No Pump + Insulin Resistant? Maybe It's Your Healthy Low Salt Diet. Low Sodium Induced Increase in Aldosterone Has Direct Negative Impact on GLUT4 Mediated Glucose Uptake

A single Triple Whopper or about six whole steaks, what do you chose to get >75% of the 2g/sodium per day the feds are telling you you should maximally consume on a daily basis?

Today I felt kind of bored with covering only the latest studies. So I dug up one from 1999 that deals with the effects of dietary salt restriction on endothelial vasodilation (increased blood flow in the arteries) and insulin sensitivity by Ross D. Feldman and Nancy D. Schmidt. Yeah, the study is 14 years old, but when you've read today's SuppVersity article you'll probably still have learned something new - at least about "common wisdom".

If you also listen to the SuppVersity Science Round-Up on the Super Human Radio Network, you should be aware that very different rules apply with respect to salt consumption for athletes and physical culturists on a whole foods diet and the average sedentary inhabitant of the Western obesity belt (check out past episodes of the Science Round-Up).

Suggested Read: On "Clean Eating" being a myth - "A Tale of Macro- & Micro-Nutrient Modifi-cations" | read more

Talking about the ScienceRound-Up: In today's installment Carl and I will be talking about the latest meta-analysis on dairy and diabetes risk and how it's possible that only low fat dairy reduces the risk of diabetes. We will discuss how this relates to the differences in the fatty acid composition of milk which in turn depend on the feed the animals receive and whether there is in fact so much estrogen in milk that it can delay menopause. From there we will segue right into a discussion of the latest study on statins showing that they make you fat and diabetic and tell you which of the statins does what. If all works well, we will close the show by addressing Sarah M. Davis' question about a recently published and heavily discussed article that's titled "Why 'Clean Eating' is a Myth" (read it). I mean, is it really? Turn in live! at 12PM EST

What some of you may yet still not have on their radar is the fat that the "common wisdom" about salt being the root cause of all evil does not even apply to the majority of those guys and girls of whom you would expect they may in fact see benefits from a reduced salt consumption.

"Salt is bad, no matter what!"

In fact, Feldman & Schmidt were able to show that the provision of either normal or salt reduced diets to subjects aged 25 to 40 year.

Figure 1: Increased aldosterone levels during salt restriction will not only make you retain salt, but also reduce glucose uptake (Luther. 2011; my edits)

"Subjects were given a standardized diet that contained 75 mmol/L sodium chloride, 60 mmol/L potassium, and 20 mmol/L calcium for 14 days. Diets contained 16% protein, 54% carbohydrate, and 35% fat. Caloric intake was 2800 kcal/day. Subjects were advised to drink approximately 2L of water/day.

To assess the effects of dietary salt restriction independent of other dietary changes, subjects were randomized on a double blind cross-over basis to a daily supplement of 16 tablets of slow release sodium (Novartis, Mississauga, Ontario; 10 mmol/L sodium chloride/tablet) or matching placebo. Each were administered for 7 days." (Feldmann. 1999)

All of the participants had normal blood glucose levels, and were free of other abnormalities on history and physical examination. They did not smoke and their blood pressures levels ranged from normotensive to high normal/borderline. So, what would happen to the poor wretches consuming the additional sodium chloride tablets? Common wisdom tells us, their blood pressure will increase and they will develop metabolic abnormalities. Truth is (I quote from the study; Feldmann. 1999, my emphases), almost the exact opposite happened:

• Did you know? Aldosterone increases are caused by falling blood pressure, increased potassium levels, a higher blood acidity and decreased sodium concentrations in the blood trigger, decreases occur when your blood pressure drops, the potassium levels get low and/or the sodium levels are high.
  Dietary sodium restriction was associated with a significant decrease in 24-h urinary sodium excretion. However, blood pressure (based on the average 24-h automatic ambulatory measurements) was not significantly decreased with dietary salt restriction.
• Moderate salt restriction was associated with a significant increase in plasma norepinephrine concentrations. Dietary salt restriction was associated with a significant decrease in the glucose-to-insulin ratio, suggesting increased systemic insulin resistance. This decrease was primarily accounted for by an increase in plasma insulin concentration.

At the same time the researchers observed a significantly reduced effect of the vasculature to the insulin-mediated increase in blood flow, of which Hornstra et al. have shown only recently that it correlates negatively with blood pressure in overweight, but insulin sensitive individuals and may be the reason why those people don't suffer from the usual obesity related increases in blood pressure as well as its cardiovascular and renal consequences (Hornstra . 2013).

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Most of you will remember the recent post about the ability of salt to block the negative effects of high intensity exercise on the cellular integrity of your heart and kidneys don't you?

Bottom line: If you are working out and sweating, even if it's not like a pig, SALT is the last thing to fear. In fact you can even increase your heart disease risk due to the negative impact on blood lipids (+10% total +12% LDL cholesterol in salt-sensitive and unsensitive normotensive subjects; Ruppert. 1991).

Now it is important to point out that it is not clear whether these effects are transient and a response to the abrupt changes in dietary salt in take that are characteristic of these short term intervention studies.

I am certainly not recommending you copy the salt intake of the average junk-food fanatic!

But let's be realistic, here: How much salt do you actually consume on a daily basis if you follow my advice and leave as much of the processed pre-packaged junk as you can right in the supermarket!? This will leave you with actually having to put salt on your foods and there really is no good reason for the average physical culturist not to so in a way that it's tasty and supplies you with one of the most important minerals in your body.

Suggest figure: Only obese people have increased risk of CVD with increasing sodium consumption | check it out the SuppVersity Facebook Wall

Reference:

• Egan BM, Lackland DT. Biochemical and metabolic effects of very-low-salt diets. Am J Med Sci. 2000 Oct;320(4):233-9. Review.
• Hornstra JM, Serné EH, Eringa EC, Wijnker MC, de Boer MP, Yudkin JS, Smulders YM. Insulin's microvascular vasodilatory effects are inversely related to peripheral vascular resistance in overweight, but insulin-sensitive subjects. Obesity (Silver Spring). 2013 Mar 20.
• Luther JM, Brown NJ. The renin-angiotensin-aldosterone system and glucose homeostasis. Trends Pharmacol Sci. 2011 Dec;32(12):734-9.
• Ruppert M, Diehl J, Kolloch R, Overlack A, Kraft K, Göbel B, Hittel N, Stumpe KO. Short-term dietary sodium restriction increases serum lipids and insulin in salt-sensitive and salt-resistant normotensive adults. Klin Wochenschr. 1991;69 Suppl 25:51-7.

Milk, Tea & Honey - Two Things Don't Belong: Milk & Sugar Potently Reduce Antioxidant Effects of Green & Black Tea

Chi Latte is a sugar bomb, but no healthy, antioxidant beverage.

Over the past couple of weeks it has become relatively quiet in the "tea is good for your health", "tea makes you lose weight magically", "tea reduces diabetes risk", etc. column of the science news here at the SuppVersity, and in general. Ok, you still got your daily "green tea reduces inflammation study", but let's face it. That's boring.

What is interesting, however, are the results of a recent study that's about to be published in Food Chemistry (Korir. 2013). In this very paper, a group of researchers from the Egerton University in Kenya, the Association for Strengthening Agricultural Research in East and Central Africa in Uganda and the Tea Research Foundation of Kenya report that...

