Measurement of breath hydrogen and methane, together with lactase genotype, defines the current best practice for investigation of lactose sensitivity.

Currently, there is no 'gold standard' for detecting patients with sensitivity to lactose. Biochemical investigation by a breath hydrogen test alone detects <50% cases. Breath methane and symptoms are not recorded as standard practice. The clinical value of analysing C/T(13910) and G/A(22018) polymorphisms, strongly associated with lactose sensitivity, has not been established. Two hundred and ten patients with unexplained gut and systemic symptoms and controls were challenged with 50 g lactose. Breath hydrogen and methane were measured and symptoms recorded. All were genotyped for two polymorphisms, C/T(13910) and G/A(22018). CC(13910)/GG(22018) in 14.5%, CT(13910)/GA(22018) in 39% and TT(13910)/AA(22018) in 46.5%. One hundred percent of CC(13910)/GG(22018) were lactose sensitive having a breath hydrogen >20 ppm within 6 h and symptoms. But the breath hydrogen test lacked sensitivity and specificity in the other groups. There was elevated breath hydrogen in 21% of CT(13910)/GA(22018) and 15% of TT(13910)/AA(22018) by 6 h, whereas 17 and 30.9% had elevated breath methane alone. Breath methane and breath hydrogen with clinical symptoms improved sensitivity and specificity, increasing detection of lactose sensitivity in genotypes CT/GA and TT/AA from <50 to >75%. The data presented define the current best practice for the clinical identification of lactose sensitivity. Patients were first genotyped. Those identified as CC with symptoms should immediately undertake a 12-week lactose-free diet. Those identified as CT or TT should undertake a breath hydrogen and methane test. Those positive for hydrogen or methane along with symptoms or with symptoms only, should also undertake a lactose-free diet. Those with high hydrogen without symptoms should be investigated for causes other than lactose sensitivity.