Our Genes and Nutrients are age-old friends!
The greatest wealth that one can ever earn is good health! In the recent years, one of the best aspects of health care reform is that it has started to emphasize on prevention, especially through lifestyle interventions. Gene-nutrient interactions epitomize the synergy of genetics and lifestyle in deciding health outcomes. ‘One size fits all’ approach to lifestyle recommendations leaves a gap which stands miles away from best desirable results for an individual. Hence, the need of the hour is a personalized health care approach focusing on gene-based lifestyle modifications. Personalized healthcare approach innovatively defines disease prevention through the indulgence of nutrigenetics. Nutrigenetics, a field of Life Science identifies an individual’s genetic susceptibility to diseases and emphasizes the vital role of genetic variation in affecting nutrient intake. The effect of dietary factors on health status has been recognized since antiquity. Food and its components directly or indirectly influence gene expression. Genetic predispositions in turn dictate unique dietary needs and requirements. A small genetic change, or variation, that occurs within the DNA sequence can have an impact on nutrient metabolism. Genetic information in relation to a nutrient metabolism has relevance to health conditions1,2,3,4,5,6,7,8.
Genetic make-up and lifestyle occupy equal shares in any health outcome. Hence, recommendations for health betterment should be tailor-made suiting the person’s tolerance/ acceptance to dietary components based on his genes. Right Food & right exercises are subjective to your genetic make-up! Let’s understand this better with the following examples.
Gene-nutrient interaction has a significant role in weight control
Genetic risks may be offset by favorable changes in lifestyle. For instance, your meal pattern, meal timings and even the type of snacks can be recommended to suit you the best if you understand the pattern of genes like FTO, LEP, LEPR and CCK which influence appetite, meal quantity, satiety response and the urge to snack. Individuals carrying a variation in such genes tend to have a difficulty in following proper meal timings and meal quantities and thereby they are likely to overeat9. Generally, a balanced diet with adequate dietary fiber, and healthy snacks timed appropriately is proven beneficial in weight control. Further on to this, an insight into nutrigenetics will personalize weight control remedies for people carrying genetic variations in weight-regulating genes. For instance, genetic variations in leptin or leptin receptor genes demand gene-specific nutrients like omega-3 fatty acids and zinc10. Another good example is PPARG gene, which is a vital regulator of carbohydrate and fat metabolism. Variations in this gene are may influence the type of macronutrient that has to be restricted by an individual for his weight management.
Track a healthy heartbeat by understanding gene-nutrient interactions
The type of cooking oil that you should be using or the type of nuts that you should be consuming to stay heart-healthy by maintaining optimal triglyceride levels is decided by multiple genes that encode lipoprotein lipase and proteins that interact with it, such as apolipoprotein (apo) A-5, apo C-III among others. For instance, Apolipoprotein A5 (APOA5) gene encodes the APOA5 protein which plays an important role in regulating the level of triglycerides in blood. A variation in the APOA5 gene decreases the amount of its encoded protein, resulting in increased levels of triglycerides and VLDL in blood. This implies a high risk for atherosclerosis and cardiovascular diseases even if n-6 fatty acid intake from cooking oil is restricted to <10% of total calories (general guideline). A revised recommendation for n-6 fatty acids, that is, <6% of total calories compared to the general guideline would help people with this genetic variation to maintain their triglyceride levels11,12,13.
Folate or vitamin B9 serves as a carrier of one-carbon units17. Folate-mediated one-carbon metabolism is important for synthesizing nucleotides (such as thymidylate and purines), for DNA replication and DNA repair, and for producing S-adenosylmethionine (SAM), the universal donor of methyl groups for DNA methylation18. Folate is metabolized by 5,10-methylenetetrahydrofolate reductase (MTHFR) and other enzymes that use riboflavin (vitamin B2), cobalamin (vitamin B12), or pyridoxine (vitamin B6) as cofactors. These B vitamins are essential for the remethylation and transsulfuration of homocysteine (a marker of inflammation), which is an important intermediate in one-carbon metabolism16. Homocysteine is a sulphur-containing amino acid formed during the metabolism of methionine to cysteine. Hyperhomocysteinemia, or increased circulating levels of homocysteine, is generally recognized as an independent risk factor for coronary, cerebral, and peripheral atherosclerosis14.