Adding milk or sweeteners to your tea will reduce its antioxidative capacity

And the effects the researchers observed in vitro and in vivo, were pretty significant, as you can see in the data I plotted for you in figure 1 & 2:

Figure 1: Antioxidant activity of green and black with different milk concentrations. No sweetener added (Korir. 2013)

Now, the first question I had, when I glimpsed at the results was "wtf. of course will the antioxidant effects of tea decrease in response to a decrease in the amount of tea per volume of liquid decreases"; I mean, that's exactly what happens when you add 10% of milk to your cup of tea at home. It becomes "dilluted" (usually you would not use that term if you put milk into something, but that's what it is). Now, the obvious question is: Was that even the case? Let's take a look at what the methods section of the paper can tell us:

Based on the results of the study at hand, we cannot really say whether adding milk to your tea after brewing it will reduce its antioxidant capacity. Luckily we do have data from a previously conducted 2011 study by Ryan et al. I wrote about in July 2011 that confirms: Adding milk after brewing reduces the FRAP (measure of antioxidant activity) value of tea more than the same amount of water does | read more

"Each infusion was prepared by infusing five grammes of coarse tea samples in 100ml of boiling distilled water in a 100ml volumetric flask and stirring with a magnetic stirrer on a hot plate for 10 minutes. Tea infusions with milk were made using 5g of tea and different concentrations of milk (2%, 4%, 6%, 8%, 10%, 20% and 40% (v/v milk/water). Infusions with milk and sugar were brewed with 3g and 10g of sugar plus the several concentrations of milk, and those with milk and stevia (0.1g and 0.3g) wereprepared. Similarly, teas with several concentrationsof milk plus 3g and 10g honey were prepared. All the above tea infusions were strained through cotton wool to remove the tea particles and left to cool to room temperature [before the antioxidant activity of the] prepared tea extracts was determined using the 2, 2’-diphenyl-1-picryhydrazyl radical (DPPH) method." (my emphasis in Korir. 2013)

I guess, you will already have gotten it, right? By adding the milk before the brewing, the scientists did manage to get around the dilution effect, but at the same time they reduced the practical relevance of their results to zero. Why? Well, do you brew your tea with the milk already in it? I don't think so... so if it were not not for the 2011 study by Ryan et al. I would say: The verdict on milk is still out there. With the pertinent results from the Ryan study, however, you can be assured that adding milk to your tea makes it a less potent ROS scavenger.

Figure 2: Mean values of antioxidant activity of sweetened plain black tea (Korir. 2013)

Obviously, the same limitations also apply to the real-world significance of the effects of pre- vs. post-addition of sugar, honey and stevia (see figure 2), of which the scientists suspect that they may be a result of

"[c]omplex compounds, such as pentagalloylglucose (PGG), tetragalloylglucose (4GG) and trigalloylglucose (3GG) [that] are likely to be formed as glucose interacts with the gallic acid in tea where by the glucose hydroxyl groups are serially substituted by gallic acid." (Korir. 2013)

These glucose complexes would then bind with the bovine serum albumin and other proline-rich proteins present in milk and thus alter the biological activity of tea molecules (Chitpan. 2007).

So why is honey the worst then?

Honey has been shown to possess significant antioxidant activity of its own. The latter is ascribed to the presence of compounds such as chrysin, pinobanksin, vitamin C, catalase, and pinocembrin that are thought to function as antioxidants (Valentini. 2010). We would therefore actually expect to see an increase in antioxidant activity, when we put honey into our teas, right? So what's the reason that the exact opposite happens and that honey was found to be the most inhibiting sweetener in both plain and black teas with milk? The answer is: We don't know.
 
What we do know, however, is the fact that we are actually not interested in the mere presence of maximal amounts of antioxidants in tea, but rather in their biological effects on the antioxidant defense system of our bodies; and the correspoding image that emerges based on the accompanying rodent study is more complex than the in vitro data would have suggested:

Lack of drive? Theacrine will get you going | read more

"The highest levels of GSH were recorded in plasma after 2 hours of tea consumption. The GSH levels due to various types of tea differed significantly (p<0.001) in the same tissue at different time intervals [...]. Highest GSH levels were recorded for black tea fortified with 2% milk in plasma, as compared with the other teas. However, in kidney and brain tissues, higher GSH levels were recorded for plain black teas after 2 hours and 4 hours of tea consumption, respectively. The GSH levels in the liver were similar to those in the brain but the peak in the liver was after 30 minutes." (Korir. 2013)

Now, while there is still no place for sugar in your tea, the reputation of milk is partly restored - but only if it's used in very tiny amounts. The Chi Latte you see in the head of this article still remains "the soda among the teas" and looking at the photograph I would assume that the effect of this particular incarnation of "sugar milk with a splash of tea in it", is probably more detrimental to your health than a whole bottle of Coke.

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Catechin content of the leaves of green, oolong, black & pu-erh tea

Bottom line: Drinking tea is more than just a means of getting your antioxidants in. Against that background I am hesitant to suggest that everyone must drink his/her tea without milk and sugar, even if he/she hates the taste.

Nevertheless, cutting back on the amount of milk (<2%) and switching from honey or table sugar to stevia (and probably most other forms of artificial sweeteners) would be something to consider, if you want to make sure that the tea works its maximal antioxidant magic in your blood and organs.

References:

• Chitpan M, Wang X, Ho CT, Huang Q. Monitoring the binding processes of black tea thearubigin to the bovine serum albumin surface using quartz crystal microbalance with dissipation monitoring. J Agric Food Chem. 2007 Dec 12;55(25):10110-6.
• Korir MW, Wachira FN, Wanyoko RM, Ngure RK. The fortification of tea with sweeteners and milk and its effect on in vitroantioxidant potential of tea product and glutathione levels in an animal model. Food Chemistry. 2013 [accepted manuscript]

8g+ (HED) of Arginine Boost Glucose Clearance & Triples GLP-1 Release in Lean and Obese Mice. Plus: 14+ Studies On Things Arginine Can Do For Diabetics & Athletes

Type II diabetes and insulin resistance has long become an issue for lean individuals as well. But can you really abuse your "pump supplement" as a means to stash away your post-workout carbs at a significantly increased pace?

Statements like "XY boosts" and figures like "+30%" are real attention-grabbers. I mean 200mg/dl glucose vs. 300mg/dl glucose after a 2g/kg glucose load that must certainly be significant, right? Well, as always, there are exceptions to the rule, but I can reassure you: it's not the case with the latest study from the College of Medicine at the University of Cincinnati (Clemmensen. 2013). How I know that? Well the I wrote about the real world significance of the increased glucose clearance, as well as the brown-adipose-tissue building and white adipose tissue burning effects of arginine, previously (see "Arginine: BAT Builder and WAT Killer" & "Arginine Enriched Biscuits for Diabetics"). Thus, the most recent revelation that the conditionally essential amino acid that's notorious for its non-existent effects on the pump is able to increase the GLP-1 response to a sugary meal and thus double the glucose clearance in lean mice only adds to what SuppVersity readers knew all along:

There is way more to arginine than "the pump"

Being aware that everybody believes to know exactly that the big bad insulin is the reason for the current obesity epidemic, I guess it's better to remind you that this is not just an unwarranted over-generalization, but completely beside the point. So I suggest you (re-)read "The "Pro-Insulinogenic" Effects of Non-Nutritive Sweeteners + Mechanisms & Consequences" (just do it!), if you feel like running away, when you take a closer look at the right hand side of figure 1:

Figure 1: AUC under the glucose curve (left), actual glucose response after oral glucose tolerance test 15min after the ingestion of arginine in lean and obese mice (middle) and insulin response to arginine and subsequent ingestion of dextrose during the OGGT (right; Clemmensen. 2013)

What you are seeing here is an insulin SPIKE that deserves to be written in capital letters, but the way it ameliorates the surge in blood glucose in the diet-induced obese (~type II diabetic) mice could actually protect the rodents from developing many of the neurological and endocrine side effects of high blood glucose levels and not insulin, which has only recently been demonstrated to ameliorate the cognitive decline in dementia and Alzheimer's (Craft. 2012).

I know you are not dietary obese

Figure 2: GLP-1 response in the lean mice in the study at hand (foreground, top-right; Clemmensen. 2013) and selected effects of GLP-1 (background; from byettahcp.com)

Now, while the data on the right hand side of figure 1 may be relevant for your obese neighbor,  we are actually more interested in the data on the left, which does, by the way, make it quite clear that the problem with being obese is not an increase in insulin release, but the mere fact that even that is not going to help you clear the sugar out of the blood stream.

Compared to the obese mice, where we see a slight, but at 60min significant improvement in glucose clearance, the lean mice did not even give the 2g/kg body weight of glucose they received a chance to accumulate in their blood. Rather than that, they cleared it almost instantly.

The researchers hypothesis that this effect was mediated by the concomitant up to 3x increase in GLP-1 production was supported by a follow up experiment using a genetically modified strain of mice that lacks the GLP-1 receptor, in whom the corresponding improvements in blood glucose management were absent. In the discussion of their results, the researchers add:

Suggested read: "Glycemic Load, the GI's Complex Brother, Turns Out to Be A Good Predictor of Postprandial GLP-1 and GIP Response" | read more

"The GLP-1 incretin effect has traditionally been ascribed to effects on intestinal L cells elicited by ingested carbohydrate, but the findings reported here support the involvement of gut hormones to link protein ingestion with insulin secretion.

