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2015 may offer a chance to get spice up your routine with kettlebells.

"Moderate evidence indicates that kettlebell training may be safe and effective for increasing certain functional strength and power measures and may show positive results with postural control in young, healthy populations," says a recent review of the literature in Physical Therapy Reviews (Girard. 2014) and does thus sound positively optimistic, but by far not as euphoric as some kettlebell warriors on the Internet.

Those of you who know me are probably aware that I am not a fan of kettle bells, but I am true to the motto of being open to good scientific evidence, like the one from the previously cited review by Girard et al. (2014).
Speaking of which, the previously cited review found only five studies satisfied the eligibility criteria and were included in this review. The populations studied age range was 18–72 years old. Methodological scores based on the PEDro scale ranged from 3 to 7 out of 10. In those studies, ...

[k]ettlebell training demonstrated improvements for a number of strength measures: time 6 group for bench press ( P < 0.05) and back extension (P = 0.053), main effect for clean and jerk (P < 0.05) and certain power measures such as improved explosive strength comparable to a jump squat control (19.8% increase). Improved postural control was demonstrated in one study (P = 0.04)" (Girard. 2014).

What the kettlebells did not do in any of the five studies by Otto et al. (2012), Manoccia et al. (2013), Lake et al. (2012) and Jay et al. (2011 & 2013) was to have an effect on aerobic endurance as measured by VO2 Max.
The non-significance of the oxygen uptake and thus the non-existence of conditioning effects may come as a surprise for those of you have already done kettlebell swings. Rightly so, as I would argue, because this result of the review is based mainly on the results of Jay et al. (2011) who invited 57 employees of a large pharmaceutical company for a physical examination. Of those only 43 showed up (motivation to work their assess off ?) of whom 40 men and women in their mid-forties then trained for 20 minutes included a 5 –10 minute warm up and a 10–15 minute interval training consisting of 10 intervals of 30 seconds with rest period of 30–60 seconds which began with ZERO workload and was progressively intensified by the participants choice!

Kettlebell, weights, or ergometer, you have to work your ass off to make progress!

Thats much in contrast to Fortner et al. (2014) who had their 14 young (18-25y), non-obese volunteers train three times a week for 8 weeks with 4.5kg and 8kg kettlebells for the female and male subjects, respectively in a "tabata style", i.e. at a twenty-second work to ten-second rest ratio and compared the VO2 response to a traditional protocol, consisting of four sets of work separated by ninety seconds of rest.

Figure 1: Subjective Borg RPE response to Tabata versus traditional kettlebell swing protocols in healthy, young adults. TAB- Tabata, TRADtraditional (left). % of peak VO2 value achieved during Tabata and traditional kettlebell swing protocols in healthy, young adults (right | Fortner. 2014).

As you can see in Figure 1 the response to the two different workouts was very different - despite the fact that the total number of swings from each individuals "tabata condition" (TBA) was equally divided into four sets for their "tradititional condition" (TRAD). From non-kettlebell studies, we know that training at an intensity like this, even if its done for only a few minutes, will just as Fortner et al. say "safely and effectively provide multi-faceted exercise adaptations with a relatively short time investment" (Fortner. 2014) - an assumption thats backed by a 2011 study by Falatic et al. that used a 15s/15s protocol and elicited significant increases in VO2max in seventeen female NCAA Division I collegiate soccer players.

Figure 2: Energy expenditure during two-hand kettlebell exercise and graded treadmill walking (Thomas. 2014).

Furthermore, James et al.  (2014) were recently able to show that a KB routine consisting of 2-hand swings and sumo deadlifts with 3-minute rest periods produces similar metabolic responses to those of a moderate-intensity treadmill walking protocol designed for the improvement of aerobic fitness in 5 women, 5 men between 21 and 31 years of age - and, as you can see in Figure 2, it also burned a few extra calories.

