Vaccenic acid

Vaccenic acid is a trans fatty acid derived from dairy fat and can be consumed from dairy products such as cow’s milk, butter, and yogurt¹. It is a major trans fat found in ruminant fats and belongs to a class of long-chain fatty acids. Vaccenic acid is a positional and geometric isomer of oleic acid, one of the dominant fatty acids found in animal and vegetable oils ². The primary source of dietary vaccenic acids is from biohydrogenation of linoleic acid, one of the most highly consumed polyunsaturated fatty acids in human diets.

Conjugated linoleic acid (CLA), another trans fatty acid, is formed in the synthesis pathway for vaccenic acid and acts as its primary dietary precursor. The cis isomer of vaccenic acid, cis vaccenic acid, can be formed by elongation of palmitoleic acid, a species of monounsaturated fatty acids. Understanding fatty acid composition in dietary sources is crucial, as it emphasizes the balance between saturated and unsaturated fatty acids, which plays a significant role in maintaining the fluidity and functionality of cell membranes.

Intake of trans fatty acids have been well studied in the context of human health. Most findings have suggested that excess intake of industrial trans fatty acids, saturated fatty acids, and a lack of unsaturated fatty acids has adverse health effects and increases the risk of metabolic syndrome (e.g. obesity and type-2 diabetes), cardiovascular disease, and cancer. However, emerging research has provided evidence for human health benefits, particularly in mitigating the negative effects on metabolism, from consuming naturally occurring trans fatty acids, including vaccenic acid.

Vaccenic Acid’s Fatty Acid Composition and Metabolic Health

Consumption of industrial trans fatty acids has been long associated with increased risk of obesity and type 2 diabetes³. Dietary consumption of these fats are linked to severe health concerns, including negative impacts on lipid metabolism, heightened inflammatory parameters, and diminished insulin sensitivity. In contrast, recent research has demonstrated that intake of naturally occurring trans fatty acids from beef, milk, and yogurt impart health benefits by ameliorating the many of the outcomes of metabolic disorders and altering free fatty acids.

For example, supplementation with vaccenic acid in obese rats significantly reduces adipocyte size⁴ and human studies have shown that vaccenic acid rich diets lowers cholesterol⁵. To understand the mechanisms that underlie the beneficial effects of vaccenic acid, one report demonstrated that vaccenic acid supplementation improves obesogenic outcomes by normalizing proinflammatory immune responses in a rat model of metabolic syndrome⁶.

While some studies have reported no effects on insulin signaling in obese rats⁴, others have demonstrated that vaccenic acid improves insulin sensitivity and decreases insulin resistance. Notably, dietary vaccenic acid significantly increased glucose turnover and increased β-cell proliferation in rats with type-2 diabetes⁷. In the same study, vaccenic acid application on human islets increased mRNA expression of GPR40 and REG-1ɑ, which are components of critical signaling pathways that mediate insulin secretion.

Vaccenic Acid as Trans Fats and Cardiovascular Disease

Cardiovascular disease (CVD) is one of the deleterious outcomes of metabolic disorders, and risk increases with excess intake of industrial trans fatty acids. However, the effects of vaccenic acid on cardiovascular health are mixed, ranging from neutral to beneficial.

In a report examining the effects of trans fatty acids on blood lipids, researchers found that high dietary intake of a vaccenic acid-rich butter raises plasma LDL-cholesterol concentrations and increases CVD risk. Interestingly, moderate intake showed neutral effects on CVD risk factors⁸. However, others have pointed to the beneficial effects of vaccenic acid on metabolic parameters (as described above) as reducing the risk of developing CVD. For example, in hypertensive rats, consumption of vaccenic acid and CLA exerted beneficial effects on cardiovascular risk biomarkers, including insulin reduction, increase of adiponectin, and improving blood pressure9. Research determining whether the consumption of vaccenic acid produces similar adverse effects on cardiovascular health as other industrial trans fats is ongoing. Regardless, these data taken together highlight the importance of moderating dietary intake of trans fatty acids and dairy consumption.

