Concerns about the use of 15:0, 17:0, and trans-16:1n-7 as biomarkers of dairy fat intake in recent observational studies that suggest beneficial effects of dairy food on incidence of diabetes and stroke.

Dear Editor: It is with interest that I read the articles by Santaren et al. (1) and Yakoob et al. (2) about the relation of circulating concentrations of pentadecanoic acid (15:0), heptadecanoic acid (17:0), and trans-palmitoleic acid (trans-16:1n–7) with the incidence of diabetes and stroke. Santaren et al. (1) reported that serum concentrations of pentadecanoic acid are associated with insulin sensitivity and β cell function, as well as a 27% decreased risk of type 2 diabetes. Yakoob et al. (2) reported no significant associations of total plasma or red blood cell pentadecanoic acid, heptadecanoic acid, and trans-palmitoleic acid with risk of stroke. Because several previous studies implicated pentadecanoic acid, heptadecanoic acid, and trans-palmitoleic acid in serum, plasma, red blood cells, and adipose tissue as valid biomarkers for dairy intake (3–9), Santaren et al. (1) suggested that their findings may contribute to future recommendations regarding the benefits of dairy products on type 2 diabetes, and Yakoob et al. (2) concluded that circulating biomarkers of dairy fat are not significantly associated with stroke. A commentary written by Arne Astrup in the same issue of the Journal (10) stated that “there is no evidence left to support the existing public health advice to limit consumption of dairy to prevent CVD [cardiovascular disease] and type 2 diabetes. ” I am concerned with the use of pentadecanoic acid, heptadecanoic acid, and trans-palmitoleic acid as biomarkers of dairy fat intake. It is true that these are present in dairy fat, although at very low amounts (pentadecanoic acid at 1.0%, heptadecanoic acid at 0.6%, and trans-palmitoleic acid at 0.3%) (11). These 3 fatty acids, however, are not limited to dairy fat. In particular, fat from beef, veal, lamb, and mutton also contains all of these fatty acids at amounts similar to those found in dairy fat (12, 13). The presence of pentadecanoic acid and heptadecanoic acid, at amounts comparable to dairy fat, has also been reported in many other common dietary fats and foods, including chicken, lard (13), marine and freshwater fish (14), marine oils (15), some vegetables (cabbage and cucumber) (16), and seaweeds (17). Several common vegetable oils also contain small amounts of heptadecanoic acid (18). Rapeseed (canola) oil contains both pentadecanoic acid and heptadecanoic acid (19). These data suggest that pentadecanoic acid and heptadecanoic acid are widely distributed in nature and present in many common foods, including dietary fats, albeit in small amounts. Unfortunately, this information is not commonly available because many scientific publications on fatty acid composition of dietary fats and foods focus only on the major and nutritionally important fatty acids and do not show data for pentadecanoic acid and heptadecanoic acid because these fatty acids are minor components and have no known nutritional or biological significance. Another factor that needs to be considered in choosing a fatty acid as a biomarker is that it should not be endogenously synthesized. Many previous studies made the assumption that circulating trans-palmitoleic acid is solely derived from the consumption of dairy fat (9). However, it was recently found that circulating trans-palmitoleic acid is not exclusively diet derived but may also be endogenously produced by the partial β-oxidation of dietary vaccenic acid (trans-18:1n–7) (20). Vaccenic acid is the major trans fatty acid isomer in dairy fats but is also present in partially hydrogenated oils. In Canadian dairy products, vaccenic acid accounts for 22–43% of total trans-18:1 isomers (21). Partially hydrogenated vegetable oils also contain considerable amounts of vaccenic acid: proportions ranging from 15% to 24% of total trans-18:1 isomers have been found in partially hydrogenated canola and soybean oil samples (22). Trace amounts of pentadecanoic acid and heptadecanoic acid are synthesized in leaves (23) and are present in common vegetables as noted above (16). It is not known whether animals and humans have the capability to synthesize pentadecanoic acid and heptadecanoic acid, but this should not be ruled out until it has been examined. A further concern is the uncertainty of correct identification of pentadecanoic acid, heptadecanoic acid, and trans-palmitoleic acid in the gas chromatography (GC) analysis of fatty acid mixtures. These fatty acids are always found in very low concentrations in blood samples and dietary fats and very often coelute with other fatty acids in GC analysis. For example, pentadecanoic acid overlaps with 9-cis-tetradecenoic acid (9c-14:1), trans-palmitoleic acid overlaps with iso-heptadecanoic acid and 3-trans-heptadecanoic acid (3t-16:1; a common trans fatty acid in plants), and heptadecanoic acid elutes close to 11-cis-hexadecenoic acid (11c-16:1) and 13-cis-hexadecenoic acid (13c-16:1) (24). Thus, if the GC conditions are not optimized, it is possible that the concentrations of pentadecanoic acid, trans-palmitoleic acid, and heptadecanoic acid may be exaggerated due to inclusion of the overlapping components. Because the fatty acid analytic methods used were not described by Santaren et al. (1) and Yakoob et al. (2), it is not known whether they have encountered any such fatty acid analysis problems. Considering these possible uncertainties of the dietary origin and the analysis of pentadecanoic acid, heptadecanoic acid, and trans-palmitoleic acid, we should be cautious in making conclusions about the role of dairy fats in diabetes and stroke.