Asparagus Extract Tops Anti-Diabetes Drug Glibenclamide. Plus: Dozens of Add. Health Benefits - From Aphrodisiac to Anti-Hangover & from Neuroprotection to Anti-Aging

Coho salmon, shrimp and asparagus with melted butter - better than any diabetes drug ;-)

Within the last couple of weeks, I have been moving news-items like this one into the "On Short Notice"  category, or simply totally discarded the dozen or so "herb XYZ" or "extract ABC ameliorates hypoglycemia in rodent model of type II diabetes" papers that are published on a weekly basis. The mere number of studies on whatever exotic, herb, spice or isolated polyphenol from the most remote areas (usually in Asia) the names of which I often even have heard about before, is simply too large to cover them all... and let's be honest: In the end, it's also downright boring to read about stuff that decreases blood glucose in a rodent model to a miniscule extend, when you already know that chances that you ever get your hands on a significant amount of that are zero, right?

There are however, two good reasons, why Rahman Md. Hafizur, Nurul Kabir and Sidra Chishti most recent paper, which has been published on November 24 in the latest issue of the British Journal of Nutrition, has still made it not just into the short, but actually the 'official' SuppVersity news are twofold: Firstly, the effects of the Asparagus officinalis extract they administered at two different dosages to their rodents were just mediocre, but - as you are about to see - right on par with the diabetes drug glibenclamide, a sulfonylurea based medication that is often sold in combination with metformin (the respective drugs are called Glucovance and Glibomet). And secondly, briefly summarizing the main results of the study provided a nice incentive to dig somewhat deeper into the already established beneficial health effects of asparagus - and I can tell you, those are about as numerous as the aformentioned boring "herb XYZ"-studies ;-)

From the scientists' petri dishes to the rodent cage and... onto your dishes?

Asparagus officinalis L. is probably what the average Westerner would call "common asparagus". It's native to most European, African and Asian countries and its medicinal usage has been reported in the British and Indian Pharmacopoeias and in traditional systems of medicine such as Ayurveda, Unani and Siddha. Most of you will probably be aware of its mild diuretic effects and the distinct smell of your urine which will betray that you are someone who loves its delicate flavor in salads, vegetable dishes, soups and (if you are like me) poundwise with melted Kerrygold butter, some potatoes a decent amount of ham or some grilled meat during the asparagus season... but I am digressing here, let's get back to the facts.

To get to the bottom of previously reported beneficial effects of asparagus in various inflammatory (metabolic) diseases, the initially conducted an in-vitro study, to test the radical scavenging ability of their Asparagus extract and found that ...

"[...] A. officinalis at a concentration of 0·5 mg/ml exhibited 86·8 % radical-scavenging activity, as shown by a significant decrease in the absorbance of DPPH radicals. These results suggest that A. officinalis has potent antioxidant activity, as the positive control propyl gallate exhibited 91·4 % radical-scavenging activity. (Hafizur. 2012)

Afterwards they injected a group of male and female Wistar rats with streptozotocin to induce diabetes. Subsequently, the rodents received either 250 or 500mg/kg body weight of an Asparagus officinalis (AO) extract or 5mg/kg body weight of glibenclamide (GIB) once daily via an oral syringe - the dosage was adapted once weekly according to changes in body weight.

Figure 1: Fasting blood glucose and insulin levels, total antioxidant status (TAS was measured using the ABTS) and beta cell area / islet expressed relative to control at the end of the 29 day study period (based on Hafizur. 2012)

A cursory glance at the data in figure 1 reveals: The initially betrayed anti-hypoglycemic effects (hypo[...] = ability to lower [blood sugar]) the high dose of Asparagus officinalis extract (AO500, figure 1) had on the fasting glucose levels of the animals were as potent as those of the diabetes drug glibenclamide.  Moreover, the treatment with AO500 had a slightly, but statistically significanty higher impact on the total antioxidant capacity and the same benificial effect on the morphology and function of the pancreas. Nevertheless, neither the A. officinalis extract, nor the glibenclamide treatment were able to restore the compromised insulin producton to more than ~70% of the value the non-streptozotocin-intoxicated animals.

There is much more to asparagus than it's antidiabetic effects

As impressive as these results may be, if we simply rely on the findings Hafizur, Kabir and Chishtiit present in this recent paper, we will actually miss not just half, but rather 95% of the potential health benefits the different genus and parts of asparagus have to offer.

Figure 2: A. racemosis administered at a dose of 200mg/kg per day makes male rats about as horny (and able to perform) as bi-weekly injections of testosterone (Thakur. 2009) - not that you would need that, but it's nice to know anyways.

