A Molecular Picture of Chocoholics

By Jeffrey M. Perkel, Journal of Proteome Research, Vol. 6, No. 11, 2007, Published by American Chemical Society

To chocolatiers, there are but two types of people: those who love chocolate and those who don’t.

In this issue of JPR (DOI 10.1021/pr070431h), Sunil Kochhar and colleagues at the Nestlé Research Center (Switzerland) and Imperial College London set out to distinguish the two populations at the molecular level. The team developed a novel approach they call “nutrimetabonomics” to correlate metabolic phenotypes with a behavioral phenotype—namely, an affinity for rich, creamy chocolate.

Metabonomics is a discipline that uses metabolic profiles of bodily fluids such as blood plasma and urine to understand drug toxicity, pharmacological responsiveness, and other biological events. Nutrimetabonomics is an offshoot of that pursuit, says Kochhar, in which the tools of metabonomics (in this case, 1H-NMR spectroscopy) are applied to examine the effects that diet has on metabolism—and ultimately on health.

“We at Nestlé are using metabonomics to understand subclinical situations” such as gut discomfort and inflammation, Kochhar says. These conditions do not rise to the level of a true disease, and thus they are unlikely either to be brought to a physician’s attention or to be properly treated if they are, he explains. “Nutrition is the only way to deal with these ‘diseases’, but you need to pick up these [metabolic] deviations early on.”

Unfortunately, such deviations can be difficult to detect. “If you are taking drugs like statins, the change in metabolism is huge,” Kochhar says. “But when you want to look at metabolic health for dietary applications, which is a mix of many different micro- and macromolecules, the effect is very subtle.” As a result, a key part of the study involved statistical analyses to tease out those molecules whose abundances correlate (either positively or negatively) with a particular behavioral class. “You need very special mathematical models to look at the effects diet is having on metabolic health,” he says.

On the basis of a survey of the chocolate preferences of 75 males, Kochhar and his team selected 22, half of whom were “chocolate-desiring” and the rest “chocolate-indifferent”, and placed them on a defined diet for 5 days. (Females were excluded to avoid the confounding effects of hormonal fluctuations.) On days 2 and 4, each subject was given either 50 g of chocolate or 50 g of bread. On day 4, those subjects who received chocolate on day 2 received bread, and vice versa. Blood samples were collected at five time points after chocolate or bread intake; urine samples were collected daily.

Upon statistical analysis, the plasma metabolic profiles of those who desired chocolate could be distinguished from those who were indifferent to its charms. The chocolate-indifferent individuals tended to display higher levels of lipid–­ lipoprotein complexes, mostly in the form of plasma low-density lipoproteins (LDLs). Those in the chocolate-desiring group had lower plasma levels of lipoproteins, whereas the level of albumin, a protein whose roles include ferrying free fatty acids around in the bloodstream, was slightly higher. 

Urinary analyses identified several metabolic differences between the chocolate-desiring and chocolate-indifferent groups, as well. For example, higher levels of phenylacetylglutamine and citrate in the chocolate-desiring group suggest that these individuals may regulate the citric acid cycle slightly differently than those who don’t fancy a daily dose of chocolate. Elevated levels of carnitine and N-acetylcarnitine in the chocolate-indifferent group, however, suggest differences in lipid metabolism in this population.

Urine analyses also highlighted differences in gut microflora between the two study populations—or at least, in their behaviors and interactions with their hosts, says Kochhar. The study identified differences in the metabolism of niacin and of aromatic compounds such as 4-hydroxyphenylacetate and 2-hydroxyhippurate, for instance. All of these findings point to differences between the two groups in the functionality of gut microflora.

The bottom line, Kochhar says, is the realization that diet leads to a sort of metabolic “imprinting”. In other words, the body (and its associated microflora) appears to become attuned to a particular diet. This finding can have both positive and negative health consequences—but which also could ultimately open the door to novel dietary regimes. “If we know how we can influence gut microflora, then we can design a nutritional regime that can trick our microflora to harvest more or less energy,” he explains. Therefore, one could nudge a person’s metabolism one way or another.

Kochhar stresses that although this study involved chocolate—it was conducted at Nestlé, after all—the nutrimetabonomics approach can be applied to any diet or population, perhaps to assess the benefits of the Mediterranean diet and lifestyle or of pre- and probiotics or to lend scientific heft to the question of whether coffee or tea is healthier. “At the end of the day, metabolism is the key,” he says.