Abstract 5894: Synergism between medium-chain fatty acid intake and global magnesium status on the risk of cancer mortality in the National Health and Nutrition Examination Survey (NHANES) 2005-2014
Authors: Fan Lei , Zhu Xiangzhu , Shingina Alexandra , Shu Lihua , Shrubsole Martha , Dai Qi 
Published: June 2022

Abstract
Medium-chain fatty acids (MCFAs), a class of saturated fatty acids that exist naturally in dairy products and tropical oils, can regulate inflammation, insulin resistance, and immune response. Furthermore, in vitro and in vivo studies found MCFAs have strong anticarcinogenic properties. Recent evidence reveals MCFAs inhibits aerobic glycolysis in tumor cells. It is conceivable that MCFAs have an “anti-Warburg effect”. In a double-blind randomized trial (Personalized Prevention of Colorectal Cancer; NCT01105169), we found that 12-week personalized magnesium (Mg) supplementation led to significantly increased circulating levels of MCFAs, particularly caprylic acid (C8:0), which was due to enhanced microbial production. These novel findings suggest individuals with Mg sufficiency can receive supplies of MCFAs from microbiome whereas people with Mg deficiency cannot and so need MCFAs from intake. Thus, we hypothesized that the associations between intakes of C8:0 and risk of cancer mortality are modified by body Mg status. We tested this hypothesis in the NHANES, a nationally representative study. We recently developed the Mg depletion score (MDS) to assess Mg status and validated it against the invasive gold standard measure of Mg status. MDS performs better than either serum Mg or Mg intake at predicting Mg deficiency. We also found higher Mg intake was associated with reduced risks of inflammation and total mortality only among those with higher MDS scores, i.e., higher risk of losing Mg in the kidney. Thus, we examined if MDS modified the associations between intakes of MCFAs and risk of cancer mortality. Among 11,890 US adults aged ≥20 years over a median follow-up of 70 person-months, the associations between C8:0 intake and cancer mortality risk differed by MDS (Pinteraction=0.12). Higher C8:0 intake was associated with increased cancer mortality risk when MDS=0 (no risk of losing Mg; P-trend=0.03) after adjusting for all covariates, including dairy product intake. C8:0 intake was not related to risk of cancer mortality when MDS=1. Conversely, C8:0 intake may be associated with a reduced cancer mortality risk among those with MDS&gt;1(high risk of losing Mg). In particular, higher C8:0 intake was significantly associated with a reduced risk of cancer mortality (P-trend&lt;0.01) with an HR (95% CI) of 0.11 (0.02-0.84) for the highest quartile of C8:0 intake when Mg intake was above the Estimated Average Requirement. No associations were found for intakes of C6:0, C10:0 and C12:0. In summary, C8:0 can be generated by human gut microbiome through optimized Mg consumption; dietary intakes of C8:0 were associated with a reduced risk of cancer mortality among those at high risk of losing Mg, but with adequate Mg consumption; and intakes of C8:0 were related to an increased risk of cancer mortality among those with no risk of losing Mg.
Citation Format: Lei Fan, Xiangzhu Zhu, Alexandra Shingina, Lihua Shu, Martha Shrubsole, Qi Dai. Synergism between medium-chain fatty acid intake and global magnesium status on the risk of cancer mortality in the National Health and Nutrition Examination Survey (NHANES) 2005-2014 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5894.