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Cobalamin deficiency results in the decrease of this conversion, resulting in high plasma levels of homocysteine, which is associated with a higher risk of cerebrovascular disease, depression, dementia, cellular stress, and apoptosis (64, 70)

However, prolonged or excessive ER stress cannot effectively be restored by UPR, thus leading to cell death

What the Evidence Actually Supports The 2025 AAOS systematic review (Vasireddi et al.) identified 35 preclinical and only 1 human study meeting inclusion criteria