Green Smoothie Genes: Oxalates, Kidney Stones, Joint Pain

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 the 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. This 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 more complete list: Foods that contain oxalates


Genetic Variants that Increase Risk of Kidney Stones:

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Take note, 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 oxalates 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 that is important 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 the kidney disease caused by calcium oxalate deposition.[ref][ref] Note that there are additional hyperoxaluria mutations 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 found in over 10% of Caucasians. Also called P11L in studies, it is the polymorphism found in 50% of people who have 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 .


Lifehacks:

If you carry one of the pathogenic hyperoxaluria genetic variants, you should talk with your doctor and consider adopting a low oxalate diet. At the least, be aware of high oxalate foods and know how much you are consuming.

Vitamin B6 (as the active form, P5P) may be helpful in preventing kidney stones if you carry the genetic variants linked to primary hyperoxaluria type 1. There have been several studies as well as one clinical trial showing the effectiveness.[ref][ref] You can get the P5P form as a supplement at most health food stores and online.  Note that vitamin B6 is unlikely to help if you carry the rare mutations in the GRHPR gene for primary hyperoxaluria type 2.[ref]

Your gut microbiome plays a big role in oxalate metabolism as well.  Oxalobacter formigenes is a gut microbe that breaks down oxalates from our diet. The presence of this bacteria reduces the risk of oxalate-based kidney stones by 70%.[ref]

Worried about passing a kidney stone? Researchers have actually done studies showing that riding in the rear cars of a bumpy roller coaster is a fairly effective way to get a kidney stone to pass.  23 out of 36 people with kidney stones in the back of the coaster passed the stones (compared to only 4 out of 34 in the front).[ref]


Related Genes and Topics:

Familial Mediterranean Fever
Familial Mediterranean fever (FMF) is a genetic condition of inflammatory episodes that cause painful joints, pain in the abdomen, or pain in the chest, and is most often accompanied by a fever. FMF is often misdiagnosed as various pain-related conditions such as fibromyalgia, myofascial pain syndrome, or gouty arthritis.

Hacking Irritable Bowel Syndrome Based on Your Genes
There are multiple causes of irritable bowel syndrome (IBS), and genetics can definitely play a role in IBS symptoms. Pinpointing your genetic cause may help you to figure out the right solution for you.

Originally publish Oct. 2015. Updated 3/2019.