Despite the fact that asparagus is a highly nutritious source of vitamin B6, calcium, magnesium and zinc, and a very good source of dietary fiber, protein (in at least in view of the fact that it's an almost zero calorie veggie ;-), vitamin A, vitamin C, vitamin E, vitamin K, thiamin, riboflavin, rutin, niacin, folic acid, iron, phosphorus, potassium, copper, manganese, selenium, highly bioavailable chromium, and even small quantities omega-3 fatty acids (Morales. 2012), so that the regular incorporation of asparagus alone into your diet will supposedly be beneficial for you, some of the more intricate health effects may in fact require the extraction of and supplementation with specific phytonutrients from Asparagus officinalis, A. racemosus, A. cochinensis and its various cousins.

In order to give you an idea of what you can expect, I have compiled a comprehensive, yet by no means extensive list of benefits which have been ascribed to root, seed, and even leaf extracts of asparagus over the past decades

• anti-cancer effects: Asparagus contains saponins that have in-vitro anti-(liver-)cancer effects (Ji. 2012); 
• neuroprotective effects: Chinese asparagus contains pregnanes that sooth neuro-inflammation (Jian. 2012; compounds could be present in regular A. officinalis as well) and can protect your liver and brain from aging (Xiong. 2011); 
• antiaging effects: A. contains enzymes that help with protein digestion (Ha. 2012); 
• hypolipidemic effects: n-butanol extracts from A. officinalis exert anti-hyperlipidemic effects (Zhu. 2011); 
• antimicrobial effects: A. has antibacterial activity against Escherichia coli, Shigella dysenteriae, Shigella sonnei, Shigella flexneri, Vibrio cholerae, Salmonella typhi, Salmonella typhimurium, Pseudomonas putida, Bacillus subtilis and Staphylococcus aureus (Mandal. 2000); 
• allows for geno-typing at home ;-) A. allows you to do a personal gene analysis to find out whether you have a single nucleotide polymorphism at rs4481887, which would make it impossible for you to smell the distinct odor the urine acquires after eating asparagus (Pelchat. 2011); 
• anti-hangover effects: A. helps your liver to metabolize alcohol and can even prevent a hangover (Kim. 2009); 
• buttery taste: A. contains phytochemicals which generate the sensation of having butter in the mouth (Dawid. 2012); 
• anti-stress effects: Ethanolic extracts from Asparagus racemosus have anti-stress activity and help your adrenals take a time out (Joshi. 2012)
• carbblocking effects: Asparagus racemosus inhibits the digestion of carbohydrates and enhances insulin action (Hannan. 2011); in this context it is interesting to remark that the in-vitro essay of the the study at hand suggested that A. officinalis, or rather the specific extract the scientists used in their study "has a very little effect on delaying glucose absorption" (Hafizur. 2012)
• immune promoting effects: A. racemosus ramps up natural killer cell activity (Thakur. 2012); AR also enhances memory and prevents amnesia (Ojha. 2012), 
• profound aphrodisiac effects: A dried root extract likewise from A. racemosus more than doubled the 'desire' of male rodents within 29 days (Thakur. 2009; cf. figure 2)
• MAO and acetylcholine breakdown inhibition: A. racemosus competitively inhibits acetylcholine and monoamine metabolizing enzymes (Meena. 2011)

As this highly incomplete list goes to show you, the health benefits are numerous. Unfortunately, this does also apply to the different phytochemicals which trigger all these effects. The probability that the next best extract you may find on the shelves or virtual outlets of a supplement store is actually going to to yield the health benefits you may be looking for are therefore pretty slim.

Although parts of it are edible as well, A. racemosus, is actually better known for its multitude of beneficial health effects that range from Antibacterial activity (some) antisecretory and antiulcer activity over mood enhancing and anti-depressive properties, and immunomodulatory effects to such profane things as libido enhancement or getting rid of superfluous water before a show or photo shoot.

Bottom line: In view of the practical problems associated with spotting appropriate extracts, I guess it would be best you take the fact that a 2003 paper in scientific journal Nutrition (Pellegrini. 2003) ranked asparagus 7th among 34 fruits and vegetables with respect to its free radical scavenging abilities, as an incentive to simply incorporate asparagus into your diets more frequently.

If, on the other hand, you are dealing with any specific health condition, it would certainly make sense to look for an extract that contains the proper genus of asparagus, is made from the right parts of the plant and - if possible - is even standardized for a specific compound: If you were interested in upping your estrogen levels, you would for example have to pick a whole plant extract of A. dumosus that would at best contain a standardized amount of 20-hydroxecysterone (Kaur. 1998). If it's rather the anti-ulcer effects you are after, your 'asparagus product of choice' should be made of the roots of A. racemosus ideally standardized for its Shatavairin content (Bhatnagar. 2005)... 

