Fish, but not Fish Oil Supplements Reduce Breast Cancer & All-Cause Mortality Risk in Women

This is another piece of information which came up in the course of my recent research into the latest studies on fish oil supplementation: Capped fish oil, obviously, is very different from the "real deal" fish... you know that stuff that is swimming in the ocean and does not come in convenient 1 gram caps; that stuff that stinks like fish and is not molecularly distilled or filtered, ...

Researchers from the University of California (Petterson. 2010) recently found that...

Women with higher intakes of EPA and DHA from food had an approximate 25% reduced risk of additional breast cancer events [tertile 2: HR = 0.74 (95% CI = 0.58-0.94); tertile 3: HR = 0.72 (95% CI = 0.57-0.90)] compared with the lowest tertile of intake. Women with higher intakes of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality [tertile 2: HR = 0.75 (95% CI = 0.55-1.04); tertile 3: HR = 0.59 (95% CI = 0.43-0.82)]. EPA and DHA intake from fish oil supplements was not associated with breast cancer outcomes. The investigation indicates that marine fatty acids from food are associated with reduced risk of additional breast cancer events and all-cause mortality.

Of course, this again is one of those epidemiological studies, I, myself tend to criticize from time to time. Nevertheless, I find it very intriguing that, whenever we switch from natural to artificial versions of foodstuff, good things lose their value - or even become detrimental for your health.

High Dose Caffeine Will NOT Allow You to Curl More Weight

Most PreWorkout products are loaden with caffeine. The reasoning behind that is twofold: Firstly, the caffeine will spike you up and thus may allow you to work more energetically. And secondly, caffeine is believed to be a potent ergogenic in itself, allowing you to lift that extra pound you would otherwise have to take off.

As far as the ergodicity of caffeine is concerned, a recent study which was part of Jared Coburns dissertation at the California State University (Coburn. 2010) suggests that these must be more of a systemic nature. Comparing the effects of a preworkout drink with either 0, 5 or 10 mg/kg caffeine Coburn found

no significant differences for maximal strength, RTD [rate of torque development], EMG [electromyographic] amplitude and frequency, MMG [mechanomyographic] amplitude, EMD [electromechanical delay] and PMD [phonomechanical delay]

in his 14 male volunteers. So, while related studies, such as the one done by Pontifex et al. (Pontifex. 2010), where athletes had to perform several consecutive bouts of sprinting, provide evidence for the ergogenic effect of caffeine, it does not appear to benefit isometric muscle actions of the elbow flexors within a single set - in how far the results would have been different, if, for example, the subjects had had to perform dropsets is another kettle of fish.

Exercise at the Anaerobic Threshold Increases GH Release and Burns Fat in Obese Patients with Type 2 Diabetes

Scientists still argue about the most important contributing factor to the ever increasing obesity epidemic in the Western World: Is it bad dietary habits or our sedentary lifestyle - honestly, I don't care... you got to work on both if you want to stay healthy.

The results of a recent study published by scientists from the Toho University Sakura Medical Center (Yamaguchi. 2010) do yet underline the importance of exercise (and I mean exercise, as in sweating and panting, not just walking to your car!) in the "health equation", i.e. "diet + exercise = health". The scientists had their 19 obese type 2 diabetics either keep their sedentary lifestyle or performed 2× 30-min bouts of exercise (treadmill walking) everyday in the morning and evening during the 4-week study period. What is of particular importance is that the exercise intensity was determined by pretesting the exercise capacity of each participant, so that all patients exercised at their individual anaerobic threshold. The results of this regimen (cf. table 1) were quite remarkable:

Table 1: Baseline characteristics and changes in clinical and biochemical variables.BMI: body mass index, VFA: visceral fat area, SFA: subcutaneous fat area, BP: blood pressure, FPG: fasting plasma glucose, HbA_1C: hemoglobin A_1C, HOMA-IR: homeostasis model assessment of insulin resistance, TC: total cholesterol, TG: triglyceride, HDL-C: HDL-cholesterol, LDL-C: LDL-cholesterol, IGF-1: insulin-like growth factor-1, LPL mass: LPL mass in preheparin serum.

In view of recent research findings about the relation of visceral fat (VFA) and metabolic derangements, the remarkable reduction of VFA by -21.7% vs. -5.5% in the control group is of paramount importance for the subjects' health. The researchers attribute this success mainly increases in growth hormone which were elicited by the exercise intervention. In that, it is important to note that we are talking about a 100% increase in growth hormone after a 30-min bout of exercise.

Although this is just speculation on my part, I think it is questionable whether walking for more than 30 minutes, but at a lower intensity would have provided similar results. Or in other words: If the key is to trigger metabolic changes (via natural hormonal pathways) intensity (not overexerting oneself, though) is key.

Dietary Oxidized Frying Oil Impairs Pancreatic Insulin Release. Vitamin E Helps!

It certainly is no coincidence that a recent study on the detrimental effects of oxidized frying oil (OFA) was published in the British Journal of Nutrition. Afterall, it suggests that the British are at risk of dying out, if they just listened to their appetite and kept over-consuming "Fish and Chips".

After feeding rats with either soy (HF) or oxidized frying oil (HO) over a period of 8 weeks the researchers found:

[...] mice in the HO group showed glucose intolerance and hypoinsulinaemia, and their islets showed impaired glucose-stimulated insulin secretion (P,0·05; HO group v. LF and HF groups). Significantly higher oxidative stress and a lower mitochondrial membrane potential were observed in the islets in the HO group compared with the LF and HF groups. Immunoblots showed that the reduction in insulin levels in HO islets was associated with activation of the c-Jun NH2-terminal kinase and a reduction in levels of pancreatic and duodenal homeobox

Furthermore, they found that, "when dietary OFO-induced tissue vitamin E depletion was prevented by high-dose vitamin E supplementation (500 IU(1·06 mmol all-rac-a-tocopherol acetate)/kg diet; [...] the OFO-mediated reduction in islet size and impairment of glucose tolerance and insulin secretion were significantly attenuated."

