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Genes & Diet: Histamines & Oxalates – Part 5

histamines, dna diet, dna puzzle

By Kelley Herring

One of the greatest lessons we have learned about health and nutrition over the last several decades is that each one of us is biologically and genetically unique. Rigorous scientific research has proven that despite our human similarities – after all, we have the same basic physiology and anatomy – our individual nutritional and dietary needs are actually very unique!

That might mean that a healthy food for one person, could make you sick. Or that a food which causes no rise in blood-sugar for one person, could send yours off the charts. Or that a “gut-friendly” diet for most people… might cause bloating, cramps and embarrassing “bathroom problems” for you.

There are myriad factors that cause each one of us to respond in a different way to various foods and lifestyle factors. But the bottom line is that we are all biologically (and genetically) unique – so you must discover what works best for YOU!

Today, we continue (and finally conclude) our discussion of how your individual genetics can affect your health, your ability to detoxify, your risk for disease… and your response to specific foods and compounds.

We’re going to cover two important compounds – histamines and oxalates – which can cause a wide variety of uncomfortable, and often confusing, symptoms, including:

  • How your genes impact your reactivity to these compounds

  • The many symptoms they cause and the foods to avoid (and include) in your diet

  • Why certain “superfoods” can increase your risk for gout, kidney stones and other diseases

  • The genetic factors that might “keep you up at night” and

  • Why you might want to avoid “leftovers” for YOUR best health!

So, let’s begin…

meat storage, CoQ10, ketogenic,

Histamines & Your AOC1 Gene

Has your face ever become flushed after your first few sips of wine? Have you ever experienced a runny nose or headache when you eat bananas, strawberries, avocados or fermented foods, like sauerkraut?

On these occasions, do you find yourself waking up at the slightest sounds, tossing and turning all night?

Or perhaps you just don’t feel right after eating certain foods and you don’t know why.

If any of this sounds familiar… you could be suffering from histamine intolerance. And while the root causes of histamine intolerance can be many… your genetics often plays a prominent role.

Your body produces an enzyme, known as DAO (diamine oxidase), that is responsible for breaking down histamine in the foods you eat. And the amount of this enzyme that you produce is largely governed by a specific gene, AOC1.

When you consume too much histamine – especially coupled with not enough DAO – it can lead to histamine intolerance. This can include a variety of symptoms including hives, acid reflux, migraines1, nausea, sinus drainage, anxiety, sleep disturbances, and more.2

The genetic variants listed below impact the amount of DAO your body produces.3 Most studies show that a single variant isn’t enough on its own to lead to histamine intolerance, but they can be a contributing factor.

Other root causes of too much histamine can include mast cell disorders and microbiome imbalances. Some gut bacteria and probiotics, such as Lactobacillus reuteri, actually produce histamine, so keep this in mind!4

rs2052129 (23andMe v5 only)

  • GG: Normal

  • GT: Reduced production of DAO

  • TT: Reduced production of DAO

rs10156191 (23andMe v4 only)

  • CC: Normal

  • CT: Reduced production of DAO

  • TT: Reduced production of DAO

rs1049742 (23andMe v4 only)

  • CC: Normal

  • CT: Reduced production of DAO

  • TT: Reduced production of DAO

Your AOC1 Personalized Diet

If you have symptoms of histamine intolerance, a low-histamine diet may be helpful. Healing Gourmet offers a full list of high-histamine foods you can use to tailor your diet. Here are the big ones to avoid:

  • Fermented foods (including sauerkraut, yogurt, and kombucha)

  • Processed meats

  • Spinach, avocados, tomatoes and strawberries

  • Red wine

  • Chocolate

  • Aged cheeses

cattle pasture scene, grassfed nutrition, back to nature

Freshness Counts… Ripeness Matters (and You Might want to Leave the Leftovers)

It’s also important to note that as food ages, the amino acid histidine can be converted to histamine. So if you have histamine issues, it’s important to buy your seafood and meat from the freshest sources possible, generally avoid leftovers, and eat fruits that are less ripe.

For convenience and a lower risk of unwanted compounds, I buy all of my grass-fed meats and wild seafood frozen from U.S. Wellness Meats. Freezing is also a great way to cut down on the histamine buildup in leftovers. If you like to cook once and then re-use some of the ingredients for other meals, freeze your leftovers (instead of refrigerating) before using again.5,6

Finally, if you suffer with histamine intolerance, a number of foods and supplements have natural histamine-balancing properties that can help:

  • Luteolin is a flavonoid found in celery, thyme, green peppers, that is also sold as a supplement. Studies show that luteolin stops the release of histamine from mast cells, thus decreasing the overall amount of histamine being produced by the body.7

  • Quercetin blocks histamine release and is often used as a natural way to mitigate allergies.8

  • Green tea extract decreases H1 receptor activation (nasal symptoms, sneezing).9

  • Chicory and Echinacea, contain chicoric acid which inhibits histamine release.10

  • DAO, the enzyme that breaks down histamine in our intestines, is available as a supplement and can help reduce histamine levels when taken before meals.11 DAO is also found in high levels in pea shoots which make a tasty addition to salads or smoothies.12

And now, let’s move on to another compound in foods that can also cause serious and confusing symptoms – and which also has a proven genetic component.

