Skip to main content Accessibility help



  • Access
  • Cited by 1


      • Send article to Kindle

        To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

        Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

        Find out more about the Kindle Personal Document Service.

        Comment on Christiansen et al.: When food met pharma
        Available formats

        Send article to Dropbox

        To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

        Comment on Christiansen et al.: When food met pharma
        Available formats

        Send article to Google Drive

        To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

        Comment on Christiansen et al.: When food met pharma
        Available formats
Export citation

Fatty acids can affect a variety of cell and tissue functions, so influence physiology and modify disease risk( 1 ). It is generally considered that many of the functional effects of fatty acids rely upon their incorporation into cell membranes from where they influence membrane fluidity, membrane protein function, lipid raft formation, intracellular signalling and the generation of bioactive lipid mediators( 2 , 3 ). Incorporation of fatty acids into cell membranes involves their covalent linkage into more complex lipids like phospholipids. However, the discovery of cell surface receptors that can bind fatty acids has raised the possibility that fatty acids could regulate cell and tissue function from the extracellular space and in the non-esterified form. Four such free fatty acid (FFA) receptors are known; these are all G-protein-coupled receptors (GPR). FFA2 receptor (GPR43) and FFA3 receptor (GPR41) bind SCFA, whereas FFA1 receptor (GPR40) and FFA4 receptor (GPR120) bind long-chain saturated and unsaturated fatty acids. FFA1 receptor is expressed in pancreas, brain and taste buds, whereas FFA4 receptor is expressed in intestinal cells, pancreas, brain, adipocytes and macrophages. These expression patterns suggest that the FFA1 and FFA4 receptors may be involved in fatty acid regulation of dietary fat intake, hormone release, hormone responsiveness (e.g. insulin sensitivity) and inflammation. Indeed Oh et al.( 4 ) demonstrated that FFA4 receptor was key to the ability of the n-3 PUFA DHA in promoting insulin sensitivity in adipocytes and in reducing inflammatory responses of macrophages. The recognition that fatty acids can act in a direct receptor-mediated fashion calls for new approaches in the study of their functional effects and of the mechanisms involved.

In a paper recently published in the British Journal of Nutrition, Christiansen et al.( 5 ) adopted a purely pharmacological (‘pharma’) approach in the study of the metabolic effects of fatty acids. They screened a wide range of medium- and long-chain saturated and unsaturated fatty acids, including arachidonic acid, EPA and DHA and their precursors, and also a number of unusual cis, trans, oxidised and branched fatty acids, for activity towards FFA1 and FFA4 receptors by performing detailed concentration-response curves using reporter assays. The outcomes were described in terms of potency (defined as the concentration required to elicit 50 % of the maximum response) and efficacy (defined as the maximum response elicited compared with that seen with lauric acid). Relatively, few fatty acids were selective for one FFA receptor over the other, but many showed greater activity towards one of the receptors than towards the other. Among the PUFA studied, the n-6 PUFA linoleic, γ-linolenic, di-homo-γ-linolenic, arachidonic and adrenic and the n-3 PUFA α-linolenic and EPA were very active towards the FFA1 receptor, whereas γ-linolenic, di-homo-γ-linolenic and stearidonic acids were very active towards the FFA4 receptor. The γ-linolenic-acid analog, pinolenic acid (5, 9, 12–18 : 3n-6), was the most potent dual agonist of both FFA1 and FFA4 receptors among the fatty acids tested. Pinolenic acid is found naturally in Korean and Siberian pine nut oils, where it contributes as much as 20 % of the fatty acids present. Christiansen et al.( 5 ) studied pinolenic acid further. It was active towards both human and mouse FFA1 and FFA4 receptors and was compared with authentic selective agonists for each receptor in concentration-response reporter assays, which confirmed its strong activity towards both receptors. Finally, acute administration of pine nut oil, pinolenic acid or pinolenic acid ethyl ester, was demonstrated to result in a lower blood glucose response to an oral glucose challenge in mice compared with maize oil, suggesting an improved metabolic response.

The strength of the work of Christiansen et al.( 5 ) is its detailed evaluation of concentration-dependent responses, an approach common in the pharma world but rarer in nutrition science. Too many in vitro or animal studies of nutrients and food-related non-nutrients fail to evaluate the influence of several concentrations of the compound under study, seriously reducing their value. Dose–response studies are more difficult to perform in humans, but studies evaluating the dose-dependent incorporation of n-3 PUFA have been reported( 6 , 7 ) as having dose–response studies, evaluating the effect of n-3 PUFA on blood lipids( 8 ), platelet reactivity( 9 ) and inflammation( 10 ). Such studies are valuable because they can identify thresholds for intakes that elicit a desired biological effect and above which no further effect is seen. Furthermore, description of dose or concentration dependence makes the report of any biological effect more robust and establishes greater evidence for a ‘cause and effect’ relationship between the provision of the food, food component or supplement and the biological outcome that is reported. Establishing such ‘cause and effect’ relationships through dose- or concentration-response studies can be a vital element in the process of substantiating a health claim. Therefore, nutrition science would be wise to adopt practices more akin to pharma when evaluating the functional properties and health impacts of foods, nutrients and non-nutrient food components. In fact, in this context the boundaries between ‘food and pharma’ are now somewhat blurred( 11 , 12 ), with the pharma industry becoming increasingly interested in food components as functional agents and the food industry and nutrition scientists being increasingly expected to adopt pharma practices as part of their normal research and development activities. This blurring of the boundaries is likely to become greater over the next years, and will certainly increase the chances of new discoveries being made by both the food and pharma industries and of translating those discoveries into new products, new claims, new preventative strategies and new treatments for human disease.


1. Calder, PC (2015) Functional roles of fatty acids and their effects on human health. J Parent Ent Nutr (In the Press).
2. Calder, PC (2012) Mechanisms of action of (n-3) fatty acids. J Nutr 142, 592S599S.
3. Calder, PC (2015) Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta 1851, 469484.
4. Oh, DY, Talukdar, S, Bae, EJ, et al. (2010) GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142, 687698.
5. Christiansen, E, Watterson, KR, Stocker, CJ, et al. (2015) Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases. Br J Nutr 113, 16771688.
6. Katan, MB, Deslypere, JP, van Birgelen, AP, et al. (1997) Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study. J Lipid Res 38, 20122022.
7. Browning, LM, Walker, CG, Mander, AP, et al. (2012) Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish. Am J Clin Nutr 96, 748758.
8. Harris, WS, Windsor, SL & Dujovne, CA (1991) Effects of four doses of n-3 fatty acids given to hyperlipidemic patients for six months. J Am Coll Nutr 10, 220227.
9. von Schacky, C, Fischer, S & Weber, PC (1985) Long-term effects of dietary marine omega-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans. J Clin Invest 76, 16261631.
10. Rees, D, Miles, EA, Banerjee, T, et al. (2006) Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr 83, 331342.
11. Calder, PC (2011) Fatty acids and inflammation: the cutting edge between food and pharma. Eur J Pharmacol 668, S50S58.
12. Calder, PC (2013) Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol 75, 645662.