Dukan Diet

If you want other to see your pump, you got to be ripped. If not, why care about reductions in BMR?

If you remember my posts about the first generation, arginine-based pre-workout products you will be aware that the only pump they produced was the word "pump" in their name or product description. The reason was and still is simple. The mere provision of l-arginine, which is a precursor to nitric oxide does not lead to an increase in nitric oxide production. Why? Well, think of a building a house: Just buying some concrete wont make you a proud home owner, either ;-)

The bad thing: Arginine didnt work. The good thing: This means it didnt decrease your BMR, either

Against that background its quite astonishing that arginine and citrulline based pre-workout products have dominated the top-seller lists of the big supplement vendors for decades. A fact thats probably partly due to other potential benefits of these amino acids, of which one - you as a SuppVersity reader know that - could be fat loss | learn more about the potential fat loss effects.
With more and more people openly declaring that they would no longer waste money on "good tasting, but expensive and disfunctional products", they industry was yet pressed to develop alternatives. Luckily, our body has two options it can chose from, when producing nitric oxide.

Fortunately, the industry has developed better alternatives...?

You know option #1, the arginine ➲ nitric oxide pathway, and - with all the hype and hyperbole that surrounded the introduction of the first nitrate supplements - I am pretty sure, you know the other one as well, the nitrate-nitrite ➲ nitric oxide pathway

Figure 1: The Arginine- and the Nitrate-Nitrite - NO pathway are the yin and yan of nitric oxide production (Lundberg. 2008).

As the illustration (Figure 1) I have "borrowed" from a comment by Jon. O. Lundberg et al. (2008) illustrates quite nicely, the arginine and nitrite nitric oxide pathway are the yin and yan of NO production.

With the "yan", i.e. the nitrate-nitrite ➲ nitric oxide pathway being a relatively "new kid on the NO block", that recycles (=reduces) inorganic anions nitrate and nitrite to form bioactive NO in blood and tissues during physiological hypoxia.

It goes without saying that there is a bottle neck to this process as well, but the rate limiting availablility of oxygen which hampers the argine-based NO generation by NOS becomes limited as oxygen levels fall is actually a signal for the nitrate–nitrite ➲ nitric oxide to really kick in.

There is more yin and yan, here

If you take a closer look at the results of a study in the America Journal of Clinical Nutrition (Figure 2), you will yet have to realize that there is "more yin and yan", here than youd probably hope for. According to the data scientists from the venerable Karolinska Institutet in Stockholm, Sweden, present in their paper, "[d]ietary inorganic nitrate reduces the RMR." (Larsen. 2014)

Figure 2: VO2 consumption (marker of fatty acid oxidation) and basal metabolic rate (BMR) relative to means (left), thyroid hormone (T3, T4) levels after 3-d dietary intervention with sodium nitrate (Larsen. 2014)

Whut? Yes, you read Larsen et al. right: In their randomized, double-blind, crossover study, in the course of which the Swedish scientists measured the resting metabolic rate (RMR) of 13 perfectly healthy 18–49 y olds (17 women) via indirect calorimetry after a 3-d dietary intervention with sodium nitrate (NaNO3 @ 0.1mmol/kg body weight) or a placebo (NaCl), Larsen, Schiffer, Ekblom et al. observed a statistically and (probably) physiologically significant reduction BMR reduction of 4.2% which correlated strongly to the degree of nitrate accumulation in saliva (r²= 0.71) and fits in nicely with the reduced O2 consumption of which Bailey et al. were the first to observe it in response to nitrate supplementation during exercise (Bailey. 2009).

Interestingly, these effects were not - as you may have been speculated - brought about by changes in thyroid hormone status. And the subjects insulin sensitivity, glucose uptake, plasma concentration of isoprostanes, as well as their total antioxidant capacity were unaffected, as well.
Reference:

• Bailey, Stephen J., et al. "Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans." Journal of Applied Physiology 107.4 (2009): 1144-1155.
• Hotta, Yuji, et al. "Oral l‐citrulline supplementation improves erectile function and penile structure in castrated rats." International Journal of Urology (2014).
• Larsen, Filip J., et al. "Dietary inorganic nitrate improves mitochondrial efficiency in humans." Cell metabolism 13.2 (2011): 149-159.
• Lundberg, Jon O., Eddie Weitzberg, and Mark T. Gladwin. "The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics." Nature Reviews Drug Discovery 7.2 (2008): 156-167.
• Neuzillet, Y., et al. "A randomized, double‐blind, crossover, placebo‐controlled comparative clinical trial of arginine aspartate plus adenosine monophosphate for the intermittent treatment of male erectile dysfunction." Andrology 1.2 (2013): 223-228.

The meager increase in glucose disposal observed in the study at hand is not likely to do anything, but be good for another confusing graph on the label of the licensees first OpunDia powered supplements.