So, obviously it is the interplay of oxidation and lack of antioxidants (in this case vitamin E) which collectively initiate these metabolic changes, which consequently are at the bottom of what is often called "the metabolic syndrome". Bottom line: Beware of oxidized fats and support your antioxidant capacity by healthy food choices and supplements.

Brewing the Perfect Green Tea: Best Brewing Time and Temperature for Optimal Potency

Here is something for all of you who have always asked themselves how to prepare their tea to "get the most out of it". Well, I know normal people would go by taste, but are we normal? No! We want maximal antioxidant-content and a decent amount of caffeine to jack us up and this is where the results from a recent study (Ziaedini. 2010) come into play.

The scientists from the Iranian Institute of Research and Development in Chemical Industries investigated the effect of different brewing times and temperatures on the amount of antioxidants and caffeine you'll get in your tea. Here are the results (cf. table 1):

Table 1: Diffusion coefficients of catechins and caffeine obtained for conventional extraction of green tea leaves.

Obviously it takes a decent temperature of ~70°C to achieve maximal diffusion of the constituents in the short and in the long term. In spite of that, a close look at one of the graphs (cf. figure 1)

Figure 1: EGCG content as a function of time for different water temperatures in °C

shows that even with decent temperatures (>70°C) it takes some time for the antioxidant content (in this case the infamous ECGC content) to achieve significant levels - and lets be honest, do you like, or even, can you really drink a tea that has been brewed for 10 or even 20 minutes? If you can, you're the man (or woman) - if not you probably better buy some capped extract ;-)

Vitamin E Exerts Positive Effects on Various Health Markers in Recreational Trainees

A study from scientists from the Azad University in Iran (Naghizade. 2010) shows that supplementation with 500mg vitamin E (~750IU) over a period of 8 weeks improved malondialdehyde (MAD, p<0.02) , creatine phosphate (CP, p<0.04), total antioxidant capacity (TAC, p<0.03), LDL (p<0.03) and Vo2max (p<0.03) over placebo values in moderately aerobically trained individuals:

In summery performing moderate aerobic exercise (HRmax 60-65%) with consumption Vitamin E may decrease membrane damage and lipid peroxidation, and cardiovascular risk factors.

These results stand in line with several other papers that have been released within the last months. Many of these found positive effects of vitamin E on moderately (mostly aerobically) training trainees, like the ones in this studies. If, however, the workloads increase way beyond the 3x45min (per week) the male subjects of this study spent in the gym, the results become equivocal and some studies even suggest that additional anti-oxidant supplementation may suppress positive adaption processes.

1.86 g EPA + 1.5g DHA Augment the Hyperaminoacidemia-Hyperinsulinemia–induced Increase in the Rate of Muscle Protein Synthesis

MPS, the acronym for "muscle protein synthesis", certainly is an eye-catchers for everyone interested in building sleeve bursting arms. Obviously, the at which (dietary) proteins are incorporated into muscle tissue is an important factor in how much and how fast your muscles will grow.

Scientists from the Washington University, School of Medicine (Smith. 2010) have now conducted a randomized placebo controlled trial on the effect of omega-3 (4g/day Lavazza(TM) = 1.86 g EPA + 1.5g DHA) supplementation on muscle protein synthesis in older adults. And despite the fact that omega-3s on their own had no effect on  MPS, the consumption of supplemental omega-3s significantly augmented the MPS-response to Hyperaminoacidemia and Hyperinsulinemia.

Figure 1: Mean (6SEM) concentrations (arbitrary units) of mTORSer2448 and p70s6kThr389 during basal, postabsorptive conditions and during the hyperaminoacidemic-hyperinsulinemic clamp before and after 8 wk of supplementation with either corn oil (n = 7) or omega-3 fatty acids (n = 8). (Smith. 2010)

The results of this study may also shed some light on a 2003 study by Fearon, et.al. (Fearon. 2009), who found that adding fish oil to a protein supplement increased lean mass gains in patients with cancer cachexia.

While, in view of these results, adding some fish oil caps to your post-workout protein + carb drink  seems to be a beneficial, yes, almost obligatory idea, I personally feel that the verdict on the effects of fish oil (especially in particularly high doses) in healthy, or even athletic parts of the population is still out there. Anyway, I will keep you posted.

On a side note: Notice that this study uses a much more "favorable" (my point of view), low EPA:DHA ratio compared to the study I reported on a few days ago, which found no influence of fish oil supplementation on weight and fat loss in obese individuals.

Loss of Trace Elements not a Concern in Well-Hydrated Athletes

If you are a hard-training athlete you need more than "trace amounts" of trace elements, don't you? No, actually not. You may be somewhat disappointed now, but the expensive trace element supplement you just ordered might turn out to be a complete waste of money - at least, this is what the results of a recently published study by Carlos González-Haro et al. (González-Haro. 2010) suggest.

Figure 1: Changes in plasma trace element levels (Zn, Mn, Se and Co) for the different relative exercise intensities studied and the 7 min recovery period.

As figure 1 (above) shows, lactate concentrations constantly increased in the course of the 7 minutes after a cycloergometer test, where, after a warm-up of 10 min at 2.0 W kg⁻¹, workload had been increased by 0.5 W kg⁻¹ every 10 min until exhaustion. The trace mineral concentration, on the other hand, remained stable over the whole study period (exercise + recovery). This observation led the scientists to conclude ...

[...] in euhydrated well-trained endurance athletes no effects on plasma levels of Zn, Se, Mn and Co were observed either during medium duration exercise, at a full range of intensities (41–92%VO_2peak), or during a seven-minute recovery period. These subjects showed no deficiency in Zn or Se and probably were not deficient in Mn or Co either (though cutoff levels are not known).

So, if you have not opened your "high quality trace element" supplement yet, make use of your 14-days conversion right ;-)

High Dose Fish Oil NOT Effective in Promoting Weight Loss on a Professionally Monitored Weight Loss Regimen

Those of you who visit the SuppVersity pretty regularly will have noticed that I am reluctant to buy into all the hype about omega-3 fatty acids and the myriad of purported health benefits of high dose fish oil supplementation. According to the results of a very recent study published in the Journal of the American Society for Nutrition (DeFina. 2010) my doubts appear to be legitimate.

