Carbohydrates are important in the diets of most people, and are consumed in the form of starches and sugars. But Greenlandic people have a long history of consuming a diet consisting mostly of protein and fat from fish, seals, whales and reindeer. There is almost no carbohydrate in their traditional diet.
Several different enzymes are involved in breaking down dietary carbohydrates to form the glucose that is then absorbed into the bloodstream. One such enzyme, known as sucrase-isomaltase (SI), acts on both sucrose and maltose and breaks them down into smaller sugars. Sometime in the history of Greenlanders, the gene that codes for this enzyme has undergone mutation that has rendered it non-functional and today, as much as 39 percent of the Greenlandic population carries the dysfunctional gene.
The mutated gene is recessive and so people who carry only one copy will still be able to produce the SI enzyme and to digest the sugars. However, those people who carry two copies of the mutated gene (homozygous) will not be able to break down sucrose or isomaltose in the usually manner. Congenital sucrase-isomaltase deficiency (CSID) has a negative impact on children who eat carbohydrates: they suffer a range of symptoms such as diarrhea, abdominal pain and bloating. But the impact on the health of adults has not been investigated.
In a recent study, published in the journal Gastroenterology, scientists from Denmark, Greenland and the USA assessed the metabolic health of 6,551 Greenlanders, two percent of whom were homozygous carriers of the mutant gene and so suffered from CSID. The researchers measured such parameters as Body Mass Index (BMI), body fat percentage, waist and hip circumference, weight, blood lipid profile and cholesterol levels.
They found that participants who carried only one copy of the mutated gene had the same metabolic profile as those who carried normal genes. However, those who were homozygous (carried two copies) for the mutated gene had markedly healthier metabolic profiles. They had a lower BMI, less body weight, a lower fat percentage, and lower levels of triglycerides and cholesterol.
“Adult Greenlanders with the genetic variation have lower BMI, weight, fat percentage, cholesterol levels and are generally significantly healthier. They have less belly fat and might find it easier to get a six pack. It is amazing and surprising that a genetic variation has such a profoundly beneficial effect,” said Professor Anders Albrechtsen from the University of Copenhagen.
The researchers also made use of genetically modified mice to investigate the effects of sucrase-isomaltase deficiency. The knockout mice had their SI gene experimentally mutated, while the wild-type mice had functional SI genes. The mice were fed different diets for eight weeks, some containing sucrose and some without sucrose, although all diets were the same in terms of calorific value.
After the experimental period, the knockout mice showed significantly lower weight gain, and lower body fat percentage than the wild-type mice, even though the calories eaten were the same for the two types of mice. These findings support the results seen in the sample of Greenlanders that were deficient for the SI enzyme and indicate that the healthier metabolic profile linked to loss of SI function, in both humans and mice, is related to changes in uptake of sucrose, rather than to changes in energy content of the food eaten.
During further analysis, the researchers found higher levels of acetate circulating in the blood of people who were homozygous for the mutation. Since sugars are not being digested in the initial part of the digestive system (stomach and small intestine), they travel further along the digestive tract and are ultimately broken down by gut bacteria instead.
“Here, gut bacteria convert the sugar into a short-chain fatty acid called acetate, which in previous studies has been shown to reduce appetite, increase metabolism and boost the immune system. That is most likely the mechanism happening here,” explained Mette Andersen, an assistant professor at Copenhagen’s Center for Metabolism Research.
The researchers discuss possible reasons why SI deficient children suffer symptoms when carbohydrates are introduced into their diets whereas the adults do not. They propose that a surplus of simple carbohydrates in the gut could favor the development of microflora that transform the carbohydrates into acetate, turning them from a potential irritant into a tool for a healthier metabolism.
“Younger carriers of the variation experience negative consequences due to their different type of sugar absorption. For them, consuming sugar causes diarrhea, abdominal pain and bloating. Our guess is that as they age, their gut bacteria gradually get used to sugar and learn how to convert it into energy,” noted Torben Hansen, a doctor and professor at Copenhagen’s Foundation Center for Basic Metabolic Research.
Ultimately, the findings may be useful in developing a treatment for people with obesity or cardiovascular disease. A drug that targets the SI enzyme and renders it non-functional would perhaps have the consequence of reducing weight gain and promoting metabolic health. However, further studies are needed to investigate the consequences of inhibiting otherwise functional enzymes in the intestines of people who struggle with weight gain.
“We can see that the genetic variation provides a better balance of fat in the bloodstream, which results in lower weight and consequently, fewer cardiovascular diseases. If you can develop a drug that inhibits the sucrase-isomaltase gene, then in principle, we might all be able to have equally strong health profiles,” concluded Hansen.
The study is published in the journal Gastroenterology.