And now, you tell me eating healthy was complicated and taking supplements was easy ;-)

References

• Bhatnagar M, Sisodia SS, Bhatnagar R. Antiulcer and antioxidant activity of Asparagus racemosus Willd and Withania somnifera Dunal in rats. Ann N Y Acad Sci. 2005 Nov;1056:261-78.
• Dawid C, Hofmann T. Identification of Sensory-Active Phytochemicals in Asparagus (Asparagus officinalis L.). J Agric Food Chem. 2012 Nov 8.
• Ha M, Bekhit Ael-D, Carne A, Hopkins DL. Characterisation of kiwifruit and asparagus enzyme extracts, and their activities toward meat proteins. Food Chem. 2013 Jan 15;136(2):989-98. 
•  Hafizur RM, Kabir N, Chishti S. Asparagus officinalis extract controls blood glucose by improving insulin secretion and β-cell function in streptozotocin-induced type 2 diabetic rats. Br J Nutr. 2012 Nov;108(9):1586-95.
• Hannan JM, Ali L, Khaleque J, Akhter M, Flatt PR, Abdel-Wahab YH. Antihyperglycaemic activity of Asparagus racemosus roots is partly mediated by inhibition of carbohydrate digestion and absorption, and enhancement of cellular insulin action. Br J Nutr. 2011 Sep 8:1-8.
• Ji Y, Ji C, Yue L, Xu H. Saponins isolated from Asparagus induce apoptosis in human hepatoma cell line HepG2 through a mitochondrial-mediated pathway. Curr Oncol. 2012 Jul;19(Suppl 2):eS1-9.
• Jian R, Zeng KW, Li J, Li N, Jiang Y, Tu P. Anti-neuroinflammatory constituents from Asparagus cochinchinensis. Fitoterapia. 2012 Oct 24.
• Joshi T, Sah SP, Singh A. Antistress activity of ethanolic extract of Asparagus racemosus Willd roots in mice. Indian J Exp Biol. 2012 Jun;50(6):419-24. 
• Kaur H. Estrogenic activity of some herbal galactogogue constituents. Ind J Anim Nutr. 1998;5:232–4.
• Kim BY, Cui ZG, Lee SR, Kim SJ, Kang HK, Lee YK, Park DB. Effects of Asparagus officinalis extracts on liver cell toxicity and ethanol metabolism. J Food Sci. 2009 Sep;74(7):H204-8. 
• Meena J, Ojha R, Muruganandam AV, Krishnamurthy S. Asparagus racemosus competitively inhibits in vitro the acetylcholine and monoamine metabolizing enzymes. Neurosci Lett. 2011 Sep 26;503(1):6-9.
• Morales P, Ferreira IC, Carvalho AM, Sánchez-Mata MC, Cámara M, Tardío J. Fatty acids profiles of some Spanish wild vegetables. Food Sci Technol Int. 2012 Jun;18(3):281-90.
• Ojha R, Sahu AN, Muruganandam AV, Singh GK, Krishnamurthy S. Asparagus recemosus enhances memory and protects against amnesia in rodent models. Brain Cogn. 2010 Oct;74(1):1-9.
• Pelchat ML, Bykowski C, Duke FF, Reed DR. Excretion and perception of a characteristic odor in urine after asparagus ingestion: a psychophysical and genetic study. Chem Senses. 2011 Jan;36(1):9-17.
• Pellegrini N, Serafini M, Colombi B, Del Rio D, Salvatore S, Bianchi M, Brighenti F. Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. J Nutr. 2003 Sep;133(9):2812-9. 
• Thakur M, Chauhan NS, Bhargava S, Dixit VK. A comparative study on aphrodisiac activity of some ayurvedic herbs in male albino rats. Arch Sex Behav. 2009 Dec;38(6):1009-15. Epub 2009 Jan 13.
• Thakur M, Connellan P, Deseo MA, Morris C, Praznik W, Loeppert R, Dixit VK. Characterization and in vitro immunomodulatory screening of fructo-oligosaccharides of Asparagus racemosus Willd. Int J Biol Macromol. 2012 Jan 1;50(1):77-81.
• Zhu X, Zhang W, Pang X, Wang J, Zhao J, Qu W. Hypolipidemic effect of n-butanol Extract from Asparagus officinalis L. in mice fed a high-fat diet. Phytother Res. 2011 Aug;25(8):1119-24.

Lose(!) 33% Body Fat in 10 Days!? The Heavy Metal Obesity Link: Study Shows "Preventive Role" for Inorganic Cobalt in Obesity-Related Diseases.

Image 1: Cobalt - certainly not what you would expect to see at a health food store or pharmacy; with Kawakami et al.'s study this may change in the future (img Alchemist-hp)

"We are living in a toxic world!" - you have probably heard or read this sentence more than once and while I cannot deny that the environmental load of, among others, heavy metals appears to be increasing, I can however tell you that, according to a recent study from scientists from the Tukushima Bunri University in Japan, exposure to some of those heavy metals produces quite unexpected results in a rodent model of the metabolic syndrome and in lean controls. Instead of making them gain weight even more rapidly, the "toxic" (maybe we will have to reconsider that, just as we did in the case of chromium) heavy metal cobalt did not only reduce the weight of the white adipose tissue of the rodents, it increased leptin, adiponectin, and HDL-cholesterol, as well, and thusly "may have a preventive role in obesity-related diseases" (Kawakami. 2011)

This is certainly the 1001st time I am writing this, but I cannot emphasize often enough that the "high fat diet" researchers use in their studies has (in most cases) nothing to do with the Atkins or even a low-carb diet. Its main characteristic is that it is hypercaloric and high in fat and carbs. Please keep that in mind whenever you read about another study on the detrimental health effects of "high fat diets".

