Nutrigenomics: The Science of How Food Interacts With Our Genes

Imagine with me for a moment: Joe, the quirky, astute, dedicated scientist, approaches his laboratory for the day's research. He opens the large double doors and begins to run routine safety checks. Equipment expiration dates are within range, ventilation systems are adequate, emergency showers and eyewash stations are functional. Joe settles upon himself a thick apron, dons industrial-type gloves, and places those classically oversized chemistry goggles over his eyes. Proceeding to the incubator, Joe reaches in, removes the day’s research specimen, and, whilst placing it on the laboratory bench, he reveals the promising item: a single, green, leafy, stalk of broccoli.

On April 1st, 1869, Friedrich Miescher, a swiss physician and biologist, first isolated deoxyribonucleic acid (DNA) from a pus-filled bandage. This discovery launched a scientific revolution, which, in 1990, prompted the beginnings of the human genome project: an attempt to sequence the instructions that make a human being. Finally, in 2003, the human genome was published, and, following closely, was the field of nutrigenomics, the science of how food interacts with our genes. Because, as we discovered, the three-billion letter sequence was not at all as simple as it seemed. In fact, as we learned, the expression of these letters can be controlled by on and off switches, of sorts. In this article, I would like to discuss the field of nutrigenomics, which attempts to explain one of the many ways in which these switches are controlled -- with food.

Let us return to the example from our fictional scientist and focus on broccoli. It is almost like a mantra at this point: eat your veggies. And, when we zoom in a little further, it is particularly the leafy green vegetables that are preached. Finally, of the leafy greens, the research seems to be biased towards broccoli, and, more specifically, its flowery head. But why? Really take a moment to think about this: it is understood that the miniature tree-looking food piece is “healthy” for humans; what are the reasons for this?

Every plant contains compounds termed phytochemicals (phyto, as in plant). These phytochemicals have been shown to be biologically active in the human body. Specifically, promising research has been targeted toward a phytochemical in broccoli which can be found in the vegetables’ sprouts called sulforaphane. In order to understand why sulforaphane has been so strongly connected with various health benefits, a brief review of molecular biology is needed. Don’t fret, however; even if the last time that you spoke about a cell was high school biology class, I will stick to the basics!

I suggest we start with free radicals and antioxidants, terms which you have likely heard of previously. Free radical formation is a natural part of human biology, and occurs very often in our lives, for example whenever we breath the oxygen that surrounds us. Oxygen tends to become a free radical due to various processes in the body, and can therefore cause cellular damage in its path, leading to a myriad of health issues as will be discussed shortly. Antioxidants are molecules that can donate an electron to these free radicals, thereby stopping their destruction, without becoming dangerous themselves, as they are satisfied in either form.

This can be easily demonstrated when you slice open an apple: when the flesh is exposed to atmospheric oxygen, oxidation begins to occur, thereby turning the flesh brown. However, if you have ever tried to slow this process by squeezing a fresh lemon over the flesh, the antioxidant process can be clearly seen. The vitamin C in lemon juice acts as an antioxidant, thereby preventing the browning process. While human biochemistry is far more complicated than this analogy, and our insides are not necessarily “browning” per say, scientists have done their best to extrapolate these concepts to human health.

At this point, it may be worth asking, what do free radicals and antioxidants have to do with our genes? This seems like a simple environmental issue: eat more antioxidants to balance out the free radicals. Alas, the situation is not quite so simple. Often times, external antioxidant consumption is unable to keep up with free radical production. However, the cell has developed an extraordinary way to keep up with the myriad of free radicals that the body is exposed to. According to several studies, including a 2007 study in the journal Clinical Interventions in Aging Medical, the genome can produce specific antioxidant enzymes that break down free radicals in immense quantities, far more than external antioxidants (Rahman et al).

This all sounds well and good. But these antioxidant enzymes require an initiation of sorts -- they aren’t simply active all the time. In fact, according to a 2013 review article in Oxidative Medicine and Cellular Longevity, intermittent activation of these enzymes complexes are preferable to continued activation (Hyun-Ae Soe et al). Thus we find our main question: how do we effectively and efficiently activate these enzyme complexes at the appropriate times? You guessed it, with broccoli, and, more specifically, with sulforaphane.