Oxalates: The AGXT Gene

Oxalates are hard, crystalline compounds that are found in most plants we eat. They are also produced in the body, as certain substances are broken down.

For most individuals, oxalates are metabolized by healthy gut bacteria or eliminated as waste products. However, for a small percentage of people, the body may absorb oxalates from the gut into the bloodstream… and then have difficulty eliminating these compounds.

What’s worse is that these jagged, sharp crystals can become lodged in healthy tissues causing a world of pain and dysfunction. And your propensity to suffer could be related to certain genetic markers.

The AGXT (alanine-glyoxylate aminotransferase) gene codes for an enzyme that breaks down glyoxylate in the amino acid glycine, and when the enzyme is missing or decreased, the glyoxylate is converted to oxalate.13

Unfortunately, the inability to rid your body of oxalates can contribute to some serious (and painful!) health conditions including:14,15,16,17,18,19,20,21

  • Gout

  • Kidney stones

  • Joint pain and inflammation (similar to fibromyalgia or arthritis)

  • Insomnia, anxiety and depression

  • Gastrointestinal problems (IBS & IBD)

  • Thyroid dysfunction

  • Autoimmune illness

  • Child developmental disorders, including autism22

  • Nutrient deficiencies

  • Chronic inflammation

  • Vulvodynia (female genital pain or irritation)

  • Chronic candida (yeast infections)

  • COPD/asthma

Excess oxalates can also lead to oxidative damage and depletion of glutathione (your body’s master antioxidant and detoxifier). This can damage your ability to repair DNA and detoxify, resulting in cellular mutation, heavy metal accumulation and more!

So, let’s take a look at the different genetic alleles and how they impact your risk for having too much oxalate (a condition known as hyperoxaluria).

rs34116584 (23andMe v4 only)

  • TT: Found in 50% of people with hyperoxaluria23

  • CT: Increased risk of hyperoxaluria (especially if coupled with another mutation) 

  • CC: Normal (wildtype)

i5012629 (23andMe v4, v5, rs180177309)

  • II: Normal (wildtype)

  • DI: Carrier of a pathogenic allele for primary hyperoxaluria type 2

  • DD: Primary hyperoxaluria type 2

i5012628 (23andMe v4, v5, rs80356708)

  • II (or G): Normal (wildtype)

  • DI: Carrier of a pathogenic allele for primary hyperoxaluria type 2

  • DD: Primary hyperoxaluria type 2

Your AGXT Personalized Diet

If you have trouble with oxalates, its critical to pay close attention to your diet. Many so-called “healthy” foods are the worst offenders including: spinach, sesame, beets, almonds, nut butters, dark chocolate and rhubarb.24

And it doesn’t take much of these foods to cause a problem…

A study published in the Journal of the American Society of Nephrology examined oxalate intake of 240,681 individuals in three studies. Among these subjects, the average oxalate intake is around 200 mg per day… and about 40 percent of oxalates of the dietary oxalates came from ONE food – spinach!25

And because just one cup of spinach contains 225 mg of oxalates, you can see how easily this one “healthy” food can make a big contribution to your body’s oxalate burden.

There are several things you can do to lessen the impact of oxalates and reduce the risk of kidney stones and other oxalate-related health issues:

  1. Avoid High Oxalate Foods: Eliminating the biggest offenders will go a long way to reducing your body’s oxalate burden.
  2. Cook Foods to Reduce Oxalate Content: Boiling was found to reduce oxalate content 30-87% in a study published by the Journal of Agricultural and Food Chemistry.26 In the case of beans, soaking prior to cooking also helped reduce oxalates.27
  3. Take Calcium Supplement or East Calcium-Rich Foods: Calcium readily binds to oxalate. Getting 1000-1200 mg of calcium per day has been found to reduce the formation of kidney stones.28,29 consider a calcium citrate supplement (250 mg/meal) or upping your intake of calcium-rich foods like grass-fed cheese and yogurt.
  4. Be Careful with Vitamin C: Studies show that vitamin C supplementation can increase the risk of kidney stones, especially if you are a man.30,31
  5. Avoid Antibiotics: A number of common antibiotics degrade Oxalobacter formigenes, a microbe with a unique ability to degrade oxalates. People with low levels of O. formigenes in their microbiome have a reduced ability to break down oxalates.32

There are many common elements as to what makes up a “Healthy Human Diet”. In general, that means a whole-foods diet that is low in sugar and carbohydrates, and rich in protein and healthy fats. But that is about where the “commonalities” end, because we each have unique tastes, biology and genetics.