For 24days Kawakami et al. fed a group of seven-weeks-old male mice either a standard diet with 357.6kcal/100g or a hypercaloric (cf. red box above) high fat diet (HFD), where the latter induced obesity and dislepidemia within 2 weeks. After this initial phase, i.e. when the HFD mice were already obese and metabolically deranged, the scientists injected the animals with Sodium Arsenite (NaAsO2: 1.0 mg/kg bw), Mercuric Chloride (HgCl2: 1.0 mg/kg bw), Manganese Chloride (MnCl2: 5.0 mg/kg bw), Cobalt Chloride (CoCl2: 0, 1.3, 5.0, 7.5 mg/kg bw) or saline (control).

Figure 1: Modulatory effects of 10 days of heavy metal injection in mice on a high fat diet; values expressed as changes relative to animals on a normal diet (data calculated based on Kawakami. 2011)

Now, if you look at the data in figure 1, you will notice that the administration of Mercuric Chloride may have been most "effective" in ameliorating the HFD-induced increase in white adipose tissue (WAT) mass (HFD +70%; HgCl2 -14% vs. normal fed control), but those "fat burning" effects went hand in hand with profound elevations of the liver enzymes AST, ALT (in this case we can safely assume that these were not coming from the muscle tissue of the animals) and the blood urea nitrogen (BUN) levels, which indicate deteriorations of the kidney metabolism. Manganese and cobalt, on the other hand, had negligible or even beneficial effects (compared to HFD alone) on liver and kidney health and ameliorated the weight gain to +10% and +17%, respectively.

Figure 2: Adiponectin and leptin serum levels and mRNA expression in mice after 10 days on a high fat diet with simulatenous injection of mercury or cobalt; data expressed relative to normal fed control (calculated based on Kawakami. 2011)

What is particularly interesting about cobalt, though, is that it did not simply starve out the adipose tissue by poisoning it (like that was probably the case for mercury), but triggered exactly those metabolic adaptations scientists have been trying to provoke with drugs for years now: elevations in adiponectin and leptin (cf. figure 2), the two adipokines, researchers currently believe to be essential for successful weight loss / maintenance.

Figure 3: pAMPK/AMPK ratio after injection of different dosages of Cobalt chloride (calculated based on Kawakami. 2011)

In a follow up experiment, the scientists, also found that cobalt dose-dependently increases AMPK phosphorylation (for more on AMPK, I would like to refer you to the Intermittent Thoughts series) in white adipose tissue (WAT), muscle and liver of the animals (cf. figure 3). Of the three tested dosages, administration of 5mg/kg CoCl2 per day resulted in the most beneficial AMPK response, while with the maximal dose of 7.5mg/kg the negative / toxic effects appear to prevail (another of these bell-shaped dose-response curves, I guess).

Figure 4: Glucose tolerance test in mice on high fat diet with or without cobalt injections compared to mice on standard diet (control); values in mg/dl (data adapted from Kawakami. 2011)

Now, you are probably asking yourselves: "So what's the catch?". A brief look at figure 4 tells you that is ain't glucose intolerance, as the cobalt treated animals had the exact same response to the glucose tolerance test, as the mice on the normal diet - in other words: cobalt completely reversed the HFD induced glucose intolerance, and it did so not only without negative effects on blood lipids, but in the presence of a profound elevation of HDL levels and a reduction in LDL levels (cf. figure 5).

Figure 5: Relative (to normal fed control) changes in blood lipid in mice on a high fat diet with or without heavy metal injections (calculated based on Kawakami. 2011)

And as if that was not enough, the cobalt injections also eradicated the iincreases in free fatty acids and ameliorated the increase in triglycerides.

From the lab to the bedside?

Last but not least, and I hardly dare showing you this graph, because I would expect that some of you will already be googling a source of injectable cobalt (which would be plain out stupid, before any reliable safety data and confirmation of these results in controlled human trials are available), cobalt had almost identical effects when it was injected to the mice on the normal diet.

Figure 6: Relative changes in body composition and liver and kidney parameters due to heavy metal injection in non-obese mice on a standard diet (calculated based on Kawakami. 2011)

As figure 6 goes to show the mice lost 33% of their white adipose tissue and liver, as well as kidney function did not take a beating (HDL stayed the same, LDL decreased by -1%). Whether we will see a obesity or even just a weight-loss drug based on cobalt in the near future, does yet still seem questionable. In view of the fact that the number of "bad things" (cobalt is in fact an essential nutrient as it is the active center of vitamin B12 = cobal-amin) that have unexpectedly positive health effects is increasing day by day, we do yet obviously have to ask ourselves, whether there may be some major flaws in our current understanding of how our body works and how it deals and is effected by "toxins", oxidants and co.

