Abstract
BackgroundAdult lactase non-persistence (LNP) is due to low lactase expression, resulting in lactose malabsorption (LM). LNP is a genetic trait, but is typically determined by LM markers including breath H2, blood glucose, and urinary galactose after a lactose tolerance test. Known validity of these markers using milk is limited, despite being common practice. Compositional variation, such as β-casein variants, in milk may impact diagnostic efficacy. This study aimed to evaluate the diagnostic accuracy to detect LNP using these commonly measured LM markers after both lactose and milk challenges.MethodsFourty healthy young women were challenged with 50 g lactose then randomized for separate cross-over visits to ingest 750 mL milk (37.5 g lactose) as conventional (both A1 and A2 β-casein) and A1 β-casein-free (a2 Milk™) milk. Blood, breath and urine were collected prior to and up to 3 h following each challenge. The presence of C/T13910 and G/A22018 polymorphisms, determined by restriction fragment length polymorphism, was used as the diagnostic reference for LNP.ResultsGenetic testing identified 14 out of 40 subjects as having LNP (C/C13910 and G/G22018). All three LM markers (breath H2, plasma glucose and urinary galactose/creatinine) discriminated between lactase persistence (LP) and LNP following lactose challenge with an area under the receiver operating characteristic (ROC) curve (AUC) of 1.00, 0.75 and 0.73, respectively. Plasma glucose and urinary galactose/creatinine were unreliable (AUC < 0.70) after milk ingestion. The specificity of breath H2 remained high (100%) when milk was used, but sensitivity was reduced with conventional (92.9%) and a2 Milk™ (78.6%) compared to lactose (sensitivities adjusted for lactose content). The breath H2 optimal cut-off value was lower with a2 Milk™ (13 ppm) than conventional milk (21 ppm). Using existing literature cut-off values the sensitivity and specificity of breath H2 was greater than plasma glucose to detect LNP following lactose challenge whereas values obtained for urinary galactose/creatinine were lower than the existing literature cut-offs.ConclusionThis study showed accurate diagnosis of LNP by breath H2 irrespective of the substrate used, although the diagnostic threshold may vary depending on the lactose substrate or the composition of the milk.Trial registrationACTRN12616001694404. Registered prospectively on December 9, 2016.
Highlights
Adult lactase non-persistence (LNP) is due to low lactase expression, resulting in lactose malabsorption (LM)
This study showed accurate diagnosis of LNP by breath H2 irrespective of the substrate used, the diagnostic threshold may vary depending on the lactose substrate or the composition of the milk
The cut-off calculated after lactose challenge for both breath H2 and plasma glucose was higher (79 ppm and 1.77 mmol/L) than the literature cut-offs (20 ppm [23,24,25] and 1.11 mmol/L [12, 26]) whereas urine galactose concentrations were generally 10 fold lower than concentrations previously reported, probably due to variation in the method used resulting in a lower threshold (0.03 mg/mg) than previously reported (0.10 mg/mg) [28]
Summary
Adult lactase non-persistence (LNP) is due to low lactase expression, resulting in lactose malabsorption (LM). LNP is a genetic trait, but is typically determined by LM markers including breath H2, blood glucose, and urinary galactose after a lactose tolerance test. Known validity of these markers using milk is limited, despite being common practice. Different methods are currently used to diagnose LNP, of which measuring lactase activity in an intestinal biopsy is the proposed “gold standard” [9, 10]. This is an invasive technique for a relatively minor condition. Cost-effective and less invasive methods are preferred [11, 12]
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