokes slow down the absorption of glucose and minimize the insulin + glucose surges (Nomikos. 2007)

This article has made quite a remarkable transformation. It started as a Facebook Short News Item, was upgraded to a mini-article for the SuppVersity Short News and, when I realized that those green thistles have surprisingly diverse beneficial effects on human health, eventually became the regular SuppVersity Article you are about to read, right now.

Artichoke leaves the future of diabesity treatment!?

I have to admit, I am not exactly and artichole expert, but I was still surprised that the paper Joanna Magielse and her colleagues from the University of Antwerp are about to publish in the scientific journal Food & Function claims to be the first to investigate the beneficial health effects of artichoke leave extracts on diabetes-induced oxidation in vivo.

I mean, we all have seen the broad range of artichoke supplements on the shelves; and my brief review of the literature yielded studies from the mid 1920s discussing how beneficial artichoke can be for patients with type II diabetes (Root. 1925).

When I kept digging through the currently available literature, though, I had to realize that the vast majority of the in-vivo studies dealt with the anti-cholesterol (Wider. 2013) and digestive benefits (Marakis. 2002) of artichokes and their leaf extracts (ALE). The proven anti-oxidant effects of its major polyphenolic constituents (Zapolska-Downar. 2002;  Betancor-Fernandez. 2003; Jimenez-Escrig. 2003; Menghini. 2010), on the other hand, haven't been tested in either animals or humans with type II diabetes. The rodent-experiment the Belgian researchers describe in the paper at hand is thus probably in fact the first to investigate the anti-oxidative effects ALE in an in-vivo scenario.

More about chlorogenic acid.

What are the active ingredients in artichoke leaves? Mono- and dicaffeoylquinic acids were the major polyphenolic constituents: The total caffeoylquinic acid (CQA) content was 1.5%, with chlorogenic acid (CGA) being most abundant (0.30%), next to cynarin (0.12%) and several isomerization products of CGA (the sum of which was 0.75%), including neo- and crypto-CGA and dicaffeoylquinic acids. Luteolin-7-O-glucoside was the major flavonoid present.

Over the course of 3 weeks the rodents who had been injected with streptozotocin (STZ) to induce a diabetic phenotype that is commonly and successfully used as a model for type II diabetes in man consumed either

• Why 0.2g/kg BW? This is the rodent equivalent of a well-tolerated amount of 2g/day that has been used for treatment of hypercholesterolemia and digestive complaints (Englisch. 2000; Holtmann. 2003; Barnes. 2007).
  0.2g/kg BW of artichoke extract (CYN1),
• 1g/kg BW of artichoke extract (CYN2),
• 50mg/kg BW alpha-tocopherol-acetate (VIT E),

or no supplement at all. To make sure to have an appropriate reference, a fifth non-streptozotocin injected group served as a healthy control. In contrast to their their com-rats (sorry, I could not resist) who had blood glucose levels of 250mg/kg, the control rats started into the 3-week treatment phase with normal (=healthy) blood glucose levels and inflammation.

Learn About Artichoke Alternatives for Glucose Management:

Lifestyle Changes

ALA, GABA, Taurine & Co.

Berberine, Banaba & Co.

Cinnamon, Curcumin & Co.

Lemon, Starch, Coffee & Co.

Chlorogenic acid, fucoxanthin & Co.

To determine the effects the provision of artichoke leaves would have on the baseline inflammation of the diabetic rats, the researchers measured the plasma malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG). The status of plasma coenzyme Q9(CoQ9, necessary for the biosynthesis of coq10 increases indicate lower coQ10 levels) and erythrocyte reduced glutathione (GSH), on the other hand, were used as indicators of the state of the endogenous antioxidative defense system.

Figure 1: MDA, 8-OHdG, CoQ9 and GSH levels expressed as rel. difference to control (Magielse. 2013)

With the information from the previous paragraph, even a rocket scientist without a clue of biology will recognize that the buffered MDA,8-OHdG and coQ10 and GSH levels (the further away from the x-axis the more "disturbed" they are compared to the CON group), indicate that the artichoke leave extract did what the were not 100% sure it would to: It survived the passage through the gastrointestinal tract and wasn't extensively metabolized by colonic microflora or liver phase II enzymes, as it is the case for other potent in-vitro antioxidants like reseveratrol.