This has also been recently suggested in studies of humans consuming meals of specific macronutrient composition (Carrel. 2011).

Also, we have recently reported that long-term dietary supplementation with L-arginine improves glucose metabolism in mice exposed to a low-protein diet (Clemmensen. 2012)." (Clemmensen. 2013)

Despite the fact that GLP-1 analogues have been used with quite some success in the treatment of type II diabetes in the recent years, our understanding of the far-reaching effects of this "satiety hormone" is still far from being comprehensive (suggested read: "Eat More, Burn More and Lose Fat Like on Crack w/ GLP-1"). What we do know is that it occupies a central position in the control of our energy intake, though. And I am pretty sure is not the SuppVersity post about glucagon-like peptide 1 (GLP-1), you are about to read.

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But does that even work for you? For (pre-)diabetics we can rely on data from Piatti et al. (2001) who found a 34% increase in insulin clearance after one months on 3g/day l-arginine and data from Lucotti (2006) who observed that the addition of 8.3g of l-arginine to a hypocaloric diet + exercise regimen boosted the loss of fat mass and and waist circumference while increasing the lean mass retention and improving daily glucose and fructosamine profiles, significantly. For the sick / obese we do also have human (H) and rodent studies (R) supporting

• 

  Whenever the word "vascularity" appears on one of the boards, this image pops up. Now we know that arginine alone won't make your veins pop, but could it be that we have hitherto overlooked that it could help you meet another more important criteria to look like that - namely to drop body fat? Learn more in a previous SuppVersity article on arginine's BAT building and WAT killing effects and it's use as a repartitioning Agent (read more)

  an anti-platelet effect of 8.4g arginine per day in hypercholesterolemic humans (Wolf. 1997; H)
• indirect anti-oxidant effects of 2x3g arginine per day in in diabetic patients with atherosclerotic peripheral arterial disease of lower extremities (Jablecka. 2012; H)
• an ameliorative effect on diabetes induced gastrointestinal malfunction (Míguez. 2004; R)
• improved wound healing when administered alone (Witte. 2002; R) or with proline (Raynaud-Simon. 2012; R)
• significantly reduced body fat mass in rodent model of diet induced diabesity (Fu. 2005; R)
• beneficial effects on the hypertensive offspring of diabetic dams (Cavanal. 2007; R) 
• direct mechanistic effects that inhibit the storage of fat in white adipose tissue (Tan. 2012; R + H + PIG)
• reductions in diabetes induced bone loss (Pennisi. 2009; R)
• amelioration of the negative effects on insulin sensitivity in response to a low (no typo!) salt diet (Ruivo. 2006; R)

The benefits for lean individuals are not that clear, studies like Gater et al. (1992), for example, tested the effect of the purportedly GH boosting combination of arginine + lysine and saw no effects in their healthy young participants. Other studies did however find ...

• 

  Suggested read: "Post-Workout Glycogen Repletion - The Role of Protein, Leucine, Phenylalanine and Insulin." | read more

  a reduced oxidation of glucose when well-trained cyclists used a mixture of 1 g carbohydrate/kg body mass and 0.08 g arginine-hydrochloride/kg body weight to refuel their muscle glycogen after a workout (Yaspelkis. 1999)
• significantly lowered blood pressure and improved renal function and carbohydrate metabolism in healthy volunteers (Siani. 2000)
• significantly increased rates of glucose disposal during exercise in trained cyclists (McConell. 2006; Linden. 2011)
• direct beneficial effects on glucose and fatty acid metabolism in muscle cells (de Castro Barbosa. 2013)
• reduced blood lactate accumulation & oxygen consumption during submax. exercise after prolonged intake of L-arginine-L-aspartate (Burtscher. 2005)

So, if it there was not the likely possibility that many of these benefits occur only with a low(ish) protein intake,  I would say: Arginine can do a lot of interesting things for you. With a possible beneficial effect on post-workout glycogen repletion being what I consider most significant for the lean physical culturist. There is yet one thing arginine cannot do and that's worth remembering, because it tells you something about the supplement business: It won't increase the pump.


References:

• Burtscher M, Brunner F, Faulhaber M, Hotter B, Likar R. The prolonged intake of L-arginine-L-aspartate reduces blood lactate accumulation and oxygen consumption during submaximal exercise. J Sports Sci Med. 2005; 4(3), 314-322.
• Carrel G, Egli L, Tran C, et al.Contributions of fat and protein to the incretin effect of a mixed meal. Am J Clin Nutr. 2011;94(4):997–1003. 
• Cavanal Mde F, Gomes GN, Forti AL, Rocha SO, Franco Mdo C, Fortes ZB, Gil FZ. The influence of L-arginine on blood pressure, vascular nitric oxide and renal morphometry in the offspring from diabetic mothers. Pediatr Res. 2007 Aug;62(2):145-50.
• Clemmensen C, Madsen AN, Smajilovic S, Holst B, Bräuner-Osborne H.L-Arginine improves multiple physiological parameters in mice exposed to diet-induced metabolic disturbances.Amino Acids. 2012;43(3):1265–1275.
• Clemmensen C, Smajilovic S, Smith EP, Woods SC, Bräuner-Osborne H, Seeley RJ, D’Alessio DA, Ryan KK. Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice. Endocrinology. First published ahead of print August 19, 2013.
• Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012 Jan;69(1):29-38.
• de Castro Barbosa T, Jiang LQ, Zierath JR, Nunes MT. L-Arginine enhances glucose and lipid metabolism in rat L6 myotubes via the NO/ c-GMP pathway. Metabolism. 2013 Jan;62(1):79-89.
• Fu WJ, Haynes TE, Kohli R, Hu J, Shi W, Spencer TE, Carroll RJ, Meininger CJ, Wu G. Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr. 2005 Apr;135(4):714-21.
• Gater DR, Gater DA, Uribe JM, Bunt JC. Effects of arginine/lysine supplementation and resistance training on glucose tolerance. J Appl Physiol. 1992 Apr;72(4):1279-84.
• Jabłecka A, Bogdański P, Balcer N, Cieślewicz A, Skołuda A, Musialik K. The effect of oral L-arginine supplementation on fasting glucose, HbA1c, nitric oxide and total antioxidant status in diabetic patients with atherosclerotic peripheral arterial disease of lower extremities. Eur Rev Med Pharmacol Sci. 2012 Mar;16(3):342-50.
• Linden KC, Wadley GD, Garnham AP, McConell GK. Effect of l-arginine infusion on glucose disposal during exercise in humans. Med Sci Sports Exerc. 2011 Sep;43(9):1626-34.
• Lucotti P, Setola E, Monti LD, Galluccio E, Costa S, Sandoli EP, Fermo I, Rabaiotti G, Gatti R, Piatti P. Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E906-12. 
• McConell GK, Huynh NN, Lee-Young RS, Canny BJ, Wadley GD. L-Arginine infusion increases glucose clearance during prolonged exercise in humans. Am J Physiol Endocrinol Metab. 2006 Jan;290(1):E60-E66.
• Míguez I, Mariño G, Rodríguez B, Taboada C. Effects of dietary L-arginine supplementation on serum lipids and intestinal enzyme activities in diabetic rats. J Physiol Biochem. 2004 Mar;60(1):31-7.
• Pennisi P, Clementi G, Prato A, Luca T, Martinez G, Mangiafico RA, Pulvirenti I, Muratore F, Fiore CE. L-arginine supplementation normalizes bone turnover and preserves bone mass in streptozotocin-induced diabetic rats. J Endocrinol Invest. 2009 Jun;32(6):546-51.
• Piatti PM, Monti LD, Valsecchi G, Magni F, Setola E, Marchesi F, Galli-Kienle M, Pozza G, Alberti KG. Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients. Diabetes Care. 2001 May;24(5):875-80. 
• Raynaud-Simon A, Belabed L, Le Naour G, Marc J, Capron F, Cynober L, Darquy S. Arginine plus proline supplementation elicits metabolic adaptation that favors wound healing in diabetic rats. Am J Physiol Regul Integr Comp Physiol. 2012 Nov 15;303(10):R1053-61.
• Siani A, Pagano E, Iacone R, Iacoviello L, Scopacasa F, Strazzullo P. Blood pressure and metabolic changes during dietary L-arginine supplementation in humans. Am J Hypertens. 2000 May;13(5 Pt 1):547-51. 
• Tan B, Li X, Yin Y, Wu Z, Liu C, Tekwe CD, Wu G. Regulatory roles for L-arginine in reducing white adipose tissue. Front Biosci (Landmark Ed). 2012 Jun 1;17:2237-46. Review.
• Witte MB, Thornton FJ, Tantry U, Barbul A. L-Arginine supplementation enhances diabetic wound healing: involvement of the nitric oxide synthase and arginase pathways. Metabolism. 2002 Oct;51(10):1269-73.
• Wolf A, Zalpour C, Theilmeier G, Wang BY, Ma A, Anderson B, Tsao PS, Cooke JP. Dietary L-arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans. J Am Coll Cardiol. 1997 Mar 1;29(3):479-85.
• Yaspelkis BB 3rd, Ivy JL. The effect of a carbohydrate--arginine supplement on postexercise carbohydrate metabolism. Int J Sport Nutr. 1999 Sep;9(3):241-50.