A comparison with treadmill walking is yet not enough to confirm that kettlebell training is also superior to "regular" HIIT training. Personally, I suspect it isnt but its at least a good way to diversify your training routines and create a new exercise stimulus that may even help you break through a plateau.
References:

• Falatic, Jonathan Asher. "The effects of kettlebell training on aerobic capacity." San José state University (2011).
• Fortner, Howard A., et al. "Cardiovascular and metabolic demands of the kettlebell swing using a Tabata interval versus a traditional resistance protocol." International Journal of Exercise Science 7.3 (2014): 2. 
• Greenwald, Samantha Leigh. The impact of an acute bout of kettlebell exercise on glucose tolerance in sedentary males. Diss. State University of New York at Buffalo, 2014.
• Jay, Kenneth, et al. "Kettlebell training for musculoskeletal and cardiovascular health: a randomized controlled trial." Scandinavian journal of work, environment & health (2011): 196-203.
• Jay, Kenneth, et al. "Effects of kettlebell training on postural coordination and jump performance: a randomized controlled trial." The Journal of Strength & Conditioning Research 27.5 (2013): 1202-1209.
• Lake, Jason P., and Mike A. Lauder. "Mechanical demands of kettlebell swing exercise." The Journal of Strength & Conditioning Research 26.12 (2012): 3209-3216.
• Manocchia, Pasquale, et al. "Transference of kettlebell training to strength, power, and endurance." The Journal of Strength & Conditioning Research 27.2 (2013): 477-484.
• McGill, Stuart M., and Leigh W. Marshall. "Kettlebell swing, snatch, and bottoms-up carry: back and hip muscle activation, motion, and low back loads." The Journal of Strength & Conditioning Research 26.1 (2012): 16-27. 
• Otto III, William H., et al. "Effects of weightlifting vs. kettlebell training on vertical jump, strength, and body composition." The Journal of Strength & Conditioning Research 26.5 (2012): 1199-1202.
• Thomas, James F., et al. "Comparison of Two-Hand Kettlebell Exercise and Graded Treadmill Walking: Effectiveness as a Stimulus for Cardiorespiratory Fitness." The Journal of Strength & Conditioning Research 28.4 (2014): 998-1006.

Insulin sensitivity is a necessary pre- requisite for much more than a profane set of sixpack abs.

You will probably have realized that the number of short-news like articles on the SuppVersity has been increasing as of late. The reasons for that are twofold: For one, its the fact that it pisses me off (sorry, but thats how it is) that all the interesting stuff I post on the SuppVersity Facebook Page disappears into an oblivion of which I can only hope that it is not Mark Zuckerbergs *** Secondly, I am currently working my regular job, doing some additional University stuff and working on another nutrition and exercise science related project and dont have the time to do the extensive research thats necessary to produce articles like part II of the "perfect frying oil" article, you may (rightly) already be waiting for.

In other words: If you dont want me to switch to a twice or thrice (max) a week schedule, you will have to live with less in-depth articles like this - sorry! If you would prefer a new schedule, on the other hand, let me know.

Artemisia dracunculus and Lixisenatide, two names to remember?

Actually the first of these names, namely Artemesia dracunculus is a herb you should be vaguely familiar with, if you remember an old SuppVersity article with the title "SuppVersity Supplement Scrutiny: Athletic Edge Nutrition Creatine RT - More Than Yet Another Marketing Gag?" (refresh your memories). In said article I acknowledged the insulin-sensitizing prowess of Tarragon extract, but doubted that its purported effects on the uptake of creatine into the muscle had any real-world relevance.

I guess, some of you will probably say the same of the observation that the tarragon bioactives "improved insulin sensitivity in diabetic-obese myotubes to the level of normal-lean myotubes despite the presence of pro-inflammatory cytokines" in a recent in vitro study by scientists from the Louisiana State University. Before you do so, I would yet like to remind you of the existing evidence that supports the insulin-sensitizing (Wang. 2011), muscle-preserving (Kirk-Ballard. 2013), anti-diabetic (Watcho. 2010; Eisenman. 2011;  Scherp. 2012),  as well as anti-NAFLD (Wang. 2013) and eye (Watcho. 2011) and nervous system protecting (Singh. 2014) effects of this herb.

If you still dont trust a supplement that failed you once,...

there is obviously still BigPharmas answer to herbal supplements: Lixisenatide, a synthetic GLP-1 analogon that has just demonstrated that it could be the future of (type II) diabetes treatment.

Lixisenatide comes in a fool-proof pen - what else?

In a study that was conducted by no one else than the inventors over at Sanofi-Aventis in Frankfurt, Germany, injecting the drug subcutaneously 2 hours before an intravenous glucose challenge accelerated the disposal of glucose to "nearly physiological intensity" (Becker. 2014) - in other words: The mere injection of the GLP-1 analog reduced the insulin requirements of the diabetics to zero and helped push the glucose into the cells at a rate thats identical to the one of non-diabetics.