Eat Whole Foods! Lose Weight, Improve Your Blood Lipids, Reduce Estrogen, Protect Yourself Against Chromosomal Damage and Defeat Prostate Cancer With Cabbage.

Image 1: The magic ingredient is in the root not in the commonly eaten leaves of "bok choy". Chances that you will find a "whole" (including the root) chinese cabbage" (lat. brassica rapa) at your local supermarket, are yet very low... but wouldn't this be a good reason to start gardening really "whole" foods in your backyard? (img. Wikigardener)

If you are a student of the SuppVersity, you are probably already annoyed by my favorite slogan "Nature knows best!" Nevertheless, I will not tire to repeat that "eating your way to a leaner and healthier you" is probably the only sustainable alternative on a side-effect ridden life on drugs such as Xenical.

As Trisha Gura points out in a newsitem on sciencemag.com,

[t]he current trio of [weight loss] drugs on the market, endocrinologists say, is, at best, weak and, at worst, plagued by side effects. Hoffmann-La Roche's Xenical, for instance, blocks fat-digesting enzymes called lipases. That prevents the gut from digesting and absorbing fat. But lipids aren't the only molecules malabsorbed; Xenical also causes cramping and severe diarrhea in many obese patients because water molecules also fail to be taken up by the gut.

Thus, the study results of Sojin An and his colleagues from five different research centers in the Republic of Korea, which although they have been published back in 2009, landed in my inbox only recently, come along quite handy. In a 8-week controlled trial the scientists found that the addition of 50mg/kg of an ethanolic extract from Brassica campestris spp. rapa roots (human equivalent: 4mg/kg) to the high fat diet (+25% more calories than standard chow) of ICR (imprinting control region) mice did not only ameliorate the weight and fat gain, but even reduced both gains in body weight (-3%), as well as white adipose tissue weight (-8%) compared to the normal fed control group.

Figure 1: Weight gain, fat gain (white adipose tissues) and energy intake of mice on a hypercaloric high fat diet (HFD) supplemented with either 50mg/kg chinese cabbage root extract or Orlistat (Xenical); values expressed relative to control group on normal chow (data calculated based on An. 2009)

The cabbage root extract outperformed Xenical not only in terms of its effect on body weight and fat accumulation, other than the pharmacological fat-blocker, it also preserved the leptin sensitivity of the mice, which was profoundly compromised (as can be seen by the +25% increase in leptin) in the Orlistat group (cf. figure 2).

Figure 2: Relative changes in blood lipids and adipokines in mice on a hypercaloric high fat diet (HFD) supplemented with either 50mg/kg chinese cabbage root extract or Orlistat (Xenical); values expressed relative to control group on normal chow (data calculated based on An. 2009)

The underlying mechanism behind all that is probably related to the 2-fold increase in beta-3 adrenergic receptor and the 3-fold increase in hormone-sensitive lipase (HSL) gene expression the researchers measured in the white adipose tissue of the animals. Both of them are intricately involved in the breakdown and release of stored triglycerides and their expression in rodents is suppressed upon high fat feeding.

In case you are as annoyed as I would be by the branding in the figures, I suggest you tell my friend "The Press" over at Anabolic Minds that "copy + pasting" the work of others like that, instead of citing only parts of the article and linking back to the source, is not what one would expect of an "anabolic mind". Thanks!

Want to plant your own veggies, but don't know how? Listen to SHR #703 "Urban Gardening: Like Your Life Depends On It"

My repeated advice to "eat whole foods", gets a whole new meaning, however, when you further consider that

• fatty acids from the pollen of brassica campestris have been shown to have a "strong inhibitory" effect on aromatase (Yang. 2009),
• the leaves protect "against in vivo genotoxicity and oxidative stress" (Tiku. 2008), and
• the chloroform extract from its pollen kills prostate cancer cells (Wu. 2007),

doesn't it? There is yet one obvious caveat to this advice. Without a green thumb, as Carl Lenore's significant other, Alisa Profumo, has one, it will be hard to get your hands on a whole brassica campestris plant, i.e. its leaves, roots and the pollen-laden blooms... ah, and just in case you take this insight as an opportunity to start gardening, I suggest you go and check out episode #703 of Super Human Radio "Urban Gardening: Like Your Life Depends On It" - who knows, one day your life could actually depend on it ;-)

Sucralose is for Diabetics Not, Scientists say. But How Significant is the Cholesterol Increase They Observed?

This way of consuming Splenda is quite certainly going to increase your cholesterol levels ;-)

I guess, all of you will still remember the show Carl and I did on the "Pro-Insulinogenic Effects of Artificial Sweeteners" (read more), right? The one where I tried to point out that even if there was a meager change in the insulin response, this would only be a problem if there was any truth to  narrow-minded condemnation of insulin as the deadly obesity hormone, so that, in the end, the whole hoopla turned out to be way less daunting than some scare-mongers would have it.

