When Genetics Matter

When Genetics Matter

I’ve written extensively about how environment is a much bigger factor in our health than our genes. However, I do want to balance the scale and discuss the instances where genetic programming does come into play. Below, I’m going to highlight a few examples where genetic variation (through so-called SNPs, or single nucleotide polymorphisms) may suggest that you act differently. In particular, nutrigenomics is an emerging field of science that explores how nutrition impacts our genome; nutrigenomics demonstrates that certain nutritional interventions can have a positive, neutral or negative effect on a sub-population of individuals, dependent on their unique genetics. 


There is ongoing debate about whether high fat diets are healthy for us. The answer may depend, in part, on your genetic make-up. There are three types of APOE variants (E2, E3 and E4). Since you get one gene from each of your parents, your unique mix of APOE genes (e.g., E2/E3, E4/E4) determines how your body metabolizes cholesterol. 

The most common genotype is APO E3/E3. People in this population exhibit normal cholesterol metabolism. However, people with APO E2 or APO E4 gene variants exhibit dysfunctional cholesterol metabolism. APO E2 is associated with lower cholesterol levels whereas APO E4 is associated with higher cholesterol levels. 

Several studies have found that diet may influence the effect of the APOE polymorphism on cholesterol levels. Because of how cholesterol is differentially metabolized, it has been suggested that E4 carriers benefit most from lower fat, higher carb diets while E2 carriers benefit most from higher fat, lower carb diets. We now know that the relationship between fat intake and cholesterol levels isn’t as clear as we used to think it was and that sugar intake might actually be a bigger mediator in cholesterol synthesis. However, in this case, the amount of dietary fat that’s optimal for you may very well depend on certain pieces of your genetic blueprint. 


The research on coffee consumption has been notoriously mixed. Some studies find that drinking coffee has many health benefits (e.g., owing to the polyphenols, etc). Other studies find that drinking coffee has many health drawbacks (e.g., makes the body overly acidic, leaches minerals, etc.). There is not one, single answer here...and the discrepancy may lie in our genetic make-up (as well as our broader dietary and lifestyle habits). 

Several studies have found that the difference in whether coffee is beneficial or detrimental depends on whether you are a fast or slow metabolizer of coffee; one study looked at the risk of heart attack and another looked at the risk of hypertension. Both studies found the same thing: slow metabolizers of caffeine have an increased risk of disease, while fast metabolizers experience no such increased risk. Fast metabolizers are able to clear caffeine from their systems quickly, allowing exposure to the beneficial compounds (like polyphenols) while decreasing the likelihood of negative side effects. Slow metabolizers, on the other hand, took a lot longer to clear the caffeine, which increased the amount of time that caffeine had to wreak havoc on the body.


We now know that one gene, CYP1A2, seems to play a role in regulating whether you are a fast or slow metabolizer. It would be remiss of us to stop the discussion there; there are absolutely other genetic and environmental factors that may play a role in how caffeine is metabolized in the body. Several other SNPs have already been implicated. However, CYP1A2 is a great place to start in understanding the role of genetics in informing our daily coffee fix. 


MTHFR is one of the most studied SNPs. MTHFR is the enzyme that converts dietary folate (and synthetic folic acid) to the active form of folate (5-mTHF) as well as converting homocysteine to methionine. People with MTHFR SNPs have decreased activity in this enzyme ranging from ~30% to 75%. Given this, for people with one or two MTHFR gene mutations, the research suggests that you should limit intake of folic acid in fortified foods and supplements since you can’t convert folic acid as efficiently into usable folate. You may also want to limit foods that increase homocysteine levels (e.g., processed foods, too much conventionally raised meat, alcohol) and incorporate foods that decrease homocysteine levels (e.g., green leafy vegetables). In addition, detox capacity may be impaired so eating a clean diet (e.g., filtered water, pastured animal products, organic produce) is especially important for those with MTHFR mutations. There are many more lifestyle suggestions for managing an MTHFR mutation, but you get the idea.

In the future, when we see conflicting evidence in nutrition studies, we may consider the fact that genetics may play a role in what works for one person but not another. We are just scratching the surface when it comes to understanding gene variants and their impact on our bodies. However, it is important that there is an interplay between our genetics and our lifestyle behaviors. Nutrition is not a one-size-fits-all prescription. As with the Pareto principle, ~80% of dietary recommendations can be applied fairly broadly to the population at large, while ~20% of recommendations may need to be tailored to your unique genetics and circumstances. 

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