SAM: Associated With Adiposity

S-adenosylmethionine (SAM) is an intermediate high energy compound of the methionine to homocysteine pathway. Methionine is an essential amino acid in human nutrition, and is derived mainly from animal protein in the diet of Westerners. Methionine is converted to SAM, and methylation by SAM produces S-adenosylhomocysteine (SAH) and subsequently homocysteine. Homocysteine is then converted to cystathionine through the SAM regulated enzyme cystathionine β-synthase, then further to cysteine (figure 1). This pathways and the compounds it contains are interesting nutritionally because high levels of plasma homocysteine are a risk factor for cardiovascular disease. In addition, the compounds of the methionine pathways have been investigated for their associations with increased body mass indices (BMI) in humans. In this regard SAM and cystathionine both show positive associations with BMI across all categories of individuals and BMI correlates strongly with SAM and SAH plasma levels in women.

methioning to cysteine metabolic pathway

Figure 1. Metabolic pathway for the conversion of methionine to cysteine. S-adenosylmethionine (SAM) is an important intermediate in this pathway.

However, the nature of the association between SAM and BMI was initially not fully understood. Therefore, further studies on SAM and its association to BMI were performed. For example, in one study1 the relationships plasma SAM with lean mass and with fat mass were investigated in a cross sectional study of just over 600 subjects including some with type 2 diabetes as well as healthy individuals with differing ranges of glucose tolerance. The results of the study showed that plasma SAM levels were not associated with lean mass in the subjects. However, erythrocyte SAM levels were positively associated with fat mass and the trunk fat to total fat ratio. As SAM levels increased in the subjects from the lowest to the highest groups, fat mass increased from 24 kg to 30 kg. The precursor methionine and product SAH were not associated with fat mass, and other lifestyle factors did not attenuate the strength of the association between plasma SAM and fat mass. Interestingly intakes of red meat were a strong predictor of the plasma SAM concentration in the subjects.

These results therefore suggest either an increased conversion of methionine to SAM or a decrease catabolism of SAM in the obese. If SAM synthesis increases in obesity, it could be caused by overnutrition that is a result of obesogenic diets. Fat deposition in the liver could drive SAM synthesis through overnutrition, and this fits with the observation that plasma SAM levels only correlate with fat mass in overweight individuals. High plasma SAM levels in the obese may therefore be an artifact of metabolic dysfunction in the hepatocytes caused by low quality foods. The fact that red meat intakes were a strong predictor of plasma SAM levels suggests that this may indeed be the case, as red meat intakes are high in the sorts of low quality obesogenic diets that cause the accumulation of fatty acids in liver tissue which then cause metabolic dysfunction. This is not to say that red meat is a bad food, just that it is a known marker for low quality diets, the latter being the direct cause of liver dysfunction and metabolic aberrations.

Dr Robert Barrington’s Nutritional Recommendation: The metabolic dysfunctions associated with poor quality diet are numerous and cause serious health consequences. One such dysfunction may the the over production of SAM. In itself it is unclear if this causes ill health, although it is unlikely not to modify some other metabolic parameter (SAM for example is a regulator of the cystathionine β-synthase enzyme). Supraphysiological levels of SAM in the obese are therefore likely to affect downstream metabolic regulation. The fact that plasma SAM correlated with truncal fat strongly indicated that SAM might be a useful marker for the metabolic dysfunction associated with abdominal obesity.

RdB

1Elshorbagy, A. K., Nijpels, G., Valdivia-Garcia, M., Stehouwer, C. D. A., Ocke, M., Refsum, H. and Dekker, J. M. 2013. S-adenosylmethionine is associated with fat mass and truncal adiposity in older adults. Journal of Nutrition. 143: 1982-1988

About Robert Barrington

Robert Barrington is a writer, nutritionist, lecturer and philosopher.
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