Intrinsic Factor (IF) is scientifically validated as essential for the treatment of pernicious anemia. Pernicious anemia is an autoimmune condition where the body’s immune system attacks the gastric parietal cells or the intrinsic factor itself, leading to a deficiency of intrinsic factor. This glycoprotein is crucial for the absorption of vitamin B₁₂ (cobalamin) in the terminal ileum. Without intrinsic factor, dietary vitamin B₁₂ cannot be efficiently absorbed, resulting in vitamin B₁₂ deficiency and subsequent megaloblastic anemia.

The relationship between intrinsic factor and pernicious anemia was first elucidated in the 1920s and 1930s, and it remains a foundational concept in hematology. Historically, patients with pernicious anemia were treated with large amounts of liver, which is rich in vitamin B₁₂. Once the necessity of intrinsic factor for absorption was understood, direct administration of vitamin B₁₂ (bypassing the need for intrinsic factor) became the standard of care. In rare circumstances, oral supplements containing intrinsic factor have been explored, but parenteral vitamin B₁₂ remains the mainstay because the autoimmune destruction of intrinsic factor often makes replacement ineffective.

In summary, the scientific evidence is robust: intrinsic factor is required for vitamin B₁₂ absorption, and its deficiency is the primary defect in pernicious anemia. However, clinical treatment focuses on bypassing the need for intrinsic factor by administering vitamin B₁₂ intramuscularly or via high-dose oral routes.