Ketones from burning fat as fuel might help fight various diseases ::Pearson Prentice Hall - Science News

Pearson Prentice Hall - Science News

Ben Harder

In times of plenty, both the mind and the body thrive. But deprived of basic sustenance, the mind perishes before the body does. That's not New Age philosophy; it's basic metabolic chemistry. While most of the body manages food shortages with relative ease, the tissues of the brain are vulnerable during periods of scarcity. So when blood sugar dips, the brain must fall back on special biochemistry to meet its energy needs. From studying that metabolic back-up system, a coterie of scientists has drawn inspiration that could lead to a new treatment for conditions as diverse as epilepsy, diabetes, Alzheimer's disease, and heart failure.

Most of the time, the body makes its fundamental fuel, glucose, from ingested carbohydrates. With each meal, the bloodstream gets replenished with glucose to replace the blood sugar that hungry cells have consumed to satisfy their metabolic needs. The body can't store glucose well, yet cells must be fed continually. So the body puts away extra energy in the form of fat, which it can break down into energy-supplying fatty acids when needed. A starving animal or a person with normal fat stores can thus sustain most of the body's cells for weeks or months without eating.

But brain cells, even hungry ones, can't avail themselves of these emergency stores. A physiological barrier that blocks toxins in the bloodstream so they can't enter the delicate brain also keeps out fat and fatty acids. As a consequence, when glucose in the blood runs low, brain cells can run into trouble.

People are uniquely vulnerable to such glucose starvation because of their disproportionate braininess. Although the brain makes up about 2 percent of a normal adult's weight, it commands roughly 20 percent of the body's resting metabolic budget.

A condition found only in people and a few ruminants can protect against this Achilles' heel. The state, known to followers of the popular Atkins diet, is called ketosis. When blood-glucose concentrations get low, the liver converts a portion of fatty acids into acids called ketone bodies or ketones. These substances can substitute for glucose and fatty acids as cellular fuel. However, unlike fatty acids, ketones can penetrate the blood-brain barrier.

While ketosis may guard the brain in times of starvation, Richard L. Veech has additional applications in mind. Veech, who works at the National Institutes of Health in Rockville, Md., argues that ketones might be therapeutic any time cells are threatened by energy deprivation. Such threats could arise both from a lack of fuels and from cells' failure to properly metabolize the fuels at their disposal. The latter category covers a broad array of diseases.

Veech and others have been suggesting for several years that ketosis could help treat, among other conditions, Alzheimer's and Parkinson's diseases, certain insulin disorders such as type 1 diabetes, and several metabolic disorders caused by rare mutations.

"These diseases appear wildly different," Veech says. Treating "all these different things with some magic substance sounds improbable," he adds. Yet across a wide range of specialties, doctors who've dabbled with ketone-based therapies are warming to that seemingly outlandish idea, and a vanguard of research on ketone therapies is appearing in scientific journals. At NIH earlier this fall, Veech hosted a gathering of researchers who have studied ketones.