Sunday, May 24, 2009

High cholesterol in anorexia nervosa

One of the (many) paradoxes of anorexia is that the excessive weight loss that accompanies the disorder often results in high cholesterol levels. This seems to go against what many doctors and researchers say about cholesterol: decreasing food and fat intake as well as increasing exercise should decrease cholesterol levels, not raise them.

It turns out that this high cholesterol (formally known as hypercholesterolemia) also happens to starving people, and is a well-known side effect of malnutrition. The question that remains, then, is why? Why this paradoxical effect?

Let me back up a bit and explain what cholesterol is and what it does. Cholesterol "is a lipidic, waxy alcohol found in the cell membranes and transported in the blood plasma of all animals. It is an essential component of mammalian cell membranes where it is required to establish proper membrane permeability and fluidity." Cholesterol is hydrophobic, meaning it doesn't dissolve in water or blood, so it is transported in the body by lipoproteins. Your total cholesterol count is a combination of triglycerides, low-density lipoproteins (LDLs, aka "bad" cholesterol) and high-density lipoproteins (HDLs, aka "good" cholesterol). Both LDLs and HDLs transport fats along with cholesterol. The lipid hypothesis holds that there is a causal link between high intake of saturated fats, hypercholesterolemia, and heart disease, promulgated by none other than Ancel Keys, he of the Minnesota Starvation Study.

So. What does this all mean?

Besides just having unusually high levels of total cholesterol, patients with anorexia were found to have unusually high levels of an enzyme called cholesterylester transfer protein (CETP), which swaps cholesterol and fat molecules between the different lipoproteins. The researchers speculated that low levels of thyroid hormones and low breakdown of existing cholesterol contributed to high cholesterol levels, and that "CETP activity increases cholesterol turnover as an adaptation to its low intake." The highest levels were seen amongst AN patients who also binged and purged. In severely malnourished AN patients, however, cholesterol levels and CETP activities drop dramatically.

Other studies have suggested that starvation results in the increased synthesis of lipoproteins. It could also be that these lipoproteins are transporting fats in the body, which the body is relying on as fuel due to insufficient food intake. If the body is going to rely on fat as fuel, it needs some way to mobilize those fat molecules and get them to a location where they can be broken down effectively. This could perhaps explain the abnormal rise in cholesterol levels. As body fat is essentially depleted in the severely malnourished AN patients, the body may rely more and more on breaking down organ and muscle tissue, thus decreasing the need for abundant lipoproteins.

Regardless of the reasons for hypercholesterolemia during anorexia, it is NOT an indication that the sufferer needs a low-fat or low-cholesterol diet. With sufficient foot (and fat!) intake, cholesterol levels typically right themselves rather rapidly.

(cross-posted at ED Bites)

Tuesday, May 19, 2009

Self-harm and glucose metabolism in women with EDs

Self-injury (such as cutting or burning oneself) is fairly common amongst people with eating disorders- approximately 25% to 45% of people with eating disorders self-injure, and approximately half of those who self-injure also have eating disorders (full article here). Many people report a sense of dissociation while self-harming, a desire to turn emotional pain into physical pain (ie, "real" pain), and also that this behavior reduces anxiety. Whether self-harm is from issues relating to impulse control, a more compulsive pattern of behavior, or something else entirely, the amount of overlap between self-injury and eating disorders is significant.

An interesting new paper from the journal Psychoneuroendocrinology looked at the relationship between self-injury and glucose metabolism in women with eating disorders, and what they found was significant. Women engaging in self-harm behaviors were given an oral glucose tolerance test, in which they were asked to drink a sweet solution to measure how the body handles sugar. The self-harming women who also had an eating disorder had higher levels of blood glucose after the test, but also higher levels of a hormone called glucagon.

Glucagon is essentially insulin's opposite: when the blood sugar is low, the pancreas secretes glucagon to prod cells into breaking down long chains of carbohydrates called glycogen into small sugars that can be released into the bloodstream and readily used by the body. When blood sugar rises after a meal, the pancreas secretes insulin, which stimulates cells to pull excess sugars out of the bloodstream and store them as glycogen for a rainy day*.

Besides low blood sugar, several other factors can stimulate the release of glucagon, including epinephrine (aka adrenaline), which is involved in the fight or flight response. Though I was unable to find any specific studies linking high levels of epinephrine and self-injury, it's certainly plausible to think that people who self-harm would have higher levels of epinephrine, especially right after an incident where such behavior occurs. Alternately, if high levels of glucagon also stem from high levels of epinephrine, the sufferer may be caught in a cycle of self-harm during episodes of low blood sugar.

For instance, a common pattern in those who binge and purge is binge-purge-self harm, where the self-harm typically occurs after the completion of the binge/purge cycle. After a binge, blood sugar goes up and glucagon levels go down. After a purge, blood sugar goes down, and glucagon and epinephrine levels go up.

No one knows at this point where the relationship between self-harm and glucose metabolism lies on the cause/effect scale. Certainly there is a feedback cycle between all of these systems. But one good point to keep in mind is the importance of helping sufferers regulate blood sugar levels by frequent meals and snacks that involve complex carbohydrates, proteins, AND fats. Food is medicine for the eating disorder, but it also might be true for self-injury.

*Aren't you glad I paid attention in my 8am biochem lecture 10 years ago?

(cross-posted at ED Bites)