After a newborn mammal human or subhuman gropes for its mother’s nipples, it starts swigging her milk. This complex fluid contains two key ingredients: a mineral, calcium, for building bones and teeth, and a sugar called lactose, for nutrition.

At first, that infant imbibes lactose in its disaccharide form a bulky, paired sugar molecule. But as the nursing baby becomes a toddler, a year or two down the road, its mother begins to wean the child from suckling to eating solid food. As this weaning process begins, an enzyme, lactase-phlorizin, in the intestinal cells kicks in to split that indigestible milk sugar into two tummy-friendly monosaccharides.

But in humans, it’s not that simple. Across the inhabited globe, people come in one of two populations lactose-tolerant or lactose-intolerant. The latter can’t abide consuming milk or any of its dairy products from cheese to ice cream. The reason: Their lactase enzyme did its post-weaning duty of turning its gene off, leaving the hard-to-digest disaccharide sugar on board.

At the opposite extreme, lactose-tolerant folks, with that enzyme doing its thing, enjoy milk and its spin-off products with impunity, thanks to a mutation in that lactase gene. Molecular geneticist Leena Peltonen, who chairs the department of human genetics at the University of California at Los Angeles, explains this epidemiological divergence:

“Lactose-tolerant people came on the scene coinciding with dairy farming and the use of dairy products around 10,000 to 8,000 B.C. That has been beneficial for human beings. Take northern Scandinavia, where you could harvest only one crop per year. Introduction of a lactase gene mutation causing lactose tolerance was a necessity to have a high-protein-content resource, which milk provided excellently. So it must have been somehow evolutionarily beneficial for the human species, that this mutation, this lactose tolerance, became quite frequent, especially in far northern Europe.”

But elsewhere in the world, large numbers of people suffer from an inability to digest milk protein. Their lactose intolerance (adult hypolactasia) begins with borborigmus rumbling or gurgling in the digestive tract produced by movement of gas, fluid or both in the bowel, which are audible at a distance. However, lactose intolerance is not merely a discomfiting embarrassment. It brings on severe abdominal distention and cramps after eating, with bloating, nausea and diarrhea. Lactose intolerance is frequent among people in warmer climates and their descendants.

Milk Intolerance: Not A Disease, Just A Trait

“In North America, 30 [million] to 50 million people can’t digest milk,” Peltonen observed, “In Africa, 80 percent of all individuals are lactose-intolerant, and in Southeast Asia nearly 100 percent. Unlike northern Europe, there was no necessity to develop tolerance; it wasn’t evolutionarily beneficial. What we know of lactase genes,” she suggested, “is that African-Americans have this trait at 80 percent prevalence, whereas only 5 percent of Finnish people are lactose-intolerant.”

She made the point that “lactose intolerance is not a disease it’s not life-threatening. Kids and grown-ups swallow over-the-counter lactase tablets to treat it. Rather, lactose intolerance is a harmful inherited trait. If you think of it as an original human trait, that was how we all were originally. Then a mutation happened, and some of us got the extra benefit of being lactose-tolerant.”

Peltonen is senior author of a paper in Nature Genetics, released Jan. 17, 2002, titled: “Identification of a variant associated with adult-type hypolactasia.”

“The mutation that we found,” she told BioWorld Today, “probably hits a regulatory element, a DNA sequence that regulates this lactase gene.”

Peltonen’s paper reports screening the DNA of individuals the world over, beginning with the population of Finland. “This all started,” she recounted, “using the wonderful Finnish clinical samples of large pedigrees with multiple lactose-intolerant individuals. First, we identified this point mutation and found that every single Finn with the trait had this same variant. Then we studied that same mutation in various populations from Koreans, French, Italians, Germans, Dutch and African-Americans. I was surprised that all carried the same variant gene.”

What molecular trigger switches off lactose tolerance after weaning? “That’s exactly what we’re trying to figure out right now,” Peltonen observed. “It involves a pretty complex strategy, because we must use cells that mimic human intestinal cells. This requires taking a fairly large piece of DNA. It’s cell biology rather than genetics.

“I think that once we figure out the trigger that shuts off the lactase enzyme,” she added, “perhaps we could keep it in the on’ position by traditional chemical competitive therapy. But I think there’s a much more general significance to this work. Once we figure out what’s going on, it will help us understand why some genes during human development are turned off and turned on.”

Anti-Lactose Milk Avoiders Court Osteoporosis

“There are diagnostic tests for lactose intolerance,” Peltonen pointed out. “However, their specificity is not very high. If you want an absolutely reliable diagnosis of the trait to differentiate it from other bowel disorders you really should perform intestinal biopsy and determine the enzyme activity from that, which is tedious. We have invented an immediate diagnostic test, based on our findings, but we must do more screening to be sure this test is applicable in different populations.

“The National Public Health Institute of Finland in Helsinki,” she observed, “has filed a patent application covering our diagnostic test and the variant gene on which it’s based. We have already distributed the sequence to research labs throughout the world.”

Peltonen described how the test will operate: “Take a drop of blood from the patient and amplify a particular DNA fragment by PCR. Then apply sequencing or other methods to see if the mutation is there or not. It’s a very trivial test, and cheap to do.”

But it could have another signal payoff: “It’s not only lactose intolerance that’s involved,” she pointed out. “This mutation could be meaningful if we start to think why some people have osteoporosis. They are the individuals who avoid milk, and are sensitive or prone to the bone disease, because their calcium intake is lower. Like all these diet consumer habits,” Peltonen concluded, “this might have wider impact. So people should think out of the box that this is not just lactose intolerance. It actually affects our diet quite deeply.”