Report from the LI Conference, part 5

I'm sure some professional jargonistas will come in here and challenge me, but for sheer brain-bending technical mumbo-jumbo in the medical field nothing is more opaquely baffling than the titles of papers on genetics. What would you do with a paper titled "The homeodomain protein Cdx2 regulates lactase gene promoter activity during enterocyte differentiation"?

Whatever that means, it was co-authored by the third presenter of the morning.

Cellular and Molecular Biology of Lactase
Eric Sibley, M.D., Ph.D.
Associate Professor
Division of Pediatrics-Gastroenterology
Stanford University School of Medicine

There are three types of lactose intolerance. If the lactase enzyme never develops at all, then newborns can't have any lactose. They literally starve to death unless a lactose-free formula is given to them almost immediately. This is how LI was first discovered as a medical condition, in fact. Because it exists from birth, this type is called Congenital LI.

Primary LI is the type that most of us have, the natural condition of all mammal. Lactase production declines after weaning, but we can drink milk until that time without symptoms.

A whole medical textbook of conditions - drugs, diseases, surgeries, anything that damages or shocks the intestines - can known out the lactase-making mechanism no matter what your age or status is otherwise. This type is known as Secondary LI.

Why is lactase so vulnerable to being knocked out? Sibley said:

Lactase is a brush border membrane protein produced by enterocytes, the absorptive epithelial cells of the small intestine. The human lactase protein is initially synthesized as a 210–220 kDa immature peptide. The precursor peptide is then processed by glycosylation and cleavage, and finally inserted into the brush border membrane as a mature 160 kDa subunit homodimer.

Lactase is made in the small intestine. Take a biopsy of a section of the inside of the small intestine and a whole invisible world is revealed under a microscope. The insides are covered in tiny projectiles. Imagine a piece of rolled-up shag carpeting and you have the idea. Each projection is called a villus and the outside of the villus, the part that interacts with the broken-down pieces of carbohydrates, proteins, and fats, the part that actually does the digestion, is a membrane called the brush border.

Lactase is made in the brush border, but not in all of it. Lactase is made only at the very tip of the villus. Scientists find that the other enzymes that digest sugars appear the farther you go down the side of the villus, toward the valley (known as the crypt). That's a more protected region than the top. So if anything is going to harm the inside of the intestine, lactase production will go first.

[Why? My guess is that throughout 99% of mammalian history, lactose wasn't very important as a nutrient except for that short time before weaning. Most animals, humans included, live the vast majority of their lifespan after weaning. So if anything has to be first or be most vulnerable, lactase production was the least valuable and bodies could chance that letting it go but protecting the others would lead to higher survival in the long run.]

Here's another fact with huge implications.

Postdecline, the level of lactase activity is 5–10% of childhood levels in most populations worldwide.

That's why most people can have some lactose, some dairy products, even if they are lactose malabsorbers (or lactose non-persisters or are LI in the common use of the term). Your lactase activity doesn't go to zero. It goes down a lot, but not to zero. That helps explain why any activity that helps to slow down the rate at which lactose travels through the intestines (having milk with a meal or having milks with more solids [like whole milk or chocolate milk]) will give your remaining lactose more time to work and reduce overall symptoms.