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Three metabolites found in coffee could be associated with bone mineral density and help increase bone mass, a study conducted in Hong Kong has found.

The study, published in Journal of Clinical Endocrinology & Metabolism*, looked at data on 564 people, found that those who habitually drank coffee had higher bone mass density than non-coffee drinkers. 

That could be important because higher levels of bone density are associated with reduced risk of fractures. 

The findings of the study seem to contradict earlier studies. The relationship between coffee and bone health has been studied before, and the results have been conflicting. Previous research has shown that the more caffeine a person drinks, the more calcium is excreted from the body. And since the main mineral component in bone is calcium, this could potentially create a calcium imbalance and inhibit bone formation.

The authors of the study suggest that three metabolites, in particular, were associated with an increase in bone density. One of the potential benefits from the research is that these metabolites in coffee that are good for bone health have been identified, which could open the door for more research and help creation of new drugs to help protect bone health in future.

The authors of the study highlighted the fact that coffee is a widely consumed beverage and contains a number of ‘bioactive’ compounds such as carbohydrates, lipids, nitrogenous compounds, vitamins, minerals, and phenolic compounds that are related to various health outcomes. Epidemiological studies suggest that habitual coffee consumption is associated with reduced risk of all-cause mortality, cardiovascular mortality and cancer. 

As reported by C&CI on a number of occasions, coffee consumption has been shown to also be associated with a reduced risk of Type 2 diabetes, liver diseases, Parkinson’s disease, and depression and, as highlighted elsewhere in this issue, based on these findings, dietary guidelines for Americans in 2015 suggested that moderate daily consumption of coffee in healthy adults was associated with reduced risk of total mortality, cardiovascular disease, Type 2 diabetes and Parkinson’s disease. A UK Biobank study demonstrated that coffee intake was associated with reduced all-cause mortality, reaffirming that coffee drinking can form part of a healthy diet.

Although coffee intake has been shown to be associated with reduced risk of several diseases and mortality, its association with osteoporosis remains controversial. That is because, as mentioned above, caffeine – one of the most studied bioactive components of coffee – adversely affects calcium balance in humans by increasing calcium excretion or reducing calcium absorption. On occasion, coffee intake has been associated with increased and reduced bone mineral density in epidemiological studies. 

Similarly, said the authors of the study, inconsistent findings have been shown in meta-analyses of observational studies and in general a null association has been suggested between coffee intake and fracture, possibly due to a potential gender-specific effect, with daily consumption of coffee associated with increased risk of fracture in women and decreased risk in men. The study’s authors believe that these inconsistent findings are likely to be ‘multifactorial,’ and that the instrument used, a self-reported food frequency questionnaire (FFQ), could be a contributing factor.

Self-reported FFQs are commonly used to estimate habitual intake in nutritional epidemiological studies. The problem with them is that they rely on participants’ memory and understanding of portion size, so are subject to measurement and recall bias and not quantifiably precise, leading to inconsistent diet-disease association. 

In contrast, a clinical trial is considered the ‘gold standard’ in inferring causality between coffee and health outcomes, but this is usually not practical unless the outcome can be observed in a short period of time. Moreover, food metabolism is affected by several factors including lifestyle, environment, gut microbiota and genetics. As a result, there is a large variation between food intake and production of bioactive metabolites among individuals, and hence their association with clinical outcomes. 

Metabolomics – the large-scale study of molecules, commonly known as metabolites, within cells, biofluids, tissues or organisms,  molecules and their interactions within a biological system – has recently been shown to be a more objective measurement to reflect individual food intake. It measures metabolites in biofluids and may capture the metabolic products of food and better reflect the dietary exposure after metabolism. 

The study used two independent cohorts totalling 564 healthy adults from a Hong Kong osteoporosis study. Coffee consumption was self-reported in an FFQ but was combined with metabolomic profiling. Bone mineral density at the lumbar spine and femoral neck was measured and techniques known as multivariable linear regression and robust regression used for the association analyses.

In total, 12 metabolites were positively correlated with coffee consumption with quinate, 3-hydroxypyridine sulphate and trigonelline (N-methylnicotinate) showing the strongest association. Among these metabolites, 11 known metabolites were previously identified to be associated with coffee intake and six of them were related to caffeine metabolism. Habitual coffee intake was positively and significantly associated with bone mineral density at the lumbar spine and femoral neck. 5-acetylamino-6-formylamino-3-methyluracil (AFMU) was significantly associated with bone mineral density at the lumbar spine, whereas 3-hydroxyhippurate and trigonelline were significantly associated with bone mineral density at the femoral neck.

These three of metabolites, AFMU, 3-hydroxyhippurate and trigonelline, could be potential biomarkers of coffee consumption and affect bone health, the authors of the study concluded.
*Serum Metabolome of Coffee Consumption and its Association with Bone Mineral Density: The Hong Kong Osteoporosis Study, Yin-Pan Chau, Philip C M Au, Gloria H Y Li, Chor-Wing Sing, Vincent K F Cheng, Kathryn C B Tan, Annie W C Kung, Ching-Lung Cheung. Journal of Clinical Endocrinology & Metabolism, dgz210, Published: 21 November 2019

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