25 g 34.6 ± 6.9 32.1 ± 7.2 31.8 ± 5.7 28.2 ± 4.6 27.9 ± 5.0 5.00 g 32.9 ±

8.4 29.1 ± 6.9 28.4 ± 8.0 27.3 ± 8.0 28.2 ± 7.4 Data are mean ± SEM. No statistically significant interaction (p = 0.99), SIS3 cell line dosage (p = 0.69), or time (p = 0.91) effects noted. Study involved a cross-over design with subjects BMS-907351 chemical structure consuming either 1.25 or 5.00 grams of betaine in a single ingestion; blood samples collected Pre, 30, 60, 90, and 120 min post intake. Table 6 Plasma nitrate/nitrite (μmol∙L-1) for subjects in Study 2 Condition Pre Intervention Post Intervention Placebo 24.3 ± 4.8 17.5 ± 2.4 Betaine 22.4 ± 3.4 19.6 ± 3.1 Data are mean ± SEM. No statistically significant interaction (p = 0.57), condition (p = 0.98), or pre/post intervention (p = 0.17) effects noted. Study involved a cross-over design with subjects consuming 2.5 grams of betaine or a placebo daily for 14 days; 21 day washout period

between each condition; blood samples collected before (Pre Intervention) and after (Post Intervention) each 14 day period. Table 7 Plasma nitrate/nitrite (μmol∙L-1) and nitrite (nmol∙L-1) for subjects in Study 3   Pre Intervention Post Intervention 30 min post intake 60 min post intake Nitrate/Nitrite 18.6 ± 3.1 18.2 ± 2.9 18.0 ± 3.2 16.4 ± 3.0 Nitrite 1418.3 ± 137.5 1466.3 ± 146.9 1366.4 ± 148.1 1369.8 ± 200.6 Data are mean ± SEM. No statistically significant effect noted for nitrate/nitrite (p = 0.97) or nitrite (p = 0.97). Study involved subjects consuming 6 grams of betaine daily for 7 days; blood samples collected before (Pre PR-171 cell line Intervention) and after (Post Intervention) the 7 day period; Post intervention, subjects consumed 6 grams of betaine and blood samples were collected 30 and 60 min post intake. Discussion When collectively considering data obtained from the three separate Doxorubicin mw studies, we report that acute or chronic ingestion of betaine does not impact plasma

nitrate/nitrite in exercise-trained men. These findings contradict those of Iqbal and coworkers [17, 18], and suggest that other mechanisms aside from increasing circulating nitric oxide are likely responsible for the reported ergogenic benefit of betaine supplementation that has been reported by others [5, 6]. Of course, our omission of exercise performance measures within the present manuscript may be considered a limitation of this work. When considering the findings presented here along with those of Iqbal and colleagues [17, 18], it is possible that differences in the subject sample may be responsible for the differing results. Specifically, our subjects were young, healthy, exercise-trained men, while those in the Iqbal work were simply reported to be “”healthy volunteers”". Further work is needed to replicate the findings of Iqbal and colleagues [17, 18] in middle and older age adults, to determine if individuals other than healthy, exercise-trained men benefit from betaine supplementation in terms of elevating circulation nitrate/nitrite.