Monday, January 11, 2016

5-aminolevulinic Acid + Iron Gets Old Mitochondria Going Again - Already Trained Older Women Work Out 10%+ More Efficiently at Every Workout Intensity Within Only 7 Days

Combination of 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) works by reviving the mitochondria.
Iron is not exactly something that has a good rep in health and fitness circles on the Internet. That's at least partly a result of a lack of understanding of the importance of iron to human health and performance. Iron, or rather heme, the non-protein, insoluble, iron protoporphyrin, which is constituent of hemoglobin, of various other respiratory pigments, and of many cells, is in fact essential to the comlex IV activity (cytochrome c oxidase). Without it, the energy production in our cells would malfunction or even come to a complete halt.

It is thus wonder that multiple studies show how even a mild iron-deficiency can significantly impair human physical and cognitive performance.  Unfortunately, eating more meat and even supplementing with iron often isn't enough to restore the iron levels to normal.
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Scientists from the Shinshu University Graduate School of Medicine in Japan did therefore take a slightly different approach to optimize the iron levels of a group of older women. More specifically, Masuki et al. speculated that the oral ingestion of  5-aminolevulinic acid (ALA), which can be found in many foods and is the sole initial material of heme biosynthesis in vivo, could be used alongside iron, instead of high and, as previously pointed out, often ineffective doses of iron to increase the exercise efficiency and thereby improve the training achievement in older women. To examine this hypothesis, the Japanese researchers conducted a randomized, placebo-controlled, double-blind crossover study in older women. The 10 subjects were recruited from 547 participants of the “Jukunen Taiikudaigaku Project,” which is a health promotion program for middle-aged and older people in Matsumoto City, Japan. The participants had performed the corresponding interval walking training (IWT) program for more than 12 mo before this study; therefore, they were familiar with the exercise testing procedures used in the present study and - more importantly fit and not the average elderly study subject from whom the training alone will yield so significant benefits that additive effects of the supplement couldn't been measured; or, as the scientists have it ...
"[the subjects'] exercise efficiency had likely reached the steady state and would thus enable us to detect only the effects of ALA intake on their exercise efficiency without accounting for the acute effects of exercise training" (Masuki. 2015b).
The study was conducted in a placebo-controlled, double-blind crossover design. All subjects underwent two trials for 7 days each in which they performed IWT with ALA+SFC (100 and 115 mg/day, respectively) or placebo supplement intake (CNT), intermittently with a 2-wk washout period.
Figure 1: Experimental protocol. Ex, graded cycling exercise test; IWT, interval walking training. The study was conducted using a randomized, placebo-controlled, double-blind crossover design. In each supplement intake, subjects ingested 250 mg of either 5-aminolevulinic acid (ALA) + sodium ferrous citrate (SFC) or placebo supplement (250 mg × 2 = 500 mg/day). See Table 2 for details of the supplement compositions (Masuki. 2015b).
Before and after each trial, subjects underwent a graded cycling test at 27.0°C atmospheric temperature and 50% relative humidity, and oxygen consumption rate, carbon dioxide production rate, and lactate concentration in plasma were measured.
ALA + iron supplementation lead to sign. improvements in glycemia in an oral glucose tolarence test in low doses in mildly hyperglycemic and in high doses in all subjects of a 2013 study by Higashikawa.
Seriously, what about iron overload? Yes, you're right to ask. After all, the iron intake per day in the ALA+SFC trial was three times higher than the RDA value. Still, even though subjects showed no symptoms of iron deficiency anemia in the health examination before participating in the study, their [Hb] did not change after ALA+SFC supplementation. Since it is also "unlikely that SFC was independently incorporated into the mitochondrial function in the ALA+SFC trial", the scientists "surmise that the simultaneous ingestion of a mixture of ALA and iron ion is necessary to attain the results" (Masuki. 2015b) - an unquestionably reasonable assumption that is also consistent with several other studies assessing the effects of ALA combined with the iron ion, studies which showed among other things blood sugar and blood pressure lowering effects, made hair regrow (Higashikawa. 2013; Rodriguez. 2012; Mingone. 2006; Morokuma. 2008).
Furthermore, for the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry.
Table 1: Total energy, protein, fat, carbohydrate, ALA, and iron intake per day (Masuki. 2015b)
In spite of the fact that the subjects' food intake didn't differ significantly (see Table 1), the scientists found that, in the ALA+SFC trial, oxygen consumption rate and carbon dioxide production rate during graded cycling decreased by 12% (P < 0.001) and 11% (P = 0.001) at every workload, respectively, accompanied by a 16% reduction in lactate concentration in plasma (P < 0.001), although all remained unchanged in the CNT trial (P > 0.2).
Figure 2: Training days (A), training impulse (B), and training time (C) at total, fast, and slow walking during the supplement intake period. Ratio of subjects performing training to total subjects (D), training impulse (E), and training time (F) at fast walking on each day in the period of supplement intake. *p < 0.05, ***p < .001 compared with the CNT trial.
All of the reductions were significantly greater in the ALA+SFC than the CNT trial (P < 0.05). Furthermore, the number of days on which the subjects actually trained, the impulse to train, and the time at fast walking were 42% (P = 0.028), 102% (P = 0.027), and 69% (P = 0.039) higher during the ALA+SFC than the CNT intake period, respectively - a result that's particularly exciting in view of the effects that the main obstacle to life-style treatments for sarcopenia, obesity & co is that people simply don't adhere to their treatment.

