Vanadium for Type II Diabetes!? Beneficial Effect of Trace Element on Blood Glucose Management in Rat Model.

Some of you may remember that vanadium has once been hailed as nutrient repartitioner (it has been shown to increase glucose uptake into muscle tissue via GLUT4-receptors) in the fitness & bodybuilding community. After reports on possible toxicity issues, which were - at least in parts - based on reports of people who dosed according to the common "more helps more" mentality of our society, vanadium supplements, stand-alone or larger doses as part of micronutrient blends, have disappeared from the market. Science, on the other hand has not given up on this promising, yet non-benign "medication".

A recent study (Kurt. 2011) published in the journal Biometals underlines that the effects of vanadium, which was named after the Scandinavian goddess of beauty and fertility, Vanadis, do in fact border on those of a pharmaceutical drug. After treating rats with streptozotocin and thus inducing a metabolic profile that is generally considered an appropriate model for human type II diabetes, the researchers from the Department of Chemistry, at the University of Istanbul, supplemented the chow of their animals (control & STZ-induced type II diabetic rats) with 100mg vanadyl sulfate per kg of body weight. For an 80kg male human this would amount to a massive dose of 1.200mg vanadium sulfate per day, the consumption of which is not advisable until definitive human data on short- and especially long-term consequences are available.

Figure 1: Blood glucose levels (mg/dl) of rats at different time-points
(data adapted from Kurt. 2011)

Regardless of the results of future studies on the effects & safety of vanadium on humans, the study results (as shown in figure 1) clearly indicate that vanadium is able to counter, maybe even reverse, the negative effects streptozotocin has on blood glucose and insulin management in rats.

Its also noteworthy that, according to the scientists, the administration of vanadium also reversed the pro-oxidative effects of streptozotocin-induced diabetes. I am yet not sure if this conclusion Kurt et al. base on a reduction of anti-oxidant activity in the tissue of the diabetic rats is valid. After all, the latter could also be a direct consequence of potential toxic effects of the trace mineral. Until further human data will be available, I would thus strongly advice against taking high dose vanadium supplements, even if you have type II diabetes.

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

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

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

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

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


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

Flavanol-Rich Lychee Fruit Extract Displays Potent Antioxidant Activity in Trained Long-Distance Runners

If I told you about each and every "new" antioxidant that produced some marvelous effects in the petri-dishes of some scientists somewhere on a random university campus, there would hardly be any space left for interesting information on this blog. In the case of the particular lychee fruit extract (FRLFE), Nishizawa et al. (Nishizawa. 2011) selected for their study, we do not only have a human study, but also direct information on how supplementation with 50mg of Oligonol (brand name of the extract) influenced inflammatory markers and performance of 20 university level marathon runners over the course of 2 months:

Some parameters, including the white blood cell count, were significantly modified by FRLFE supplementation [46.3 FRLFE vs. 57.6 control]. Compared with the placebo group, the change in the serum interleukin-6 level between pre- and mid-training were significantly lower in the FRLFE group, while the change in the transforming growth factor-β level between pre- and post-training was significantly greater in the FRLFE group.

This increase in TGF-Beta is significant, because...

...TGF-β controls cell growth and proliferation (Massagué, 1998), and may be secreted in response to strenuous physical training and cell damage during training.

TGF-beta is thus another case, where an "inflammatory marker" indicates repair and (possibly) hypertrophy rather than damage and catabolism. Consequently, it is unlikely that the consumption of a highly anti-oxidant flavanol-rich lychee fruit extract hampers muscle growth. Who knows, maybe we are going to see respective supplements in the near future - meanwhile, I suggest you get yourself some of these Chinese soapberries at your local fruit store ;-)

Licorice for Diabetes!? Licorice Extract Reverses (!) Diabetic Nephropathy in Rats

Diabetes is the big "D" in the metabolic synDrome and probably the most destructive of the various faces of the plague of the century. Now researchers from the United Arabian Emirates have found that licorice may ameliorate the destructive effects of high blood glucose levels on your kidneys.

In a rat experiment, Kataya et al. (Kataya. 2011) found that...

... oral ingestion (1 g/kg body weight) of licorice extract for 60 days after the onset of diabetes reversed the adverse effect of diabetes on rats. Licorice extract alleviated blood glucose levels, restored renal function, and attenuated body-weight loss. In addition, licorice extract modulated the adverse effect of diabetes on renal malondialdehyde, glutathione, superoxide dismutase, and catalase activity. Further, licorice extract restored the total antioxidant capacity of diabetic rat kidneys.

