By Dr. Shawna Darou, ND
Personal genetics continue to gain popularity, and more and more can provide insight into personalized medicine. We can learn about extra nutrient requirements, slow or fast detox pathways, response to medications, response to dietary changed (ex. lower or higher fat intake), and even how your body is best adapted to exercise. Although we never treat directly from the genes, it can provide insight and a lot less trial and error in the process of finding an optimal nutrition plan, nutrient needs, and more. I have summarized just a few of the things that I look at through personal genetics – some you may already be familiar with, and others that are based on new research. Here are some questions that may be answered through your genes:
(1) Does caffeine increase or reduce your heart disease risk?
The CYP1A2 gene is a reflection of whether you are a fast or slow detoxifier through Phase I liver detox pathways. Research shows that if you are a fast detoxifier, consuming 2-3 cups of coffee or caffeinated beverages per day, can significantly decrease your risk of having a myocardial infarction (heart attack). Conversely, if you are a slow detoxifier, drinking extra caffeine can increase your cardiovascular risk. (1,2) Given how ubiquitous coffee-drinking is, this is great information to know!
(2) Are turmeric supplements good for you?
We typically view turmeric supplements as being helpful for everyone as a great natural anti-inflammatory herb. What many people don’t know however is that turmeric, slows the action of the same CYP1A2 gene as discussed above. If you are a fast detoxifier, this is a good thing, just as extra caffeine is positive for your health. For a fast metabolizer, slowing down the CYP1A2 gene reduces their chemical sensitivity by lowering the load of toxic intermediates. If you are a slow CYP1A2 detoxifier however, extra turmeric can impair your clearance of caffeine, acetaminophen, charred meats and medications like ciprofloxacin and fluvoxamine, which may not be healthy for you. If you are a slow detoxifier, eating extra raw cruciferous vegetables (broccoli, kale, cauliflower, cabbage), and herbs like peppermint and echinacea are helpful to support and speed up this gene. (3)
(3) Are you prone to gaining weight with a higher saturated fat diet?
With the recent popularity of ketogenic diets, butter coffee, and high-fat/low-carb diets, some people are surprised when they gain weight instead of losing it. There are several genes associated with extra weight gain from eating more saturated fats, and ApoA2 and FTO, and these genes dictate your response to a higher-saturated fat diet. Saturated fats are found in dairy products, eggs, meats, coconut oil, dark chocolate and MCT oil. Depending on the your genes, you may find that butter coffee, extra eggs and MCT oil are not beneficial for maintaining optimal weight. (4,5,6,7)
(4) Do you need to eat a lower-fat diet to maintain healthy cholesterol levels?
The ApoE gene which is most known as a predictor of inherited Alzheimer’s disease risk also influences the body’s response to dietary fats, and extra fish oil supplements. With a high-fat diet, a moderate-fat diet, and even with fish oil supplements in the case of ApoE 3/4 and ApoE 4/4 (the two phenotypes associated with higher Alzheimer’s risk), overall LDL cholesterol goes up and HDL cholesterol goes down. This ratio change is very unfavorable for cardiovascular wellness. The fact that fish oil supplements have the same effect is interesting – this does not apply to eating actual oily fish though, only extra supplementation.
This is significant in that emerging therapies used to prevent, treat and reverse early Alzheimer’s often use high dose fish oil supplements and a modified ketogenic diet. It is therefore important to keep an eye on lipid levels, especially in cases of ApoE 3/4 and 4/4 so that the treatment of one issue is not creating an issue somewhere else. (8,9,10)
(5) Is your blood pressure sodium-sensitive?
Although we often recommend reducing sodium as part of a heart-healthy diet, salt intake does not raise everyone’s blood pressure in the same way. In fact, two genes in particular: ACE and AGT can tell us whether your blood pressure is particularly sodium-sensitive, and restricting sodium is a favourable step to either prevent hypertenion, or reduce blood pressure. The ACE gene codes for the angiotensin-converting enzyme which regulates blood pressure through its control of fluid and salts in the body. The AGT gene is controls the prodcution of angiotensinogen, another part of the renin-angiotensin system. (11,12)
(6) Can your body thrive on a fully plant-based diet?
There are several genes that may indicate difficulty thriving on a fully-plant based diet. For example, plant foods contain some pre-nutrients such as beta carotene (which must be converted to vitamin A) and alpha-linolenic acid (which is converted to active omega-3 fatty acids like DHA and EPA). You may also carry genes that indicate a higher than average requirement for vitamin B12, which is only found in animal foods. Here are the details:
- BCMO1 gene – may show reduced ability to convert dietary beta-caroteine to vitamin A. Vitamin A is essential for vision, immune system health, skin health and in the active form is only found in animal foods such as cod liver oil, dairy products, liver and fish. A plant-based diet will only contain beta carotene.