When Hype Meets Reality: D-Aspartic Acid Turns Out to Be Another Supplemental Nonstarter in First Human Trial With Any Relevance for Healthy Young Men

Training "on" D-Aspartic Acid is like training on guar gum.

Busted! D-Aspartic acid aka DAA is another "natural anabolic agent" that turns out to be more of a revenue- than a hormone-booster with muscle building prowess.

And you know what? It took Darryn S. Willoughby and Brian Leutholtz from the  Exercise and Biochemical Nutrition Lab, Human Performance, and Recreation at Baylor University exactly 28 days and 20 apparently healthy, recreationally active, resistance trained (3x per week or more in the past year) men with an average age of 22.8 ± 4.67 years (BMI 24.65 kg/m²) to prove that d-aspartic acid (DAA) supplements belong to this never-ending list of supplemental non-starters.

Things that work: 28 days, 4x per week heavy resistance training; things that don't work DAA capsules

Better supplement w/ "K" than with DAA - potassium (K) (in German it's Kalium)!

Potassium vs. Diet-Inducded Insulin Resis.

In the Lime Light: The Ill Effects of Low K Intakes

Bad News: Most Americans are Sign. K Deficient

Lean, Healthy ... Correlates of High Hair Potassium

Eating a High Protein Diet? Better Watch K!

Potassium Bicarbonate = Anabolic!?

Willoughby and Leutholtz assigned their participants in a random, double-blinded fashion to one of the two study arms. Subjects in both arms of the study followed a standardized periodized 28-day resistance training program split into 2 upper-extremity (A1, A2) and 2 lower-extremity (B1, B2) exercise sessions each week. With an overall training volume of 16 exercises sessions with 9x upper- and 8x lower-body exercises

• A1, A2 - upper body: bench press, lat pull, shoulder press, seated rows, shoulder shrugs, chest flies, biceps curl, triceps press down, and abdominal curls
• B1, B2 - lower body: leg press, or squat, back extension, step ups, leg curls, leg extension, heel raises, and abdominal crunches

the same workout has shown to elicit significant improvements in body composition in two previous studies on VPX' preworkout products (learn more; cf. Shelmadine. 2009; Spillane. 2011). The participants performed 3 sets of 10 repetitions at 70% - 80% of the previously established 1-RM for all exercises and had 2 minutes of passive rest between the sets. Contrary to the said VPX studies, the participants had to refrain from taking any kitchen-sink pre-/post-workout supplements, as well as the obvious roids, prohormones or other ergogenic substances that would compromise the study results. Instead, they received either...

• 4 capsules containing 3 g of guar gum (PLA), or
• 4 capsules containing 3 g of D-ASP (Better Body Sports, Ventura, CA, USA)

The dosing was identical to the manufacturer's recommendation and based on the previous study by Topo et al. (2009) that caused the whole DAA hype back ~5 years ago (see figure 2, as well).

Figure 1: Endocrine and body composition changes with placebo or DAA supplementation (Willoughby. 2013)

That fact the whole hoopla was exactly that: All hype! is difficult to refute, if you take a look at the study outcomes in figure 1 or the researchers' conclusion:

"[...] 28 days of D-ASP of supplementation at a daily dose of 3 g is ineffective in upregulating the activity of the HPG axis and has no preferential effects in which to increase skeletal muscle mass and strength in resistance-trained men." (Willoughby. 2013)

In their discussion of what might be the physiological reasons for the non-existent effects on the gonadal production of testosterone the researchers state:

Figure 2: Comparison of the hormonal effect of DAA in sedentary men with low testosterone levels (Topo. 2009) vs. trainees with normal to high levels of testosterone (Willoughby. 2013)

"Based on our data presented herein, this [=the fact that the serum levels of DAA were higher than normal, but nothing happened] may indicate another potential mechanistic reason why the HPG [hypothalamus > pituitary > gonads] axis was not affected by D-ASP supplementation. Although we observed nonsignificant increases in serum D-ASP in the DAA group, we showed significant increases in DDO levels in response to D-ASP supplementation. The degradative role of DDO is to catalyze the oxidative deamination of D-amino acids to generate the corresponding 2-oxo acids, along with hydrogen peroxide and ammonia (or methylamine).

In rodents, the administration of D-ASP was shown to increase DDO activity (Nagasaki. 1994; Yamada.1989), suggesting that DDO activity is induced by increased levels of D-ASP. Based on this information, in the present study, it is possible that because of the higher baseline levels of testosterone, as a means of androgen-regulated feedback of the HPG axis, the level of serum D-ASP induced by supplementation was conceivably being degraded by DDO at a rate that rendered it unable to effectively activate the HPG axis." (Willoughy. 2013)

Or to put is simply: If DAA works at all, it works only in guys like the participants of the 2009 study by Topo et al. who had baseline testosterone levels at the lower end of the normal range (4.5ng/ml) at the beginning of the study and average levels (6.4ng/ml) at the end of the study period. In trained athletes with testosterone levels in the range of 8ng/ml such as the guys in the Willoughby study, the negative feedback will prevent any further increase in testosterone.

Does testosterone actually build muscle and are any of the bazillions of purported natty testosterone boosters worth your money? (learn more)

Bottom line: Before we have counter-evidence (this is science guys, you can't say something definitive based on one study) there is no good reason for someone with normal testosterone levels to spend money on D-Aspartic acid supplements.

Whether the same would be true for guys on post-cycle therapy or those who want to combat diet- / overtraining induced reductions in testosterone would certainly be worth investigating. Other aspects that could make a difference are the form of delivery (although this did not seem to be a problem; after all the DAA levels rose) and the provision of adjuvants to block the negative feedback on the HPG (see explanation above).

References:

• Nagasaki H. Gender-related differences of mouse liver-D-aspartate oxidase in the activity and response to administration of D-aspartate and peroxisome proliferators. Int J Biochem 1994;26:415–23.
• Shelmadine B, Cooke M, Buford T, Hudson G, Redd L, Leutholtz B, et al. Effects of 28 days of resistance exercise and consuming a commercially available pre-workout supplement, NO-shotgun, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers in males. J Int Soc Sports Nutr
  2009;6:16.
• Spillane M, Schwarz N, Leddy S, Correa T, Minter M, Longoria V, et al. Effects of 28 days of resistance exercise while consuming commercially available pre- and post-workout supplements, NO-shotgun and NO-synthesize on body com position, muscle strength and mass, markers of protein synthesis, and clinical safety markers in males. Nutr Metab (Lond) 2011;8:78
• Topo E, Soricelli A, D'Aniello A, Ronsini S, D'Aniello G. The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats. Reprod Biol Endocrinol 2009;7:120
• Willoughby DS, Leutholtz B.  d-Aspartic acid supplementation combined with 28 days of heavy resistance training has no effect on body composition, muscle strength, and serum hormones associated with the hypothalamo-pituitary-gonadal axis in resistance-trained men.  Nutrition Research, Available online 15 August 2013. 
• Yamada R, Nagasaki H, Nagata Y, Wakabayashi Y, Iwashima A. Administration ofD-aspartate increasesD-aspartate oxidase activity in mouse liver. Biochim Biophys Acta 1989;990:325–8.

