It is well known that caloric restriction leads to an increased longevity by forestalling age-related diseases.
Dietary restriction of methionine also renders similar benefits. In this review, we report studies on the effect of methionine
restriction on epithelial barrier function in a renal epithelial LLC-PK1 cell, a rodent gastrointestinal model and a clinical
trial using Crohn’s patients. In LLC-PK1 cell culture, a reduction of culture medium methionine by 80% resulted in
altered tight junctional claudin composition with improved epithelial barrier function as exemplified by increased transepithelial
electrical resistance and decreased paracellular leak to 14C-D-mannitol. In addition to small but significant
reductions in plasma and intracellular colonocyte methionine levels, dietary methionine restriction tightens intestinal
epithelium and reduces mannitol permeability in rat colonic, but not ileal tissue. Crohn’s patients on methionine-restricted
diet reported improved symptoms as demonstrated by a reduced CDAI index, but this diet was not able to significantly
reduce the plasma methionine level in patients recruited. An increased urinary lactulose/mannitol ratio was also the result
of the regimen in Crohn’s patients, suggesting an increased, rather than decreased ileal leakage. Overall, our results
showed that reduction in dietary intake of methionine is promising in improving at least some epithelial barriers and this
may be through altering tight junctional protein compositions. Methionine restriction might result in contrasting effects
depending on the tissue type and possible disease conditions, thus wider range of studies are required.