Oxalates, Kidney Stones, Joint Pain: Green Smoothies and Your Genes

Green smoothies have been a health fad for quite a while now, but these health drinks can be a double-edged sword for some people due to their high oxalate content.

Oxalates, Kidney Stones, Joint Pain

Not all people benefit from large amounts of spinach due to its high oxalate content. Oxalates are chemical compounds found in foods. They can bind with calcium and be excreted through your intestines, or they can enter the bloodstream and eventually be excreted through the kidneys. It is where the problems can arise with oxalates causing kidney stones or other joint problems for some people.

As it turns out, genetics – along with the gut microbiome – play a role in your body’s ability to handle oxalates. Approximately 80% of kidney stones are composed of oxalates bound to calcium. A study from 2005 states that “5% of American women and 12% of men will develop a kidney stone at some time in their life, and prevalence has been rising in both sexes.”[ref]

Oxalates are found in fruits and vegetables – some fruits and vegetables contain high oxalate levels, and others just a tiny amount. When we eat plants high in oxalates, first, our gut microbiome takes care of breaking down part of the oxalates, and then our intestines will absorb some of the oxalates we have eaten.

Our body also creates different forms of oxalates when metabolizing various substances. The AGXT gene creates the enzyme responsible for breaking down glyoxylate into glycine.

When any of these pieces go awry — gut microbiome issues, too much absorption in the intestines, genetic variants — you can end up with kidney stones.[ref]

In addition to forming kidney stones, oxalate crystals can sometimes be deposited in joints, skin, and retina.[ref][ref] This can cause joint pain and inflammation.

Foods high in oxalates include:

  • spinach
  • Swiss chard
  • certain varieties of kale
  • arugula
  • blackberries
  • blueberries
  • raspberries
  • rhubarb
  • buckwheat

Here is a list: Foods that contain oxalates

Oxalates Genotype Report

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Take note that most of these genes increase the risk of calcium oxalate kidney stones, but some just increase the risk of kidney stones in general (not just oxalate kidney stones).

CaSR (calcium-sensing receptor) gene: This gene codes for a receptor that senses extracellular calcium levels in the kidneys.

Check your genetic data for rs1501899 (23andMe v4 only):

  • A/A: increased risk of calcium kidney stones[ref], increased risk in those with hyperparathyroidism[ref]
  • A/G: slightly increased risk of calcium kidney stones
  • G/G: typical

Members: Your genotype for rs1501899 is .

DGKH gene: Diacylglycerol Kinase Eta

Check your genetic data for rs4142110 (23andMe v4, v5; AncestryDNA):

  • T/T: decreased risk of kidney stones[ref]
  • C/T: decreased risk of kidney stones
  • C/C: typical risk of kidney stones

Members: Your genotype for rs4142110 is .

CLDN14 gene: The claudin-14 gene codes for a protein necessary for the tight junctions between epithelial cells.

Check your genetic data for rs219780 (23andMe v5; AncestryDNA):

  • C/C: typical
  • C/T: decreased risk of kidney stones
  • T/T: decreased risk of kidney stones[ref], no increased risk of hyperparathyroidism[ref]

Members: Your genotype for rs219780 is .

UMOD gene: The UMOD gene codes for uromodulin, the most abundant protein in the urine. It is responsible for inhibiting calcium crystals in the urine.

Check your genetic data for rs4293393 (23andMe v4, v5; AncestryDNA):

  • A/A: typical
  • A/G: increased risk of kidney stones[ref], lower uromodulin
  • G/G: lower uromodulin[ref] increased risk of kidney disease in diabetes[ref]

Members: Your genotype for rs4293393 is .

Primary hyperoxaluria genes:

The disease associated with a more serious metabolic defect causing too many oxalates to build up in the kidneys is called hyperoxaluria. It is caused by a deficiency in alanine-glyoxylate aminotransferase which can be caused by polymorphisms in several genes.[ref] There are three types of primary hyperoxaluria.

Primary Hyperoxaluria Type 1

AGXT (alanine-glyoxylate aminotransferase) is a gene coding for an enzyme found in the liver. It helps convert a form of oxalate made by the body (glyoxylate) into glycine. Insufficient enzyme production leads to excess oxalate for the kidneys to clear.

Primary Hyperoxaluria Type 1 is the name of kidney disease caused by calcium oxalate deposition.[ref][ref] Note that there are additional hyperoxaluria mutations that cannot be determined from 23andMe or AncestryDNA data.

Check your genetic data for rs34116584 (23andMe v4 only):

  • T/T: found in 50% of people with hyperoxaluria[ref][ref]
  • C/T: increased risk of hyperoxaluria (especially if coupled with another mutation)[ref]
  • C/C: typical

Members: Your genotype for rs34116584 is .

More information on rs34116584: This is one of the more common variants thought to contribute to hyperoxaluria and is found in over 10% of Caucasians. Also called P11L in studies, the variant is found in 50% of people with hyperoxaluria. Most who are affected carry two copies of the mutation.[ref] This variant is thought to act in conjunction with other SNPs to cause hyperoxaluria.[ref]

The genetic change causes the AGXT enzyme to be located in the mitochondria instead of the peroxisome, where it should be found to break down glyoxylate into glycine.[ref]

Primary Hyperoxaluria Type 2:

23andMe data includes a couple of mutations for hyperoxaluria, including i5012629 and i5012628 on the GRHPR gene.

Check your genetic data for rs180177309 (23andMe i5012629 v4, v5):

  • II or AAGT/AAGT: typical
  • DI or -/AAGT: carrier of a pathogenic allele for primary hyperoxaluria type 2
  • DD or -/-: primary hyperoxaluria type 2[ref]

Members: Your genotype for rs180177309 is .

Check your genetic data for rs80356708 (23andMe i5012628 v4, v5):

  • II (or G/G): typical
  • DI (or – / G): carrier of a pathogenic allele for primary hyperoxaluria type 2
  • DD (or -/-): primary hyperoxaluria type 2[ref]

Members: Your genotype for rs80356708 is .


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Originally published Oct. 2015. Updated 3/2019.

About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.

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