Table 1: Mean change in adiposity measures in the omega-3 supplement and placebo groups

The scientist investigated the effect of 3.0 g eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) at a 5:1 ratio (EPA:DHA) [standard fish oil caps usually have a ratio of 3:2 and you would have to take about 10 caps to get to that amount of EPA + DHA combined] on the weight loss of 128 obese and overweight individuals. Although fish oil treated individuals tended to lose a few more grams of body fat (cf. Table 1), this effect was no statistically significant, so that the researchers consequentially conclude:

No significant weight-reduction benefit was seen with the addition of omega-3 fatty acid supplementation in this weightloss study with lifestyle intervention. Overall, the participants in both arms lost .5% of their body weight, which was considered clinically significant in prior trials of diet, exercise, or medication.

A final word, before you throw away your fish oil supplies: There is one thing, which to my mind could have changed the outcome of the study considerably and that would be the use of a standard or even better a high DHA fish oil preparation. I've been following this discussion for quite some time now and whenever there were negative effects associated with fish oil supplementation, i.e. blocking the immune system, downregulation of the HPTA, etc. these were related to the highly anti-inflammatory EPA content of the oils. So, if you insist on taking your fish oil. Look for a brand that has a low EPA:DHA ratio and do not forget that for hard training athletes on low carb diets the "bad" saturated fats are "essential", as well.

Anti-obesity & Anti-diabetic effect of Trehalose in Rats on a High Fat Diet

I know, I know, rats on a high fat diet are a topic on their own: "Are they a valid model for metabolic disease in man?" etc. - Be that as it may, the findings of scientists from the Biomedical Institute, Research Center, Hayashibara Biochemical Laboratories in Okayama (Arai. 2010) suggest that, of all things, a sugar(!) molecule may help prevent the negative effects of a high fat diet on fat mass and insulin resistance, which are commonly observed in the rat-model of the typical western-world high-fat diet.

Other than rats on a glucose [Glc], a maltose [Mal], a high-fructose corn syrup, or a fructose [Fru] rich high-fat-diet [HFD], the rats which were fed the natural alpha-linked disaccharide trehalose did not exhibit the typical signs and symptoms subsumed under the keyword "metabolic syndrome":

After 7 weeks of HFD and saccharide intake, fasting serum insulin levels in the Tre/HFD group were significantly lower than in the Mal/HFD and Glc/HFD groups (P < .05). Furthermore, the Tre/HFD group showed a significantly suppressed elevation of homeostasis model assessment–insulin resistance compared with the Mal/HFD group (P < .05) and showed a trend toward lower homeostasis model assessment–insulin resistance than the Glc/HFD group. After 8 weeks of feeding, mesenteric adipocyte size in the Tre/HFD group showed significantly less [fat] hypertrophy than the Glc/HFD, Mal/HFD, high-fructose corn syrup/HFD, or Fru/HFD group. Analysis of gene expression in mesenteric adipocytes showed that no statistically significant difference in the expression of monocyte chemoattractant protein–1 (MCP-1) messenger RNA (mRNA) was observed between the Tre/HFD group and the distilled water/standard diet group, whereas a significant increase in the MCP-1 mRNA expression was observed in the Glc/HFD, Mal/HFD, Fru/HFD, and distilled water/HFD groups.

While these results certainly appear promising, I better add that the laboratory that did the study is financed by the Hayashibara company, the same company which recently developed a new technique to produce or rather to extract trehalose commercially. So treat these results with a grain of skepticism, if you understand what I mean ;-)

Vitamin D Supplementation(!) Increases Testosterone in Men

Thanks to Dashforce from the MindAndMuscle-Forum we finally have evidence for the direct effect of vitamin D3 supplementation on testosterone in men. Dashforce reports on a study by scientists from Austria and Germany (Pilz. 2010) who provided 54 men, whose serum levels were previously at the lower range ~30ng/ml (the referential  minimum varies depending on which source you cite from 30-50ng/ml),with either 83 μg (3 332 IU) vitamin D daily or placebo for 1 year.

Table 1: Characteristics of the study groups at baseline and at the end of the study

As you can see in table 1,vitamin D supplementation lead to a significant increase in total testosterone from 10.7 nmol/l to 13.4 nmol/l. What's even more important, this increase (+25%) was not compensated by and an increase of SHGB, so that the amount of free testosterone rose from 0.222 n/mol to 0.267 nmol/l, i.e. by +20% (vs. +5% in the placebo group).

What is particularly interesting about this study is the fact that supplementation actually raised the level of testosterone. This is different from most previous studies, which observed a correlation between higher vitamin D levels and higher testosterone levels. If for example some probands would simply have been more healthy and thus exhibit higher levels of both, we would have had the same correlation. In the case of the Pilz study there is a clear causative effect between restauration of adequate vitamin D levels and increases in total and free testosterone.

I hope we see more trials with a similar design - also to investigate if there is a dose response relationship and whether even higher vitamin D levels would further increase testosterone. Until then, keep an eye on your vitamin D level and take a supplement to get to the upper ranges of the "normal" range ~80ng/ml.

A Scientific Approach to Bodybuilding: Measuring the Quality of Execution to Predict Hypertrophy

This post is a little different from what you normally find on this blog. This time I'd rather invite you to read a study on your own, than to summarize the main findings. The study (Ivan. 2010) was done by a group of Romanian scientists and published recently in the Body Building Science Journal. What is particular interesting about the authors' approach is that they try to capture "effective" training methods in physical/mathematical equations. The main ideas behind their quantitative analysis is the following:

Indicators for measuring the quality characteristics of exercises 

The level of quality is analyzed using the following indicators:

• the number of repetitions for each exercise;
• the number of sets included in each training program;
• the way in which the athlete executes the exercises taking into consideration the correct position in each key stage of the execution;
• the weights used for each exercise.

