By Nanci Guest
An individual’s dietary and supplement strategies greatly influence sport performance. This holds true for all ages, ethnicities, and levels of skill, regardless of whether the goal is optimizing physical activity for health and fitness or training for high performance sport. An individually tailored sports nutrition and supplement plan is key, as highlighted in the most recent “Nutrition and Athletic Performance” joint position statement by the American College of Sports Medicine, the Academy of Nutrition and Dietetics, and Dietitians of Canada, which states that “Nutrition plans need to be personalized to the individual athlete… and take into account specificity and uniqueness of responses to various strategies.”1
These strategies encompass overall dietary patterns, macronutrient ratios, micronutrient requirements, eating behaviors (e.g., nutrient timing), food sensitives and intolerances, and the potential benefits or harms of using supplements (e.g., vitamin, minerals, protein powders) and ergogenic aids (e.g., caffeine, creatine, buffers). A shift away from our standard, one-size-fits-all team approach toward tailored nutrition and a focus on individual needs is what nutrigenomics, from science to practice, aims to address.
It’s in Your Genes
Personalized nutrition, based on an individual’s genotype, is not new, and there are several examples of rare (e.g., phenylketonuria) and common (e.g., lactose intolerance, celiac disease) genetic disorders, where specific dietary recommendations are implemented to manage metabolic deficiencies2. For commonly seen conditions such as lactose intolerance and celiac disease, the avoidance of dairy and gluten, respectively, is part of the personalized dietary plan. And if you either embrace your daily cup of java or completely avoid it because of the way it makes you feel (e.g., awake and energized or perhaps anxious and jittery), this is also due to genetic variation.
Many athletes aren’t sure if caffeine is helpful or harmful. Genetic testing for rate of caffeine metabolism (more on this later) may help to reinforce their suspicions or motivate them to experiment with and without caffeine during exercise rather than assuming it works, or never trying it and missing out on its benefit. Although genetic testing is well-established in the clinical setting to help manage diseases and conditions, the growth in nutrigenomics research has created opportunities to improve health, wellness, and sport performance in athletes through nutrition-focused genetic testing. As the sporting world battles with risky supplements and unprecedented occurrences of doping violations, the sport science community is embracing new ways to help athletes safely and legally reach their peak performance.The goal of nutrigenomics is to determine the right diet (food, nutrients) for you as an individual, says @NanciGuestRDPhD. Click To Tweet
Following the right diet for you is the hallmark of what nutrigenomics is aimed at, but those working with athletes often seek information beyond the performance diet (i.e., advice on the use of supplements and ergogenic aids), and for which athletes and at what times. Even if we have evidence that a supplement is effective, it may not be so for all athletes. For example, there is evidence that nitrates (beetroot), creatine, and caffeine appear to have wide variability in their erogenicity, and in some cases, may be ergolytic. In the case of caffeine, there are dozens of studies reporting wide variability in the effects of caffeine on performance, and nutrigenomics, in part, may explain the source of these differences. A detailed discussion on caffeine and genetics is highlighted below.
While it has long been suspected that genetics play an important role in determining how we respond to foods and nutrients, the surge in nutrigenomics research over the past decade has demonstrated this scientifically. Our genetic makeup affects the way we absorb, metabolize, and utilize nutrients, and these gene-by-diet interactions translate into differences that are relevant to both health and sports performance. A practical application of nutrigenomics is the use of personal genetic testing, which can provide information that will guide recommendations for dietary and supplement (if needed) choices that are more effective at the individual level than current dietary advice. This advice has been set out by governments and other health and sport organizations, and is geared, for the most part, toward the general “active” population. You are not a population.
