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we’ve discovered a far better predictor of health



For over a century, we have based ourselves on a simplistic measure to determine if someone is a "healthy" weight or not. This is the body mass index (BMI) – the relationship between a person's weight and the square of their height. The limits of this relationship are clearly demonstrated by professional rugby players; most of which would be classified as "overweight", despite having less than 10% of body fat.

Studies have also shown that not all obese people develop health problems, such as diabetes and heart disease. This "fat but fit" cohort seems to be protected in some way. On the flip side, people with a "normal" BMI are not immune from getting diabetes or heart disease.

Most preventive medicine and health advice is based on BMI cuts. But these cuts can be falsely reassuring, especially for those who are TOFI (Fat on the Inside) ̵

1; people who have large amounts of fat around their organs. Finding out who, in the general population, is TOFI and who is not, would still be prohibitive, as it requires an MRI scan.

MRI of a TOFI and a normal control.
ImagingFat / Wikimedia Commons, CC BY-SA

Blood Drop

A better predictor of future health can be obtained from a drop of blood. Our latest research, published on cell metabolism, shows that measuring metabolites (substances involved in metabolism) in a blood sample can predict a person's risk of becoming obese (and unhealthy) with an accuracy of 80-90. %. They can also predict health outcomes, including heart disease, diabetes, kidney problems, visceral fat, and biological age.

For our study, we analyzed data from approximately 2000 middle-aged British twins from our TwinsUK cohort. These twins were followed for an average of 13 years with blood tests, weight and height measurements and gene sequencing. We replicated our results in 427 Americans undergoing health screening.

Although many studies have shown the importance of genes in influencing obesity and more than one hundred specific genes have been found, they explain less than 2% of why people differ in their behavior. IMC, so they are useless for the individual prediction of future obesity. We examined about 1,000 blood metabolites, measured from a drop of blood plasma, and found that a third was associated with weight gain and obesity. Of these, 49 metabolites were also strongly associated with weight gains and obesity in the American group, showing their reliability as indicators. We used these 49 metabolites for our main analysis.

These metabolites together allowed us to predict obesity quite well (accounting for over 50%) and this classification of a metabolic BMI (mBMI) correlated better with poor health outcomes compared to BMI alone. We have grouped subjects into different categories, depending on BMI and healthy or unhealthy metabolism. Most were as expected, with obese people having unhealthy metabolism (mBMI), but about one in five people was incorrectly classified. Some obese people had a healthy metabolic profile, and some with normal weight had an unhealthy mBMI profile.

Metabolites are a better predictor of health than genetic risk.
Cirulli et al / Cell Metabolism

Those with a normal BMI, but an unhealthy unhealthy metabolism profile, had 50% more chance of becoming obese in the next decade and had an increased risk of 200- 400% of heart disease. He also predicted an increased risk of many other common medical conditions, such as hypertension, abnormal lipids, insulin resistance, and increased fat around the abdomen.

These metabolites were not associated with the many obesity genes, suggesting that the genes detected so far are only detecting an increase in body size, not an abnormal metabolism.

Each of us has thousands of blood metabolites and, in addition to being biomarkers of disease and future risk, can play a key role in triggering the disease. There is a large individual variability in the metabolites between people, both in the blood and in our bowels. At least a third of our blood metabolites are produced or strongly influenced by our intestinal microbes, which are themselves influenced by diet and weight. So the weight or body mass index as a simple measure of health is imperfect and to deal with it simply by reducing the intake of energy is misleading.

The quality, not just the quantity, of the diet is important to reduce the future risk of obesity and its consequences on health. We need to pay less attention to calories and old-fashioned scales and more to the metabolism of our body and to the diets and microbes that produce these healthy chemicals. This study shows that it can be done.


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