Organ Specific Resting Metabolic Rates and Diet-Induced "Metabolic Damage". Plus: At Rest Heart, Liver & Kidney Consume 83x More Energy/kg Organ Mass Than Muscle

No, your muscles are not the primary gas guzzler in your body.

The problems arising as a consequence of a diet-induced reduction of the metabolic rate are among the recurring themes here at the SuppVersity. For a good reason, as I would say. After all, they are the #1 reason for weight loss plateaus and the yoyo effect. Although the notion that "calories count" is not very popular these days there is no debating that an energy deficit is a necessary prerequisite for weight loss. The problem however is that you cannot determine your energy balance with a calculator, a body fat caliper and a scale. There are way too many other factors involved - the amount, macro- and micronutrient composition, timing, frequency, volume, texture and palatability of the ood you eat, stress, hormonal factors, etc - all of which will affect the amount of energy you expend and subvert the results of over-simplistic calories-in vs. calories-out calculations.

What are the most notorious gas guzzlers in our body?

Things would actually already be complex enough, if we focused solely on that "input" <> "output" recursion, but unfortunately, even the notion of a "global" (=valid for the whole body) metabolic rate is nothing we can really rely on. If we wanted to have a somewhat more accurate estimate of our basal energy requirements, i.e. the amount of energy we need if we don't move all day (which is basically what the average Westerner does, these days ;-), we would have to know the individual energy requirements of all our major organs and add them up, using a formula like this:

The more you eat, the more you burn. You can find more evidence that men & women are no bomb-calorimeters here

240x brain mass in kg

+ 440x heart mass in kg
+ 200x liver mass in kg
+ 440x kidney mass in kg

+ 13x skeletal muscle mass in kg
+ 4.5x adipose tissue mass in kg

+ 12x residual mass in kg

This formula, which was developed based on studies of Elia et al. in 1998, assumes that the metabolic activity of an organ increases linearly with its mass and that the specific metabolic rates (ki-values, i.e. 240 for the brain, 440 for the heart, etc.) are accurate. In the average, normal weight non-dieting individual these values are constant and have been confirmed lately in a set of experiments that were conducted by Wang et al. (see figure 1)

Figure 1: ki-Values of adipose tissue, skeletal muscle, liver, brain, heart, kidneys, residual volume from the Wang studies; all values expressed relative to the reference values from Elia (1998)

These studies, which were published subsequently in 2010, 2011 and 2012, also reported that there are distinct trends for decreasing ki-values and thus lower resting energy expenditures at identical organ masses in both obese / lean and older / younger individuals - an effect which can be explained by either lower cellularity or lower specific metabolic rates of the respective organs and tissues. In light of the fact that the "organ weight x ki-value"-calculations are very accurate and that

"there is only a small and nonsignificant difference between REEm [measured resting energy experience] and REEc [the energy experience calculated based on ki-values and organ masses] of about 13 to 80 kcal/day" (Müller. 2013b)

it should be obvious that both aging and already being obese put you at a higher risk of weight gain in a society where energy dense foods and large portion sizes are the rule, not the exception.

Is there something like organ specific metabolic damage?

A couple of recent studies have investigated the effects of weight loss and regain on organ-specific energy expenditure in order to find out if this may be the, or at least one of the underlying reason for the reduced resting energy expenditure in formerly obese individuals (Müller. 2013a; Bosy-Westphal. 2009 & 2013). These studies support the idea of a fall in the organ size and weight and the corresponding ki-values of high metabolic rate organs (heart, kidney, liver) with weight loss. Bosy-Westphal (2009), for example report a -136kcal/day reduction in resting energy expenditure (REEm = measured) with 4-6% loss of liver, heart and kidney mass in obese women after 9.5kg body weight loss (2.6% fat free mass).

Figure 2: Difference between measured and calculated energy expenditure in MJ/day at baseline, after weight loss and regain in  47 obese men and women who lost 12kg (weight stable) and 9kg (weight regainers) in a study by Bosy-Westphal et al. from 2013

"In addition, the effect of weight loss and weight regain over a longer follow-up period of 6 months had been studied in 47 obese males and females (Bosy-Westphal. 2013). There were considerable differences between weight-reduced/weight-stable individuals compared with weight regainers. Over a period of 6 months, weight-reduced/weight-stable individuals had lost 12 kg body weight, the weight change-associated changes in the REEm - REEc values were 33 and 45 kcal/day, with initial weight loss and with long-term follow-up (i.e. between 12 weeks and 6 months). By contrast, weight regainers regained 6.3 kg body weight after an initial loss of about 9 kg. The corresponding data on the weight changeassociated changes in the REEm - REEc values were 69 and 10 kcal/day, respectively. Individual data for the group ‘regainers’ at basal before and after weight loss, as well after weight regain, are shown in [figure 2]. The changes in the REEm- REEc values argue for changes in specific metabolic rates with weight changes." (Müller. 2013b)

What? Ok, I have to admit that this paragraph from Müller's 2013 review of the literature is not actually easy to understand. So let's take a look at the data in figure 2 again. The main message here is that the weight loss narrows the natural spectrum of REEs down to the minimal requirements of your organs. In other words, the body is running on low fumes and is thus particularly prone to weight regain which can - but does not have to - lead to an increase in the per pound organ weight energy expenditure that would then become obvious in the form of a larger difference between the measured (REEm) and calculated (REEc) resting energy expenditure (green and red circles in figure 2). With the pre-post weight regain difference being 69 vs. 10, it is yet unfortunately more common that the initial organ energy expenditure is not being restored (red circle in figure 2) and the energy expenditure remains low although people regain a lot if not all of their weight.

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Suggested read: "Do Chronic Energy Deficits Make Athletes Fat? The Longer & More Severe You Starve, the Fatter You Are. Irrespective of What the Calories-in-VS-Calories-Out Formula May Say" | read more

What can you do with this information? Not that much, I have to admit. If anything the major contribution of non-muscle tissue to the diet induced reduction of the resting metabolic rate should remind you that it may be at least equally important to spare the mass of the organs in your splachnic bed as it is to maintain as much lean muscle tissue as possible when your dieting.

I don't know if you remember the recent study about citrulline and it's effect on the maintenance of muscle and visceral tissue mass (see figure 1 in the respective article) or previous SuppVersity posts on other non-essential amino acids, such as glutamine or arginine? All of them are primarily "organ food" and an adequate provision of these conditionally essential amino acids should be considered as important as the provision of the purportedly muscle-protecting BCAAs if you want to keep the loss of organ mass at a minimum and your resting metabolic rate up. Whether and how you can influence the individual metabolic rate, of these organs is yet a totally different question to which no one has found a definitive answer, yet.

References:

• Bosy-Westphal A, Kossel E, Goele K,et al. Contribution of individual organ mass loss to weight-loss associated decline in resting energy expenditure. Am J Clin Nutr 2009; 90:993–1001.
• Bosy-Westphal A, Schautz B, Lagerpusch M,et al.Effect of weight loss and regain on adipose tissue distribution, composition of lean mass and resting energy expenditure in young overweight and obese adults. Int J Obes 2013.
• Elia M. Organ and tissue contribution to metabolic rate. In: Kinney J, Tucker HN, editors. Energy metabolism: tissue determinants and cellular corollaries. New York: Raven Press; 1992. pp. 61–79
• Müller MJ, Bosy-Westphal A. Adaptive thermogenesis with weight loss in humans. Obesity 2013a; 21:218–228.
• Müller MJ, Wang Z, Heymsfield SB, Schautz B, Bosy-Westphal A. Advances in the understanding of specific metabolic rates of major organs and tissues in humans. Curr Opin Clin Nutr Metab Care. 2013b Sep;16(5):501-8.
• Wang Z, Ying Z, Bosy-Westphal A,et al.Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure. Am J Clin Nutr 2010; 92:1369–1377.
• Wang Z, Ying Z, Bosy-Westphal A,et al.Evaluation of specific metabolic rates of major organs and tissues: comparison between men and women. Am J Hum Biol 2011; 23:333–338.
• Wang Z, Ying Z, Bosy-Westphal A,et al.Evaluation of specific metabolic rates of major organs and tissues: comparison between nonobese and obese women. Obesity 2012; 20:95–100.

