On Nutrigenomics

Yesterday, I spent my lunchtime browsing the Health and Wellness section at a major bookstore. I was amazed by the sheer number of “diet experts” proclaiming to have the nutritional advice we all need to hear. Keto. Paleo. Veganism. The Carnivore Diet. Intermittent Fasting. The Blood Type Diet. Low carb. The list is endless. Everybody thinks they have the answer. Diets are like cults. In our secular Western world, the collapse of religion has created a vacuum. This void has been filled by many things, and diet is one of them. Diets provide two things that humans crave: social support, and a common sense of purpose. Nutritional evangelists do a phenomenal job of exploiting these fundamental motivators. How can we move past this sad state of affairs? Why is nutrition so contaminated by dogma and ideology? Can’t we just do some experiments, figure out what we should be eating, and quell the hand waving? Well, technically we can’t, for a couple of reasons.

First, nutrition studies are not experiments. Experiments hold relevant variables constant, manipulate one variable and track outcomes. This is the ONLY way to distinguish cause from effect. Let’s imagine I want to experimentally study the impact of egg consumption on the development of atherosclerosis. I would draw two random samples of individuals, and randomize them into two conditions: one that eats eggs and one that doesn’t. At the end of the trial, I would compare the incidence of atherosclerotic disease between the groups. But of course, I would need to control for confounding variables. I would need to ensure that subjects slept identically, endured equal stress, and exercised in precisely the same way. And to make matters worse, it turns out that people are inherently different (gasp). Different genes endow people with different metabolic machinery. Thus, two people can respond differently to the same diet. So to truly control a nutrition experiment, I would need a set of genetic clones. On balance, I’m thankful that I don’t live inside a Huxley novel, and can’t perform such experiments. But as someone who simply wants answers to questions, I’m left feeling truly cynical about our situation. Almost all nutrition research commits the cardinal sin of being epidemiological, which means that it draws correlations between people’s diets and their health outcomes. Though such studies control for as much as they can, epidemiologists are fighting a losing battle. Epidemiology is so fraught with problems that it will probably get its own post at some point. But I digress. The point of this preamble is to introduce an essay I wrote back in 2014, which delves more deeply into this story, and seems particularly relevant today. Please forgive my teenaged over-writing, and insufferable wordiness.

Without further adieu, I give you 18 year old Leo’s thoughts on genetics and nutrition:

Nutrition, DNA, and Human Health: an examination of the emerging science of Nutrigenomics

Nutrition is considered by many to be a “soft” science – one that is overloaded with information, but in dire need of precision. For decades, opposing nutritional camps have quarrelled over what constitutes a good diet. Fad diets have come and gone with regularity over the past 50 years; the Zone diet, the Atkins diet, Veganism, and the Paleo diet are just a few contemporary examples of philosophical ‘sects’ into which the health and fitness industry has divided. Each sect, often in the interest of financial gain, touts its own philosophy as the single proper method of eating. While disagreement and deception are to be expected in the commercial marketplace, ideological inconsistencies surrounding nutrition also extend to the world of empirical science. Indeed, even in the objective world of academia, experts often disagree on issues as basic as whether grains can be part of a healthy diet, or whether humans should consume dairy products. At the root of much of the confusion in nutrition science is the following puzzling phenomenon: precisely the same diet can affect different people in different ways. For example, some people can eat a high fat diet and have no problem with their cholesterol levels, while others who eat precisely the same diet experience the opposite response (Glatz et al., 1993). The important question, then, is how two people who consume the same nutrient in the same amount can have different responses. Amid the ideological warfare of modern nutrition, the emerging science of nutrigenomics may be on the verge of answering that question, and along with it, clarifying many other inconsistencies present in the “soft” science of nutrition.

Nutrigenomics, a bridge between genetics and nutrition, provides a novel lens through which to examine how food impacts the human body. Nutrigenomics investigates how the foods humans eat interact with their genes to affect their health. In 2001, after decades of slow scientific progress, the National Institute of Health completed the much anticipated Human Genome Project. The main goal of the project was to provide a “map” of the chemical base pairs which comprise the human genome. Once the project was completed, science had finally elucidated mankind’s chemical blueprint; that is, it had a working roadmap of the location of all of the genes which are found in the human DNA sequence. Following their momentous discovery, Collins and Mckusick (2001) postulated that genomic medicine holds the key to revolutionizing the diagnosis and treatment of many illnesses. The question then arose: might the important insights of genetics have an impact on the young field of nutrition science? In order to properly approach this question, it is useful to have a basic understanding of elementary genetics.