Based on these indicators, grades are given for each exercise like very good, good, satisfactory and unsatisfactory. Based on these grades, a trainer or referee evaluates and differentiates the athletes. Depending on the deviations from the correct execution, the corresponding grade is given.

Their results confirm the concept that form is key to muscular development. The way the scientists present their data unfortunately obscures their findings.

Figure 1: Correlation between biceps size and execution indicator.

The graph in figure 1, for example, would have appeared much more impressive, if the authors had decided to present just the relevant part, i.e. y-axes values from 0.6-1.0. In that case the linear regression would have been much steeper and nobody would have hat to have a second look at the data to accept the conclusion that...

The quality of an exercise influences the obtained results. The higher the execution quality the higher the results obtained by the athlete. Based on the execution quality, an aggregated indicator was defined, that is able to estimate the growth of arm size of an athlete. This indicator is very useful for athletes in order to estimate the arm size over 1 to 6 months of training.

There are other interesting details in the study as well, so go ahead and have a look.

BAT: Brown Adipose Tissue in Humans - An Update

In the latest edition of Current Opinion in Lipidology we find a mini-summary (COL. 2010) on current findings on the existence and metabolic purpose of brown adipose tissue (BAT) in human beings. These days the previously accepted position that adults have little to no BAT is put into question by the results of PET, where brown fat becomes especially visible upon cold exposure, when its metabolic activity is increased as a result of thermogenesis.

The author points out that adipocytes (fat cells) and myocytes (muscle cells) do not only share the same origin, the metabolically active BAT exhibits other similarities to muscle cells, as well - it is a metabollically active tissue and of particular importance in the context of insulin sensitivity and glucose disposal:

BAT glucose uptake rate is 10-15-fold higher in cold than in normal room temperature. Other factors that may increase the activity of sympathetic nervous system and uncoupling protein 1 are several including the complex network of hormonal and neuronal signals. Preliminary results suggest that BAT resembles skeletal muscle not only by origin but also by the effect of insulin on the tissue.

Doubtlessly, more research has to be done on the issue of BAT vs. WAT (white adipose tissue) and their relation to obesity, diabetes and the metabolic syndrome. In spite of that, even what we know today suggests that a better understanding of this hitherto overlooked remainder from the days when our ancestors ran around naked could help to find a solution for some of the "fat" health problems of the western societies.

Hydroxycitrate (HCA) for Weight Loss - Revisited

The hype around hydroxycitrate (HCA) as a remedy for obesity and general weight problems has long abated. Nevertheless, in a recent review (Onakpoya. 2010), scientists from the Peninsula Medical School at the University of Exeter reexamine past studies and come to the (surprising?) conclusion that

The evidence from RCTs suggests that Garcinia extracts/HCA generate weight loss on the short term. However, the magnitude of this effect is small, is no longer statistically significant when only rigorous RCTs are considered, and its clinical relevance seems questionable.

So, although the data from the study shows that there is a minor improvement in weight loss in the supplemented groups (cf. fig. 1, below)

Figure 1: Forest plot of comparison showing the effect of hydroxycitrate on body weight. The vertical line represents no difference in weight loss between HCA and placebo. (Onakpoya. 2010)

buying a pure HCA supplement for weight loss purposes is probably not worth it. There are certainly better fat-burners out there.

Leptin & AMPK Activation in Muscle - Did Scientists Investigate the Wrong Species?

Actually, this is something I have been reminding people of for years: Human beigns are no mice and although some people may be rats, genetically they are still very different. Usually I put this argument forward if anyone presents me with a study done on rodents that "shows" how bad dietary protein, especially from meat, is for you - thin of it: when was the last time you saw a mouse eating a cow? This time the issue is a little more sophisticated, though...

Australian scientists (Laker. 2010) have recently investigated the effect of leptin on AMP-activated protein kinase (AMPK) in muscle of sheep and (I do not know if to their, but maybe to some of the proclaimed experts surprise) they found that...

[...] leptin infusion reduced (P<0.05) food intake and body weight and it also increased plasma adrenaline concentration at 6 h and 7 days, suggesting increased sympathetic nerve activity. Despite this, and in contrast to rodent studies, central leptin infusion did not increase skeletal muscle AMPKα Thr172phosphorylation or ACCβ Ser221 phosphorylation.

With sheep being genetically closer to human beings than mice, this is an interesting finding and could possible lead into new insights into why leptin, once proclaimed as possible panacea for the obesity epidemic, does work on rodents, but has little positive effect on obese human beings. Hitherto, the most accepted theory is "leptin resistance", which, similar to insulin resistance, is supposed to prevent leptin from doing its magic. This study, however, suggests that there might be genetic issues involved, as well. As always, I will keep you posted...

Both, Protein and Carbohydrate After Workout Ineffective in Ameliorating CK-Response and Muscle Soreness After Exercise

While people keep debating, whether you need or you do not need carbs post workout, a very recent US-study (Dahlstrom Burnley. 2010) shows that neither protein nor carbs effectively protect against CK-elevation and muscle soreness following an excentric strength training session.

Figure 1: Serum creatine phosphokinase (CPK) activity according to treatment.
*There was no significant difference in CPK activity (ANOVA) among treatment groups.

There are however two major drawbacks to this study. Firstly, the scientists do not quantify the amount of protein or carbohydrate the subjects consumed after their strength training session. And secondly, both CK elevations, as well as muscle soreness are part of the adaptation process, we actually train for. So, if protein & carbs do not reduce these overs signs of an ongoing adaptive response, this does not have to be a bad thing.

After all, this is thus another one of those studies especially protein-phobic Drs will cite in order to convince you that your protein drink, of which they will tell you that it will kill you, does not even help with muscle gains ;-)

Potratz on SHR: Grape Fruit Oil for Enhanced Oral Steroid Resorption

Just for those of you who are not yet addicted to the Super Human Channel, i.e. Carl Lenore's radio program on exercise, nutrition and longevity: Wednesday, 15 December 2010, Carl had Eric Potratz from Primordial Performance on the show and talked to him about what could be the future of oral drug/steroid delivery. Although the show certainly smacks of a product pimpjob, the general information Potratz provides is scientifically correct.