So, do not blindly accept that all “healthy foods” are going to be good for you. They might not be. So, listen to your body! And if you don’t feel well, consider “subtracting before you add”. That means, it’s probably best to eliminate foods from your diet – starting with “plant-based” foods first – and gauge how you feel.

Have you used your genetics to personalize your diet and alleviate symptoms? If so, what was your experience?

Read more of Kelley Herring’s Health and Wellness articles on our Discover Blog.

kelley herring

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.

References

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  2. Kovacova-Hanuskova E, Buday T, Gavliakova S, Plevkova J. Histamine, histamine intoxication and intolerance. Allergol Immunopathol (Madr). 2015 Sep-Oct;43(5):498-506. doi: 10.1016/j.aller.2015.05.001. Epub 2015 Aug 1. PMID: 26242570.
  3. Maintz L, Yu CF, Rodríguez E, Baurecht H, Bieber T, Illig T, Weidinger S, Novak N. Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities. Allergy. 2011 Jul;66(7):893-902. doi: 10.1111/j.1398-9995.2011.02548.x. Epub 2011 Apr 13. PMID: 21488903.
  4. Harata, G., He, F., Takahashi, K., Hosono, A., Miyazawa, K., Yoda, K., … Kaminogawa, S. (2016). Human Lactobacillus Strains from the Intestine can Suppress IgE-Mediated Degranulation of Rat Basophilic Leukaemia (RBL-2H3) Cells. Microorganisms, 4(4), 40. http://doi.org/10.3390/microorganisms4040040
  5. Hongpattarakere T, Buntin N, Nuylert A. Histamine development and bacterial diversity in microbially-challenged tonggol (Thunnus tonggol) under temperature abuse during canning manufacture. J Food Sci Technol. 2016 Jan;53(1):245-56. doi: 10.1007/s13197-015-2042-6. Epub 2015 Sep 25. PMID: 26787946; PMCID: PMC4711466.
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  7. Parrella, E. et al. (2016). PEA and luteolin synergistically reduce mast cell-mediated toxicity and elicit neuroprotection in cell-based models of brain ischemia. Brain Research, 1648(Pt A):409-417. doi: 10.1016/j.brainres.2016.07.014.
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  10. Lee NY, Chung KS, Jin JS, Bang KS, Eom YJ, Hong CH, Nugroho A, Park HJ, An HJ. (2015). Effect of Chicoric Acid on Mast Cell-Mediated Allergic Inflammation in Vitro and in Vivo.
    J Nat Prod. 2015 Dec 24;78(12):2956-62. doi: 10.1021/acs.jnatprod.5b00668.
  11. Yacoub MR, et al. (2018). Diamine Oxidase Supplementation in Chronic Spontaneous Urticaria: A Randomized, Double-Blind Placebo-Controlled Study. International Archive of Allergy and Immunology. 176(3-4):268-271. doi: 10.1159/000488142.
  12. Güvenilir YA, Deveci N. (1996) The isolation and purification of diamine oxidase of pea seedlings and pig liver. Appl Biochem Biotechnol. 56(3):235-41.
  13. Coulter-Mackie MB, Rumsby G. Genetic heterogeneity in primary hyperoxaluria type 1: impact on diagnosis. Mol Genet Metab. 2004 Sep-Oct;83(1-2):38-46. doi: 10.1016/j.ymgme.2004.08.009. PMID: 15464418.
  14. Baggish MS, Sze EH, Johnson R. Urinary oxalate excretion and its role in vulvar pain syndrome. Am J Obstet Gynecol. 1997 Sep;177(3):507-11. doi: 10.1016/s0002-9378(97)70137-6. PMID: 9322615.
  15. Ogawa, Y., Miyazato, T. & Hatano, T. Oxalate and Urinary Stones. World J. Surg. 24, 1154–1159 (2000). https://doi.org/10.1007/s002680010193
  16. Mitchell T, Kumar P, Reddy T, Wood KD, Knight J, Assimos DG, Holmes RP. Dietary oxalate and kidney stone formation. Am J Physiol Renal Physiol. 2019 Mar 1;316(3):F409-F413. doi: 10.1152/ajprenal.00373.2018. Epub 2018 Dec 19. PMID: 30566003; PMCID: PMC6459305.