The human body consists of about 50 trillion cells. Each cell contains a complete genetic blueprint, encoded in molecules of Deoxyribonucleic Acid (DNA), for the replication of the organism in which it resides. DNA is a ladder shaped molecule, with complementary chemical “letters” (A, T, G or C) on either side of each rung of the ladder. If the DNA in one cell were stretched out, it would span a length of about two metres. To avoid this issue, DNA is compressed and coiled up into packages called chromosomes, of which humans have 23 pairs. Chromosomes are found in a cell’s nucleus. If one imagines a chromosome as a cookbook for making a human being, a gene might be thought of as an individual recipe in that cookbook. Each gene, which is simply a designated region of DNA, consists of a string of “letters”, the sequence of which determines what protein that gene makes. It is the variation in these sequences which ultimately leads to individual differences between humans. If three letters are missing on a gene called “CFTR,” for example, that gene makes a defective membrane protein that causes cystic fibrosis (Kerem et al., 1989). Amazingly, humans all share 99.9 % identical DNA. In other words, the sequence of letters which comprises each human genome is practically identical, and the 0.1 % of variability in our chemical alphabet accounts for all the wonderful diversity of our species. It is these common areas of variability – called single nucleotide polymorphisms (SNPs) – that are vital for this discussion of genes and food.

A simple example of how a genetic variation can have a profound effect on one’s metabolic profile involves coffee. Though coffee is one of the most widely consumed beverages in the Western world, there remains a great deal of controversy over whether it is good for one’s health. Many experts tout the antioxidants in coffee beans as protective of cardiovascular function, while others claim that the effects of caffeine are biologically adverse. What accounts for this inconsistency? Cornelis et al. (2006) answered this question by examining it through a Nutrigenomic lens. They performed a study which examined how genetically different individuals respond to similar caffeinated coffee intake. Researchers identified two different versions of a gene (called CYP1A2) which codes for the major enzyme that breaks down caffeine in the liver. About half of the population has one version of this gene, which metabolizes caffeine rapidly, while the other half has a version which metabolizes caffeine slowly. Results showed that individuals who had what the “slow” version of the gene had an increased risk of a heart attack when increasing consumption of caffeinated coffee. Conversely, those who had the “fast” version of the gene had a lower risk of heart attack when they consumed the same amount. The reason why the fast version of the gene confers a benefit is that it is the antioxidants, not the caffeine, which offer protection for the heart. Due to their unique genomic makeup, the fast metabolizers can break down caffeine very rapidly, eliminating it quickly while preserving the healthy antioxidants in the coffee. The slow metabolizers, by contrast, are subject to the adverse effects of caffeine for a longer duration, negating the benefits conferred by the antioxidants in the beans. Identical consumption. Different genotypes. Disparate outcomes. This is just one example of how nutrigenomics has added a degree of precision to the field of nutrition. Indeed, studies like these clearly offer a meaningful foothold to clearing up the many inconsistencies present in 20th century nutrition science.

Genetic testing might demystify another peculiar nutritional oddity: the “sweet tooth.” Anecdotally, many people admit to feeling a strong physical compulsion to consume sugary food, while others report that they have no trouble abstaining from it. The question is this: are sugar cravings common to all, leaving only the weak-willed among us unable to maintain discipline? Once again, nutrigenomics provides an apt toolkit with which to examine why some find sugar abstinence so much harder than others. A fascinating line of research has posited the idea that food addiction is neurochemically analogous to drug addiction – that is – cocaine, methamphetamine and sugar all act as positive reinforcers, activating a common neurological circuit called the mesolimbic system. This reinforcement circuit runs on a “learning” neurotransmitter called dopamine (Kenny, 2013). In fact, Lenoir et al (2007) showed that when rodents are given the choice between sugar and cocaine, they chose sugar 94% of the time. Though useful to understanding addiction, this reward learning framework does not account for individual variability in the intensity and type of cravings. In a recent study, however, Eny et al (2009) found that people who possess a version of a gene which codes for a subtype of dopamine receptor tend to eat more sugar than those with a different version of that same gene. They suggest that although the specific SNPs (variations in DNA sequences) that constitute food preferences are not perfectly understood, they are clearly a driving force in food cravings. This is yet another illustration of the clear-cut field of genetics quantifying the contentious field of nutrition.