Audio 1: Super Human Radio - 631 - Oral Hormone Delivery And Bioavailability

Potratz main argument that grape fruit blocks the intestinal esterase, i.e. the removing of the ester attached to a steroid to render it absorbable via the lymphatic system, has been confirmed in several studies. More recently, Li et. al. (Li. 2009) reported:

[..]oral coadministration of GFJ [Grape Fruit Juice] or an esterase inhibitor, bis-(p-nitrophenylphosphate), with the prodrugs led to respective increases in plasma area under the curve by 70% or 57% for enalaprilat and 279% or 141% for lovastatin acid. In addition, portal vein-cannulated rats pretreated with GFJ at –15 and –2 h before lovastatin administration (10 mg/kg p.o.) as a solution, 1) in water and 2) in GFJ, showed, respectively, a 49% increase (CYP3A-inhibited) and a 116% increase (both CYP3A and gut esterase-inhibited) in the portal plasma exposure to the active acid, compared with a non-GFJ pretreatment group. Overall, along with the CYP3A inactivation by GFJ, the decreased esterase activity also played a significant role in increasing the metabolic stability and permeability of esters leading to enhancement of exposure to the active drugs in rats.

Yet, obviously, the claims Potratz makes on a 15x-20x enhanced bioavailability of the "new" esterified designer-prohormones of the Andro Series still have to be confirmed by independent testing. Also, his claim that the specific oil (from the rind of the grape fruit) Primordial will be using is much more potent than the juice itself, seems logical, but has - to my knowledge - not been scientifically investigated, yet. What certainly is false, however, is Carl's ad-hoc calculation of a compound exhibiting a oral bioavailability of 2% suddenly having one of 60%-70% - probably his personal excitement that made him miscalculate ;-)

Melatonin for Patients With Metabolic Syndrome!?

When was the last time your mother asked you, whether you would get enough sleep? Can't remember? Well, a recent study by scientists (Kozirog. 2010) from the Department of Internal Diseases and Clinical Pharmacology at the Medical University of Lodz suggests you better listen to your mothers words and get a decent amount of sleep, just to make sure you reap the benefits of melatonin.

In the study 30 patients with metabolic syndrome (MS) were treated with 5mg/day of melatonin 2hr before bedtime for 2 month. The results were quite remarkable:

Melatonin administered for 2 months significantly improved antioxidative defense (increase in CAT activity, decrease in TBARS level) and lipid profile (decrease in LDL-C), and lowered blood pressure.

It is not news that lack of sleep contributes to metabolic disorders. What is interesting, however, is that direct supplementation with melatonin, which is secreted at dawn and in the course of the night reverses existing symptoms of the metabolic syndrome. In view of the complex endocrine interactions and the various hormonal responses which depend on sufficient and regular sleep, my suggestion is however not (only) to supplement tons of melatonin, but just to get a good nights sleep everyday, or, in other words, to practice "sleep hygiene", instead.

Positive/Negative Effects of Normal/High DHT on Metabolic Pathways

Regular visitors of the SuppVersity will certainly remember some of my previous posts about the false demonization of DHT. A new study coming from the Institute of Endocrinology in Prague (Duskova. 2010) supports the view that "optimal" and not low DHT levels are what men should be striving for.

Theorizing that DHT as a non-aromatizable androgen could be responsible for a male type fat distribution, the scientists reviewed the results of both animal and human studies and found that "physiological levels of DHT [do not only] inhibit growth of mature adipocytes", but also have positive levels on body composition in patients on hormone replacement therapy (HRT). On the other hand, there is also evidence that high (super-physiological) DHT levels are associated with obesity:

In obese people, DHT metabolism in adipose tissue is altered. Local abundance of non-aromatizable androgen has a negative effect on adipose tissue and it could be involved in pathogenesis of metabolic and cardiovascular diseases.

So, in view of getting/staying lean and healthy, you want your DHT levels within normal ranges and you certainly don't want to block it by taking Saw Palmetto or (God forbid) Finasteride or other drugs out of fear of developing prostate cancer, even if you do not even know if your DHT levels are pathologically elevated.

Date Palm (Phoenix dactylifera) as a Natural Test Booster and Ergogenic

A very recent study (Saddiq. 2010) published in the Journal of the International Society for Horticultural Science found that the seeds of Phoenix dactylifera can raise testosterone, norepenephrine (NE), dopamine (DA) and GABA levels and may counteract the negative effect of prednisolone administration in rats.

[...] the daily oral administration of pits of date palm caused the maximal increase in NE, DA and GABA content that was found in the brain stem after 2 weeks. The daily oral administration of methylprednisolone caused a decrease in NE, DA and GABA content found in the brain stem after 2 weeks. Moreover, the daily oral administration of pits of date palm and methylprednisolone caused an increase in NE content found in the brain stem after 2 weeks. The daily oral administration of pits of date palm and methylprednisolone caused a significant increase in testosterone level in serum blood of male albino rats.

While all this sounds promising, further studies would have to clarify whether it needs the cortisol-like effects of prednisone for the testosterone-boosting effect of the date seeds to take place or whether taking adequate amounts of pits of date palm would provoke similar (or even superior) increases in testosterone in rats and, most importantly, in men. Be that as it may, even the increase in neurotransmitters (NE, DA, GABA) certainly could provide real-world benefits for athletes, as well as people suffering from fatigue.

B-Vitamins & Diabetes: Protective or Causative?