What's the mechanism and what do we already know about artichoke?

With respect to the underlying mechanism that could explain the improvements the researchers observed in the study at hand, Magielse et al. point out that...

"...it should be emphasized that not only direct antioxidant actions, but also indirect mechanisms affecting gene expression of inflammatory pathways and modulating antioxidant enzyme synthesis have been reported for polyphenols and may contribute to the reduction of oxidative stress." (Magielse. 2013)

In that, the scientists are referring to the previously established beneficial effects on lipid metabolism and glucose absorption other researchers have observed in previous studies:

• Boiled wild artichoke reduces postprandial glycemic and insulinemic responses in normal subjects by inhibiting the glucose absorption (100g of boiled plant on 50g of glucose in complete meal). Interestingly, this trick doesn't work in patients with type II diabetes (Nomikos. 2007)
• Significant increase in bile secretion and thus improved fat digestion.  1.92g of artichoke extract lead to increase of up to ~140% in a randomised placebo-controlled double-blind cross-over study published in Phytomedicine (Kirchhoff. 1994). 
• Beneficial improvements in endothelial function (-21% VCAM-1; - 17% ICAM-1 brachial +37% FMV) in hyperlipidemic patients with only 20ml of "self-made"* artichoke juice per day (*juiced by the researchers; Lupattelli. 2004).
• Provides "food" for probiotic Lactobacillus paracasei (LMGP22043) that have beneficial effects on faecal bacteria and biochemical parameters in human subjects (Valerio. 2011).
• Has UV protective effects, when applied to the hair (Fernandez. 2012) - not that important for your overall  health, but still quite telling, right?)
• 2x 200mg of ALE per day decrease total cholesterol and LDL and increase HDL in subjects with existing hypercholesterolaemia (Rondanelli. 2013)

I know that you'd probably love another 200 references to studies that support the beneficial health effects of artichoke and artichoke extracts, but you know what? I think that's enough for a preliminary conclusion.

Diabetes or Not-Diabetes - That's not just about the foods you eat, but also about what your body does with them: "Dietary Fructose vs. Endogenous Fructose Production: Is The Aldose Reductase Mediated Production of Fructose to Blame for Diabesity & NAFLD? Could Amla Help? " | more

Bottom line: With the existing evidence for its acute anti-hyperglycemic effects, its beneficial effects on lipid digestion and metabolism and reliable evidence from a 2005 study by Wittemer that the antioxidant caffeoylquinic acids and flavonoids are orally bioavailable in humans (Wittemer. 2005), it appears as if artichokes would make a a highly underrated, yet profoundly beneficial addition to everyone's diet.

With commercially prepared extracts, on the other hand, you do not just run the risk of buying not / incorrrectly standardized products without active ingredients, but could also be missing out on the actue anti-hypoglycemic effects, which are probably mediated by the fructan-content of the whole "fruit"; not the caffeoylquinic acids and flavonoids you can buy in capsule-, pill- or tablet-form (cf. Rumessen. 1990; the dosage of fructans that did the trick here was 20g!)

Reference:

