Effects of 7 days of arginine-alpha-ketoglutarate supplementation on blood flow, plasma L-arginine, nitric oxide metabolites, and asymmetric dimethyl arginine after resistance exercise

Journal Title (Medline/Pubmed accepted abbreviation): Int. J. Sport Nutr. Exerc. Metab
Year: 2011
Volume: 21
Page numbers: 291-299

Summary of background and research design:

Background: Nitric oxide is a molecule that causes blood vessels to dilate, thereby allowing nutrients to be delivered to and waste products from cells more efficiently.  Nitric oxide is synthesized from the amino acid arginine, so pure arginine and arginine-containing compounds (ex. arginine-alpha-ketoglutarate, AAKG) are marketed as supplements that increase levels of nitric oxide in the blood and therefore promote blood flow.  However, the effectiveness of these supplements is controversial.

Hypothesis: Because many studies have not seen benefits of alleged nitric oxide-promoting supplements, the authors hypothesized that NO2 Platinum would not have an effect on athletes’ hemodynamics (blood flow parameters).

Subjects: In total, 24 men who routinely weight train, age 22 ± 2 y, participated.

Experimental design: randomized, double-blind, placebo-controlled

Treatments:  NO2 Platinum- 12 tablets/day containing AAKG, distributed throughout the day or a placebo (apple pectin)

Protocol:  Participants were first familiarized with the protocol and their 1 repetition maxima were determined for elbow flexors.  The participants performed a resistance-exercise protocol before and after 7 days of supplementation.  The protocol included 3 sets of 15 reps of bicep-flexion exercises with as much weight as they could lift (approximately 70-75% of their 1RM) with 10 sec in between sets.  One blood sample was taken before exercise, one immediately after, and one 30 min after.  Blood was analyzed for l-arginine, nitric oxide metabolites (e.g., nitrate and nitrite), and ADMA (an arginine antagonist).  The participants were also assessed for blood flow, heart rate, blood pressure, and mean arterial blood pressure at the same 3 time points.

Summary of research findings:
  • Heart rate, blood flow, systolic and diastolic blood pressure, and mean arterial blood pressure were greater immediately after exercise compared with before exercise for both groups, both before and after supplementation.  There were no differences between groups.
  • The concentration of l-arginine was significantly increased in the NO2 Platinum supplementation group compared to their levels pre-supplementation and compared to the placebo group (p = 0.003).
  • Nitrate and nitrite concentrations were significantly greater immediately after exercise for both groups both before and after supplementation with no difference between groups.
  • The ADMA concentration was less in the NO2 Platinum group before resistance training after supplementation.  (This compound competes with arginine in arginine transport.  Therefore, higher levels mean that nitric oxide production will be hindered.  In other words, low levels are best.)

Key practice applications:

Despite the significant increase in plasma arginine levels, there was not a difference in the supplemented athletes versus placebo before or after the resistance exercise in regard to blood flow or other hemodynamics.  Based on other literature, it is thought that a larger dose of arginine (perhaps about 15 g/day or higher) is required to impact hemodynamics.  It is clear that the vast majority, if not all, of the commercial arginine-based “nitric oxide boosters” do not provide this level of arginine

Because nitric oxide is very difficult to measure directly, the nitrate and nitrite concentrations was measured as a surrogate.  Also, performance during resistance training was not measured.  It would have been interesting to observe whether athletes could lift heavier weight, experienced less perceived effort, etc. during the exercise bout with supplementation.
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