HIIT Economy: 30s Intervals + 2:1 Work-To-Recovery Ratio Allow For Maximal Peak Oxygen Uptake at Minimal Power Output During HIIT Exercises in Advanced Trainees

We all know and follow the fundamental rules of the marketplace, but when we are in the gym we tend to forget about profit maximization and the minimal investment, maximal returns principle.

It is quite funny that our gyms are among the few places in our economy-driven society where people tend to forget about the fundamental rules of the marketplace. The way many of weekend-warriors and fitness junkies train is in fact the exact opposite of the all-governing principle of profiteering. In their desperate and in many cases misinformed efforts to maximize their muscle gains, fat loss or overall fitness, many of them fail to realize that the "optimal" training strategy is not the one that leads to suboptimal results at a maximal level of exhaustion. Think about the 2h cardio sessions in the non-existent fat burning zone, for example, or the two hour resistance training workout with 10 different exercises per body part.

Even if you don't belong to this group of miserably misguided souls, I believe there is this innate masochistic side in all of us that makes us believe that the degree of post-workout exhaustion is an adequate measure of the efficacy of a given workout. It does not matter if we are talking about classic cardio training, weight lifting or the high intensity interval training - all of them could benefit from goal-specific modifications, such as those that researchers from the Lillehammer University College in Norway have recently tested in a small scale intervention trial involving 13 well-trained male cyclists (Rønnestad. 2013).

Note: Your Tmax is the time to exhaustion during continuously cycling to exhaustion at the minimal power output (MAP) that elicits peak oxygen uptake (VO2max).

The goal Rønnestad and Hansen had had in mind, when they came up with the study design  was to investigate the effect of interval durations of 30s, 50% of Tmax [Tmax = ], and 80% of Tmax on the corresponding time-periods the athletes would exercise at ≥90% of their peak oxygen uptake. The three workouts that were performed on three different occasions had a work-to-rest ratio 2:1 and the intensity during the active recovery periods was 50% of the minimal power output (MAP) that elicits peak oxygen uptake (VO2max).

The latter, i.e. the time spent at a minimal power output that elicits peak oxygen uptake, was obviously also the criteria to define the "optimal" HIIT workout. After all, it can be expected that the "cardiovascular" (=fitness) benefits and the corresponding increases in the max. VO2 will be most pronounced, when you work out close to your individual VO2max without subjecting yourself to a potentially detrimental strain.

Figure 1: Maximal rate of perceived exertion, lactate levels and rtime at >90% heart rate in % of the total exercise time (left); VO2 levels at different timepoints expressed as percentage of time to exhaustion (Rønnestad. 2013)

As the scientists point out, their observation that their interval protocol using 30 s work periods induced a longer time ≥90% of VO2peak, longer time ≥90% of HR peak, and longer work durations at MAP intensity than the interval protocols using work periods of 50% of Tmax and 80% of Tmax

"diverge somewhat from the findings of Millet et al. (2003) [who] compared, amongst others, intermittent runs at MAP with a work duration of 30 s and 50% of Tmax with a 1:1 work:recovery ratio and a recovery intensity of 50% of MAP [and] found that work intervals lasting 50% of Tmax resulted in greater time ≥ 90% of VO2peak than work intervals of 30 s (~ 8 min vs. ~ 2.5 min, respectively)." (Rønnestad. 2013)

According to the authors this difference is probably a direct consequence of the extended active rest periods in the Millet trial. While the study at hand used rest periods of 15s (50% of the time spent ad MAP intensity), the participants in Millet's study rested for 30s. Enough time for the heart rate to recover and the "workout economy to decline".

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Suggested read: "Eight HIIT Sessions on the Rowing Ergometer Cut Body Fat, Increase Adiponectin, VO2Max & Performance in National Level Rowers - Workmatched Classic "Cardio" Does Nothing" | read more

Bottom line: "Cardio" as in "cardiovascular exercise" is supposed to be a form of training that is challenging enough to elicit beneficial adaptation processes that will results in increased exercise performance and/or VO2max. For most advanced trainees, a conventional "cardiovascular training" at say 70-80% of the individual VO2max is not going to deliver the stimulus that would be necessary to elicit significant adaptation processes.

For the advanced trainee looking to increase his cardiovascular capacity, high intensity interval training should thus be the training method of choice and as the study at hand confirms, the most economic form of HIIT is one that maximizes the time spent in the magic >90% of your HR peak training zone, at minimal intensities.

References:

• Millet, GP, Candau, R, Fattori, P, Bignet, F, and Varray, A. VO2 responses to different intermittent runs at velocity associated with VO2max. Can J Appl Physiol 28: 410-423, 2003.  
• Rønnestad BR, Hansen J. Optimizing interval training at power output associated with peak oxygen uptake in well-trained cyclists. J Strength Cond Res. 2013 Aug 12. [Epub ahead of print] 

Saffron, Bread & Diabetes: Rye Bread Does Not Even Have to be "Saffronized" to Help With Type II Diabetes

Saffron-rye breads? Not necessary, if you can achieve the same beneficial effects with nothing but rye bread alone.

The World Health Organization estimates that the diabetic population will increase from 195 to 360 million people by 2030 (4.5% of the global population; Wild. 2004; Shaw. 2010). Needless to say that it would be a real problem for a whole industry, if these prognoses did not come true. Against that background, it may not be such a problem that the results Bajerska et al. report in their recent paper in the Journal of Medicinal Food show that Saffron is not an uberpotent super-antidiabetic. What is however pretty interesting is the fact that the pharma- and the corn-industry could actually have a common interested in the world being fed wheat instead of rye bread.

Rye + Safron is not better than rye alone

When they were trying to come up with another (dys-)functional food, the researchers from the Poznan University of Life Sciences in Poland speculated that the addition of some expensive saffron powder that was extracted from S stigma (Crocus sativus) and contained 2% safranal as its purportedly active ingredient would exert anti-diabetic effects in streptozotocin-induced diabetic rats on a high-fat (HF) diet.

Figure 1: Glucose management, antioxidant status and lipid management in streptozotocin-induced diabetic rats after supplementation with either saffron (S), rye bread (RB) or both (RB+S) after 5 weeks (Bajerska. 2013)

Now what the researchers observed, when they added the saffron to the rye dough the bread that was part of the rodent chow was made of, was not exactly what they had expected. While the total phenolic content and total antioxidant value of the breads made from the dough increased linearly, the changes in lipid parameters, antioxidant capacity and leptin levels (figure 1) as well as the -50% reduction in blood glucose levels (not shown) were virtually identical with both the regular, as well as the "saffron enhanced" rye bread.

Pasta! From a satiety perspective even white bread would be a better choice (learn more).

"In relation to the aim of the current study, it is important to note that incorporation of S powder in the RB did not additionally improve the regeneration of damaged pancreas b-cells or the secretion of insulin, nor did it decrease blood glucose levels above that seen in the case of S powder and RB alone.

Moreover, it should be mentioned that the amounts of S powder added to the HF diet, and of S powder contained in RB added to the HF formula were matched to the similar dose of bioactive components." (Bajerska. 2013)

The scientists do however have a first hypothesis to explain the absence of synergistic effects in response to the saffron supplementation: The heat damage during the baking process. In the course of the latter the saffron-containing dough will be heated to temperatures way above the tolerable range of > 60 C° - a temperature at which a non-negligible fraction of the carotenoids in saffron begin to degrade. In conjunction with the low bio-accessible in the digestive tract may (in fact the latter is not much better than that of curcumin, cf. Vitaglione. 2012) being further decreased by the interactions and bindings with the processed food components of the bread (proteins and starch), this may in fact explain why the saffron didn't do the trick.

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King or Pauper, who's breaking the fast "right" (learn more)?

Bottom line: If there was one take home message from the study at hand, it would probably read: Not all bread is created equal and not all bread is necessarily bad. In fact, the results of the study at hand are in line with previous research that supports the notion that part of a our problem with "bread" is that the assortment of E-numbers we call "bread" has little or nothing to do with what bakery has previously been all about. A classic sourdough rye bread, for example, can be consumed by celiac patients without side effects (Di Cagno. 2010) and its fiber content will have highly beneficial effects on the gut health of gluten-insensitive individuals (McIntosh. 2003).

