By Kelley Herring
In the article below, we continue our discussion of genetics – and how YOUR unique genetic code can impact your health and risk for disease. Plus, how to optimize your diet for your individual biology.
If you missed my previous article, I encourage you read that first, as we cover the basics of genetics and how your genes impact your optimal diet. We also discuss Single Nucleotide Polymorphism (SNPs) – the small changes in genetic code that make you biologically unique.
You will discover how specific SNPs impact your risk for autoimmunity, how you process alcohol and your ability to detoxify… PLUS, plus the nutritional “hacks” you can use to optimize the expression of your genes!
As we continue on this topic today, you will discover:
If you are a “slow metabolizer” or “fast metabolizer” of caffeine (and what this means for your risk of heart disease, exercise endurance and breast cancer risk)
If you produce the enzymes to digest milk (plus three hacks if you don’t!)
How well you convert beta-carotene to vitamin A (and the two foods you should eat regularly if you are an inefficient converter)
How many carbs your body is designed to handle (plus how to personalize your macronutrient ratio to your genes!)
Caffeine Metabolism: CYP1A2 Gene
The CYP1A2 gene is part of a family of genes (known as CYP450 genes) that metabolize many of the medications, supplements (and toxins) you are exposed to each day.
There are several genetic variants of CYP450 genes that impact the speed at which you break down different substances. It is these variants that cause us to have unique individual responses to various substances.
CYP1A2 is the specific gene that breaks down caffeine. Your response to caffeine depends in large part on which genetic variant you carry. So, if you’re wondering why that afternoon cup of coffee keeps you awake at night – your genes probably hold the answer!
This gene can also tell you if caffeine will benefit your exercise performance. In fact, a randomized control trial published in Medicine and Science in Sports and Exercise found that only those athletes with the AA genotype experienced improvement in cycling endurance when using caffeine.
Surprisingly, the researchers also found that the AC genotype actually experienced worsening athletic performance under the influence of caffeine!1 The researchers go on to state:
“The CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for enhancing endurance performance.”
How you metabolize caffeine also impacts your heart…
A 2006 study of CYP1A2 fast and slow metabolizers concluded that slow caffeine metabolizers under age 60 are at an increased risk of heart attack when drinking more than two cups of coffee per day. It is also quite interesting to note that fast metabolizers actually decreased their heart attack risk, when drinking the same amount of coffee.2
And if you’re a woman, your daily “Cuppa Joe” may help reduce your risk for breast cancer…
Researchers from University of Toronto found that among BRCA1 mutation carriers (a mutation that increases the risk for breast cancer), drinking caffeinated coffee was associated with a significant reduction in breast cancer risk!
Among the women who were “medium” or “slower” metabolizers (AC or CC), those who consumed coffee had a 64% reduction in breast cancer risk, compared with women who never consumed coffee. No significant protective effect was observed among coffee-drinking women with the AA genotype.3
Here are the variants to look for:
rs762551 (23andMe v4, v5 and AncestryDNA)
AA: Fast metabolizer of caffeine4
AC: Medium caffeine metabolizer
CC: Slower caffeine metabolizer (CYP1A2*1F)
Your CYP1A2 Personalized Diet
As you can see, this gene has a number of different activities – both positive and negative. This brings the importance of personalization to the forefront!
If you are a slow metabolizer of caffeine, you may want to drink fewer cups of coffee to reduce heart risk. And stop your caffeine intake earlier in the day, so it doesn’t disturb your sleep.
And if you carry the BRCA1 gene, and are a “medium” or “slow” metabolizer, note that regular coffee consumption may offer some protective effect against breast cancer.
Digesting Milk: LCT Genetic Variants
The LCT gene codes for the lactase enzyme, which breaks down lactose in milk. And this is one genetic variant that varies greatly across different population groups.
For example, the majority of Asians carry the variant of this gene that causes adults to no longer produce lactase (causing lactose intolerance). However, the majority of Caucasians carry the variant that still produces lactase as an adult, which is why “lactose intolerance” is comparatively uncommon among Caucasians.
rs4988235 (23andMe v4, v5 and AncestryDNA)
- AA: Produces lactase as an adult (lactose tolerant)
- AG: Produces some lactase as an adult (lactose tolerant)
- GG: No longer produces lactase as an adult (lactose intolerant)
Your LCT Personalized Diet
Lactose isn’t the only compound in milk that could impact your health. So even if you are genetically lactose tolerant, you may still have problems with dairy.
Worried about osteoporosis from not drinking milk?