- FADS1 gene – may show reduced ability to convert omega-3 fatty acid precursors (linolenic acid from flaxseed oil and other plant sources) to active omega-3 fatty acids (EPA and DHA). Omega-3 fats are essential for cell membranes, cardiovascular health and skin health.
- MTHFR, MTR and MTRR genes – may show increase need for vitamin B12 due to slower action of these genes involved in methylation. What this may mean is that even if your blood levels look adequate, you may still experience symptoms of low vitamin B12 such as fatigue, numbness and tingling, depression, and other neurological effects. Vitamin B12 is the main nutrient we watch with a plant-based diet, as there are no true plant-based food sources for this nutrient. It is found in all animal foods (meat, poultry, fish, eggs, dairy).
Examining these genes can show were additional supplementation would be needed to optimize health on a fully-plant based diet, and how well your body will thrive without deficiency. Issues with these genes are extremely common, and lack of nutrients can affect mood, energy, skin, body pain, hair and joints.
(7) Are prenatal vitamins containing methyl-folate rather than folic acid better for you to prevent neural tube defects?
Everyone is aware of the need to take folate supplements during pregnancy, and ideally for 3 months preconception to reduce the incidence of neural tube defects in babies. What many people are not aware of is the different types of folate available in supplement form. First to clarify the terminology:
- Dietary folate is naturally occurring in leafy green vegetables, and also legumes, avocado and citrus fruits.
- Folic acid is a synthetic form of folate available in vitamins and supplements.
- L-5-Methyltetrahydrofolate (methylfolate) is the main form of folate that circulates in your blood and is involved in biological processes.
Neither dietary folate, nor folic acid are metabolically active – they must be converted to methylfolate in the body to be useful.
A gene that we look at regarding folate status is called “MTHFR.” Many people have a version of this gene that slows enzymatic activity making them poor metabolizers of folate. This means that they may require higher amounts of folate to have the same activity, and also that an l-methylfolate supplement will work better to maintain red blood cell folate concentration compared to folic acid. (13)
Furthermore, one study showed a 2 fold increased risk of neural tube defects in mothers with the MTHFR C677T polymorphism, and an 80% increased risk with infants having this polymorphism. Follow-up studies need to look at whether giving these mothers a prenatal vitamin containing methylfolate rather than the standard dose of folic acid could reduce this risk, by providing a biologically active form of folate. (14)
(8) Is aspirin helpful to reduce your cardiovascular risk?
The answer, is that it depends. This partially relates to the COMT V158M gene, where the women’s genome health study showed that women with the Val/Val phenotype of this gene had an 85% increased risk of cardiovascular disease when they took aspirin, and also increased risk of cardiovascular disease with vitamin E supplementation. Conversely, those with the opposite phenotype (Met/Met), showed a 40% reduced risk of cardiovascular disease with daily aspirin use. (15)
(9) Do your genes put you at higher risk of psychosis with early use of cannabis products?
There has been a long-time association with early use of cannabis products (before age 21) and the development of schizophrenia. One gene that can impact this susceptibility is the COMT V158M gene as discussed above. In this case, those with the Val/Val phenotype, meaning they clear dopamine, norepinephrine and epinephrine more quickly, are more likely to experience psychosis relate to early use of Cannabis. With the recent much easier access to marijuana in Canada, this is an important discussion to have with our teenagers. (16,17)
(10) What can we learn about the safety of hormone replacement therapy through your genetics?
The first criteria in checking for safety with hormone replacement (including bioidentical hormones) it to check or a personal or family history of breast cancer or other hormonal cancers. After this however, there are certainly more safety checks. We can look at the liver detox pathways that will metabolize hormones to see if there are any issues with clearance. Slow detox pathways can potentiate the effect of the hormones and increase risk of hormone-sensitive cancers as well as other side effects. Genes that can be checked include CYP17A1 (phase 1 pathway – converts pregnenolone to DHEA), CYP1A1 (phase 1 pathways – converts to protective 2-OH estrone), CYP1B1 (phase 1 pathway – converts to genotoxic 4-OH estrone), CYP3A4 (phase 1 pathways – important for HRT and oral contraceptive metabolism), and phase 2 pathways such as COMT and GSTP1.
To simplify, looking at each of these pathways gives an idea of whether a woman will be able to detoxify extra hormones well, or whether the hormones may be creating additional risk based on slow pathways. We could perhaps greatly reduce the risk of using hormone replacement if we took a detailed look at personal genetics, and discouraged use in situations with poor detox.
This short article was written as a quick snapshot of some of the useful ways we can use the information found in personal genetics to make better choices about nutrition, supplements, medications, hormones, and more. Although this will never replace a full work-up with a thorough health intake, physical exam and concrete lab testing, the world of personal genetics is becoming increasingly valuable in customizing health plans.
**Please note that Naturopathic Doctors in Ontario cannot provide you with a kit to test your genes directly. We are able however to help you interpret results that you have gotten through independent labs or through other practitioners.