Multiple genes influence folate metabolism and homocysteine levels in the blood. Amongst them MTHFR gene is an important one. The MTHFR gene influences folate metabolism by encoding MTHFR enzyme, and thereby it has a vital role in maintaining homocysteine within normal limits19,20. A variation in this gene is associated with a reduction in MTHFR enzyme activity resulting in homocysteine elevation and a disturbance in vasculature22. Individuals cannot change their genetics, but they can eat the right foods to support genetic predispositions8. Hence, an improved folate intake which suggests 600mcg/day as against the general requirement of 400mcg/day is a specific nutrigenetic recommendation21. To cope with the reduced MTHFR enzyme activity, nutrients like riboflavin, pyridoxine, vitamin B12, choline, vitamin C and directly supplementing with 5-methyl folate prove as enhancers of this enzyme’s catalytic activity 14,15,18.
How much of coffee is risk-free for you? The answer lies in your genes
Adults commonly consume caffeine in coffee and tea, both of which contain natural caffeine in their leaves or beans. Energy drinks often contain caffeine from natural products such as extracts from guarana leaves. In addition to coffee, tea, and energy drinks, caffeine is also naturally present in cocoa beans and thus in chocolate26,27. The amount of caffeine in chocolate varies by the percentage of cocoa it contains, with 100% cocoa chocolate (unsweetened baking chocolate) containing around 240 mg caffeine/100 g, 55% cocoa (bittersweet) containing 124 mg caffeine/100 g, and 33% cocoa (milk chocolate) containing 45 mg caffeine/100 g. Synthetic caffeine is also added to soda and energy drinks, which are commonly consumed by children and adolescents worldwide25,28,41,42.
Coffee, a nonalcoholic beverage is the most popular social drink, owing to its refreshing aroma and tiredness-averting qualities. 100 grams of coffee generally contains 40 to 60 mg of caffeine40. The threshold of caffeine toxicity appears to be around 400 mg/day in healthy adults (19 years or older), 100 mg/day in healthy adolescents (12–18 years old), and 2.5 mg/kg/day in healthy children (less than 12 years old)24,25,26.
Can you drink 2 or 3 cups of coffee in a day or should it necessarily be alternated with another refreshing beverage like green tea? Is another question to which the answer is in your genes like CYP1A2 and AHR predominantly, among others29,30,36. CYP1A2 gene encodes a liver detoxifying enzyme (cytochrome P450 oxidase) that catalyses caffeine metabolism, while AHR gene encodes Aryl Hydrocarbon Receptor which is involved in the regulation of CYP1A2. A variation in these genes can slow down the caffeine metabolism37; as a result, caffeine is retained in the blood for a longer time, increasing the risk for caffeine-associated health disturbances like rise in blood pressure and heart ailments23,31,32,33,34,35,38. Individuals carrying such genetic variations are required to restrict their caffeine intake below 100 milligrams in day as against 400mg of caffeine a day being perfectly safe for the general population39.
Genetic variation is known to affect food tolerances
Your digestive tolerance for milk and its products is also decided by your genes. Variations in MCM6 gene may demand from you fermented milk products52’ intake to compensate for reduced lactase activity43,44,54. Nutrigenetic recommendations for this variation suggest foods rich in lysine (from rice milk, tofu), arginine (from soaked almonds) and medium chain triglycerides (from coconut milk) as their active components act as substitutes for lactose in enhancing small intestinal calcium absorption45,50,53. Individuals with genetic predisposition for lactose intolerance are less likely to experience symptoms after ingesting up to 12 grams of lactose (the equivalent of 1 cup of milk) in a single dose, especially if taken with other foods46,51. Most people with lactose intolerance, including children, may tolerate up to 2 cups of milk a day, divided into smaller quantities47,48. The digestion of milk is slowed down when it is taken with a meal, resulting in a slower release of lactose in the small intestine, thereby reducing the lactose load to be digested at a given time. Ingestion with other solid foods, particularly those high in soluble fibre, also delays gastric emptying, which provides additional time for intestinal lactase to digest the lactose49.