Sulforaphane has, along with various other phytochemicals, been shown to activate the Nrf2 pathway. According to a 2013 study on cancer prevention, this is how it works: Sulforaphane, the compound in broccoli, interacts with another compound called Keap1. Once Keap1 is activated, a subsequent compound, Nrf2, accumulates in the nucleus of the cell. Nrf2 is what we call a transcription factor, it helps express specific genes along the genome. In the case of Nrf2, the gene for Antioxidant Response Element (ARE) is activated. This is where the magic happens. The ARE spurs a release of several of the aforementioned enzyme complexes, ultimately preventing large amounts of free radical damage to the biological system (Kensler et al).

The bottom line of all this is that, while not containing many antioxidants of their own, the phytonutrients in broccoli enhance our body's ability to produce antioxidants when necessary, and thus serves as a highly efficient guard against the dastardly effects of free radicals.

Now that we have our baseline biology covered, let us move to the macroscale and figure out with this may mean for human health.

In recent years, many aspects of human health have been connected to the Nrf2 pathway. The list is lengthy and includes topics such as general inflammation, mental health disorders, gastrointestinal diseases, and arthritis to name a few. However, I would like to focus on three areas in particular: obesity, cancer, and neurodegenerative diseases.

Let’s start with obesity. The excess body mass accumulated in the form of fat tissue causes detrimental effects on an obese individual’s health. How might the Nrf2 pathway impact obesity? The article cited previously, “The Role of Nrf2: Adipocyte Differentiation, Obesity, and Insulin Resistance” published in the Journal of Oxidative Medicine and Cellular Longevity covers this topic well. According to its findings, the precise biochemical relationship between the Nrf2 pathway and obesity is unclear. When you feed both wild-type mice (normal mice) and Nrf2 KO mice (mice in which the Nrf2 gene pathway does not work) a high fat diet, inconsistent results ensue. Notice, however, that the gene pathway was completely knocked out in these cases. Subsequently, the researchers concluded, “intermittent Nrf2 activation reduces total body weight and fat tissue content under HFD (high fat diet) conditions”. This is consistent with the idea that bioactive compounds in food may be the ideal modulator of the Nrf2 pathway, and, even more, that this may stem from its antioxidant effects, according to the authors (Hyun-Ae Soe et al).

In regards to a cancer, a similar, albeit different mechanism is thought to be at play. In a 2014 study published in the journal Topics in Current Chemistry, the authors stated, “sulforaphane is a potent inducer of Nrf2 signaling and blocks the formation of dimethylbenz[a]anthracene-evoked mammary tumors in rats as well as other tumor types in various animal models”. Translated into English, this is a good sign. Ultimately, the authors concluded, “the overall potent and multimodal actions of sulforaphane makes it appealing to use in both preventive and therapeutic settings” (Kensler et al).

Finally, in an article titled “Nrf2-regulation in brain health and disease: implication of cerebral inflammation” published in the journal Neuropharmacology, authors concluded: “emerging evidence suggests that Nrf2, in addition to its antioxidant functions, may also play an important role in regulating inflammation in the brain” (Sandberg et al). Moreover, depression is often cited to be a result of cerebral inflammation. As an article in the journal Psychoneuroendocrinology states, “A causative relationship between inflammation and depression is gradually gaining consistency” (Martín-de-Saavedra et al).

I digress for a moment: the subject of the Nrf2 pathway and antioxidant regulations invoke temptations of radical conclusion, even with certain causal relationships. It should be understood that the sheer number of individual molecular pathways in human physiology surpasses our comprehensive abilities at this point in time.

Evidently, nutritional science is complicated; yet, it has immense promise. Nutrigenomics, including broccoli, sulforaphane, and the Nrf2 pathway, as an example, is just one of the many ways in which the foods we eat are being evaluated for human health. Looking to the future, I will actively search and simultaneously wait with patience for what may emerge in the scientific literature. Until then, I, as well as you, should stay curious, yet questioning -- the foods we eat are far more powerful, and biochemically active than once thought -- a concept which will only advance with time.