Sunday, January 25, 2009

Fatty Liver--Not Just for Geese Anymore

Foie gras, French for "fat liver," is a delicacy produced by force-feeding ducks or geese with corn meal. However, ducks and geese aren't the only species that can get a fatty liver.

Nonalcoholic fatty liver disease (NAFLD) is a condition that can occur in humans. NAFLD, defined as a liver fat content greater than 5.5%, is found in about one third of the U.S. adult urban population. As shown in the figure below, NAFLD (also called hepatic steatosis) progresses from fat deposits that cause liver enlargement, to fibrosis and the formation of scar tissue, to cirrhosis and the actual destruction of liver cells. It occurs in 45% of adult Hispanics, 33% of adult whites, and 24% of adult blacks.

According to the Mayo Clinic website, as diabetes and obesity increase, the incidence of NAFLD is increasing in both adults and children. Unfortunately there is no standard medical treatment for nonalcoholic fatty liver disease. Although several possible treatments are under investigation, none of them has yet proven effective.

With all of that in mind, there is encouraging news from a pilot study performed at Duke University by Eric Westman's group. Westman and his colleagues studied five obese patients who had been diagnosed with fatty liver disease by liver biopsy. They were instructed to follow a low-carbohydrate diet (less than 20 grams of carbohydrate per day) for six months. At the end of that time the patients were biopsied again and they showed significant reductions in liver fat and liver inflammation.

A recent study in Hepatology by Browning et al. explains why a ketogenic diet might reverse fatty liver disease. The investigators divided a group of 14 weight-loss patients into two groups. For two weeks 7 of the patients followed a calorie-restricted diet and the other 7 patients followed a carbohydrate-restricted diet. The scientists used radioactive tracers and NMR spectroscopy to determine how each group was performing gluconeogenesis in their livers.

They learned that the carbohydrate-restricted group produced more of their glucose from lactic acid and amino acids than did the calorie-restricted group. Not only that, the carbohydrate-restricted group burned their liver fat to provide the energy required to perform gluconeogenesis, while the calorie-restricted group tended to use liver glycogen to fuel gluconeogenesis. The researchers also found that the low-carbohydrate group increased fat burning throughout their entire body.

While these studies do not offer conclusive proof that a low-carbohydrate diet should be used to counteract and possibly reverse nonalcoholic fatty liver disease, the findings are encouraging and will be followed up by Dr. Browning and his associates in their next study.

Monday, January 19, 2009

Sweetness and Light Dopamine

Just the taste of a sweet beverage can result in liking, wanting and sipping of more of the sweet beverage. (Please see the previous blogpost for details.) The liking-wanting-sipping phenomenon happens even when the sweet beverage is not actually consumed, and happens in less than a minute. What causes this reaction to the taste of sweet?

In 1989, L.H. Schneider observed that dopamine receptors in the brain are stimulated when rats are allowed to feed themselves sweet solutions. Since that time, many investigators have noticed a relationship between either the taste of sweet or the actual consumption of sweet and the response of dopamine receptors in the brain, both in rats and in humans.

Dopamine is a neurotransmitter found in the midbrain. It has many functions, but one of them is the ability to produce prolonged feelings of pleasure. Increased dopamine signaling is involved in the mechanism of addiction to cocaine, amphetamines, and nicotine. At a more moderate level, novel foods, sweet foods, and overeating also cause increases in brain dopamine.

In order to investigate possible rebound effects of overstimulation with dopamine followed by abrupt dopamine withdrawal, a group of rats was treated for five days with l-dopa (a substance which is converted to dopamine in the brain). The research is described in an article in the December 2008 issue of Nutrition & Metabolism. After treatment was completed, the rats in the previously-treated l-dopa group were compared with an untreated control group. Over the next 12 weeks both groups of rats were allowed to eat as much food as they desired. At the end of that time, the previously-treated rats had gained 15% more weight than the control group.

Why did this happen? The authors hypothesize that treatment with the dopamine precursor l-dopa caused overstimulation of the dopamine signaling system in the rats. This, in turn, caused downregulation of dopamine receptors and decreased endogenous dopamine production. When the l-dopa treatment ceased, the rats were left with few dopamine receptors and low endogenous dopamine production. To compensate for this, the rats used the mechanism of overeating to compensate for their relative dopaminergic deficiency.