In a very interesting study, scientists from China and Japan (Zhou. 2010) found that "long-term exposure to high level of the B vitamins may be involved in the increased prevalence of obesity and diabetes in the US in the past 50 years". At first this appears to be counterintuitive, since we have been told over and over that B-Vitamins are not only good for our health, but that we could not even "overdose" them. While the latter has been questioned for years and certainly is not the case for e.g. B6 and niacin, even the former seems questionable, if you read the results from the above mentioned study:

The prevalences of diabetes and adult obesity were highly correlated with per capita consumption of niacin, thiamin and riboflavin with a 26- and 10-year lag, respectively (R2 = 0.952, 0.917 and 0.83 for diabetes, respectively, and R2  = 0.964, 0.975 and 0.935 for obesity, respectively). [...] The relationships between the diabetes or obesity prevalence and per capita niacin consumption were´similar both in different age groups and in male and female populations. The prevalence of adult obesity and diabetes was highly correlated with the grain contribution to niacin (R2 = 0.925 and  0.901, respectively), with a 10- and 26-year lag, respectively.

These results (especially those referring to the detrimental effect of niacin) confirm test-tube studies conducted by a group of scientists from South Korea earlier this year (Choi. 2010), who found that

NA [nicotinic acid] alters gene expression in insulin-sensitive tissues by various mechanisms. Some of the NA-induced changes in gene expression are discussed as potential mechanisms underlying wanted and unwanted effects of NA treatment.

Just anecdotal: My personal perspective on B-vitamins has changed since my overall energy and well being, as well as my physique have largely improved after stopping to take those B-vitamin (over-)loaden mulit-vitamin preparations like Now ADAM, CL Orange Triad, Animal Pak, ON Opti-Men etc. But remember: it is mere speculation that this could in fact be related to their high B-vitamin contents - could be any other constituent, as well.

New Study Says: Boron Does Indeed Raise Free Testosterone

There have been rumors on the Internet for quite some time - "Did you hear? Boron increases testosterone!" Hitherto, however, these claims have not been substantiated by reliable scientific research. A recent study done by a group of scientists from Iran (Naghii. 2010) yet seems to prove that this is more than the steroid-loaden phantasy of an average gymrat.

In a placebo controlled study, the scientists found that supplementation with 10mg Boron/day did not only lower SHGB and thus raise testosterone, it did also lower three inflammatory biomarkers (Interleukin-6 (IL-6), high sensitive CRP (hsCRP) and tumor necrosis factor-alpha (TNF-α)):

Table1: Hormones and inflammatory biomarkers concentration (mean ± SD) plus hormone ratios following consumption of placebo (day 0) and weekly boron supplementation (day 7)

As you can see in table 1, the testosterone to estrogen ratio more than doubled (0.31 to 0.67). This alone makes me believe that it won't take too long for supp companies to notice this little trace mineral and to include it in more and more of their products. Hitherto it is already found in some formulations, like multi-vitamins, meal replacements and other stuff that is enriched with minerals the dosages, however, are minuscule and far from the 10mg used in the present study.

The scientists also investigated the time-course of the effect of boron supplementation on day 1 of the study and interestingly it took only 6 hours for free testosterone to rise from 8.55pg/ml to 11.25pg/ml. To me, this suggests that there is more to boron supplementation than just repleting exhausted blood and/or tissue levels.

Update: I have been digging a little into the possible mechanism of action behind the increase in testosterone and my personal take it that boron is a (weak) anti-estrogen. By cutting estrogen by 50% (cf. table 1) your body will automatically reduce SHGB, which is up-regulated by estrogen. This frees testosterone and may in fact provide (minor) benefits in muscle gain, libido & fat loss. I suspect that in the end this could be related to a reduction in manganese and an increase in magnesium & calcium retention (cf. Acu-Cell information about boron) that follows the administration of large amounts of boron. These is highly speculative and may only be part of the picture, though.
Also, in view of conflicting evidence from previous studies (e.g. Nagghi. 2006), which found that supplemental boron increased (not decreased) estrogen in men, further investigations are warranted.

Chromium Ain't Dead Yet: Positive Effects of Chromium Glycinate on Glucose Metabolism and Memory Acquisition in Rats Fed High-Fat Diet

"Chromium"? Sounds familiar, eh? Not too long ago, everybody was all over supplementing with chromium picolloniate to improve insulin sensitivity, to lose fat and to gain muscle. Most human studies, however, failed to reproduce the encouraging results from rodent studies. From todays perspective fat loss and muscle gain, if they occurred would probably have to be considered an indirect effect due to improvements in insulin management, the latter, on the other hand appear to be very real and may even benefit your cognitive performance.

When an international team of scientists supplemented male Wistar rats (n = 60; weighing 200–220 g) on a high-fat (40%, high-fat diet (HFD)) diet with either chromium-glycinate (CrGly) or chromium-acetate (CrAc) at doses of 0, 40, or 80 μg/kg body weight (BW) for 12 weeks, chromium supplementation ameliorated the detrimental effects of HFD on GLUTs, and Memory (32% reduction in expressions of glucose transporters 1 and 3 (GLUTs) in brain tissue and a 27% reduction in mean percentage time spent in the target quadrant and a 38% increase in spatial memory acquisition phase (SMAP)):

Compared with supplemental Cr as CrAc, CrGly was more effective to ameliorate response variables (i.e., restoration of tissue Cr concentration, enhancement of cerebral GLUTs expressions, and reduction of the glucose/insulin ratio and SMAP) in a dose–response manner, especially in rats fed HFD. Supplemental Cr as CrGly may have therapeutic potential to enhance insulin action and alleviate memory acquisition in a dose-dependent manner, through restoring tissue Cr reserve and enhancing cerebral GLUTs expressions.

So, after all chromium certainly ain't no magic bullet, it is likely, however, that patients who suffer from obesity and diabetes, as well as athletes who have been found to be at risk of chromium deficiency, may in fact benefit from your occasional dose of supplemental chromium.

Eat Rice, Stay Healthy!?