If you would like to learn more about how to use information from personal genetics to better your health, or customize your long-term nutrition and supplement plan, please ask at your next appointment.
Book an appointment with Dr. Darou online.
Contact us: 416.214.9251, email@example.com
- Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction. JAMA. 2006;295(10):1135–1141. doi:10.1001/jama.295.10.1135
- De Caterinaa R, El-Sohemy A. Moving towards Specific Nutrigenetic Recommendation Algorithms: Caffeine, Genetic Variation and Cardiovascular Risk. J Nutrigenet Nutrigenomics 2016;9:106–11. DOI: 10.1159/000446801
- Chen, Y., Liu, W.-H., Chen, B.-L., Fan, L., Han, Y., Wang, G., … Zhou, H.-H. (2010). Plant Polyphenol Curcumin Significantly Affects CYPIA2 and CYP2A6 Activity in Healthy, Male Chinese Volunteers. Annals of Pharmacotherapy, 44(6), 1038–1045. https://doi.org/10.1345/aph.1M533
- Corella D, Peloso G, Arnett DK, et al. APOA2, dietary fat, and body mass index: replication of a gene-diet interaction in 3 independent populations. Arch Intern Med. 2009;169(20):1897–1906. doi:10.1001/archinternmed.2009.343
- Lai CQ, Smith CE, Parnell LD, Lee YC, Corella D, Hopkins P, et al. (2018). Epigenomics and metabolomics reveal the mechanism of the APOA2-saturated fat intake interaction affecting obesity, The American Journal of Clinical Nutrition 108(1),188–200, https://doi.org/10.1093/ajcn/nqy081
- Corella D, Arnett DK, Tucker KL, et al. A high intake of saturated fatty acids strengthens the association between the fat mass and obesity-associated gene and BMI. J Nutr. 2011;141(12):2219–2225. doi:10.3945/jn.111.143826
- Phillips CM, Kesse-Guyot E, McManus R, Hercberg S, Lairon D Planells R, Roche HM, (2012). High Dietary Saturated Fat Intake Accentuates Obesity Risk Associated with the Fat Mass and Obesity–Associated Gene in Adults, The Journal of Nutrition. 142(5), 824-831. https://doi.org/10.3945/jn.111.153460
- Barberger-Gateau P, Samieri C, Féart C, Plourde M. Dietary omega 3 polyunsaturated fatty acids and Alzheimer’s disease: interaction with apolipoprotein E genotype. Curr Alzheimer Res. 2011;8(5):479–491. doi:10.2174/156720511796391926
- Minihane, Anne & Leigh-Firbank, Elizabeth & Talmud, P & Wright, J.W. & Murphy, M.C. & Griffin, Bruce & Williams, C.M.. (2000). ApoE Polymorphism and Fish Oil Supplementation in Subjects With an Atherogenic Lipoprotein Phenotype. Arteriosclerosis, thrombosis, and vascular biology. 20. 1990-7. 10.1161/01.ATV.20.8.1990.
- Patric, RP. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer’s disease. The FASEB Journal 2019; 33(2), 1554-1564.
- Doaei S, Gholamalizadeh M. The association of genetic variations with sensitivity of blood pressure to dietary salt: A narrative literature review. ARYA Atheroscler. 2014;10(3):169–174.
- Friere IV, Casotti CA, Ribeiro JS, Silva JRD, Barbosa AAL, Pereira R. Daily sodium intake influences the relationship between antiotensin-converting enzyme gene insertion/deletion polymorphism and hypertenion in older adults. J Clin Hpertens (Greenwich). 2018; 20(3):541-550. doi: 10.1111/jch.13224
- Lamers Y, Prinz-Langenohl R, Bramswig S, Pietrzik K. Red blood cell folate concentrations increase more after supplementation with [6s]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006; 84(1):156-61.
- 5,10‐Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol. 2000; 151(9):862–877. , .
- Hall, K. T., Nelson, C. P., Davis, R. B., Buring, J. E., Kirsch, I., Mittleman, M. A., Loscalzo, J., Samani, N. J., Ridker, P. M., Kaptchuk, T. J., & Chasman, D. I. (2014). Polymorphisms in catechol-O-methyltransferase modify treatment effects of aspirin on risk of cardiovascular disease. Arteriosclerosis, thrombosis, and vascular biology, 34(9), 2160–2167. https://doi.org/10.1161/ATVBAHA.114.303845
- Alemany S, Arias B, Fatjo-Vilas M, Villa H, Moya J, et al. (2013). Psychosis-inducing effects of Cannabis are related to both childhood abuse and COMT genotypes. Acta psychiatrica Scandinavica, 129(1), 54-62. https://doi.org/10.1111/acps.12108
- Lynch MJ, Rabin RA, George TP. The Cannabis-Psychosis Link: Mind Your Mind. Psychiatric Times, 29(6), June 28, 2012.
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