Yet while something deep inside of me is telling me that the latter is probably going to be the same with the recently published study that's at the focus of today's SuppVersity article, cannot refute that the data from that very rodent study that was published in the Journal of Nutrition Sciences does clearly suggest that...

...sucralose increases cholesterols!

That certainly doesn't sound so scary to you, as it does to someone who still adheres to the "cholesterol is the root cause of all evil" paradigm, yet still. The fact that the administration of  11 mg/kg body weight of SPLENDA® over the course of 6 weeks to "intensifie[d the already existing] hypercholesterolemia in STZ-induced diabetic rats" (Saada. 2013) does sound as if there must be something to the rumors about sucralose being one of the main ingredients of devil's excrements.

Would having your coffee with Splenda instead of sugar make this cookie even more hazardous to your glucose levels and what about your waistline? Read more about the effects of artificial sweeteners on glucose-management, insulin and obesity in a previous article.

Now 130-150mg of sucralose per day is unquestionably a whoppy dose of artificial sweeteners. After all, this stuff is approximately 600x sweeter than sugar. Sounds like a total overkill, but if you do the math, i.e. 150mg x 600 = 90,000 mg, you will realize that this is not more than the non-caloric sweetness equivalent of ~1.5 Snickers bars. And if the figures a Scivation rep mentions in a post on the most popular bodybuilding website on the planet are correct this would be exactly 10 servings of their highly popular BCAA formula. Considering the fact that for most people Xtend is probably not the only dietary source of sucralose in the diet it is thus not a totally unrealistic dose (especially for those diabetic or non-diabetic sugar addicts, who are using splenda as a means to sweeten their tea, coffee and whetever else, as well).

Good you've made it past the introduction

That being said the message that sucralose "intensifie[d the already existing] hypercholesterolemia in STZ-induced diabetic rats" (Saada. 2013) appears to be even more scary.

Fortunately (or unfortunately for the "sweeteners are devil's excrements"-faction out there), this is not your average "Pubmed-Warrior blog", where the authors read a headline copy and paste the conclusion of the abstract and try to sell it as "science news" and I do not leave you hanging with the inappropriately overgeneralizing conclusion of the author's that

"[...] diabetic people consuming high amount of sucralose must check their lipid profile to avoid diabetic complications" (Saada. 2013)

Now, it is obviously right that diabetics should "check their lipid profile" on a regular basis, but if you look at the actual study outcomes, it is hard to argue that this would be particularly important for those of them who use SPLENDA® on a regular basis.

Figure 1: Changes in blood glucose, insulin, triglyceride and total (TC), HDL, and LDL cholesterol, as well as the TC/HDL levels after 6 weeks on 150mg/day sucralose (Saada. 2013)

After all, the "dangerous" increase in cholesterol the scientists observed in their lab animals (remember: we are not even 100% sure the same is going to happen in human beings) is not just accompanied by highly desirable desirable reduction in glucose (-22%) and triglycerides (-22%), it also leaves the CVD-relevant ratio of total to HDL cholesterol literally unchanged (+2%, n.s.).

Moreover, if you look at the way statins help managing cholesterol, but increase diabetes risk, you could even speculate that there is a yin and yang connecting the two metabolic pathways, where a lower strain on the one side will precipitate a higher strain on the other. Within this paradigm, the increase in cholesterol, which is by the way something many people who are "going paleo" will see, as well, could be a totally normal part of a "balancing" process that has nothing to do with the pathological overprodcution (always remember this is not about eating too much cholesterol) of highly oxidizable small and very small density lipoproteins people fear like the plague.

---

In addition to reductions in blood glucose and triglyceride compared to cornflakes & co, the regular consumption of whole eggs increases HDL's ability to carry lipids out of the macrophages. If these accumulate, they will turn the macrophage into pro-atherogenic foam cells (learn more).

Bottom line: At least in my humble opinion, the results of this study don't imply that diabetics should stay away from sucralose. In the end, the benefits of lower glucose & triglyceride levels will outweigh the "downsides". This is all the more true, in view of the fact that we (a) the total-cholesterol-to-HDL-ratio remained essentially the same and (b) don't have data on the changes in lipoprotein particle profile. After all, improved glycemia and reduced triglyceride levels often go hand in hand with heat-healthy changes in the particle size distribution that is still totally ignored by way too many researchers.

That being said, the reduction in 10% reduction in TBARs, a marker of oxidative damage, clearly indicates that the rats with "increased" cholesterol levels were less inflamed than their sugar guzzling peers.

Needless to say that the same applies for the healthy rodents, where the changes in blood glucose, triglycerides and total, HDL and LDL cholesterol were much less pronounced, but the tendencies identical.

References:

• Saada H, Mekky N, Eldawy H, Abdelaal A. Biological Effect of Sucralose in Diabetic Rats. Food and Nutrition Sciences. 2013; 4(7a):82-89.

