♦ Vitamin D-Dependent Active Transport Pathway
In the conventional pathway, calcium absorption occurs primarily through an active transport mechanism regulated by vitamin D in the small intestine, particularly the duodenum. The active form of vitamin D, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), upregulates the expression of calcium-binding proteins such as calbindin-D9k. This protein facilitates the transcellular movement of calcium ions (Ca²⁺) across enterocytes. Upon entering the bloodstream, approximately 40% of this absorbed calcium rapidly binds to albumin, a major plasma protein, forming a protein-bound calcium complex. An additional 10% complexes with anions (e.g., phosphate, citrate), leaving only about 50% as free, ionized calcium (Ca²⁺). The protein-bound fraction is physiologically inactive, as it cannot readily participate in cellular signaling, muscle contraction, or other Ca²⁺-dependent processes.
♦ SAC Calcium Passive Transport Pathway
In contrast, SAC (Sigma Anti-bonding Calcium) is absorbed via a passive transport mechanism, independent of vitamin D and calbindin. This paracellular pathway relies on diffusion through tight junctions in the intestinal epithelium, driven by concentration gradients. Once in the bloodstream, SAC calcium exists as a hydrated ion, stabilized by a coordinate covalent bond of six water molecules (Ca(H₂O)₆²⁺). This coordinate covalent bond sterically hinders binding to albumin and other plasma proteins, maintaining a higher proportion of calcium in its free, ionized form (Ca²⁺). As a result, SAC-derived calcium remains bioavailable as physiological ionic calcium, capable of directly influencing cellular functions, suppressing parathyroid hormone (PTH), and enhancing bone mineralization or other Ca²⁺-mediated effects without the limitations imposed by protein binding.
♦ Summary
Vitamin D Pathway: Active transport → ~40% albumin-bound calcium, ~50% free Ca²⁺ → limited physiological activity of bound fraction.
SAC Pathway: Passive transport → coordinate covalent bond (Ca(H₂O)₆²⁺) prevents albumin binding → predominantly free Ca²⁺ → enhanced physiological activity.
This distinction SAC calcium’s unique ability to increase bioavailable Ca²⁺ in plasma, potentially offering therapeutic advantages over conventional calcium sources.