The Rise of Genetic Testing
The demand for genetic testing for personalized nutrition and fitness, by athletes and active individuals, is growing, and there is an increased need for dietitian-nutritionists, fitness professionals, coaches, and other sports medicine practitioners to understand the current evidence in this developing field. The sport environment is dynamic, progressive, innovative, and extremely competitive. Providing athletes with individually tailored dietary and other performance-related information based on their unique DNA is a novel competitive edge embraced by both practitioners and scientists working in the world of sport.Providing athletes with tailored dietary information based on their DNA is a novel competitive edge, says @NanciGuestRDPhD. Click To Tweet
Those working with athletes seek a better understanding of the practical applications and actionable measures that they can take to improve athletic performance based on genetic information, which includes how genetic testing is performed, what it measures, and how to effectively interpret the results. The growing body of science in nutrigenomics in sport is the foundational building block by which we can help athletes reach their genetic potential through implementation of dietary and supplement strategies that are aligned to their genome.
A Deeper Dive into the Science: Caffeine
In the field of nutrigenomics, caffeine is the most well-studied compound with regard to trials that investigate direct impacts of gene-nutrient interactions on athletic performance. Caffeine has widespread use in athletics in the form of coffee, tablets, energy drinks, gels and chews, and “pre-workouts,” based on the belief that athletes can train harder or compete more successfully after ingesting caffeine3. However, it appears that caffeine does not benefit all athletes equally, and may in fact impair performance in some. Recently published results by the author highlight the importance of considering CYP1A2 genotype in the development of personalized sport nutrition and sport supplement protocols4.
Numerous studies have investigated the effect of supplemental caffeine on exercise performance, but there is considerable inter-individual variability as to the magnitude of these effects5-7or lack of an effect8,9when compared to placebo. The large variation in individual response to caffeine is often overlooked in caffeine performance studies, and due to infrequent reporting of individual data, it is difficult to determine the extent to which variation in responses may be occurring. The performance of some individuals is often in stark contrast to the average findings reported, which may conclude beneficial, detrimental, or no effect of caffeine on performance. Some of these inter-individual differences appear to be due to variations in genes such as CYP1A2, which is associated with caffeine metabolism and caffeine response10.
Over 95% of caffeine is metabolized by the CYP1A2 enzyme, which is encoded by a gene of the same name: the CYP1A2 gene11. A genetic variation or single nucleotide polymorphism (SNP) in this gene has been shown to alter CYP1A2 enzyme activity12,13, and has been used to categorize individuals as “fast” or “slow” metabolizers of caffeine. Individuals with the AC or CC genotype (slow metabolizers) have an elevated risk of myocardial infarction14, hypertension15,16, and pre-diabetes17, with increasing caffeinated coffee consumption, whereas those with the AA genotype show no such risk. Additionally, regular physical activity appears to attenuate the increase in blood pressure induced by caffeine ingestion but only in individuals with the AA genotype, providing further evidence that genetics can act as a confounding variable when trying to establish the effects of caffeine across entire populations16.Genetics can be a confounding variable when studying the effects of caffeine on entire populations, says @NanciGuestRDPhD. Click To Tweet
In the largest caffeine-exercise study to date, Guest et al.examined the effects of caffeine and CYP1A2 genotype, on 10km cycling time trial (TT) performance in competitive male athletes after ingestion of caffeine at 0 mg, 2 mg (low), or 4 mg (moderate) per kg body mass4. There was a 3% improvement in TT time in the moderate dose in all 101 subjects, which is consistent with previous studies using similar doses5,18. However, there was a significant caffeine-gene interaction where improvements in performance were seen at both caffeine doses, but only in those with the AA genotype who are “fast metabolizers” of caffeine. In that group, the 6.8% improvement in cycling time at 4 mg/kg was greater than the 2-4% mean improvement seen in several other cycling TTs studies, using similar doses5,18-23. Among those with the CC genotype, the “slow metabolizers,” 4 mg/kg of caffeine impaired performance by 13.7%, and in those who have the AC genotype there was no effect of either dose4.
The findings are consistent with a previous study by Womack et al., who observed a caffeine-gene interaction and improved TT cycling performance with caffeine only in those with the AA genotype24. In contrast, previous studies either did not observe any impact of the CYP1A2 gene on caffeine-exercise studies25,26, or reported benefits only in slow metabolizers27. There are several reasons that may explain discrepancies in study outcomes, including smaller samples sizes that cause very low numbers and/or no subjects in one genotype26-28,and shorter distance or different type (power versus endurance) of performance test27than those of Guest et al.4and Womack et al.24.
