LCT/MCM6 (rs4988235): Lactose Tolerance

January 2026

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The ability to digest lactose (milk sugar) as an adult is actually a relatively recent genetic adaptation in humans. The rs4988235 variant near the LCT gene determines whether you maintain lactase enzyme production into adulthood, affecting your ability to consume dairy without digestive distress. This is one of the clearest examples of recent human evolution driven by diet.

Disclaimer: This information is educational. Lactose intolerance symptoms can overlap with other conditions. Consult a healthcare provider for proper diagnosis and guidance.

What is Lactase Persistence?

Lactase is the enzyme that breaks down lactose, the primary sugar in milk. All human infants produce lactase to digest breast milk. In most mammals (and most humans historically), lactase production decreases after weaning - this is the ancestral state called "lactase non-persistence" or "lactose intolerance."

However, some populations developed genetic variants that maintain lactase production throughout life - "lactase persistence" - allowing continued dairy consumption as adults.

The rs4988235 Variant

This SNP is located in the MCM6 gene, which regulates expression of the nearby LCT (lactase) gene:

  • TT (T/T): Lactase persistent - maintains lactase production into adulthood; can digest lactose
  • CT (C/T): Lactase persistent - one copy is sufficient for continued production
  • CC (C/C): Lactase non-persistent - lactase production declines after childhood; lactose intolerant

Note: This is the primary European lactase persistence variant. Other populations have different variants (e.g., African pastoralist populations have distinct mutations).

Evolutionary History

Lactase persistence is a remarkable example of recent human evolution:

  • The European T allele arose approximately 7,500-10,000 years ago
  • Coincides with the spread of dairy farming (cattle domestication)
  • Spread rapidly due to strong selective advantage (additional nutrition source)
  • One of the strongest signals of recent positive selection in the human genome
  • Multiple independent mutations arose in different dairy-farming populations

Prevalence

Lactase persistence frequency reflects historical dairy farming practices:

  • Northern European ancestry: 80-95% lactase persistent
  • Southern European: 50-70% persistent
  • Middle Eastern: 20-50% persistent
  • East Asian: 5-10% persistent
  • African (varies by region): 5-50% (higher in pastoralist groups)
  • Native American: 0-20% persistent

Symptoms of Lactose Intolerance

If you have the CC genotype and consume lactose, undigested lactose passes to the colon where bacteria ferment it, causing:

  • Bloating and gas
  • Abdominal cramps
  • Diarrhea
  • Nausea
  • Symptoms typically occur 30 minutes to 2 hours after dairy consumption

Dietary Strategies

For Lactose Intolerant Individuals (CC)

Foods typically tolerated:

  • Hard, aged cheeses: Parmesan, cheddar, Swiss - most lactose removed during aging
  • Butter: Very low lactose content
  • Yogurt and kefir: Bacterial cultures pre-digest much of the lactose
  • Lactose-free dairy products: Treated with lactase enzyme
  • Small amounts: Many people can tolerate small amounts (threshold varies)

Foods to limit or avoid:

  • Milk (whole, skim, low-fat)
  • Ice cream
  • Soft cheeses (cottage cheese, ricotta)
  • Cream-based sauces and soups
  • Many processed foods (check labels for milk ingredients)

Calcium alternatives:

  • Fortified plant milks (almond, oat, soy)
  • Leafy greens (kale, bok choy, broccoli)
  • Fortified orange juice
  • Canned fish with bones (sardines, salmon)
  • Tofu (calcium-set)

Lactase Supplements

  • Over-the-counter lactase enzyme tablets can be taken before dairy consumption
  • Allow enjoyment of dairy on occasion
  • Effectiveness varies by individual and dosing

Health Considerations

Bone Health

If avoiding dairy, ensure adequate calcium and vitamin D intake through alternatives or supplements to support bone health.

Gut Microbiome

Interestingly, some research suggests that regular small amounts of lactose may benefit gut bacteria (prebiotic effect) even in lactose-intolerant individuals - though this needs to be balanced against symptoms.

Not the Same as Milk Allergy

Lactose intolerance is different from milk protein allergy, which is an immune response to casein or whey proteins. Lactase supplements won't help with milk allergy.

Testing with NutraHacker

NutraHacker analyzes the lactase persistence variant along with other genes affecting nutrient metabolism and food sensitivities.



Frequently Asked Questions

Can lactose tolerance change over time?

Your genetics don't change, but some people notice they tolerate dairy better or worse at different life stages. This may relate to gut microbiome changes, overall gut health, or simply variation in dairy consumption habits. Some evidence suggests regular dairy consumption may help maintain some tolerance.

Is lactose intolerance harmful?

Lactose intolerance itself is not harmful - it's actually the ancestral human condition. The discomfort from consuming lactose is unpleasant but not dangerous. The main concern is ensuring adequate calcium intake if avoiding dairy.

Why do some people with "intolerant" genetics seem to handle dairy fine?

Individual variation exists in how much lactose triggers symptoms. Gut microbiome composition affects lactose fermentation. Additionally, many dairy products (cheese, yogurt) have reduced lactose that most people tolerate regardless of genotype.

References

  1. Enattah NS, et al. Identification of a variant associated with adult-type hypolactasia. Nat Genet. 2002;30(2):233-237.
  2. Burger J, et al. Absence of the lactase-persistence-associated allele in early Neolithic Europeans. PNAS. 2007;104(10):3736-3741.
  3. Segurel L, Bon C. On the Evolution of Lactase Persistence in Humans. Annu Rev Genomics Hum Genet. 2017;18:297-319.
Educational Content Only: The information on this page is for educational and informational purposes only and is not intended as medical advice. Genetic information should be interpreted in consultation with qualified healthcare providers. Individual health decisions should not be based solely on genetic data. NutraHacker does not diagnose, treat, cure, or prevent any disease.