What I find most intriguing is that licorice ingestion at a dosage that would amount to roughly 12g for an average male human being could reverse, i.e. not only ameliorate, diabetic nephropathy. Yet, the sheer amount of extract you would have to consume raises the question if there would not be other complications / unwanted side effects of this protocol. According to Isbrucker & Burdock (Isbrucker. 2006), the "acceptable daily intake" of licorice is "0.015-0.229 mg glycyrrhizin/kg body weight/day" - depending on the concentration of the extract the scientists used, 12g may well exceed this critical limit (high cortisol, high BP, water retention could be the consequences).

Acquittal: Anti-Oxidants do not Blunt the Beneficial Effect of Endurance Training on Insulin Sensitivity!

Regular visitors of the SuppVersity will remember that there has been and still is a controversy about whether or not athletes and average gymrats benefit from antioxidants or whether this may even blunt training induced adaptation effects. Other than a 2009 study by Ristow et al. (Ristow. 2009), a more recent investigation into the effects of antioxidant supplementation (Yfanti. 2011), coming from my northern neighbors from Denmark, did not find any negative effects of antioxidants on the exercise induced rise in insulin sensitivity.

In the study 21 young, healthy men, who received 500 mg vitamin C and 400 IU vitamin E (α-tocopherol) daily, completed a 5-days-a-week supervised intense endurance-training (interval training on Tuesday & Thursday; steady-state cardio on Wednesday & Friday). Insulin response, maximal oxygen consumption (VO_2max), maximal power output (P_max) and body composition (fat mass, fat-free mass) were measured and "muscle biopsies were obtained for determination of the concentration and activity of proteins regulating glucose metabolism". The scientists summarize their results as follows:

Although plasma levels of vitamin C (P < 0.05) and α-tocopherol (P < 0.05) increased markedly in the AO group, insulin-stimulated glucose uptake increased similarly in both the AO (17.2%, P < 0.05) and the PL (18.9%, P < 0.05) group in response to training. VO_2max and P_max also increased similarly in both groups (time effect: P < 0.0001 for both) as well as protein content of GLUT4, hexokinase 2 and total Akt (time effect: P ≤ 0.05 for all).

I don't know if you consider this "good" or "bad" news, but in any case, I suspect you will want to know what happened to the participants body composition (at least I would want). Well, the scientists say, there were no significant pre-post changes and from a statistic point of view, this is unquestionably right. I find it interesting, nevertheless that the average decline in fat mass was somewhat larger in the placebo (-21%)  vs. the anti-oxidant group (-8%); the intra-group differences are however so large that, with the given count of subjects, this is hardly meaningful.

Go for Gold: Golden Kiwifruit Outperforms her Green Sister in Terms of Antioxidant Potential

Groundbreaking research ;-) at the Faculty of Pharmaceutical Sciences at the Teikyo University in Tokyo, Japan, did now reveal that Kiwis, especially the golden variate outperforms other highly acclaimed health foods in terms of their antioxidant potential.

Comparison of the anti-oxidant effects in vitro demonstrated that kiwi fruit had stronger anti-oxidant effects than orange and grapefruit, which are rich in vitamin C; gold kiwi had the strongest anti-oxidant effects. Kiwi fruit inhibited oxidation of biological substances in the human body. In particular, kiwi fruit may inhibit early lipid oxidation.

While it is common knowledge that Kiwis contain a lot of vitamin C, the scientists underline that most of its beneficial effects come from the various forms of polyphenols in the fruits.

Fig. 1: Inhibition of Lipid Oxidant by Fruit Juices (Iwasawa. 2011)

So, next time you see some of these hairy little Chinese gooseberries at your local grocery store, grab some golden ones and bump up your antioxidant defenses.



On a side note: According to Dr. Smith from the Life Extension Foundation, Kiwi is also the common food with the highest amount of PQQ ("the new CoQ10" LEF is promoting) you can possibly find - unfortunately, you would probably have to eat truckloads to get the desired effect ;-)

1.5g of Vitamin C do not Alter Neutrophil Function in Athletes: ROS & SOA Elevations Remain Unchanged

The verdict is still out there on whether antioxidant supplementation before or around exercise is a good or a bad thing for professional athletes. A recent study by Yamai et al. (Yamai. 2011) which investigated the effect of 1.5g of vitamin C /day on the neutrophil function of judoists found no evidence for either of the propositions - neutrophil counts were not statistically different between the two groups of the 22 male judoists after a 7-day intensified training camp for:

[...]although the typical changes seen following a single bout of normal exercise, namely an increase in SOA [serum opsonic activity] and ROS [reactive oxygen species], and a decrease in PA [neutrophil phagocytic activity], were recorded following the pre- and post-camp ULEs in both groups, significant difference in change rates were not seen between both groups.