A large study of almost 100,000 people found that neither milk intake nor LCT genotype made a difference in risk of fracture. Those carrying the LCT lactase persistence allele (in other words, those who still have the lactase enzyme as adults) did have a higher femoral neck bone mineral density. But that did not impact fracture risk.
Does your genotype show that you no longer produce lactase as an adult?
If you’d still like to enjoy some dairy products in your diet, studies show that Lactobacillus probiotics can help.5 Consider adding probiotics or consuming lacto-fermented foods like homemade kimchi or sauerkraut.
Vitamin A: BCMO1 Gene
Beta-carotene is converted to the active form of vitamin A using the BCMO1 enzyme.
For some people, this enzyme works great. And foods rich in beta-carotene – such as winter squash, carrots and sweet potatoes – are good sources of vitamin A.
But for many others, the genetic variant of this gene reduces the function of the enzyme, causing an inefficient conversion of beta-carotene into vitamin A.6
rs7501331 (23andMe v.4, v.5 and AncestryDNA)
CT: Decreased beta-carotene conversion
TT: Decreased beta-carotene conversion
rs12934922 (23andMe v.4, v.5)
AT: Decreased beta-carotene conversion
TT: Decreased beta-carotene conversion
Your BCMO1 Personalized Diet
Vitamin A is a vital nutrient involved in everything from immunity to bone health to eyesight, so getting enough is imperative for good health.7,8,9
If you carry the genetic variants for decreased beta-carotene conversion, ensure that you are getting adequate pre-formed vitamin A from your diet. Good sources include grass-fed beef liver, grass-fed butter, pasture-raised eggs, and wild fish.
Carbohydrate Digestion: AMY1/AMY2 Genes
Every time you bite into a piece of bread or eat a potato, digestion of the starchy components begins in your mouth with a salivary enzyme, called amylase. Digestion of starches continues in the gut, aided by pancreatic enzymes. These salivary and pancreatic enzymes are encoded by AMY1 and AMY2 genes, respectively.
Some people carry a greater number of copies of the amylase gene than others. The more copies of the gene, the more amylase you produce, and the easier it is to break down starchy carbs.10
Your 23andMe results do not include the number of copies of a gene. But there is a SNP that correlates to the amount of amylase activity.11 People with higher amylase amounts are able to digest carbohydrates more easily.
Therefore, it is not surprising that studies show people with lower amylase activity are more likely to be overweight and have metabolic syndrome than those with higher amylase activity.12,13,14
rs11185098 (23andMe v.4 only)
AA: Higher amylase activity
AG: Intermediate amylase activity
GG: Lower amylase activity
Your AMY1/2 Personalized Diet
If you have lower amylase activity, you may find that you feel better – and stay leaner – by limiting the amount of carbohydrates you eat (especially starchy carbs like rice, bread, pasta and potatoes).
For optimal body composition, most of us need to reduce our carbohydrate significantly from what is recommended or considered “standard”. And certainly if you have lower or moderate amylase activity, consider a very low-carb or ketogenic diet to optimize these genes!
Need some ideas for healthy substitutes?
Swap zucchini noodles or heart of palm noodles for traditional pasta. Swap cauliflower for potatoes and rice. And make low-carb breads and baked goods using almond flour, sunflower seed flour or coconut flour.
And please stay tuned for the final article in the series, where you will continue to learn how to optimize your genetics by making wise (and informed) choices about your diet and lifestyle!
Here’s a taste of what we’ll cover next…
Whether eating processed meat increases your risk for colon cancer (and if it does, be sure to do THIS!)
How sensitive you are to histamines, the many symptoms they can cause, plus the foods to avoid and include
If eating foods like spinach and beets can increase your risk for diseases like gout and kidney stones (PLUS: How to reduce your risk with THESE cooking techniques)
If saturated fat increases your blood pressure, plus the simple natural inhibitors of this gene
Ed Note: Need some kitchen inspiration? Grab Kelley’s free guide – Instant Pot Keto Dinners – made exclusively with Paleo-and-Keto ingredients, for quick and delicious meals that taste just as good – of not better – than your restaurant favorites. Get your free guide here.
- Guest N, Corey P, Vescovi J, El-Sohemy A. Caffeine, CYP1A2 Genotype, and Endurance Performance in Athletes. Med Sci Sports Exerc. 2018 Aug;50(8):1570-1578. doi: 10.1249/MSS.0000000000001596. PMID: 29509641. https://pubmed.ncbi.nlm.nih.gov/29509641/
- Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006 Mar 8;295(10):1135-41. doi: 10.1001/jama.295.10.1135. PMID: 16522833. https://www.ncbi.nlm.nih.gov/pubmed/16522833.
