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Insulin resistance and type 2 diabetes have been treated with the PPARγ agonists thiazolidinediones, or TZDs, since the 1990s. One mechanism by which these drugs may work is through PPARγ-mediated upregulation of adiponectin, an endogenous adipokine that has been shown to increase insulin sensitivity. Interestingly, α- and γ-tocopherol, two vitamin E vitamers, have structural similarities to the TZDs and have also been linked to enhanced insulin sensitivity. A recent study identified a novel function of α- and γ-tocopherol in 3T3-L1 preadipocytes: upregulation of an endogenous ligand involved in activating PPARγ. This study also found that tocopherols dramatically enhanced adiponectin expression and that this effect was mediated through a PPARγ-dependent process. These findings illustrate a possible mechanistic link between vitamin E and insulin sensitivity.

Several mechanistic studies in cell culture and mouse models suggest possible estrogen receptor-mediated and non-estrogen receptor-mediated benefits of pomegranate juice with respect to breast cancer risk. These studies demonstrate that various constituents of pomegranates can inhibit aromatase and 17beta-hydroxysteroid dehydrogenase enzymes or have antiestrogenic activity. Additional large, well-controlled human studies are warranted to elucidate the effects of pomegranate juice intake on serum hormone levels. Clarifying the effects of pomegranate constituents on key hormones known to be involved in breast cancer could result in important information for consumers and shed further light on the impact of diet on breast cancer risk.

Tuberculosis is highly prevalent worldwide, accounting for nearly two million deaths annually. Vitamin D influences the immune response to tuberculosis, and vitamin D deficiency has been associated with increased tuberculosis risk in different populations. Genetic variability may influence host susceptibility to developing active tuberculosis and treatment response. Studies examining the association between genetic polymorphisms, particularly the gene coding for the vitamin D receptor (VDR), and TB susceptibility and treatment response are inconclusive. However, sufficient evidence is available to warrant larger epidemiologic studies that should aim to identify possible interactions between VDR polymorphisms and vitamin D status.

Arsenic-contaminated groundwater is a global environmental health concern. Inorganic arsenic is a known carcinogen, and epidemiologic studies suggest that persons with impaired arsenic metabolism are at increased risk for certain cancers, including skin and bladder carcinoma. Arsenic metabolism involves methylation to monomethylarsonic acid and dimethylarsinic acid (DMA) by a folate-dependent process. Persons possessing polymorphisms in certain genes involved in folate metabolism excrete a lower proportion of urinary arsenic as DMA, which may influence susceptibility to arsenic toxicity. A double-blind placebo-controlled trial in a population with low plasma folate observed that after 12 weeks of folic acid supplementation, the proportion of total urinary arsenic excreted as DMA increased and blood arsenic concentration decreased, suggesting an improvement in arsenic metabolism. Although no studies have directly shown that high folate intake reduces the risk of arsenic toxicity, these findings provide evidence to support an interaction between folate and arsenic metabolism.