A recently published study (Fulgoni. 2010) analyzing data from 25 374 eligible participants identified as rice consumers study on the correlation of rice-eating to several markers of metabolic health showed that people who ate at least one serving of rice (white or brown) a day tend to have

better health and diet parameters including less total fat, saturated fat, and added sugars; higher amounts of more than 12 essential vitamins and minerals, including iron, folate, and other B vitamins; more fruit and legumes; nearly 4 tsp (16 g) less added sugar; and 7 g less solid fats. For the 19- to 50-year-old subgroup, main results (P < .05) also showed rice consumption associated with reduced likelihood of being overweight or obese, 34% reduced risk of high blood pressure, 27% reduced likelihood of having an increased waist circumference, and 21% reduced risk of metabolic syndrome.

This, however, should not encourage you to just add one serving of rice to your bad diet habits, because the most important information coming from the study is the first one: Rice eaters tend to have better diet parameters. In other words their general dietary regimen is more healthy, no wonder they have a reduced likelihood of obesity and health issues. Overall, rice is still a very dense source of energy and overeating on it would not be advisable, both from a caloric, as well as (this is more important) from a nutritious point of view - with its high amount of carbohydrate one serving of rice may well amount to all the carbs you may eat, if you follow a heart healthy low carbohydrate diet. Bottom line: Moderation is the key!

An In-Depth Look at How You Get Fat: You Acquire More Rather than Bigger Fat Cells

Scientists from the National Institute of Health in Bethesda, Maryland (Jo. 2010) have investigated the exact cellular pathways of weight or rather fat gain. They report:

We found a qualitatively universal adipose tissue remodeling process in all four fat depots: 1), There is continuous recruitment of new cells under weight gain; 2), the growth and shrinkage of larger cells (diameter >50 μm) is proportional to cell surface area; and 3), cell loss occurs under prolonged weight gain, with larger cells more susceptible.

It needs some interpretation of the results to understand their significance in view of staying lean in the first place. Normally, you would mean it does not depend if one fat cell holds a certain amount of fat or if this fat is held by two different cells. Unfortunately, it is a) much easier to "empty" one big fat cell which is about to burst anyway than two smaller cells and b) even if you emptied them completely that would leave you with more fat in the case of two cells than in the case of just one. In the end, by continuously multiplying the amount of fat cells you carry, you end up in a state, when even with all of them being empty you look either still obese or carry leaps of "empty fat" which has to be removed surgically. Consider that before you go onto your next 6 week "bulk" Mr BodyBuilder ;-)

Viscous Circle: Low Testosterone > Increased Visceral Fat > Insulin Resistance > Even Lower Testosterone

E.J. Hamilton and colleges (Hamilton. 2010) investigated the effect of androgen deprivation therapy (ADT) in prostate cancer patients on subcutaneous and visceral fat. There results are far from being surprising:

Twelve months ADT increased visceral abdominal fat area by 22% (from 160.8 ± 61.7 to 195.9 ± 69.7 cm²; p<0.01) and subcutaneous abdominal fat area by 13% (from 240.7 ± 107.5 to 271.3 ± 92.8 cm²; p<0.01). Fat mass increased by 14% (+3.4 kg; p<0.001) and lean tissue mass decreased by 3.6% (-1.9 kg; p<0.001). Insulin resistance (HOMA-IR) increased by 12% (2.50 ± 1.12 to 2.79 ± 1.31, p<0.05).

All that by itself is bad enough, but in the end, by the medical suppression of androgens doctors put their poor patients in a viscous circle, from which it will be very difficult to escape, as obesity and insulin resistance will further reduce testosterone production and overall metabolic health regardless of whether they are secondary to low testosterone, come from bad eating habits or whatever.

Opposing Effects of Resveratrol Depend on Dosage

While the hype about resveratrol appears to be over, it is still one of the cornerstones of many people seeking to improve health or promote longevity. If you belong to this group of people, you might find it interesting that without proper dosing, resveratrol may in fact do the exact opposite of what you were paying for.

A recent review published in Human and Experimental Toxicology (Calabrese. 2010) summarizes the literature as follows:

The current assessment indicates that low concentrations of resveratrol can be potentially beneficial or harmful, depending on the endpoint of interest. The data suggest that low doses of resveratrol would have the capacity to increase the risk of tumor development of a number of organs based on its capacity to enhance cell proliferation in multiple human tumor cell lines. In contrast, a strong case can be made that low doses of resveratrol can be significantly cardio-protective. It is likely that these general conditions could occur simultaneously within individuals. While the data are insufficient to answer this question, this type of conflict is not uncommon and we are likely to encounter it more often as investigators become more knowledgeable of the general nature of the hormetic dose response and its capacity to enhance potentially beneficial or harmful effects depending on the biological system, tissue and chemical agent.

Unfortunately, actual human data is sparse and it is still questionable in how far dosing schemes from in-vitro and animal studies are applicable to oral resveratrol supplementation in man. I will have an eye on future studies into that direction and let you know as soon as there is more reliable information out there, so stay tuned ;-)

Absurd: Will Supplemental Zinc Gluconate Deplete Your Zinc Levels?

Normally, I restrict myself to very recent studies, but the results of this 2007 (Tompkins. 2007) study on the bioavailability of zinc-enriched yeast and zinc gluconate in healthy volunteers that recently resurfaced on the Mind&Muscle boards, is too counter-intuitive and, if not scientifically flawed, important not to make it into the news.

In the study, which used a randomized, two-way crossover design, the volunteers were randomly assigned in groups of three to consume a single dose of either 20 mg of total Zn in the form of Zn gluconate or Zn yeast with 150 ml of water, after that urine, blood, and fecal samples were collected and analyzed over a 48-h period. The results were surprising, while "Zinc gluconate gave higher Zn concentrations in the blood in the first 6 h" it did not only show greater loss in the feces, but ...

the net Zn balance after 48 h for Zn yeast was 9.46 but for Zn gluconate it was -2.00, indicating that Zn gluconate supplementation contributed to a net loss of Zn.

As far as the reasons for this observations are concerned, the scientists speculate:

Presumably, this “extra” Zn lost was released from the body’s store of Zn metallothionein; however, we do not have any evidence of the source of the Zn material. This may suggest that the Zn salts stimulated a Zn detoxification pathway.