In view of the fact that it did not impair the counter-regulation to low glucose levels by glucagon, its probably just feasibility question (can you time it properly), if and when at least some diabetics will have Lixisenatide pens (see image to the right), instead of insulin syringes in the neat "I want that piece of cake now, so I have to inject tons of insulin"-bags they are carrying wherever they go.

And if you dont do drugs, ...

... a very simple and, as a recent study appears to confirm, effective way to improve your glucose management would be to increase your intake of calcium containing foods and/or "hard" (=high calcium) water around meals.
Why? Well, as a SuppVersity veteran you should actually remember that rumors had it for years that a high calcium intake would help with weight loss, but the observations in corresponding experiments were mixed and the contemporary scare about the connection between calcium supplements, on the one hand, and cardiovascular heart disease (CHD) and/or prostate cancer, on the other hand, put another question-mark, this time one that corresponds to safety issues, behind the "calcium for weight loss" paradigm.

Figure 1: Relative serum / blood levels of GIP, GLP-1, insulin, glucose, lactate and NEFA after meals with high calcium content compared to isocaloric meal w/ identical macronutrients w/ low calcium (Gonzalez. 2013).

Now, the results of a recent study from the Northumbria University in the UK wont make this question.mark disappear. What they definitely do, though, is clarify the underlying mechanism of action, which is - and this should be obvious, when you look at the data in Figure 1 - mediated by the calcium-induced 47 % and 22 % increases in GIP1–42 and GLP-1 respectively (Gonzalez. 2013).

Figure 2: Overview of the purported anti-obesity + anti-diabetic effects of calcium + vitamin D (Soares. 2014)

In conjunction with the 19 % increase in insulin areas under the curve for the 120 min following consumption of the macronutrient-matched meals these hormonal changes induced a 12 % reduction in appetite in the 10 healthy male subjects.

The combination of increased insulin levels and improved blood glucose clearance, on the one, and an increased production of the fat-burning satiety hormone GLP1, on the other hand, renders these observations interesting for both: The overweight, insulin resistant couch potato and the normal-weight individual on his / her way to a physique model body.
Reference:

• Becker, et al. "Lixisenatide Resensitizes The Insulin-Secretory Response To Intravenous Glucose Challenge In People With Type 2 Diabetes – A Study In Both People With Type 2 Diabetes And Healthy Subjects." Diabetes, Obesity and Metabolism (2014) - Accepted Article.
• Eisenman, Sasha W., et al. "Qualitative variation of anti-diabetic compounds in different tarragon (Artemisia dracunculus L.) cytotypes." Fitoterapia 82.7 (2011): 1062-1074. 
• Gonzalez, Javier T., and Emma J. Stevenson. "Calcium co-ingestion augments postprandial glucose-dependent insulinotropic peptide1–42, glucagon-like peptide-1 and insulin concentrations in humans." European journal of nutrition (2013): 1-11.
• Kirk-Ballard, Heather, et al. "An extract of Artemisia dracunculus L. inhibits ubiquitin-proteasome activity and preserves skeletal muscle mass in a murine model of diabetes." PloS one 8.2 (2013): e57112.
• Scherp, Peter, et al. "Proteomic analysis reveals cellular pathways regulating carbohydrate metabolism that are modulated in primary human skeletal muscle culture due to treatment with bioactives from< i> Artemisia dracunculus</i> L." Journal of proteomics 75.11 (2012): 3199-3210.
• Sakhaee, Khashayar, et al. "Meta-analysis of calcium bioavailability: a comparison of calcium citrate with calcium carbonate." American journal of therapeutics 6.6 (1999): 313-322.
• Singh, Randhir, Lalit Kishore, and Navpreet Kaur. "Diabetic peripheral neuropathy: Current perspective and future directions." Pharmacological Research 80 (2014): 21-35. 
• Soares, Mario J., Kaveri Pathak, and Emily K. Calton. "Calcium and Vitamin D in the Regulation of Energy Balance: Where Do We Stand?." International Journal of Molecular Sciences 15.3 (2014): 4938-4945.
• Vandanmagsa, B. et al. "Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture." Diabetes, Obesity and Metabolism (2014) - Accepted Article.
• Wang, Zhong Q., et al. "An extract of Artemisia dracunculus L. enhances insulin receptor signaling and modulates gene expression in skeletal muscle in KK-A y mice." The Journal of nutritional biochemistry 22.1 (2011): 71-78.
• Watcho, Pierre, et al. "High-fat diet-induced neuropathy of prediabetes and obesity: effect of PMI-5011, an ethanolic extract of Artemisia dracunculus L." Mediators of inflammation 2010 (2010).
• Wang, Zhong Q., et al. "< i> Artemisia scoparia</i> extract attenuates non-alcoholic fatty liver disease in diet-induced obesity mice by enhancing hepatic insulin and AMPK signaling independently of FGF21 pathway." Metabolism 62.9 (2013): 1239-1249.
• Watcho, Pierre, et al. "Evaluation of PMI-5011, an ethanolic extract of Artemisia dracunculus L., on peripheral neuropathy in streptozotocin-diabetic mice." International journal of molecular medicine 27.3 (2011): 299-307.