Rats are not humans. Nevertheless, it is possible to suggest that eating or tasting sweet food causes an overstimulation of the dopamine signaling system. This produces a downregulation of dopamine signaling such that, in the absence of sweet, there is a noticeable decrease in energy, motivation and mood. Sweets are legal, cheap and easy to obtain. If the sweet-eater wishes to experience the pleasant feelings associated with dopamine overstimulation, it will be very easy to continue eating sweets. And if he is unable to wait several days to a week to allow the body to return to its normal level of dopamine production and receptor activity, it will be harder than he might have expected to eliminate sweet tastes from his diet.

Sunday, January 11, 2009

Detecting, Liking and Wanting Sweetness

Those who read food labels realize that high fructose corn syrup is added to all sorts of products, from pickles to yogurt to spaghetti sauce. The Corn Refiners Association says this is because high fructose corn syrup enhances flavor and increases shelf life. A recent article in the journal Physiology and Behavior suggests that there may be another reason.

The article, called Modified sham feeding of sweet solutions in women with and without bulimia nervosa, was designed to show whether people who experience binge-eating episodes might overrespond to the stimulations of taste and smell. As it turns out, they do not, or at least they did not in this study. However, the study did produce an interesting outcome in terms of the way people respond to sweet tastes.

The study compared two groups of women--ten healthy women (termed NC, or Normal Control) and eleven women with Bulimia Nervosa (termed BN). The women were given solutions of cherry-flavored Kool-Aid sweetened with aspartame in concentrations of 0, 0.01, 0.03, 0.08 and 0.28%. (The 0.08% solution approximates the sweetness of commercial soda.) There were three trials in which the five solutions were prepared in five opaque containers, each fitted with a straw. The solutions were presented in a random order, using a one-minute access period during which the women could sip as much as they wanted of that particular solution, but they could not swallow it. They were instructed to spit out the solution into another opaque container. (The amount sipped and the amount spit out was later measured by the investigators.) The women were then asked to

1. Rate the sweetness of the solution

2. Rate how well they liked the solution

3. Rate how much they wanted more of the solution

Even though the solutions were presented in random order, both the Normal Control group and the Bulimia Nervosa group were able to accurately distinguish among the five levels of sweetness provided in the solutions. Again, although the solutions were presented randomly, both the Normal Control group and the Bulimia Nervosa group reported liking the solutions in direct proportion to how sweet the solutions were. Consistent with the self-reported preference rating, both groups sipped an increasing amount of the solution as the sweetness of the solution increased. (Remember, they were not allowed to swallow the solution, but they could sip as much of it as they wanted.) Finally, as shown in the graph below, both groups reported that they wanted more of the solution as the sweetness of the solution increased.
For both groups of women, more sweetness led to more liking, more sipping and more wanting. This was not a function of actually consuming the sweetened solutions, but simply of having the solutions in their mouths for a few seconds. Using this information, it not unreasonable to suggest that the increased use of another sweet substance, high fructose corn syrup, in all sorts of foods, may have the unintended result of producing more liking, more eating and more wanting of the products that contain it.

Friday, January 2, 2009

But you have to eat carbohydrates!

Perhaps you overdid it a bit at Christmas and are looking for a weight-loss plan. Although low-carb diets are currently out of fashion, they have one big advantage over low-calorie, low-fat diets. They work.

Ordinary people can lose weight and keep it off by following a low-carb eating plan. Not only that, they will notice an improvement in blood pressure, HDL cholesterol, triglycerides, and insulin responsiveness. So why don't more people attempt weight loss through the low-carb lifestyle?

One big reason is that people are told (incorrectly) that their body requires them to eat a certain amount of carbohydrate every day. The brain requires glucose to function, and several other tissues require carbohydrate-derived fuels as well. If a person doesn't eat any carbohydrates, where does this fuel come from?

It comes from proteins. After proteins are eaten, they are broken down into their building blocks, which are called amino acids. These amino acids can be reassembled into other proteins. Some of them can be converted into fat. And thanks to a metabolic process called gluconeogenesis, up to 400 grams of them per day can be converted into carbohydrates.

Since the brain requires only about 120 grams of carbohydrates a day, that's well within a safe range. It does take a few days for the enzymes of gluconeogenesis to be induced, permitting conversion of enough glycogenic amino acids into glucose to supply the tissues that require it. During the transitional period, typical symptoms may include body aches, nausea and headaches. These will subside after about three days, and energy levels and alertness will improve noticeably. To figure out how much protein to eat to permit adequate carbohydrate synthesis, Jenny Ruhl has provided this convenient Protein Need Calculator.

If you need to start a weight-loss plan, there are many good diets available, including many versions of low-carb diets. Check out your options and pick the diet that suits you the best. And if you choose the low-carb lifestyle, be assured that thanks to gluconeogenesis, you can safely drop most or even all of the carbohydrates from your menus!