If this were true and the results are not biased by the background of the Institut Rosell, which is obviously financed by Lallemand Inc. who produce (pro-)biotic products (i.e. yeast based products), you might want to reconsider your own supplementation practices. The high doses of Zn Salts commonly used by bodybuilders and fitness enthusiasts (many suggest >50mg Zinc per day) may in fact lead your body to believe he becomes intoxicated with zinc. It is then a very natural reaction to excrete zinc and as the data from this study shows, this "excess" zinc (i.e. more zinc than you supplied) must - at least in parts - stem from zinc stores somewhere in your body.

Vitamin D & Insulin: A Question of Race?

Could it be that vitamin D intake is more important for people with an African American (AA) background than for their European American (EA) neighbors? This is exactly, what a study that was recently published in Nutrition&Metabolism (Alvarez. 2010) seems to suggest.

In 115 African American (AA) and 137 European American (EA) healthy, premenopausal women the scientists  determined with 4-day food records and assessed the individual insulin sensitivity indexes (SI), as well as the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) values. The results are quite unequivocal:

Vitamin D intake was positively associated with SI (standardized β = 0.18, P = 0.05) and inversely associated with HOMA-IR (standardized β = -0.26, P = 0.007) in AA, and the relationships were independent of age, total body fat, energy intake, and % kcal from fat. Vitamin D intake was not significantly associated with indices of insulin sensitivity/resistance in EA (standardized β = 0.03, P = 0.74 and standardized β = 0.02, P = 0.85 for SI
and HOMA-IR, respectively). Similar to vitamin D, dietary calcium was associated with SI
and HOMA-IR among AA but not EA.

While the scientists refrain from premature speculation about the underlying reasons of the observed discrepancy, they highlight the importance of both, adequate vitamin D, as well as dietary calcium consumption for premenopausal women of African American descent. What I consider noteworthy is the fact that the mean vitamin D intake of both groups was way beyond even the currently suggested 400IU (most experts already suggest 1.000-2.000 IU per day). With a mean vitamin D intake of 111.5IU and 133.7IU per day. All subjects carry the risk of being "vitamin D deficient" and this is where increased intake may produce significant positive effects on various health marker (cf. More on Vitamin D).

Omega-3 Fatty Acids PRO(!)-Inflammatory in Athletes

Although I am aware of the magnitude of studies providing evidence for the positive effects of omega-3 fatty acids in general and EPA and DHA, in particular. I think you should be aware that research on its effects in athletes (as the general effect of anti-oxidants on healthy people) are less unequivocal than those on positive effects on your average pre-diabetic fatso.

In a very recent study, scientists from the Unité de Formation en Sciences et Techniques des Activités Physiques et Sportives in France (Filaire. 2010) found that judo athletes who took a standardized omega-3 supplement (600 mg EPA and 400 mg DHA) for 6 weeks had significantly increased stress markers compared to placebo:

Significant interaction effects between supplementation and time on resting MDA [malondyaldehide] concentrations and Rmax were found (p = .03 and p = .04, respectively), with elevated values in the n-3 LCPUFA group after supplementation and no change in the placebo group's levels. The authors observed a significantly greater NO and oxidative-stress increase with exercise (MDA, Rmax, CDmax, and NO) in the n-3 LCPUFA group than with placebo.

I've also read reports from (recreational) athletes all over the Internet claiming that whenever their PUFA supplementation goes beyond 1-2g per day, they start feeling drowsy, lose energy, recover slower and show other signs typically associated with increased inflammation. Feel free to use the comment function to let us know how fish oil or other omega3 sources make you feel.

Overweight Boys More at Risk of Obesity Related Health Problems than Girls

In a recent study from Egypt, Hassan et.al. took anthropometric measures of adiposity from 150 pupils between the ages of 7 to 18. Along with data on body composition and serum total lipids profiles the scientists intended to find correlation between obesity and adverse health effects at younger age. The results are interesting in that no correlation was found between lipid profile and body composition in the adolescent group (12-18 years). On the other hand, in the younger children , ...

For young age [7-11 years], triglycerides and HDL-C are correlated to most of the body composition and anthropometric parameters in boys and not in girls.

The scientists speculate on whether the different fat distribution pattern in young boys (centrally dominant) could be one of the underlying reasons for this observation. Be that as it may, I consider this another good reason to encourage boys (and girls, alike) to act out their natural desire to move and exercise before they  become PlayStation cambling couch potatoes.

Mitochondrial Density in Muscle is Key Determinant of Metabolic Flexibility

If you happened to have listened to Carl Lenore's interview with Mike T Nelson's on SuperHumanRadio, last week, you will be familiar with the concept of metabolic flexibility and how important it is for your body to be able to adapt quickly to varying energy demands and sources. A recent study by scientists from the Pittsburgh School of Medicine (Chomentowski. 2010) had a similar background. Along with several markers of metabolic flexibility the group measured intermyofibrillar and subsarcolemmal (SS) mitochondrial content in a sample of forty sedentary adults with a wide spectrum of insulin sensitivity (insulin-sensitive lean subjects, insulin-resistant nondiabetic subjects, and subjects with type 2 diabetes mellitus).

Intermyofibrillar mitochondrial content was lower in the insulin-resistant nondiabetic subjects and type 2 diabetes mellitus groups, significantly correlating with glucose disposal in both men (R = 0.72, P < 0.01) and women (R = 0.53, P < 0.01). In contrast, SS mitochondrial content was similar among groups. Lower intermyofibrillar mitochondrial content was not explained by mitochondrial size, altered fiber-type distribution, or differences in maximum aerobic capacity. Intermyofibrillar mitochondrial content was significantly correlated with fasting respiratory quotient (R = -0.46, P = 0.003) and metabolic flexibility (R = 0.38, P = 0.02).

The correlation between low intermyofibriallar mitochondrial content and insulin-resistance the researchers found seems to substantiate the longstanding recommendation to exercise and build muscle or make existing muscle work more effectively to prevent and treat diabetes and the metabolic syndrome. However, dietary factors and genetics may as well be important factors influencing mitochondrial density.