In a discussion of genetics and food, I would be remiss not to mention the new field of epigenetics. Only in the last ten years has it been discovered that genes can actually be chemically altered by environmental signals. Epigenetics does not study the sequence of chemical letters in a gene – that is invariably static; rather, epigenetics studies how environmental stimuli alter the proteins that a gene makes. For example, it is possible for external stimuli to cause a tumor suppressor gene to be “turned off,” leading to the proliferation of cancer cells (Yu et al., 2008). Ironically, one of the many external stimuli that can turn such genes on or off are the very foods we eat (Choi & Friso, 2010). So as it stands, current research suggests that the relationship between genes and food is multidirectional, and more complex than we previously thought; not only do our genes affect the way we eat, but the way we eat also affects the expression of our genes.

Will genetic testing revolutionize the field of nutrition? Will our genetic code turn out to be a faultless indicator of what we should eat? Though nutrigenomics is clearly playing a role in solving many of the problems that have plagued nutrition science for decades, the field is still fraught with controversy and disagreement. Journalist Michael Pollan brilliantly captures this reality with the following statement: “Nutrition science, which after all only got started less than two hundred years ago, is today approximately where surgery was in the year 1650 – very promising, and very interesting to watch, but are you ready to let them operate on you? I think I’ll wait awhile” (Pollen, 2009, p. 2). Despite the uncertainty surrounding the implications of nutrigenomics, one thing is clear: it constitutes a step function improvement in our understanding of nutrition, and serves as a bulwark against the dogmatism that so often characterizes nutritional discourse.

References

Choi, S. W., & Friso, S. (2010). Epigenetics: A new bridge between nutrition and health. Advances in Nutrition: An International Review Journal, 1(1), 8-16. Retrieved from http://advances.nutrition.org.ezproxy.library.uvic.ca/content/1/1/8.short

Collins, F. S., & McKusick, V. A. (2001). Implications of the Human Genome Project for medical science. Journal of the American Medical Association, 285(5), 540-544. doi:10.1001/jama.285.5.540.

Cornelis, M. C., El-Sohemy, A., Kabagambe, E. K., & Campos, H. (2006). Coffee, CYP1A2 genotype, and risk of myocardial infarction. Journal of the American Medical Association, 295(10), 1135-1141. doi:10.1001/jama.295.10.1135.

Eny, K. M., Corey, P., & El-Sohemy, A. (2009). Dopamine D2 receptor genotype (C957T) is associated with habitual consumption of sugars in a free-living population of men and women. Journal of Nutrigenetics and Nutrigenomics, 2(4), 235-42. doi: 10.1159/000276991.

German, J. B., Zivkovic, A. M., Dallas, D. C., & Smilowitz, J. T. (2011). Nutrigenomics and personalized diets: what will they mean for food? Annual Review of Food Science and Technology, 2, 97-123. doi: 10.1146/annurev.food.102308.124147

Glatz, J. F., Turner, P. R., Katanf, M. B., Stalenhoef, A. F., & Lewis, B. (1993). Hypo‐and hyperresponse of serum cholesterol level and low density lipoprotein production and degradation to dietary cholesterol in mana. Annals of the New York Academy of Sciences, 676(1), 163-179. doi: 10.1111/j.1749-6632.1993.tb38732.x.

Kenny, P. J. (2013). The food addiction. Scientific American, 309(3), 44-49. doi:10.1038/scientificamerican0913-44

Kerem, B. S., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., & Tsui, L. C. (1989). Identification of the cystic fibrosis gene: Genetic analysis. Science, 245(4922), 1073-1080. doi: 10.1126/science.2570460.

Lenoir, M., Serre, F., Cantin, L., & Ahmed, S. H. (2007). Intense sweetness surpasses cocaine reward. PloS one, 2(8), 698. doi: 10.1371/journal.pone.0000698.

Pollan, M. (2009). Food rules: An eater’s manual. Penguin.

Yu, W., Gius, D., Onyango, P., Muldoon-Jacobs, K., Karp, J., Feinberg, A. P., & Cui, H. (2008). Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature, 451(7175), 202-206. doi:10.1038/nature06468