The unmasking of the effects of genotype on performance may occur during exercise of longer duration or where an accumulation of fatigue is occurring (aerobic or muscular endurance), where caffeine often provides its greatest benefits, and where the adverse effects to slow metabolizers are more likely to manifest29. Indeed, in a study of basketball performance in elite players, caffeine improved repeated jumps (muscular endurance) but only in those with the AA genotype; however, there was no genotype effect in in the other two performance components of the basketball simulation30. Similarly, in a crossover design of 30 resistance-trained men, caffeine ingestion resulted in a higher number of repetitions in repeated sets of three different exercises, and for total reps in all resistance exercises combined, which resulted in a greater volume of work compared to placebo conditions, but only in those with the CYP1A2 AA genotype31.
Taken together, the weight of the evidence buttresses that variants in the CYP1A2 gene likely play an important role when trying to determine which athletes are most likely to benefit from caffeine ingestion during aerobic or muscular endurance-type exercise. Trials that include performance outcomes are very valuable to nutrigenomics research as it applies to athletic performance, and these results highlight the importance of considering genetics when deciding whether athletes should use caffeine or other ergogenic aids to improve performance.
The Practical Side
What Will a Genetic Test Tell You?
Different versions of a gene or genetic variations (called single-nucleotide polymorphisms or “SNPs”) can cause us to have different responses to certain components of food. For example, the symptoms felt by individuals who react to lactose and caffeine in their diet (i.e., lactose intolerance and caffeine sensitivity) are caused by certain genetic variations. While general dietary recommendations might be prudent to follow, the one-size-fits-all approach to nutritional advice could limit some individuals from reaching their full potential—their full “genetic potential.”One-size-fits-all nutritional advice can keep people from reaching their full ‘genetic’ potential, says @NanciGuestRDPhD. Click To Tweet
How Would My Diet Change?
Nutrigenomics testing includes several micronutrients that have modified requirements due to genetic variation, such as vitamins A, B12, C, D, and E, calcium, iron, choline, and bioactives such as caffeine. Here are some examples of what information is gained: A genetic test can tell you if you are inefficient at converting beta-carotene into the active form of vitamin A based on the BCMO1 gene32or if your conversion is normal/efficient, based on a gene that modifies the activity (normal/slow) of the enzyme responsible for this conversion.
The good news is, you can take action and resolve it easily by consuming more beta-carotene foods or foods that already contain pre-formed vitamin A. In athletes, vitamin A is important for its antioxidant roles, the immune system, and eye heath, which is a critical asset in most sports (e.g., hand-eye coordination). A similar situation occurs for vitamin D, which is key for immunity, muscle recovery, and bone health. Do you convert vitamin D normally into its active form, and do you transport it efficiently throughout your body? Again, a gene that controls an enzyme is involved here, but we also have a transporter (of vitamin D) that is controlled by another gene. Therefore, two genes, the GC and CYP2R1 gene, are analyzed to determine your risk of vitamin D deficiency33.
This situation is easily remedied through vitamin D supplements (good dietary sources are few). In addition, nutrigenomics testing addresses ideal macronutrient ratios, which can also tell you if your ideal body composition would be more easily achieved and maintained with a lower fat diet or a higher protein diet depending on your genotype34,35. You will also find out if caffeine (CYP1A2 gene) is good for your heart14, if it’s likely to improve your endurance performance4, or if are you better off limiting this substance for better health and to optimize your endurance.
To date, the science supports the use of roughly 50 genetic markers to guide recommendations for personalized nutrition and supplementation. This is an important fact, as many genetic testing companies use (and sell) hundreds of genetic markers that are based on the weak evidence of associations studies, which do not provide enough evidence to create recommendations that are both accurate and actionable. This may do more harm than good, as more is not always better.Science supports the use of ~50 genetic markers to guide tailored nutrition and supplement advice, says @NanciGuestRDPhD. Click To Tweet
It’s important to research the companies that interest you and ensure their science team is made up of individuals with doctorate degrees in the areas of both genetics and nutrition, preferably who are actively researching in the field, and who can properly interpret study findings. With the surge in research groups worldwide conducting nutrigenomics studies, the science is progressing rapidly, and the number of valid genetic markers will likely double over the next few years.
