In defense of the Holman index: Defining fatty acid deficiency

Essential fatty acid deficiency (EFAD) is a rare but serious condition with significant consequences including delayed growth and development, decreased immune response and reproductive dysfunction, among others. EFAD is of particular concern in vulnerable populations such as preterm infants and those receiving long-term parenteral nutrition (PN). As essential fatty acids (EFAs) must be supplemented in the diet due to the inability to synthesize these endogenously, EFAD develops secondary to inadequate EFA intake. The Holman Index, defined by the ratio of Mead acid to arachidonic acid (triene: tetraene (T:T)) in the plasma, has historically served as the method for diagnosis, with the threshold diagnostic value at ≥0.20. This index is derived from the body's natural metabolic response to EFA deprivation, increasing synthesis of Mead acid, and thus remains broadly applicable across various populations. Concerns regarding the established ratio and alternative use of absolute fatty acid values and profiles have been raised that question the utility of the Holman Index. Although recent developments in fatty acid profiling have allowed for increased precision in measurement and development of population-specific reference ranges, reliability of this data in diagnosing EFAD is controversial given variability amongst different studies and population dietary confounders. Data from animal and human studies have demonstrated that the Holman index has continued to reliably detect EFAD even in the era of new lipid emulsions and technological advancements. The Holman Index remains a vital tool in the diagnosis and monitoring of EFAD, offering consistency and early detection capacity in at-risk populations.