These results go hand in hand with many other more recent investigations into the beneficial effects of vitamin C and combinations of antioxidants (a factor the scientists raise in their discussion of the results) on exercise performance in (elite) athletes. So, even if vitamin C won't hurt you, it probably won't help either.

Ginkgo, Ginseng, Green Tea: Only one of the G's may be worth Supplementing

In the most recent episode of their supplement review (which is usually very critical) the British Journal of Sports Medicine (BJSM Review. Part 17) has a look at studies on the ergogenic potential of ginkgo, ginseng and green tea, all of which are heavily advertised for their beneficial effects on health, long jeopardy and mental, as well as physical performance.

In the case of Ginkgo an Ginseng, the studies that have been considered in this review provide very inconclusive evidence for and against their use as ergogenics or medical plants. With regards to the underlying reasons for the discrepancies which have been reported, the reviewers argument that both, the origin, as well as the processing techniques may have influenced the efficiency of ginkgo and ginseng products. green tea, on the other hand, "shows some promise" - regular readers of this review series will know that this is already a great praise!

Although evidence is limited, green tea extract, and particularly the active component EGCG, has shown some consistency from animal to human models regarding a delay in fatigue during prolonged exercise. In humans this appears to be due to the effect of an increase in fat oxidation.

Against this background and in view of the declining prices of quality green tea products (especially if bought in bulk) green tea should obviously be the "G" of choice in your supplement regimen. Ah, and before I forget: green tea is actually something you drink, basically the counterpart to real food, which is what you probably have forgotten to eat facing the stash of capsuled supplements you're popping everyday ;-)

Resveratrol Fails to Ameliorate inflammatory response and Delayed Onset Muscle Soreness After a Marathon

Resveratrol, an antioxidant polyphenol from the skin of red grapes, has now been around for quite a while and as it was in the case of almost every other antioxidant which was hailed as a powerful panaceum (e.g. vitamin E) it slowly transpires that the real life value of resveratrol may well fall short of the expectations its potency in (mostly) in vitro studies rose among scientists and laymen alike.

For some of you it may yet still come as a surprise that the results of a double placebo-controlled randomised trial conducted at the London Marathon 2010 (Laupheimer. 2011) fall short of the expectations the colorful advertisements and cited abstracts from in vitro studies may raise in many half-informed customers:

There was no significant difference between the two groups in terms of changes occurring between pre and post-tests for WBC [white blood cell count], CRP [C reactive protein] or VAS [a measure of muscle soreness] (p=0.857, 0.629 and 0.70 respectively).

And, although the author remarks that the dose and loading protocol (600mg of resveratrol /day for 7 days before the event) may have been insufficient to produce favorable results, I would like to remind everyone that these 600mg is three times the dose one would get from the suggested usage of NOW's high quality Resveratrol 200. So, even if 1.200mg would work, this would be quite an expensive supplementation protocol.

And again: Vitamin E Supplementation has no Effect on All Cause Mortality

I suppose, only few of you will be surprised to read this: A very recent review by scientists from the University of Kentucky (Abner. 2011) confirmed the results of previous reviews of the available literature:

Based on the present meta-analysis, supplementation with vitamin E appears to have no effect on allcause mortality at doses up to  5,500 IU/d.

The scientists had compiled a selection of randomized, controlled trials published between 1988 and 2009 that investigated the treatment effect of vitamin E supplementation in adults for at least one year. What they got was a data pool comprising 246,371 subjects and 29,295 all-cause deaths with an overall risk ratio of 1.00 that was independent of whether or not the subjects received supplementary vitamin E.

On a side note: Instead of another review of the literature, I would have liked to see a study investigating the differential effects of the various forms of tocopherols and tocotrienols, of which I assume that the interaction / ratio between those is where the magic happens. So, if you happen to own a big laboratory and do not know what to do with it, I would certainly post the results of such a study ;-)

Reactive Oxygen Specimen (ROS) Trigger Muscle Hypertrophy via IGF-1 Signaling

I have touched on the "usefulness" of oxidation, only yesterday. Now, a very recent study appears to confirm the notion that a controlled amount of inflammation is necessary in order to achieve metabolic and muscular adaptations.

Figure 1: Eesult of the quantitative analysis of myotube diameter after IGF-I and NAC treatment (Handayaningsih. 2011)

Scientists from Division of Diabetes and Endocrinology and Division of Cellular and Molecular Medicine at the Kobe University Graduate School of Medicine published a paper (Handayaningsih. 2011) describing an investigation into the role of Reactive Oxygen Specimen (ROS) in the IGF1-signaling pathway. In this study N-Acetyl-Cystein (NAC), commonly used by recreational athletes as an "ergogenic" aid, blunted myocyte response to IGF1 and thus inhibited muscle hypertophy (cf. Figure 1):

While treatment with H2O2 significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. The downstream signaling pathway, Akt-mTOR-p70S6K was subsequently down-regulated. Furthermore, thephosphorylationof FoxO1by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy.

