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For example, one study conducted by Vogiatzoglou and colleagues shows that, when tHcy and MMA reached their breakpoints of 334 and 393 pmol/L respectively as defined as B12 replete, the B12 levels were 400 pmol/L.8 Another study by Selhub and colleagues shows similar results and suggests that tHcy and MMA, as metabolic markers, may replace or augment B12 level in the diagnosis of B12 deficiency.5 In a clinical trial of determining the relationship between the treatment effect and tHcy levels on brain atrophy over 2 years, half of the participants were treated with B12, B6 and folic acid to lower their tHcy levels.9 Results showed that brain atrophy was slowed by 30% compared to placebo, tHcy was lower by 30%, and plasma B12 was raised from 330 to 672 pmol/L

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174, 175 In the absence of placebo controls, it is difficult to know the size of the true treatment effect and the precise balance between benefits and risks/burdens