• Barnes, J., Anderson, L.-A., Phillipson, J.-D. (Eds.), Herbal Medicines, Pharmaceutical Press, London 2007. 
• Betancor-Fernandez, A., P´ erez-G´ alvez, A., Sies, H., Stahl, W., Screening pharmaceutical preparations containing extracts of turmeric rhizome, artichoke leaf, devil’s claw root and gar lic or salmon oil for antioxidant capacity. J. Pharm. Pharma col. 2003,55, 981–986. 
• Englisch, W., Beckers, C., Unkauf, M., Ruepp, M. et al., Effi cacy of artichoke dry extract in patients with hyperlipopro teinemia. Arzneimittel-Forschung. 2000,50, E260–E265. 
• Fernandez, E., Martínez-Teipel, B., Armengol, R., Barba, C., & Coderch, L. Efficacy of antioxidants in human hair. Journal of Photochemistry and Photobiology B: Biology.  2012
• Holtmann, G., Adam, B., Haag, S., Collet, W. et al., Efficacy of artichoke leaf extract in the treatment of patients with functional dyspepsia: a six-week placebo-controlled, double blind, multicentre trial.Aliment. Pharmacol. Ther. 2003,18, 1099–1105.
• Jimenez-Escrig, A., Dragsted, L.-O., Daneshvar, B., Pulido, R. et al., In vitro antioxidant activities of edible artichoke (Cynara scolymusL.) and effect on biomarkers of antioxi dants in rats.J. Agric. Food Chem. 2003,51, 5540–5545.
• Kirchhoff, R., Beckers, C. H., Kirchhoff, G. M., Trinczek-Gärtner, H., Petrowicz, O., & Reimann, H. J. Increase in choleresis by means of artichoke extract. Phytomedicine. 1994, 1(2), 107-115.
• Lupattelli, G., Marchesi, S., Lombardini, R., Roscini, A. R., Trinca, F., Gemelli, F., ... & Mannarino, E. Artichoke juice improves endothelial function in hyperlipemia. Life sciences. 2004, 76(7), 775-782.
• Marakis, G., Walker, A. F., Middleton, R. W., Booth, J. C. L., Wright, J., & Pike, D. J. (2002). Artichoke leaf extract reduces mild dyspepsia in an open study. Phytomedicine, 9(8), 694-699.
• Menghini, L., Genovese, S., Epifano, F., Tirillini, B. et al., Antiproliferative, protective and antioxidant effects of arti choke, dandelion, turmeric and rosemary extracts and their formulation.Int. J. Immunopathol. Pharmacol. 2010,23, 601– 610. 
• Nomikos, T., Detopoulou, P., Fragopoulou, E., Pliakis, E., & Antonopoulou, S.. Boiled wild artichoke reduces postprandial glycemic and insulinemic responses in normal subjects but has no effect on metabolic syndrome patients. Nutrition Research. 2007, 27(12), 741-749.
• Root, H. F., & Baker, M. L. Inulin and artichokes in the treatment of diabetes. Archives of Internal Medicine. 1925, 36(1), 126.
• Rondanelli, M., Giacosa, A., Opizzi, A., Faliva, M. A., Sala, P., Perna, S., ... & Bombardelli, E. (2013). Beneficial effects of artichoke leaf extract supplementation on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: a double-blind, randomized, placebo-controlled trial. International Journal of Food Sciences and Nutrition, 64(1), 7-15.
• Rumessen, J. J., Bodé, S., Hamberg, O., & Gudmand-Høyer, E. Fructans of Jerusalem artichokes: intestinal transport, absorption, fermentation, and influence on blood glucose, insulin, and C-peptide responses in healthy subjects. The American journal of clinical nutrition. 1990, 52(4), 675-681.
• Valerio, F., et al. Role of the probiotic strain Lactobacillus paracasei LMGP22043 carried by artichokes in influencing faecal bacteria and biochemical parameters in human subjects. Journal of applied microbiology 2011, 111(1): 155-164.
• Wider, B., Pittler, M. H., Thompson-Coon, J., & Ernst, E. (2013). Artichoke leaf extract for treating hypercholesterolaemia. status and date: New search for studies and content updated (no change to conclusions), published in, (3).
• Wittemer, S. M., Ploch, M., Windeck, T., Müller, S. C., Drewelow, B., Derendorf, H., & Veit, M. Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans. Phytomedicine. 2005, 12(1), 28-38.
• Zapolska-Downar, D., Zapolski-Downar, A., Naruszewicz, M., Siennicka, A. et al., Protective properties of artichoke (Cynara scolymus) against oxidative stress induced in cultured endothelial cells and monocytes .Life Sci.2002,71, 2897–2908. 

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