  17. Konstantynowicz J, Porowski T, Zoch-Zwierz W, Wasilewska J, Kadziela-Olech H, Kulak W, Owens SC, Piotrowska-Jastrzebska J, Kaczmarski M. A potential pathogenic role of oxalate in autism. Eur J Paediatr Neurol. 2012 Sep;16(5):485-91. doi: 10.1016/j.ejpn.2011.08.004. Epub 2011 Sep 10. PMID: 21911305.
  18. Marchini GS, Sarkissian C, Tian D, Gebreselassie S, Monga M. Gout, stone composition and urinary stone risk: a matched case comparative study. J Urol. 2013 Apr;189(4):1334-9. doi: 10.1016/j.juro.2012.09.102. Epub 2012 Sep 25. PMID: 23022002.
  19. Ormanji MS, Rodrigues FG, Heilberg IP. Dietary Recommendations for Bariatric Patients to Prevent Kidney Stone Formation. Nutrients. 2020;12(5):1442. Published 2020 May 16. doi:10.3390/nu12051442
  20. Garland V, Herlitz L, Regunathan-Shenk R. Diet-induced oxalate nephropathy from excessive nut and seed consumption. BMJ Case Rep. 2020 Nov 30;13(11):e237212. doi: 10.1136/bcr-2020-237212. PMID: 33257378; PMCID: PMC7705561.
  21. Sitkin SI, Tkachenko EI, Vakhitov TY. METABOLIC DYSBIOSIS OF THE GUT MICROBIOTA AND ITS BIOMARKERS. Eksp Klin Gastroenterol. 2016 Jul;12(12):6-29. English, Russian. PMID: 29889418.
  22. http://www.westonaprice.org/health-topics/the-role-of-oxalates-in-autism-and-chronic-disorders/
  23. Fargue S, Lewin J, Rumsby G, Danpure CJ. Four of the most common mutations in primary hyperoxaluria type 1 unmask the cryptic mitochondrial targeting sequence of alanine:glyoxylate aminotransferase encoded by the polymorphic minor allele. J Biol Chem. 2013 Jan 25;288(4):2475-84. doi: 10.1074/jbc.M112.432617. Epub 2012 Dec 10. PMID: 23229545; PMCID: PMC3554916.
  24. Harvard T.H. Chan School of Public Health Nutrition Department. Oxalate Content of Foods. https://regepi.bwh.harvard.edu/health/Oxalate/files/Oxalate%20Content%20of%20Foods.xls
  25. Eric N. Taylor, Gary C. Curhan. Oxalate Intake and the Risk for Nephrolithiasis
    JASN Jul 2007, 18 (7) 2198-2204; DOI: 10.1681/ASN.2007020219
  26. Chai W, Liebman M. Effect of different cooking methods on vegetable oxalate content. J Agric Food Chem. 2005 Apr 20;53(8):3027-30. doi: 10.1021/jf048128d. PMID: 15826055.
  27. Shi L, Arntfield SD, Nickerson M. Changes in levels of phytic acid, lectins and oxalates during soaking and cooking of Canadian pulses. Food Res Int. 2018 May;107:660-668. doi: 10.1016/j.foodres.2018.02.056. Epub 2018 Mar 5. PMID: 29580532.
  28. Holmes RP, Knight J, Assimos DG. Lowering urinary oxalate excretion to decrease calcium oxalate stone disease. Urolithiasis. 2016 Feb;44(1):27-32. doi: 10.1007/s00240-015-0839-4. Epub 2015 Nov 27. PMID: 26614109; PMCID: PMC5114711.
  29. Pearle MS, Goldfarb DS, Assimos DG, Curhan G, Denu-Ciocca CJ, Matlaga BR, Monga M, Penniston KL, Preminger GM, Turk TM, White JR. Medical management of kidney stones: AUA guideline. J Urol. 2014;192(2):316–324.
  30. Ferraro PM, Curhan GC, Gambaro G, Taylor EN. Total, Dietary, and Supplemental Vitamin C Intake and Risk of Incident Kidney Stones. Am J Kidney Dis. 2016 Mar;67(3):400-7. doi: 10.1053/j.ajkd.2015.09.005. Epub 2015 Oct 14. PMID: 26463139; PMCID: PMC4769668.
  31. Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z. Ascorbic Acid Supplements and Kidney Stones Incidence Among Men and Women: A systematic review and meta-analysis. Urol J. 2019 May 5;16(2):115-120. doi: 10.22037/uj.v0i0.4275. PMID: 30178451.
  32. Duncan SH, Richardson AJ, Kaul P, Holmes RP, Allison MJ, Stewart CS. Oxalobacter formigenes and its potential role in human health. Appl Environ Microbiol. 2002;68(8):3841-3847. doi:10.1128/AEM.68.8.3841-3847.2002