Differential effects of dietary supplements on metabolomic profile of smokers versus non-smokers

Abstract

Background: Cigarette smoking is well-known to associate with accelerated skin aging as well as cardiovascular disease and lung cancer, in large part due to oxidative stress. Because metabolites are downstream of genetic variation, as well as transcriptional changes and post-translational modifications of proteins, they are the most proximal reporters of disease states or reversal of disease states.

Methods: In this study, we explore the potential effects of commonly available oral supplements (containing antioxidants, vitamins and omega-3 fatty acids) on the metabolomes of smokers (n = 11) compared to non-smokers (n = 17). At baseline and after 12 weeks of supplementation, metabolomic analysis was performed on serum by liquid and gas chromatography with mass spectroscopy (LC-MS and GC-MS). Furthermore, clinical parameters of skin aging, including cutometry as assessed by three dermatologist raters blinded to subjects' age and smoking status, were measured.

Results: Long-chain fatty acids, including palmitate and oleate, decreased in smokers by 0.76-fold (P = 0.0045) and 0.72-fold (P = 0.0112), respectively. These changes were not observed in non-smokers. Furthermore, age and smoking status showed increased glow (P = 0.004) and a decrease in fine wrinkling (P = 0.038). Cutometry showed an increase in skin elasticity in smokers (P = 0.049) but not in non-smokers. Complexion analysis software (VISIA) revealed decreases in the number of ultraviolet spots (P = 0.031), and cutometry showed increased elasticity (P = 0.05) in smokers but not non-smokers.

Conclusions: Additional future work may shed light on the specific mechanisms by which long-chain fatty acids can lead to increased glow, improved elasticity measures and decreased fine wrinkling in smokers' skin. Our study provides a novel, medicine-focused application of available metabolomic technology to identify changes in sera of human subjects with oxidative stress, and suggests that oral supplementation (in particular, commonly available antioxidants, vitamins and omega-3 fatty acids) affects these individuals in a way that is unique (compared to non-smokers) on a broad level.

Figure 1

Study flowchart.

Figure 2

Decreased deviation of metabolites from normal distribution after 12 weeks of study supplement, most notably in the smoker group. Scatterplots showing absolute values of z-scores for all metabolites at baseline and after 12 weeks of taking the study supplement. The mScore is an average of all z-scores in the entire population. An mScore of 0.77 indicates a normal distribution. Red spot = smokers; blue spot = non-smokers.

Figure 3

Heat maps demonstrating fold change of metabolites in smokers and non-smokers. The heat maps show that smokers had significantly decreased levels of (long chain fatty acids) but not the cofactors and vitamins listed below, after 12 weeks of study supplementation. Green band = decrease; red = increase

Figure 4

Patient skin glow and UV spots. (a, b) Example of an increase in glow at week 12 (b) compared to week 0 (a) as determined by a panel of four blinded dermatologists. (c, d) Example of a decrease in UV spots at week 12 (Figure d) compared to week 0 (c) in a participant as determined by VISIA Complexion Analysis System.