Lactose intolerance (adult-onset)

Clinically, lactose intolerance presents with symptoms such as bloating, abdominal pain, flatulence, and diarrhoea after consuming lactose-containing foods. Symptom severity varies widely and depends on residual lactase activity, the amount of lactose ingested, and individual gut microbiome composition. While symptoms are typically benign, they can significantly affect quality of life and dietary habits. Importantly, lactose intolerance must be distinguished from cow’s milk protein allergy, irritable bowel syndrome, and other gastrointestinal conditions.

Lactose intolerance is one of the most common enzyme deficiencies worldwide, but its prevalence varies by population. High rates are observed in East Asian, African, Middle Eastern, and South American populations, while lactase persistence is more common in individuals of Northern European ancestry. These global patterns reflect evolutionary adaptations to dairy consumption and are closely linked to specific population genetics mechanisms.

Adult-type lactose intolerance is primarily caused by genetically programmed down‑regulation of lactase expression. Intestinal lactase activity declines physiologically from approximately age 5 years onwards, and clinical symptoms typically manifest from late childhood through early adulthood, progressing with advancing age. This process is controlled by regulatory variants in the MCM6 gene, which influence expression of the adjacent LCT gene. The most studied variant is the −13910C>T polymorphism, where the T allele is associated with lactase persistence. Individuals with the ancestral C allele typically experience reduced lactase activity in adulthood.

Lactase persistence and non‑persistence follow an autosomal dominant pattern with incomplete penetrance. Individuals carrying at least one persistence allele (e.g., −13910T) usually maintain lactase activity into adulthood, while those homozygous for the non‑persistence allele (−13910C) are predisposed to lactose intolerance. Therefore, genetic testing provides a clear and lifelong indicator of lactase status.

Diagnosis may involve hydrogen breath testing, lactose tolerance testing, or symptom-based dietary trials. However, genetic testing provides a reliable, non‑invasive method to determine lactase persistence or non‑persistence by analysing regulatory variants upstream of the LCT gene. Molecular diagnostics are particularly useful when breath testing is contraindicated, inconclusive, or impractical. Our laboratory offers validated assays for the key variants associated with adult-type hypolactasia.

Symptoms of lactose intolerance overlap with several gastrointestinal disorders, including irritable bowel syndrome, small intestinal bacterial overgrowth, , and inflammatory bowel disease. Additionally, secondary lactose intolerance may occur temporarily after gastrointestinal infections or in association with mucosal damage. Accurate differentiation is essential to avoid unnecessary dietary restrictions and to identify underlying conditions requiring treatment.

• Genetic testing offers a precise method to determine lactase persistence status and supports clinicians in distinguishing primary lactose intolerance from other causes of gastrointestinal symptoms.
• It provides lifelong, unchanging information that can guide dietary counselling, prevent misdiagnosis, and reduce the need for more invasive or burdensome diagnostic procedures.
• For laboratories, LCT genotyping is a robust and clinically valuable component of personalised nutrition and gastroenterological diagnostics.

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• Malyarchuk BA. Genetic aspects of lactase deficiency in indigenous populations of Siberia. Vavilovskii Zh Genet Sel. 2024;28(6):650-658. doi:10.18699/vjgb-24-72. PMID: ; PMCID: PMC11491482.