- Kotsopoulos J, Ghadirian P, El-Sohemy A, Lynch HT, Snyder C, Daly M, Domchek S, Randall S, Karlan B, Zhang P, Zhang S, Sun P, Narod SA. The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers. Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):912-6. doi: 10.1158/1055-9965.EPI-06-1074. PMID: 17507615. https://pubmed.ncbi.nlm.nih.gov/17507615/
- Koonrungsesomboon N, Khatsri R, Wongchompoo P, Teekachunhatean S. The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis. Pharmacogenomics J. 2018 Dec;18(6):760-768. doi: 10.1038/s41397-017-0011-3. Epub 2017 Dec 27. PMID: 29282363. https://www.ncbi.nlm.nih.gov/pubmed/29282363.
- Oak SJ, Jha R. The effects of probiotics in lactose intolerance: A systematic review. Crit Rev Food Sci Nutr. 2019;59(11):1675-1683. doi: 10.1080/10408398.2018.1425977. Epub 2018 Feb 9. PMID: 29425071. https://pubmed.ncbi.nlm.nih.gov/29425071/
- Lietz G, Oxley A, Leung W, Hesketh J. Single nucleotide polymorphisms upstream from the β-carotene 15,15′-monoxygenase gene influence provitamin A conversion efficiency in female volunteers. J Nutr. 2012 Jan;142(1):161S-5S. doi: 10.3945/jn.111.140756. Epub 2011 Nov 23. PMID: 22113863. https://www.ncbi.nlm.nih.gov/pubmed/22113863.
- Semba RD. Rise of the ‘anti-infective vitamin’. World Rev Nutr Diet. 2012;104:132-50. doi: 10.1159/000338594. Epub 2012 Aug 27. PMID: 23006920. https://pubmed.ncbi.nlm.nih.gov/23006920/
- Semba RD. Milk, butter, and early steps in human trials. World Rev Nutr Diet. 2012;104:106-31. doi: 10.1159/000338593. Epub 2012 Aug 27. PMID: 23006919. https://pubmed.ncbi.nlm.nih.gov/23006919/
- Yee MMF, Chin KY, Ima-Nirwana S, Wong SK. Vitamin A and Bone Health: A Review on Current Evidence. Molecules. 2021 Mar 21;26(6):1757. doi: 10.3390/molecules26061757. PMID: 33801011; PMCID: PMC8003866. https://pubmed.ncbi.nlm.nih.gov/33801011/
- Carpenter D, Dhar S, Mitchell LM, Fu B, Tyson J, Shwan NA, Yang F, Thomas MG, Armour JA. Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes. Hum Mol Genet. 2015 Jun 15;24(12):3472-80. doi: 10.1093/hmg/ddv098. Epub 2015 Mar 18. PMID: 25788522; PMCID: PMC4498156. https://www.ncbi.nlm.nih.gov/pubmed/25788522.
- Heianza Y, Sun D, Wang T, Huang T, Bray GA, Sacks FM, Qi L. Starch Digestion-Related Amylase Genetic Variant Affects 2-Year Changes in Adiposity in Response to Weight-Loss Diets: The POUNDS Lost Trial. Diabetes. 2017 Sep;66(9):2416-2423. doi: 10.2337/db16-1482. Epub 2017 Jun 28. PMID: 28659346; PMCID: PMC5566300. https://www.ncbi.nlm.nih.gov/pubmed/28659346.
- Nakajima K. Low serum amylase and obesity, diabetes and metabolic syndrome: A novel interpretation. World J Diabetes. 2016 Mar 25;7(6):112-21. doi: 10.4239/wjd.v7.i6.112. PMID: 27022442; PMCID: PMC4807301. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807301/
- Vázquez-Moreno M, Mejía-Benítez A, Sharma T, Peralta-Romero J, Locia-Morales D, Klünder-Klünder M; National Obesity Network Mexico, Cruz M, Meyre D. Association of AMY1A/AMY2A copy numbers and AMY1/AMY2 serum enzymatic activity with obesity in Mexican children. Pediatr Obes. 2020 Aug;15(8):e12641. doi: 10.1111/ijpo.12641. Epub 2020 Apr 20. PMID: 32314532. https://pubmed.ncbi.nlm.nih.gov/32314532/
- Elder PJD, Ramsden DB, Burnett D, Weickert MO, Barber TM. Human amylase gene copy number variation as a determinant of metabolic state. Expert Rev Endocrinol Metab. 2018 Jul;13(4):193-205. doi: 10.1080/17446651.2018.1499466. PMID: 30063422. https://pubmed.ncbi.nlm.nih.gov/30063422/