Vaccenic Acid and Oncology

Alterations in lipid metabolism have been identified as a significant risk factor for the development of numerous cancers. While intake of fats generally increases cancer risk, recent studies have highlighted the importance of elucidating the composition of dietary fats to assess cancer risk. Notably, vaccenic acid and other trans fatty acids have emerged as having treatment potential for several cancers including prostate cancer, breast cancer¹⁰ and colon cancer. 

For instance, in vitro studies using human colon adenocarcinoma cells showed that supplementation with milk lipids containing CLA and vaccenic acid altered lipid composition and inhibited cell growth¹¹. Other reports have found that vaccenic acid application in cancer cells reprograms signaling cascades that mediate anti-tumor immunity¹². 

Research on Vaccenic Acid

As of March 2024, there are 899 citations for vaccenic acid in research publications (excluding books and documents) on PubMed. The growing number of publications linking this metabolite to a broad range of physiological functions suggests that any research program seeking to better understand metabolic, cardiovascular, and oncological health may benefit from quantitative analysis of vaccenic acid. Considering the importance of vaccenic acid in biological functions, preclinical research may also benefit from vaccenic acid quantification to further the understanding of biomarkers, diagnosis, and disease monitoring.

References

1. Lock AL and Bauman, DE. Modifying milk fat composition of dairy cows to enhance fatty acids beneficial to human health. Lipids 2004;(39):1197-1206.
2. Huth PJ, Fulgoni VL 3rd, and Larson BT. A systematic review of high-oleic vegetable oil substitutions for other fats and oils on cardiovascular disease risk factors: implications for novel high-oleic soybean oils. Adv Nutr 2015;(6):674-693.
3. van Dam RM, Willett WC, Rimm EB, et al. Dietary fat and meat intake in relation to risk of type 2 diabetes in men. Diabetes Care 2002;(25):417-424.
4. Mohankumar SK, Hanke D, Siemens L, et al. Dietary supplementation of trans-11-vaccenic acid reduces adipocyte size but neither aggravates nor attenuates obesity-mediated metabolic abnormalities in fa/fa Zucker rats. Br J Nutr 2013;(109):1628-1636.
5. Tholstrup T, Raff M, Basu S, et al. Effects of butter high in ruminant trans and monounsaturated fatty acids on lipoproteins, incorporation of fatty acids into lipid classes, plasma C-reactive protein, oxidative stress, hemostatic variables, and insulin in healthy young men. Am J Clin Nutr 2006;(83):237-243.
6. Blewett HJ, Gerdung CA, Ruth MR, et al. Vaccenic acid favourably alters immune function in obese JCR:LA-cp rats. Br J Nutr 2009;(102):526-536.
7. Wang X, Gupta J, Kerslake M, et al. Trans-11 vaccenic acid improves insulin secretion in models of type 2 diabetes in vivo and in vitro. Mol Nutr Food Res 2016;(60):846-857.
8. Motard-Belanger A, Charest A, Grenier G, et al. Study of the effect of trans fatty acids from ruminants on blood lipids and other risk factors for cardiovascular disease. Am J Clin Nutr 2008;(87):593-599.
9. Herrera-Meza MS, Mendoza-Lopez MR, Garcia-Barradas O, et al. Dietary anhydrous milk fat naturally enriched with conjugated linoleic acid and vaccenic acid modify cardiovascular risk biomarkers in spontaneously hypertensive rats. Int J Food Sci Nutr 2013;(64):575-586.
10. Ip C, Scimeca JA, and Thompson HJ. Conjugated linoleic acid. A powerful anticarcinogen from animal fat sources. Cancer 1994;(74):1050-1054.
11. Degen C, Lochner A, Keller S, et al. Influence of in vitro supplementation with lipids from conventional and Alpine milk on fatty acid distribution and cell growth of HT-29 cells. Lipids Health Dis 2011;(10):131.
12. Fan H, Xia S, Xiang J, et al. Trans-vaccenic acid reprograms CD8(+) T cells and anti-tumour immunity. Nature 2023;(623):1034-1043.