The Link Between Lactose Intolerance, Dairy & Obesity (MCM6/LCT)

If you get unpleasant digestive symptoms after consuming dairy, especially milk, you’re likely among 70% of lactose-intolerant people worldwide.

Lactase is an enzyme that breaks down lactose into glucose and galactose, simple sugars that your intestines can absorb. If there’s not enough lactase in the gut, undigested lactose moves into the colon, attracts water, and causes diarrhea. Lactose fermentation in the colon can cause bloating, pain, and sluggish digestion [R, R, R].

The frequency of lactose intolerance greatly varies among different populations. It reaches up to 100% in some East Asian populations, over 80% in Africans and Arabs, and only 30% in Europeans [R].

Lactose intolerance occurs due to reduced lactase activity and results in digestive issues upon dairy consumption. The frequency of lactose intolerance greatly varies between populations.

Genetic Background: MCM6 & LCT

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

The LCT gene encodes lactase, and it’s active in the small intestine lining [R, R]. 

In most mammals, LCT becomes active 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]. 

Interestingly, lactose intolerance due to LCT gene variations (congenital lactase deficiency) is quite rare and manifests from birth. The most common type of lactose intolerance is due to variations in the MCM6 gene [R].

MCM6 encodes a protein that acts as the master “switch” for LCT activity [R, R]. MCM6-related lactose intolerance appears in early adulthood and gets worse with aging. Lactase activity typically drops to 5%-10% of that in babies [R].

The MCM6 gene encodes a protein that controls the activity of a lactase-producing gene, LCT. MCM6 variants are the most common cause of lactose intolerance in adults.

Did you know?

From an evolutionary perspective, lactose intolerance is our natural or original state. We became capable of digesting lactose past childhood about 5,000-8,000 years ago [R, R].

Scientists suggest that lactose digestion emerged as an evolutionary advantage when humans started farming. It likely helped our ancestors survive and thrive by consuming milk. That may explain why lactose intolerance is much less common in people of European descent [R]. 

Read this post for more information about the genetics of lactose intolerance.

One SNP in the MCM6 gene is primarily responsible for lactose digestion in adulthood or lactase persistence. People with at least one copy of the “A” allele at rs4988235 will likely maintain high lactase activity and enjoy milk & dairy products [R].

According to a review of 25 studies and nearly 185K participants, rs4988235-A correlates with a higher body mass index (BMI). People with this variant also consume more dairy. However, the link with BMI was significant only in older people (50+) of European ancestry [R].

A large Danish study tested nearly 98,000 subjects and came to similar conclusions. People carrying the “A” allele consumed more milk (5 vs. 3 glasses weekly) and had slightly higher obesity rates [R].

Two European studies (940 Spanish and 3,575 French subjects) also found a link between this variant and body-weight measures but only in people with moderate-to-high dairy consumption [R, R].

Note: Some papers refer to this SNP as “-13910C>T”, where “C>T” indicates the allele change on a negative DNA strand. Unlike them, we always report on a positive (forward) strand, where “C>T” becomes “G>A”.

The “A” allele at rs4988235 enables lactose digestion in adulthood. People with this variant tend to consume more dairy and are more prone to obesity.

Limitations

As mentioned, the effect of this SNP and lactose digestion on obesity may be limited to older people. One study failed to confirm the association in 298 children [R]. In 580 Portuguese children, it was associated with abdominal but not overall obesity when milk intake was higher [R].

The frequency of rs4988235-A greatly varies between populations, and it’s not likely to have a meaningful impact on ethnicities with common lactose intolerance, such as Africans and Arabs [R, R].

In summary, this variant will have a more significant effect in people who:

• Are of European (Caucasian) ancestry
• Have 50+ years
• Consume more milk & dairy

How It Works

Increased dairy consumption is the primary mechanism by which rs4988235-A can impact weight gain. Most dairy products are energy-dense and significantly contribute to total caloric intake.

In support of this claim, the genetic effect was more significant in people who consumed more dairy [R, R]. In the mentioned review of 25 studies, increased dairy intake correlated with a higher BMI [R].

Lactose-intolerant people tend to avoid dairy, which might protect them from weight gain. Additionally, digestive issues and diarrhea may reduce their nutrient absorption [R].

Lactose-tolerant people usually consume more dairy, which can greatly increase their caloric intake and make them prone to weight gain.

Gut Microbiome — the Hidden Link

Researchers have found that lactose-intolerant individuals carrying the “GG” genotype have more Bifidobacterium probiotics in their guts [R].

According to one interesting explanation, undigested lactose can act as a prebiotic in the colon and feed the beneficial bacteria. Hence, lactose-intolerant people who still consume small amounts of dairy may have a more diverse microbiome [R].

Given the crucial roles of probiotics in metabolism, lactose intolerance might provide the edge for weight control [R, R]. In animals, boosting gut Bifidobacteria helped reduce belly fat [R, R]. 

People with rs4988235-A may have a less diverse gut microbiome, which may negatively impact metabolism and weight control.

SNP Summary

Primary SNP:

MCM6 rs4988235

• ‘G’ = associated with lactose intolerance; not associated with weight gain
• ‘A’ = associated with normal lactose digestion and with higher obesity rates

Population Frequency: Around 70% of European descendants carry at least one copy of the “A” allele. It’s much less common in South Asians (21%) and Africans (5%) and nearly non-existent in East Asians.