Nutrigenomics, Lutein and the Future of Nutrition
Nutrition is an interesting yet perplexing subject. Why do some people seem to be able to eat whatever they want without putting on weight, while others have a diet that would put most dietitians to shame, yet remain overweight? How do some people manage to keep their cholesterol levels low through a sedentary lifestyle and high-fat diet, while others only need to look at a piece of cheese for their cardiologist to give them a call? Why can some people maintain normal levels of vitamin A on a plant-based diet, while others have to supplement? While there are many reasons for why nutrient status can differ with diet and lifestyle, an important difference is due to genetics. This was explored in a recent publication by Borel and colleagues in the American Journal of Clinical Nutrition. The authors looked at variation in lutein absorption, and the effect of genetic polymorphisms on the response to lutein from food and a supplement.
Lutein is a carotenoid found mainly in yellow, dark green and orange fruits and vegetables (the American Optometric Association provides a table with the richest lutein sources). Lutein (along with related carotenoid zeaxanthin) accumulates in the retina of the eye, and may protect the delicate vision sensor cells there from light damage. In general, the more lutein that people consume, the more is taken up in the blood, and the more accumulates in the retina. However, the relationship is not cut-and-dried. This was known already back in 1997, when Hammond and co-workers reported on how lutein levels in the eye can be changed by dietary intakes. There, subjects were classified as “responders” in the blood or the eye to dietary manipulation. While they could only speculate on the causes of these differences, the current study by Borel uses information on single nucleotide polymorphisms (SNPs) to identify genetic factors that could explain variation in response to supplementation.
The Borel study was conducted in 39 healthy male subjects. They were provided with either 15 mg lutein as a supplement, or 0.1 mg in tomato puree. While tomatoes are more well known for the lycopene they contain, they also contain small amounts of lutein and other carotenoids, and this particular food was chosen for convenience by the study group, as they will also be publishing a parallel study on lycopene absorption. Blood samples were taken regularly up to 8 hours after the meal, and the cross-over study was repeated after a wash-out period of 3 weeks.
The authors found a very high variability in response to lutein supplementation, and this was particularly pronounced from tomato puree. Responses varied 10-fold in the 8-hour AUC curve, and the standardized variation was 75% for the lutein supplements. The authors found that there was correlation in response within individuals, that is, some individuals’ lutein levels tended to increase a lot after both meals, whereas others had a lower response to both meals. They also found that people with higher baseline levels of lutein had a greater response to the meals, consistent with overall higher absorption of lutein prior to the study. The authors also screened 1785 SNPs for their relationship with lutein responses, and found 29 SNPs in 15 genes that appeared to have an effect. The authors were able to construct a model that could predict lutein response according to these SNPs. For example, the two genes with the highest predictive value were ELOVL2 with the SNP at rs9468304, and ABCG2 with the SNP at rs17731631. ELOVL2 is involved in the elongation of fatty acids, and the presence of fatty acids is important for the absorption of carotenoids, including lutein. ABCG2 is involved in the transport of various molecules across cell membranes. Both these genes could therefore mechanistically be involved in the absorption of lutein into the blood.
We are still a long way off from being able to personalize nutrition based on our genes (although this is already happening to a limited extent, for example in people with familial hypercholesterolemia). Perhaps in the future, we will be able to advise people who do not absorb lutein as well as others due to their genetic makeup to consume very rich lutein sources on a regular basis to ensure enough lutein reaches the eye to be of use there. This is a long way off. Studies like these, however, help us get a little bit closer to being able to make specific dietary recommendations to help people overcome whatever genetic hurdles their DNA has placed before them on the path to good health.
Patrick Borel, Charles Desmarchelier, Marion Nowicki, Romain Bott, Sophie Morange, and Nathalie Lesavre. Interindividual variability of lutein bioavailability in healthy men: characterization, genetic variants involved, and relation with fasting plasma lutein concentration. Am J Clin Nutr 2014 ajcn.085720; First published online May 7, 2014. doi:10.3945/ajcn.114.085720
Hammond BR Jr, Johnson EJ, Russell RM, Krinsky NI, Yeum KJ, Edwards RB, Snodderly DM. Dietary modification of human macular pigment density. Invest Ophthalmol Vis Sci. 1997 Aug;38(9):1795-801. http://www.ncbi.nlm.nih.gov/pubmed/9286268
Nagao A, Kotake-Nara E, Hase M. Effects of fats and oils on the bioaccessibility of carotenoids and vitamin E in vegetables. Biosci Biotechnol Biochem. 2013;77(5):1055-60. Epub 2013 May 7. http://www.ncbi.nlm.nih.gov/pubmed/23649270