Its not just about more protein its about significantly more protein and - possibly - also about whey!

Just to make sure: Yes, I know the study I am about to discuss in todays SuppVersity article is a rodent study - a rodent study by researchers from the University College Cork and the University College Dublin (Mc Allan. 2014).  And yes, I know that you aint no fury little mouse or rat...

... but I do also know that the beneficial metabolic effects of high protein intakes appear to be even more, not less pronounced in human beings and will thus not mention 500x that the assumption that wed see similar benefits in men and women would obviously require experimental confirmation... alright?

Now that we are clear, dear non-dams and non-bucks...

... you are probably already drooling at the sought of reading yet another "high protein is good for you" study. Dont worry I am not going keep you on the tenderhooks longer than absolutely necessary. What is necessary, though is a very brief summary of the study design, which was designed to elucidate the effects macronutrient quality and composition on energy balance and the gut microbia - probably two of the hottest topics in todays discussions on the health and fitness bulletin boards of this world.
As the Irish researcher point out, their goal was to investigate how changes to protein quality (casein versus whey protein isolate; WPI) and the protein to carbohydrate (P/C) ratio within a high fat diet (HFD) impacts on the aforementioned parameters. The questions the experiment was supposed to answer were thus:

• Protein Quality ? Would adding whey protein on top of an obesogenic high fat rodent diet yield to a different weight and microbiota response than casein protein?
• Protein Quantity ? Would diets with 20%, 30% or 40% of the total energy intake from protein have different effects on body weight and microbiota in the rodents?

In view of the fact that casein is the standard protein in many of the high fat diets that are used in experiments like this, the study would thus also be able to give us an idea of whether or not the use of the slow-releasing IGF-1 boosting dairy protein contributes to the obesogenic effects.

As it turned out, the analysis of issues related to question #2, i.e. "Would diets with 20%, 30% or 40% of the total energy intake from protein have different effects on body weight and microbiota in the rodents?" did produce the more intriguing results, though.

Figure 1: Weight gain, fat and lean mass, as well as energy intake and respiratory exchange ratio (RER) after 21-weeks on diets with different amounts of whey protein in them (McAllan. 2014),

If you take a look at the data in Figure 1, its easy to see that (a) in comparison to casein (data from casein experiment not shown, because it was not discussed in detail | maybe there will be a follow up paper!?), WPI at a similar energy content normalised energy intake, increased lean mass and caused a trend towards a reduction in fat mass (P= 0.08). You may find that surprising, but its actually been known for quite some time now that whey buffers many of the ill-health effects of high fat diets in rodents.

Figure 2: Adipose tissue mRNA expression of selected genes (McAllan. 2014)

Although the addition of whey protein did not alter the oxygen consumption or locomotor activity, it was able to ...