Before you now go and flush all your vitamins and antioxidants down the toilette, you should consider that this is an in-vitro study with a narrow and limited ROS stimulation and not a large scale exercise supplementation study showing that the 500-1.000 mg of NAC you take on a daily basis will completely forestall muscle growth. If anything, it should remind you that excessive "inflammation" could be the "root of all evil" (cf. Super Human Radio), but excessive antioxidant supplementation certainly ain't a solution.

N3-PUFA Beneficial Only When Combined With Antioxidants

All of you who have been following this blog, lately, will have noticed that I tend to be skeptic whether fish oil and other PUFA supplements are recommendable without certain reservations. A recent study by Filaire et al. (Filaire. 2011) seems to support the view that poly-unsaturated fatty acids increase the potential for oxidative damage and should thus be combined with appropriate amounts of antioxidants to "compensate" this effect.

Over a period of 6 weeks the researchers supplemented a group of 36 judoists with either 600 mg EPA and 400 mg DHA per day or the same amount of long chain polyunsaturated fatty [LCPUFA] acids plus 30 mg vitamin E, 60 mg vitamin C and 6 mg β-carotene and measured resting and exercise-induced lipid peroxidation in their subjects. Here are the results:

At T (1) [before supplementation], there were no significant differences among treatment groups with respect to lipid peroxidation, lag phase, and levels of α-tocopherol or retinol. The consumption of an n-3 LC PUFA supplement increased oxidative stress at rest and did not attenuate the exercise-induced oxidative stress. The addition of antioxidants did not prevent the formation of oxidation products at rest. On the contrary, it seems that the combination of antioxidants added to the n-3 LCPUFA supplement led to a decrease in, CD(max) [conjugated dienes], R (max) [maximum rate of oxidation], and POOL [lipoperoxide ] and MDA [malondialdehyde] concentrations after a judo training session.

So, in a way LCPUFA work like "exercise in a pill": At rest, they increase similar stressors as exercise does. This holds true regardless of additional anti-oxidant supplementation. When you exercise, however, a combination of LCPUFA + antioxidants appears to provide some protection from exercise induced stressors, so that overall, athletes would probably benefit from LCPUFA + antioxidants consumption.

Notice, I purposefully wrote "consumption" and not "supplementation", because let's be honest: If we have a look at the combination of nutrients a natural diet would provide, you always get your LCPUFAs with adequate amounts of antioxidants. So, keeping or switching to a healthy diet should still be your priority - if you then still see the need for additional supplementation, you may want to give a quality fish oil and some vitamins a try.

Tinospora Cordifolia as in LG Sciences' Natadrol is a Potent Antioxidant and Metal Chelator

This is only a small news-item, but unfortunately scientific background info on commercially available supplements is pretty rare - so here we go...

Scientists from India (Bhawya. 2010) investigated the antioxidant potential of various extracts of Tinospora Cordifolia (the primary ingredient in LG Sciences Test Booster Natadrol) and found that ...

Methanolic, ethanolic and water extracts showed significant antioxidant potential compared to other solvents and also possess metal chelation and reducing power activity. In the DPPH radical scavenging activity, methanolic extract  (98.13%)  showed high antioxidant potency, ethanolic  extract (90.34%) was a potent scavenger of superoxide radical. At the same time, both methanolic (97.08%) and ethanolic extracts  (95.21%)  inhibited hydroxyl radical along with other extracts. The metal chelation  in methanolic  (60.62%), ethanolic  (57.62%),   aqueous extracts  (40.89%)  and reducing of ferrous ions was significant found increasing in methanolic, ethanolic and aqueous extracts.

Although this is an in-vitro study, it may well explain the beneficial effect LG claims their product exerts on testosterone production via an antioxidant and metal-chelating pathway. Or in other words: Less oxidation and metal accumulation at the cellular level equals higher testosterone output. Interestingly, a methanolic extract would even be more potent than the "highly specialized ethanolic extract" LG uses.

What you may however be interested in, as well, is the fact (mentioned in an older blog post) that - just as many other testboosting, cortisol-lowering, etc. herbs tinospora tends to be toxic (especially in the testes) in high does in-vitro studies. This suggests that, despite all antioxidant activity, going overboard on respective supplement may not be advisable.