Eventually, there's thus little debating that the ALA+SFC based iron-boost did the old ladies good, augmented exercise efficiency and thereby improved interval walking training achievement, even though the general consensus in the non-reference hearsay blogosphere is that older women have to stay away from "everything iron" (dietary or supplemental, not as in "weights" in the gym ;-).
Figure 3: In a previous study, Masuki et al. have just been able to show that there is a linear inverse relationship between older women's adherence to prescribe walking days (APWD; A) and fast walking time (APFWT; B) over the 22-mo training period with the change in lifestyle-related disease score (ΔLSD score) from baseline to 22 mo (Masuki. 2015a).
Bottom line: As the scientists point out in the conclusion to their paper, the higher training achievements they observed in response to ALA+SFC supplementation as a result of an increased exercise efficiency in older women who - and I'd like to highlight that - had performed habitual training before this study,  is associated with greater improvements in physical fitness and risk factors for lifestyle-related disease (Masuki. 2015a).

Therefore, it is correct that Masuki et al. assume that "this regimen would be useful to help older women continue habitual exercise training and thus improve their health" ... and let's be honest: isn't that what "supplements" are meant to do? | Comment!
  • Higashikawa, Fumiko, et al. "5-aminolevulinic acid, a precursor of heme, reduces both fasting and postprandial glucose levels in mildly hyperglycemic subjects." Nutrition 29.7 (2013): 1030-1036.
  • Masuki, Shizue, et al. "The factors affecting adherence to a long-term interval walking training program in middle-aged and older people." Journal of Applied Physiology 118.5 (2015a): 595-603.
  • Masuki, Shizue, et al. "Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women." Journal of Applied Physiology 120.1 (2015b): 87-96.
  • Mingone, Christopher J., et al. "Protoporphyrin IX generation from δ-aminolevulinic acid elicits pulmonary artery relaxation and soluble guanylate cyclase activation." American Journal of Physiology-Lung Cellular and Molecular Physiology 291.3 (2006): L337-L344.
  • Morokuma, Yuki, et al. "Hair growth stimulatory effect by a combination of 5‐aminolevulinic acid and iron ion." International journal of dermatology 47.12 (2008): 1298-1303.
  • Rodriguez, Beatriz L., et al. "Use of the Dietary Supplement 5‐Aminiolevulinic Acid (5‐ALA) and Its Relationship with Glucose Levels and Hemoglobin A1C among Individuals with Prediabetes." Clinical and translational science 5.4 (2012): 314-320.