High Dose Caffeine + Non-Alcoholic Fatty Liver Disease = 355% Increased Very Low Density Lipoprotein (VLDL)

Image 1: Already in "pill form" - Coffee beans

Caffeine, the world's #1 drug certainly is a remarkable substance. It does not only have myriads of well-established physiological effects, already, but it seems that - if you wanted to - you could identify another one everyday. It is thus not really surprising that a recently published study by Abd El-Ghany, M.A., Rasha, M. Nagib and Hagar, M. El-Saiyed from the Mansoura University in Egypt casts yet another, in this case, however, pretty scary light on the lifeblood of the average Starbucks junkie (El-Ghany. 2012).

Caffeine prevents weight gain - whohooo! Or not?

The scientists set out to investigate the differential effects the oral administration of 10mg/day of pure caffeine, or dose-equivalents from coffee, (black) tea, cacao and Nescafe (note: this is my understanding of the somewhat sloppy English translation of the methods) would have on the lipid levels of rats who had been pretreated with a lard-based high fat diet and CCl4 for three months. This treatment had elucidated the expected inflammatory response and fatty acid deposition in the livers of the animals that were then randomly assigned to either one of the 5 treatment or a non-treated control group.

Figure 1: Weight gain (relative to initial weight) and food intake in non-treated, caffeine, cacao, Nescafe, coffee, or black tea treated rodent model of NAFLD (data adapted from El-Ghany. 2012)

And when you peak at the study outcome in figure 1 I would bet that your first reaction is: "Hey, cool! I must ramp up my caffeine intake even more, then!" We are in fact so conditioned to believe that weight loss, or the absence of weight gain is a "good thing" that I made the same stupid mistake, when I first looked at the (in the study) tabular data of the El-Ghany study. Then, I began to wonder: "How come that coffee and cacoa, of which I have repeatedly read that they help with weight loss, did increase the weight gain to levels that were higher than those in the non-treated control group." Finally, it dawned on me: What we are dealing with, here, is not weight loss or ameliorated weight gain, what we are seeing in all the groups is more of a special form of "failure to thrive"! After all, the non-CCL4 treated 'real' control group (data not shown in figure 1) did gain 45% of their initial body weight and thus still 15% more than the coffee group, of which I was mislead to believe that they "performed" worst.

High dose caffeine is for NAFLD sufferers not!

Looking at the rest of the data it became increasingly clear, the whopping dose of 10mg of caffeine per rodent per day, a dose, by the way, which happens to translates into a human equivalent dose of 10mg/kg (i.e. 800mg for an 80kg adult), did a pretty decent job in liberating fatty acids from the adipose tissue. So "decent", in fact, that the already compromised weight gain in those sick creatures was further attenuated.

Figure 2. Lipid levels in the treatment groups expressed relative to non-treated NAFLD rodents (left); selected liver slices (right; based on El-Ghany. 2012)

But it gets even worse, the sudden influx of fatty acids from the adipose tissue was so overwhelming that the already damaged livers of the NAFLD rodents started to spill out copious amounts of very low density lipoprotein (VLDL) - those nasty little cholesterol molecules of which researchers believe that they are the cause of cardiovascular disease. And despite the fact that we do not have any tissue images of the heart, the congested vein in the liver slice from one of the caffeine guzzling rodents appears to confirm the causal relationship of VLDL and clogging of the blood vessels; an effect, by the way, which could neither be countered by the -71% reduction in triglyceride levels, nor the -44% reduction in total lipids (compared to non-treated NAFLD control). 

Figure 3: Total cholesterol (CHO) and LDLc to HDL-c ratios in the non-treated, as well as the treated groups expressed relative to non-NAFLD control (data calculated based on El-Ghany. 2012)

In a 1985 letter to the editor of the Journal of the American Medical Association (Jama) William and Simpson explain the sudden occurrence of enormous amounts of VDLD in response to the lipolytic (=fat liberating) effects of caffeine as follows:

Upon liberation from the adipocyte, fatty acids are transported to the liver, where they are reesterified and the resultant triglycerides packaged for release in very-low-density lipoprotein (VLDL), which also contains apolipoprotein B.

If we assume that this hypothesis is correct, coffee, cacao and even Nescafe must obviously contain substances which help the liver to cope with the additional influx of fatty acids, as the animals in the respective groups do not only have significantly lower VLDL levels than the poor critters in the caffeine group, but also exhibit the most beneficial total cholesterol-to-HDL and LDL-to-HDL ratios (cf. figure 3) of all groups.

Say no to stims, energy drinks and coke and chose natural caffeine sources

In view of the ameliorative effects all the caffeine containing preparations had on the pathological features of NAFLD (cf. figure 2, right), and based on the results from previous studies and the assumption that the VLDL increase in the tea group was similarly well-handled in the rest of the body as it was in the liver, which did not present any of the congested veins that were so characteristic of the livers of the animals in the caffeine only group, the take home message of this study is one every SuppVersity student should be familiar with, by now: Nature knows best!