Lastly, along with improvements in dietary precision, nutrigenomics testing has also been shown to enhance motivation and behavior change, where disclosure of genetic information has been associated with adherence to favorable dietary changes36-40. This aspect of personalized nutrition is certainly welcomed, because even in our highly motivated athletes41, nutrition professionals still encounter significant barriers to behavioral change when trying to convince athletes to adopt healthier nutrition practices.
Sport Nutrigenomics vs. Talent ID and Exercise Prescription
Although there is much overlap in how we design diets and create training programs for our athletes, to achieve specific sport goals it is important to underscore the distinction between the strength of evidence supporting DNA-based advice for personalized nutrition versus that for exercise and training protocols.
There is keen interest in using genetic testing to improve athletic performance42,43; however, it is important to acknowledge the lack of evidence surrounding the ability to identify future (athlete) talent and predict the likelihood of creating the next Serena Williams or Usain Bolt44. Using genetics to determine a training program based on your personal genotypes is in its early stages and is not currently supported as a scientifically sound approach, although it is likely to be a viably employed training tool in the next decade45. Many of the outcomes in athletic talent or athlete phenotypes (e.g., VO2max, power) are complex traits determined by potentially thousands of genes, and therefore not easily tested for in a way that would make the information useful or “actionable,” which is necessary when you get back to the gym.
In contrast, nutrigenomics works by identifying genetic variations that can help to determine individual nutritional requirements, the presence of food intolerances and sensitivities, and optimal dietary patterns that will help to improve health, body composition, and sports performance. These usually involve only a few specific genes as opposed to hundreds or thousands that are associated with a naturally high VO2max (since this is primarily genetic and not as trainable as muscle mass increases, for example). Several micro- and macronutrients impacting athletic performance have been studied in nutrigenomics research and can be applied to nutritional counseling in athletes.
One or a few SNPs can identify an individual dietary-related modification that aims to improve precision for nutritional recommendations, requirements, or optimal intakes, and provide information that will help to tailor supplement protocols. Therefore, coaches and other sport professionals should be cautious and diligent when entering the marketplace in search of genetic tests to improve athletic performance, beyond nutrition and some basic performance measures, as they may also include invalid and unreliable training or exercise advice.
A Step-by-Step Guide to Genetic Testing
*Note this info pertains to the company the author uses in practice. Each company has different standards for their security/privacy and time to get results (wide range: 3-12 weeks), and not all lab testing is of the same quality, so do your research.
- Ask your health care provider, nutritionist, or other sports professional to order the genetic testing kit for you.
- The saliva collection kits include a tube in which you provide a saliva sample (approx. ¼ teaspoon), which is then mixed with a preservative, sealed, and sent back to the lab for analysis. This takes 30-60 seconds.
- Your results are encrypted and sent to a secure server that is only accessible to the person who ordered the test (dietitian, coach, etc.) through their account on the company website.
- Two to three weeks later, you will receive your personalized “Nutrigenomics and Sport Performance Profile” report. The report will identify what genotype you are for each SNP that has been tested (each company has a different number of SNPs that they test for).
Nutrigenomics: A Future Competitive Edge
It is becoming increasingly clear that, among other performance parameters, our genes determine our specific and unique nutritional needs when it comes to health and performance. Providing athletes with individually tailored dietary and other performance-related information based on their unique DNA is a novel competitive edge embraced by both practitioners and scientists working in the world of sport. The growing body of science in nutrigenomics in sport is the foundational building block by which we can help athletes reach their genetic potential through implementation of dietary and supplement strategies, such as caffeine use, that are aligned to their genome. When it comes to sports nutrition, this emerging science is the nutritional competitive edge of our future.
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