Should You Avoid Dairy? The Genetics of Lactose Intolerance (MCM6)

The typical scenario goes: you’re almost certain that you don’t tolerate dairy. You don’t even like it that much. But, every once in a blue moon, you give in to the temptation to have a big latte or ice cream. 

That’s when the same annoying symptoms come back: stomach pain, bloating, diarrhea, gas, and nausea. Only sometimes–such as when your diary portions are smaller–you seem to do fine. What is going on? Is it lactose intolerance or not? [R]

As with most food intolerances, diagnosing lactose intolerance is not straightforward. Your doctor will ask about your symptoms and probably suggest that you go through a dairy avoidance phase, possibly followed by some tests [R]. 

Although other factors can cause lactose intolerance, genetics is the main contributor in most cases [R, R].

However, there’s not just one type of lactose intolerance–nor is there just one type of genetic variation that can contribute to it. Your genes can also send mixed signals, making you only somewhat lactose intolerant. As you age, these genes become even less active, worsening intolerance symptoms [R, R]. 

People with lactose intolerance experience gut issues when they consume large amounts of lactose-containing dairy products. Genetics is the main culprit in most cases. 

Lactose & Lactase

Lactose is a sugar found only in milk and dairy. 

The only enzyme that can digest lactose is called lactase. It works by breaking down lactose into glucose and galactose, simple sugars that your intestines can absorb. If there’s not enough lactase in the gut, lactose sticks around and triggers the typical side effects of intolerance. 

As undigested lactose moves along the digestive tract, it attracts water, making watery diarrhea likely. Once lactose reaches the large intestine, probiotic bacteria ferment it, releasing gas. This leads to bloating, pain, and sluggish digestion [R, R, R].  

Symptoms of lactose intolerance typically do not occur until lactase activity drops to under 50% [R].

The Lactase (LCT) Gene

The gene that codes for lactase is called LCT. It is active in cells that line the small intestine [R]. 

In most mammals, LCT gets activated before birth, remains high during the nursing period, and then takes a steep drop after weaning. Thus, most mammals become lactose intolerant once they grow up. This phenomenon is also called lactase non-persistence [R]. 

Humans seem to be the only exception. And even so, the ability to continue making lactase into adulthood or lactase persistence in humans is relatively uncommon on a global scale. 

Usually, you’ll hear that over 70% of adults worldwide have lactose intolerance. While this is true, it is a very rough estimate. In reality, anywhere from 5% to almost 100% of adults have lactose intolerance, with huge differences between different populations [R].

In the USA, over 30 million people have some degree of lactose intolerance by age 20 [R, R].

At first thought, it would make sense that problems with the gene that makes lactase (LCT) form the genetic basis of lactose intolerance. But that’s usually not the case!

Lactose intolerance due to LCT gene variations (congenital lactase deficiency) is rare, evident from birth, and causes severe diarrhea [R]. 

The most common type of lactose intolerance is due to variations in the MCM6 gene [R]. 

The LCT gene produces the lactase enzyme, which digests lactose. Variations in the LCT gene are rare, though. 

The MCM6 Gene: the Master “Switch” for Lactose Digestion

MCM6 works as a sort of a proxy for the lactase (LCT) gene. Many genes have such proxies nearby on DNA that scientists call regulatory elements. Each person’s MCM6 gene sequence acts as the master “switch” for their LCT activity [R, R].

MCM6-related lactose intolerance appears in adulthood and gets worse with aging. Lactase activity typically drops to 5%-10% of what it is in babies [R].

Rare MCM6 variations might make some people able to handle large amounts of lactose-containing dairy well into old age.  

Lactose intolerance is usually due to MCM6 gene variations. MCM6 controls lactase gene activity. 

Evolutionary Perspective–Are Your Ancestors to Blame?

Humans became capable of digesting lactose into adulthood recently on an evolutionary scale: about 5,000 to 8,000 years ago [R].

It’s likely that all humans who walked this Earth over 10,000 years ago were lactose-intolerant hunter-gatherers. But by 4000 BC, a shift occurred in Europe: farming became the norm. Hunter-gatherer societies were pushed out of the picture [R]

This overlaps with the origins of animal domestication and the practice of dairying. Scientists proposed that lactose digestion emerged as an evolutionary advantage. It likely helped some of our ancestors survive during times of famine [R]. 

Fast forward to the modern era, people who can digest lactose are thought to be descendants of those early dairy farmers. This might explain why the lactase-persistence MCM6 variants are more common among people of European descent [R]. 

Remember, though, that there’s still a lot we don’t know about the evolutionary and genetic origins of lactase persistence. Other theories might provide more accurate answers with additional research. 

If your genes don’t tolerate dairy, it’s fair to say that you can blame your distant ancestors. They probably didn’t have to rely on dairy to survive and could get plenty of nutrients from other sources. 

Limitations 

Have in mind that other compounds in milk can also trigger unwanted reactions. Some people are allergic to cow’s milk. Others may be intolerant to cow’s milk protein (casein) and the symptoms are similar to lactose intolerance. Lactose intolerance can also be confused with other gut disorders [R].

Additionally, not all types of lactose intolerance are genetic. Damage to the small intestine and premature birth can also cause lactose intolerance in some cases [R]. 

If you experience digestive symptoms after eating dairy, it’s important to see a doctor and get adequate diagnosis and treatment. 

Scientists recently uncovered that MCM6 gene variants may also impact your gut microbiome and ability to lose weight on a high-protein diet. Read more about this little-known aspect of MCM6 in this post. 

You can see your genotypes for MCM6 in the table below. However, keep in mind that these associations are based on studies from certain ethnic populations—so you should interpret your results with caution if you are not descended from one of these specific groups!

SNP Summary and Table

Primary SNP: MCM6 rs4988235 

• ‘AA’ = Can digest milk (lactase persistence)
• ‘AG’ = Likely can digest milk, but slight lactose intolerance is possible
• The ‘A’ allele is more common in people of European descent  
• ‘GG’ = Likely to be lactose intolerant; more common in people of Asian and African descent

Other Important SNPs:

MCM6 rs182549

• ‘TT’ and ‘TC’ = Likely can digest milk (lactase persistence); 
• ‘CC’ = Likely to be lactose intolerant
• Inherited together with the previous SNP (rs4988235)
• May only apply to people of European ancestry
• Unlikely to predict lactose intolerance in sub-Saharan Africans and Tibetans  

MCM6 rs41380347

• ‘CC’ and ‘CA’ = Ability to digest milk (lactase persistence)
• ‘AA’ = Possibly lactose intolerance
• Over 99% of people are ‘AA’
• Associations likely apply only to sub-Saharan Africans

MCM6 rs145946881

• ‘CG’ and ‘GG’ = Ability to digest milk (lactase persistence)
• ‘CC’ = Possibly lactose intolerance
• Over 99% of people are ‘CC’
• Associations likely apply only to sub-Saharan Africans

Population Frequency

Lactose intolerance is most common in American Indians and Asians. Additionally, up to 80% of Blacks, Arabs, and Latinos have lactose intolerance. Prevalence is lowest among people who are from, or whose families are from, Europe–especially northwestern Europe [R].