Image 2: I don't have to tell you that the study at hand suggests that those sugary caffeine bombs people call "energy drink" could give many of their livers their quietus.

Note: If you live in Dallas County, it does take no more than three attempts to identify a neighbor, friend, someone from your family or simply a pedestrian being in the early stages of NAFLD. And given the fact that the 33.6% NAFD rate in Dallas County was measure in 2005 already (Szczepaniak. 2005), it is almost certain that your neighbors' liver, which may still have been comparably healthy in 2005 has caught meanwhile. The results of this study could thus have greater implications on public health than you may initially have thought and it clearly suggest that the use of high dose "fat burners" and / or pre-workout supplements, as well the regular consumption of caffeine and sugar laden "energy drinks" or even coke is absolutely contra-indicated; and that not just in the obese, but also in the insulin resistant normal weight, whose liver is often similarly clogged with fat as the one of his 200lbs heavier comrade in crime.

If the caffeine is ingested in the absence of its natural adjuvants bad things happen. If they remain where they belong, however, the same whopping dose of caffeine that makes things worse could actually turn into a decent "liver fat burner".

While Coffee, tea and cacao drinkers can thus breathe a sigh of relieve, the average stim junkie who is already squirreling caffeine laden, geranium (DMAA) intoxicated pre-workout supplements and fat burners for the days after the DMAA ban, should better watch his liver health. Otherwise it may well be that he or she will end as a "case study" in the library of the FDA - filed under "death by fulminant liver failure induced by geranium + caffeine containing pre-workout supplement" - btw. isn't it strange that the FEDs don't have such a case study for one of the commercially available energy drinks, or even plain Coke, already?

DHEA the Slimming Hormone? Study Finds: Dehydroepiandrosterone Directly Inhibits Cortisol Synthesis in Rodent Adipocytes

After initially being hailed as the fountain of youth, the pharma-financed medical sciences dropped DHEA, when investors realized that a naturally occurring hormone would not be patentable. This and some discouraging and/or inconclusive results from long-term studies had DHEA literally disappear from the research scene for quite some time. Therefore, I am positively surprised that on the forthcoming European Congress of Endocrinology 2011 researchers from the Kobe University in Japan are going to present a paper (Tagawa. 2011) that shows that there may in fact be more to the initial findings of DHEA induced weight loss than follow-up studies would have it.

Tagawa et al. investigated the possible mechanism behind the weight loss effects of DHEA and found that there is a direct inhibitory effect of DHEA on glucocorticoid (re-)synthesis in adipose tissue:

Using differentiated 3T3-L1 adipocytes, we demonstrated that DHEA inhibited 11β-HSD1 activity at a concentration of 1 μM within 10 min. Inhibition was also observed in a cell-free system comprised of microsomes prepared from rat adipose tissue and NADPH, a coenzyme of 11β-HSD1. A kinetic study revealed that DHEA acted as a non-competitive inhibitor of 11β-HSD1. Further, DHEA did not inhibit 11β-HSD type 2, which inactivates cortisol or corticosterone in tissues involved in water and electrolyte metabolism, in rat kidney microsomes at a concentration <25 μM. Moreover, no conversion from DHEA to other sex steroid hormones or their precursors was observed under the present experimental conditions.

These are three significant observations. Firstly, the presence of DHEA inhibits the synthesis of cortisol via 11Beta-HSD1. Secondly, it does not prevent exogenous cortisol to be converted to the "inactive" cortisone via 11Beta-HSD2 and thirdly, the dreaded conversion into estrogen, testosterone or DHT does not take place. All this would make the naturally occurring hormone DHEA a perfect selective 11β-HSD1 inhibitor, of which Stewart et al. from the University of Birmingham write (Stewart. 2011):

Selective 11β-HSD1 inhibitors lower blood glucose, improve insulin sensitivity and cause weight loss in animal models. Biomarkers have been validated to confirm target inhibition in primate and human studies. Recent clinical trials show reduction in HbA1c and blood pressure in obese patients with diabetes mellitus who have failed on metformin therapy. Potentially the therapy offers a ‘magic bullet’ for patients with Metabolic syndrome with reduced blood glucose accompanying improved insulin sensitivity, lower lipids and blood pressure and reversal of hepatic steatosis secondary to reduced autocrine generation of cortisol in liver, adipose tissue, pancreas and muscle. Liabilities include activation of the HPA axis secondary to increased cortisol clearance with hyperandrogenism, though the extent and significance of this is debated.

One thing, though, before you now go about eradicating cortisol to zero. Your body needs a healthy level of cortisol to function. It goes hand in hand with thyroid hormone, helps you manage stress, perform in the gym and is even necessary to "burn" body fat. Again, moderation is key and you certainly want to know where you stand before you start tweaking your cortisol levels into the wrong direction.