Moreover, epidemiological data suggests that the consumption of rye could protect against cancers of the upper digestive tract and entails significant reductions in myocardial infarction, diabetes and ischaemic stroke risk ( Hallmans. 2003). So, if you don't want to join the current hysteria about bread being (yet another) root cause of all disease, and keep eating bread on a regular basis, it may not be the worst idea to switch from "W" as in wheat to "R" as in rye. And by the way, if you are into porridge, having some whole grain rye porridge for breakfast has been shown to have an 8h satiety effect (Isaksso. 2008) - certainly not bad, if you are one of those people who are having a hard time not to snack in between meals, right?

Reference:

• Bajerska J, Mildner-Szkudlarz S, Podgórski T, Oszmatek-Pruszyńska E. Saffron (Crocus sativus L.) Powder as an Ingredient of Rye Bread: An Anti-Diabetic Evaluation. J Med Food. 2013 Aug 3. [Epub ahead of print]
• Di Cagno R, Barbato M, Di Camillo C, Rizzello CG, De Angelis M, Giuliani G, De Vincenzi M, Gobbetti M, Cucchiara S. Gluten-free sourdough wheat baked goods appear safe for young celiac patients: a pilot study. J Pediatr Gastroenterol Nutr. 2010 Dec;51(6):777-83.
• Hallmans G, Zhang JX, Lundin E, Stattin P, Johansson A, Johansson I, Hultén K, Winkvist A, Aman P, Lenner P, Adlercreutz H. Rye, lignans and human health. Proc Nutr Soc. 2003 Feb;62(1):193-9. Review.
• Isaksson H, Sundberg B, Aman P, Fredriksson H, Olsson J. Whole grain rye porridge breakfast improves satiety compared to refined wheat bread breakfast. Food Nutr Res. 2008;52.
• Shaw JE, Sicree RA, Zimmet PZ: Global estimates of the prevalence of diabetes for 2010 and 2030.Diabetes Res Clin Pract. 2010;87:4–14.
• Vitaglione P, Barone Lumaga R, Ferracane R,et al.: Curcumin bioavailability from enriched bread: the effect of microencapsulated ingredients.J Agric Food Chem. 2012;60:3357–3366.
• Wild S, Roglic G, Green A, Sicree R, King H: Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047–1053

Electrolyte Supplement Blocks Exercise Induced Elevations in LDH, Urea, Leucocyte Infiltration into the Heart & the Congestion of Renal Blood Vessels

For the average gymrat it is probably not a question of life or death, but an increase in recovery due to a decrease in detrimental muscle damage in response to dehydration should be an very good argument to get some salt and glucose in after / around your workouts.

Electrolytes have been at the heart of several SuppVersity articles as of late (check them out). Few of them did however have a direct link to exercise. Reason enough to discuss the results of a pertinent paper that was published by two scientists from Cairo University (Osman. 2013). At first sight, the study Hala F. Osman and  Azza M. Atya conducted does not appear to be very exciting. After all, the effects of electrolyte supplements on re-hydration after a workout are nothing that would not have been analyzed in previous studies. Moreover, the study at hand, which has been published in the latest issue of the World of Applied Sciences Journal, is a rodent study and the results would actually be pretty boring if the poor critters had not been sacrificed right after a lengthy HIIT session comprising 5x4 min intervals at 25m/min with 2min break in between, in order to beyond the conventional blood analyses and take a look at their hearts and kidneys.

Rodents don't complain

Now based on human studies we already know what happens in the blood, when we exercise vigorously, CK rises, LDH rises, the serum electrolyte levels get messed up, etc.

Figure 1: Changes in serum electrolyte levels (chloride, magnesium, calcium, phoporus, potassium, natrium) after the HIIT-esque workout w/ or w/out electrolyte supplementation (Osman. 2013)

The exercise induced changes in the electrolyte levels Osman & Atya observed in the rodents were in fact very similar to those that have been reported in human studies. What's more important, though is the fact that they persisted only those rats that did not receive the Rehydran-N solution daily for 45 days + immediately after the workout (see figure 1).

"[...] sodium ions decreased significantly  (P 0.05) after exercised while after  supplementation  by  Rehydran-n  and  Rehydran-n+ (Mg+Ca) citrate in group III and IV the level of sodium ion restored near to the control value. While  potassium ions level increased significantly (P 0.05) in exercised group. The supplementation by Rehydran-n and Rehydran  n+ (Mg+Ca) citrate in group III and IV not affected on the level of potassium and not return the value near to control value." (Osman. 2013)

One thing that is at odds with previous research in humans, is the acute -18.6% drop in magnesium levels. Interestingly, this drop was blunted even when the rodents received the magnesium free NaCl + K electrolyte supplement. The immediate provision of magnesium in the Rehydran-n + Mg + Ca arm of the study, on the other hand, raised the Mg2+ levels by +18% and did thus also result in a transient electrolyte imbalance.

Rehydration prevents organ stress

As I already hinted at in the introduction, having slightly screwed electrolyte levels, as well as elevated amounts of creatine kinase, lactate dehydrogenase and urea in the blood are more or less negligible problems compared to any direct ill health effects the dehydration and the corresponding loss of electrolytes could have on the structural integrity and health of your heart and kidneys. Effects such as those Osman and Atya saw when they analyzed the organs of the animals who did not compensate for the electrolyte loss by the immediate provision of adequate amounts of salt after a workout:

Figure 2: Sections of heart tissue after the workout (Osman. 2013)

"Figure [2] microscopic sections of heart from exercised group [2b] showed leucocytic cells infiltration in cardiac myocytes. Whereas other sections from Rehydran-n treatment  group [2c]  revealed  few  focal intermuscular  inflammatory  cells  infiltration.  While  Rehydran-n+  (Mg+Ca)citrate  treatment  group [2d] showing  no  histopathological  changeslike  those  in control group [2a]." (Osman. 2013)

Kidney sections of rat from control group revealed no histopathological changes. While in  prolonged exercising group showing hyalinosis [=degeneration] of  glomerular tufts. Moreover in Rehydran-n group vacuolations of epithelial lining renal tubules [=accumulation of waste that will be flushed out later on]. Rehydran  n+ (Mg+Ca) citrate treatment group congestion of renal blood vessel was observed [=one reason the better stick to salt, only].

Now, these results certainly sound more frightening than they actually are. Our bodies are (just like those of rodents, by the way) well equipped to handle the occasional cell / organ damage. And the heart is - believe it or not - "only" a muscle. It works slightly different, but can take at least as much beatings as our skeletal muscle tissue. Beatings of which the creatine kinase (CK) and lactate dehydrogenase (LDH) levels in the supplemented groups clearly show that they are are ameliorated by the the provision of electrolytes.

Figure 3: Creatine kinase (CPK), lactate dehydrogenase (LDH) and urea elevations (in %) after 5x4min treadmill runs with 2 min rest in-between (Osman. 2013)

"The present results are in accordance with the exhausted exercised rats resulted in an increased growth in serum CPK activity. This increase, however was markedly reduced in the rats after administration of antioxidant. For instance, 16h exercise in rats caused a marked rise in  activity levels of serum LDH. Increase in serum LDH  activity is mainly due to release from heart and skeletal muscles into blood stream. [...] Different  types  of  stressors  cause  an  increase in activities of serum creatine phosphokinase and lactate dehydrogenase in humans and animals which is an indication of tissue damage." (Osman. 2013)

Now you may be asking yourselves, whether similar effects can be expected in human beings!? Well, the answer should be obvious: "Similar", yes. 100% identical, no. Maughn et al., for example, demonstrated similar (re-)hydration benefits in human subjects in the 1994 - it should be obvious thought that they refrained from cutting their subjects open and checking what happened to their hearts so that we can only speculate about the extend of cellular / structural damage and the corresponding compensatory effects in humans.

Table 1: Ingredients of a single sachet of Rehydran-N which was bought by the reaserchers at a local pharmacy - no sponsorship involved

What can be said for with some certainty, though, is that it is unlikely that you would need more than one sachet of the electrolyte formula with its 0.3g K, 0.7g NaCl, 0.58g tri-sodium citrate and 4g glucose to achieve similar effects. After all, Osman & Atya modeled the amount of electrolytes the rodents received to what human beings would get from one serving of Rehydran-N. It is thus for once not necessary to calculate a human equivalent dose of the electrolytes in the water of the lab animals.

