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. 2021 Aug 11;11(8):784. doi: 10.3390/jpm11080784

Table 2.

Biochemical outcomes for treatment studies of cobalamin injections for autism spectrum disorder. Clinical global impression scale (CGI); subcutaneous (SC); years old (yo).

Study Participants Treatment Outcomes
Subcutaneous Methylcobalamin Injections
Bertoglio et al., 2010 [55]
DBPC Crossover
30 64.5 µg/kg SC every 3 days Significant improvements in GSH and the GSH redox ratio in a subgroup of 9 children who were considered “responders”
Hendren et al., 2016 [35]
DBPC Parallel
57 75 µg/kg SC every 3 days Clinical improvements were positively associated with increased plasma methionine, decreased SAH, and improved methylation compacity as measured by the SAM/SAH ratio
James et al., 2004 [8]
Prospective Uncontrolled
8 75 µg/kg 2x/wk for 1 month with folinic acid and betaine Decreased adenosine and GSSG; increased methionine, cysteine, tGSH, SAM/SAH, and tGSH/GSSG
James et al., 2009 [11]
Prospective Uncontrolled
40 75 µg/kg 2x/wk for 3 months with folinic acid Increased cysteine, cysteinylglycine, and GSH;decreased GSSG
Frye et al., 2013 [53]
Prospective Uncontrolled
Clinical improvements associated with biochemical improvements in GSH redox status
Geier and Geier 2010 [56] Retrospective, controlled 24 75 µg/kg SC every 1–3 days Urinary and plasma cobalt levels higher in mB12 group
Intramuscular Methylcobalamin Injections
Nashabat et al., 2017 [51]
Retrospective Uncontrolled
cB12 switched to mB12; one child received hB12 Improvement in anemia and metabolic acidosis when cB12 was changed to mB12; homocysteine normalized with 10 mg of hB12 orally in one child
Oral Cobalamin with Other Vitamins
Adams et al., 2011 [49]
DBPC Parallel
141 500mcg Daily Orally Improvements in total sulfate, SAM, reduced GSH, GSSG:GSH, nitrotyrosine, ATP, NADH, and NADPH
Kaluzna-Czaolinska et al., 2011, [44]
Prospective Uncontrolled
30 B12 1200 mcg per day with vitamin B6 200 mg and folic acid 400 µg Reduction in urinary homocysteine
Cobalamin with Route of Administration Not Specified
Delhey et al., 2017 [45]
Prospective Uncontrolled
127 Any B12 taken in 38% of Patients along with other supplements Improved coupling of Complex I and Citrate Synthase mitochondrial enzymes
Nakano et al., 2005 [52]
Prospective Uncontrolled
13 mB12 25–30 µg/kg/day (up to 1500 µg) for 6–25 months Increased B12 blood concentrations