Nutrigenetic recommendations benchmark improvements even in the fitness arena
Nutritional recommendations based on genetic insights have also carved a niche in the area of fitness. Gene-based nutritional recommendations can elevate the ease with which you perform your activities, alongside improving your exercise response in terms of health benefits. For instance, while exercising if you feel breathless or if your muscles get fatigued very soon, then, there may be genetic reasons55. For instance, Peroxisome proliferator-activated receptor α (PPARA) gene regulates body’s adaptive response to exercise by facilitating more energy fuel provision to the target organ and improves energy utilisation by muscles during exercise. A variation in this gene relates to sub-optimal energy utilization in muscles and hence makes its carrier more prone to fatigue and tiredness while doing exercise56,57. Similarly, Adenosine-mono-phosphate-deaminase 1(AMPD1) encodes the AMPD1 enzyme which actively participates in the catabolism of adenine nucleotide. When muscles use up energy during physical activity, the energy molecule AMP (Adenosine monophosphate) needs to be converted to IMP (Inosine monophosphate). The accumulation of AMP in muscle causes muscle pain and weakness, a sign of fatigue. AMPD1 gene supports AMP degradation to IMP thus diminishing muscle fatigue. A variation in this gene is associated with sub-optimal activity of AMPD1 enzyme, thus posing a risk for AMP accumulation in exercising muscle and consequently spasms, tiredness and muscle pain after training sessions80.
To cope with such genetic variations, a start slow and steady approach along with adequate rest periods prove remedial. Additionally, gene-specific nutrients like Coenzyme Q10 or CoQ10 and magnesium can improve your oxygen utilization capacity thereby averting breathlessness. CoQ10 is a cofactor for mitochondrial uncoupling proteins and serves as an integral component of the mitochondrial oxidative phosphorylation system. Its primary dietary sources include oily fish (such as salmon and tuna), organ meats (such as liver), and whole grains58,59,60,61,62,63,64,65,66,67. Magnesium is critical for basic mitochondrial functions, including the production of ATP, and confers a protective role to skeletal muscle mitochondria. Magnesium increases glucose availability in muscle tissue and favours lactate clearance from muscle68,69,70,71,72,73,74.
Similarly, if post-exercise muscle pain disturbs your regularity of physical activity then it might be related to a genetic reason as well. Genes like COL5A1 (encoding type 5 collagen), COL1A1 (encoding type 1 collagen) and GDF5 (encoding growth differentiation factor 5) have a crucial role in maintaining ligaments and tendons in proper health80,81. As ligaments and tendons are natural lubricants that are essential for flexibility, genetic variations in such genes may cause exercise-induced muscle injury or tendinopathy75. This genetic variation can be managed and your exercise can be regularized with collagen-strengthening dietary components like anthocyanins, glutathione, vitamin C and certain amino acids like Methionine, Cysteine and Taurine. Flexibility-improving fitness recommendations such as proper pre & post exercise stretching, and random exercising of different muscle groups can also prove beneficial76,79,83.
The degree of flexibility helps in determining how well an individual can adapt to his workout based on his propensity for developing swelling and inflammation in joints after exercise77,78. Sometimes the delay that you witness in recovering from exercise-induced stress and strain may affect your exercise regimen. This again has an association with genes like TNFα, IL6, CRP, amongst others82. Variations in these genes can disrupt the balance between pro and anti-inflammatory markers, prolonging exercise-induced inflammation for undesirably longer. Nutrigenetic recommendations focus on dietary components like omega-3 fatty acids and probiotics which have anti-inflammatory benefits and thus can hasten recovery76,79,83. Longer rest periods in between exercises are also helpful along with intake of Branched chain amino acids (BCAA) including leucine, isoleucine and valine. In athletic community, BCAA gained particular interest since they can stimulate protein synthesis in the muscle84,85.
Diet is focal in lifestyle management as other lifestyle components including activity are based on this. An understanding of the interplay between nutrients and genes in the context of health recognizes that the current nutritional guidelines may not be ideal for a proportion of the population owing to their genetic variations. And hence it becomes necessary to understand such variations and plan their nutrient needs accordingly. Afterall, nutritional recommendations are meant to promote health and wellbeing in every individual. So let’s value individualized nutrient needs based on genetic make-up, and ensure right food choices are just right for you. Individuals cannot change their genetics, but they can eat the right foods to support genetic predispositions.
Author Bio: Anusha holds a PhD in Human Nutrition from the University of Madras, and ranks in the top 3. She has been the recipient of several esteemed awards and endowment prizes including the NSI award for consecutive years. She has also authored several research publications. Life Science, an exhaustive field where every minute innovations pile up is her consciously chosen domain of education and career. With a rich experience in nutrigenetic counselling, research data analysis, and scientific content writing, she is deeply passionate about exploring how gene-based lifestyle changes can assure good health sustenance and disease prevention in an individualistic manner. She reads extensively and draws concepts from wide ranging researches which are translated into reader-friendly documents. Such documents aim to educate people on the importance of knowing their health demands based on genetic predispositions and the need to harmonize the same with gene-specific nutritional recommendations.