Against the background that insulin still has a pretty bad rep, it is actually quite funny that its fiercest enemies and most loyal followers of low-carb diets are usually the guys and girls who spent tons of money on 100% useless "insulin mimetics". Insulin mimetics like the cactus extract thats at the heart of a recent study by Louise Deldicque, Karen Van Proeyen, Monique Ramaekers, Ivo Pischel, Hartwig Sievers and Peter Hespel? Or could it be possible that Opuntia Ficus-Indica is the infamous exception that proves the rule?

To answer this question, it is obviously necessary that we take a closer look at the corresponding paper in the Journal of the International Society of Sports Nutrition (ISSN). I mean, it is not impossible that this is finally the "next big thing" weve all been waiting for, right?

Leucine + Herb = Win?

Before we dig further into the methods and results of the study, it it probably suitable for me to tell you about the meaningful letters "™" behind the word OpunDia and the openly declared competing interests of Ivo Pischel and Hartwig Sievers.
Enough of the foreplay , though, lets finally take a look at the design and the results of this human trial that was conducted by the Exercise Physiology Research Group at the Department of Kinesiology of KU Leuven in Belgium (Deldicque. 2013).

There were 11 male subjects who participated in the study. All were physically active and the mean age was 21.1 ± 0.9 years. With a body weight of of 74.5 ± 4.2 kg and a VO2 max (~fitness level) of 65 ± 4 ml·min/kg), they are probably representative of the average, but not necessarily the extra-extraordinaire trainee.

After the usual pre-testing procedures, the guys were randomized to receive either

• 1,000 mg LUVOS Heilerde serving as placebo (PL),
• 1,000 mg OpunDia™ (OFI), 
• 3,000 mg of old-fassioned leucine (LEU), or 
• 1,000 mg OpunDia™ + 3,000 mg leucine (OFI+LEU).

After each of the four randomized cross-over testing session that involved 30min of rather casual cycling at 70% of the predetermined VO2 max (90-100 rpm) the subjects received capsules containing one of the above formulations and the 75g of glucose that were used for the oral glucose tolerance tst.. Needless to say that all capsules had identical appearance and the number of capsules ingested was the same for each condition.

It works, but what does that tell us?

In a previous trial, Van Proeyen et al. had already observed that the ingestion of an identical supplement stimulates the peripheral disposal of oral glucose before and after exercise in healthy men. If you will, you may thus call the study at hand a follow up, which did - what a surprise (!) - confirm the effects of OFI and a certain, but not exactly impressive synergism between the plant extract and everyones favorite amino acid leucine, one of the branched chain amino acids and, as SuppVersity readers know, likewise highly pro-insulinogenic (learn more about leucine).

Figure 1: Glucose and insulin iAUC after oral glucose test performed subsequent to the ingestion of PL, OFI, LEU or LEU + OFI supplement and 30min of "cardio" at 70% of the VO2max (left); glucose levels in the 2h after the OGGT (Deldicque. 2013)

A cursory glance at the data in Figure 1 should suffice to see two things: (1) There was the expected / hoped for synergistic effect of leucine and OFI, but (2) only the OFI-only trial, and not the combination treatment led to significant reductions in the area under the glucose curve.

Is this even an improvement?

Remember that chromium picolinate can worsen the insulin sensitivity in  healthy non-diabetic, non-obese individuals by up to 25% | learn more

"Add Leucine and get more insulin, but a lower rate of glucose disposal"... I dont know what youd say, but for me this sounds much like insulin resistance or lets rather say no improvement over the provision of OFI alone. The first take-home message is thus that the addition of leucine to OFI may produce a synergistic effect on insulin, the effect we are actually looking for, namely the increase in blood glucose uptake and glycogen synthesis is however absent. And whats more, neither I nor the researchers have an real clue as to what it is that triggers the short-lived increase in insulin production thats brought about by the ingestion of 1,000mg Opuntia Ficus-Indica extract.

Accordingly, it is very difficult to give any prognosis whether more would help more, or the whether wed see similar detrimental effects as with chromium upon dose escalation.
References:

• Manders RJ, Little JP, Forbes SC, Candow DG. Insulinotropic and muscle protein synthetic effects of branched-chain amino acids: potential therapy for type 2 diabetes and sarcopenia. Nutrients2012. 4:1664–1678.
• Van Loon LJ, Saris WH, Kruijshoop M, Wagenmakers AJ. Maximizing postexercise muscle glycogen synthesis: carbohydrate supplementation and the application of amino acid or protein hydrolysate mixtures. Am J Clin Nutr. 2000,72:106–111.
• Van Loon LJ, Kruijshoop M, Verhagen H, Saris WH, Wagenmakers AJ. Ingestion of protein hydrolysate and amino acid-carbohydrate mixtures increases postexercise plasma insulin responses in men. J Nutr. 2000, 130:2508–2513.
• Van Proeyen K, Ramaekers M, Pischel I, Hespel P. Opuntia ficus-indica ingestion stimulates peripheral disposal of oral glucose before and after exercise in healthy men.Int J Sport Nutr Exerc Metab 2012,22:284–291
• Wiese J, McPherson S, Odden MC, Shlipak MG. Effect of Opuntia ficus indica on symptoms of the alcohol hangover. Arch Intern Med. 2004 Jun 28;164(12):1334-40.