No glucose no effective rehydration

What is however necessary is the inclusion of the sugar or rather glucose in the rehydration formula, because the latter increases the efficacy of the formula significantly.

"The discovery that sodium transport and glucose transport are coupled in the small intestine so that glucose accelerates absorption of solute and water was potentially the most important medical advance this century."(Anonymous in Lancet. 1978)

So don't skip on the miniscule amount of glucose - even if you are suffering from carbophobia and believe that any amount of carbohydrates is going to make you hold water. Trust me, if anything will make you hold water its their absence and the suboptimal uptake of the electrolytes in the absence of glucose that will make you look like a watery version of the Michelin Man.

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NaHCO3 loading increases performance & decrease LDH activity.

Bottom line: Despite the fact that they may have been derived in a rodent study, the results Osman and Atya present in their most recent paper re-emphasis the need for adequate (re-)hydration before, during and even more so after workouts. In the vicinity of a workout, the latter is best achieved, using a simple salt + glucose mixture that can, but does not necessarily have to include ~360mg magnesium- and ~800mg calcium-citrate. You should yet keep in mind that the the increased levels of Mg2+ and Ca2+ can become burden on your kidney, although they appear to have beneficial effects on the heart (see figure 2).

And as far as the ostensibly beneficial decrease in LDH in the Rehydran-N + Mg + Ca group is concerned, this may well be a simple result of the alkalizing effect of magnesium and calcium ions. Assuming this is correct, similar benefits should occur in response to sodium bicarbonate, aka baking soda supplementation (learn more). The latter is after all part of the standard anti-rhabdomyolysis (=rapid breakdown of damaged skeletal muscle tissue) protocol where it does prevent both, further damage to the musculature and permanent damage to the kidneys (Vanholder. 2000).

References: 

• Anonymous. Water with sugar and salt. Lancet. 1978 Aug 5;2(8084):300-1.
• Maughan RJ, Owen JH, Shirreffs SM, Leiper JB. Post-exercise rehydration in man: effects of electrolyte addition to ingested fluids. Eur J. Appl. Physiol. Occup Physiol., 69: 209-15.
• Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol. 2000 Aug;11(8):1553-61. Review.

Sex, HIIT & Perceived Readiness: Any News on the Optimal Rest Times for Self-Paced HIIT Regimen in Men & Women?

Surrender bro, women are tougher than we'll ever be... and let's not talk about the other tactics by the means of which they trick us into doing whatever they want without us even noticing :-o

In the world of search engines for scientific papers on training and exercise science the acronym "HIIT" is currently what the word "sex" has always been on Google & co. Against that background it is actually surprising that no one else but me has taken notice of a paper on the "Sex specific  responses  to  self-paced,  high-intensity  interval  training  with  variable  recovery periods". The corresponding research was conducted by C. Matthew Laurent et al. from the School of Human Movement, Sport and Leisure Studies at the Bowling Green State University in Ohio and the paper is about to be published in an upcoming issue of the Journal of Strength and Conditioning Research (Laurent. 2013)

Men are different, women too

The results of previous experiments suggest that women are tougher than men, when it comes to steady state high intensity exercise at a self-selected pace. In their most recent study that involved 16 subjects (8 men and 8 women) between 19 and 30 years of age who had been participating in at least one session of interval training per week within the past months, Laurent et al. set out to test whether this would apply to HIIT sessions with fixed rest periods, but also variable, self-selected intensities. To this end, they had their subjects perform three bouts of HIIT.

"Each session consisted of 6, 4-minute intervals interspersed with either 1, 2, or 4 minutes of recovery. The recovery duration was counterbalanced and subjects  were  informed  of  the  specific  work-to-rest ratio  prior  to  performing  each  session.   Each  trial began  with  a  5-minute  warm-up  that  consisted  of  walking  4.8  km/h at  5%  incline." 

Suggested read: "8x Increase in PGC1-Alpha Cycling in Glycogen Depleted State" (read more)

The subjects were told to set the treadmill to the highest possible speed they felt they could maintain for 4 minutes knowing they were to perform 6 intervals.

The treadmill remained elevated at 5% incline for the duration of the whole session. Prior to each interval, subjects estimated their level of readiness using a perceived readiness scale.

Throughout and at the end of each interval, VO2(ml/kg/min), heart rate (bpm), and rate of perceived exertion (RPE) were measured, recorded and statistically processed.

At the conclusion of the fourth minute, the treadmill was slowed to 4.8 km/h for an active recovery.

"These procedures were followed identically for each of the 6 intervals and across all 3 trials. At the conclusion of the final interval of each session, subjects were disconnected from the metabolic system and sat quietly in a chair in the laboratory for approximately 15-20 minutes whereupon they provided a session RPE (SRPE) using the OMNI scale. "

All subjects were given at least 72 hours but no more than 10 days of rest between HIIT sessions, at the end of which the scientists had made the following observations:

• 

  Triple your energy expenditure by doing shorter shuttle runs (learn more)

  Men ran at significantly higher relative velocities (i.e., %VO2peak) during the  1-minute  recovery  trial  with  the  effect size suggesting a large difference.
• The same velocity and effect size advantage for the strong sex was evident during the trial with 2 min rest times, as well, but in this case the difference was no longer significant.
• Even during the 4-minute recovery trial, men ran at higher velocities but the values were not significantly different and the effect size was considerably low.

Interestingly the women still had the higher %VO2 peak values during all conditions - in other words, relative to their physical constitution, they were performing at a higher intensity than the men irrespective of the fact the latter were running faster. Interestingly the difference was only significant during the 4-min rest condition (if you look at the data in figure 1 you will realize they had to pay for that dearly).

"Apropos active rest - what's the best?"
If you take a closer look at the data in figure 1, you will realize that the 4-min-condition with a work-to-rest ratio of 4:2 (in other words, the 2min rest-condition) appears to have a slight advantage over the other conditions. While the VO2 max may be ~1% higher in the short rest condition (VO2 data not shown), this is not worth the increased exertion both men and women experienced when they ran their 4-min intervals with only 1min of active rest in-between.

Figure 1: Lactate levels, perceived readiness before the HIIT bout, rate of perceived exertion right after and 15min the self-paced HIIT bout with 1, 2 and 4min active rest between sets in male and female subjects; all data expressed relative to the mean value for the respective parameter, data calculated for men and women separately (Laurent. 2013)

As far as the 4:4 condition is concerned it is certainly remarkable that the female participants appear to totally exhaust themselves during that condition. It is difficult to determine, whether this is a result of "getting out of the groove" due to the long rest period (if you are jogging you may know that once you stop for more than a minute it's very difficult to get into the groove again), or whether that may be a result of the fact that they were pushing themselves harder when they knew there would be a long recovery period. Personally I tend to believe that it's the latter effect. Otherwise, the male participants of the study at hand should have experienced a similar negative effect of resting too long. Now, whether that's a sign of toughness or rather one of hubris is a question I'd rather not answer ;-)

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(Re)read the SuppVersity HIIT Series and learn about the optimal interval:rest ratios for your personal training goals (click here)

Bottom line: Whether you can truly argue, that 4:2 is the optimal ratio is at least in my humble opinion still open - regardless of your sex by the way. So, if you are not sure what to do, try a couple of different interval:rest ratios and see how you feel. Meanwhile, I'd suggest you remember that the word "training" comes from "to train" and refers to the "sustained practice [...] in an art, profession, occupation, or procedure, with a view to proficiency in it" (Oxford English Dictionary). Proficiency in this context means that you achieve performance increases and those are not a necessary (and in most cases not even a likely) consequence of feeling like you have been run over by a train.

Once you've figured out what works best for you, stick to it! I don't care if it's 2:1 or 30s:1min, as long as it works for you and you don't have to drag yourself to the track or the gym, whenever your HIIT sessions are due, that's your personal optimum. You should still keep in mind that this optimum may change with your current performance / weight loss / hypertrophy goals and the corresponding amount of energy you consume. Previous research, for example, suggests that long(er) intervals (in the 4min range) could have a slight edge over very short ultra-intense ones, especially when your primary goal is to shed body fat (learn more in the HIIT Special Part I & Part II)

References: 

• Laurent CM, Vervaecke LS, Kutz MR, Green JM. Sex specific responses to self-paced, high-intensity interval training with variable recovery periods. J Strength Cond Res. 2013 Jul 8. [Epub ahead of print]