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It typically begins with declining blood levels (stage I), followed by low cellular levels (stage II), increased homocysteine levels and reduced DNA synthesis (stage III), and finally macrocytic anemia (stage IV)

Symptoms include severe, persistent abdominal pain radiating to the back, often accompanied by nausea and vomiting that differs qualitatively from the typical GI side effects

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This is considered the ceiling for research and advanced applications

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