• reduce the plasma leptin and liver triacylglycerold levels, and...
• attenuate the reduction in adipose FASN mRNA 

in HFD-fed mice (compared to what the researchers observed in rodents on the casein chow). Moreover, a high throughput sequence-based analysis of faecal microbial populations revealed that the

"[...]microbiota in the HFD-20% WPI group clustering closely with HFD controls, although WPI specifically increased Lactobacillaceae/Lactobacillus and decreased Clostridiaceae / Clostridiumin HFD-fed mice." (McAllan. 2014)

To understand the potential implications of these changes we will have to take a closer look at the recent evidence linking Clostridiaceae and Lactobacillaceae to the diabesity epidemic:

• Lactobacillus reuteri has anti-breast-cancer effects as well  (Lakritz. 2014).

  certain types of clostridiaceae are characteristic for obesity prone animals; their transplanation to normal mice will make them similarly vurnerable to the obesogenic effects of HFDs (Duca. 2014); similar differences, i.e. higher levels of clostridiaceae in obese individuals, have been observed in human studies, as well (Ferrer. 2013)
• lactobacilli, above all those of the reuteri type, have recently been used in several studies for their anti-obesogenic (Million. 2013a, b), anti-autoimmune (Forsberg. 2013), anti-caries (Stensson. 2013), anti-helicobacter plyori (Francavilla. 2013), pro-vitamin-D (Jones. 2013), and a whole host of other beneficial effects; for other types of lacutobacilli researchers have observed that they exert similar anti-obesity effects that may be mediated by the intestinal productino of the anti-obesity isomer of CLA, i.e. trans?10, cis?12?conjugated linoleic acid (Lee. 2007)

If we look at the previously listed metabolic effects, these changes in the make-up of the gut microbiome obviously correspond with the remarkable health improvements that occured in the whey-fed rodents.

High protein, low carb - What does it do?

Table 1: Plasma amino acid levels (mmol/L); blue bars to the right indicate sign. inter-group difference (McAllan. 2014)

Contrary to what youd expect based on appetite increasing effects researchers ascribe to high protein diets (Weigle. 2005), the increase in protein-to-carbohydrate ratio (P/C) did not lead to measurable reductions in energy intake, but ....

"[...]the highest ratio [40% of the total energy intake from protein] reduced HFD-induced weight gain, fat mass and plasma triacylglycerol, non-esterified fatty acids, glucose and leptin levels, while it increased lean mass and oxygen consumption." (McAllan. 2014)

As the scientists point out, similar effects were observed on adipose mRNA expression, where the highest ratio of protein to carbohydrates reduced HFD-associated expression of UCP-2 (a protein that has the fat stores eat themselves up), the inflammatory marker TNF-alpha and CD68 a gylcoprotein that messes with LDL cholesterol.

On the other hand, the (really) high protein diet increased the diet-associated expression of the b3-adrenergic recepto (b3-AR), lipoprotein lipase, a water soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins (VLDL), as well as the expression of insulin receptors and the glucose transporters GLUT4 - all of which should be old acquaintances of loyal SuppVersity readers.

References: 

• Duca, Frank A., et al. "Replication of obesity and associated signaling pathways through transfer of microbiota from obese prone rat." Diabetes (2014): DB_131526.
• Forsberg, Anna, et al. "Pre?and post?natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy." Clinical & Experimental Allergy 43.4 (2013): 434-442.
• Jones, Mitchell L., Christopher J. Martoni, and Satya Prakash. "Oral Supplementation With Probiotic L. reuteri NCIMB 30242 Increases Mean Circulating 25-Hydroxyvitamin D: A Post Hoc Analysis of a Randomized Controlled Trial." The Journal of Clinical Endocrinology & Metabolism 98.7 (2013): 2944-2951.
• Lakritz, Jessica R., et al. "Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice." International Journal of Cancer (2014).
• Lee, K., et al. "Antiobesity effect of trans?10, cis?12?conjugated linoleic acid?producing Lactobacillus plantarum PL62 on diet?induced obese mice." Journal of applied microbiology 103.4 (2007): 1140-1146.
• McAllan, Liam, et al. "Protein Quality and the Protein to Carbohydrate Ratio within a High Fat Diet Influences Energy Balance and the Gut Microbiota In C57BL/6J Mice." PLOS ONE 9.2 (2014): e88904.
• Million, M., et al. "Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli." International Journal of Obesity (2013a).
• Million, Matthieu, and Didier Raoult. "The role of the manipulation of the gut microbiota in obesity." Current infectious disease reports 15.1 (2013b): 25-30.
• Stensson, Malin, et al. "Oral Administration of Lactobacillus reuteri during the First Year of Life Reduces Caries Prevalence in the Primary Dentition at 9 Years of Age." Caries research 48.2 (2013): 111-117.
• Weigle, David S., et al. "A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations." The American journal of clinical nutrition 82.1 (2005): 41-48.