cognition

UGT2A1

Is Your Low Glutathione Causing Brain Fog? (UGT2A1)

Written by Matt Carland, PhD on August 27th, 2019

Oxidative stress can be responsible for a wide variety of health problems, such as inflammation and DNA damage. Your brain is particularly sensitive to these negative effects, which means that reducing oxidative stress is critical for ensuring optimal cognitive function! Read on to learn more about UGT2A1, a very important gene for fighting the negative influence of oxidative stress throughout your body and brain.

What Is Oxidative Stress, And Why Is It Important?

Oxidative stress is caused by the build-up of reactive oxygen species (ROS), sometimes also known as “free radicals”. These are types of molecules that can cause damage to many different types of cells [R].

Normally, your body uses free radicals to do helpful things, such as killing invading bacteria, or causing damaged cells to “self-destruct” so that they don’t go on to cause cancers or other major health problems [R, R, R].

However, when too many free radicals build up, they can start having negative effects on normal, healthy cells. This can cause widespread problems throughout the body and brain, such as damaging cells’ DNA, or triggering systemic inflammation [R].

Therefore, your body needs to keep a careful balance between producing just enough free radicals to be useful, while also producing enough of the natural antioxidant compounds that help break these down so that they don’t build up and cause widespread damage [R].

Oxidative stress is caused by the excessive build-up of “free radicals,” which can trigger a variety of health issues such as chronic inflammation and DNA damage.

What Does The UGT2A1 Gene Do?

This is where the UGT2A1 gene comes in. This important gene codes for a protein called UDP glucuronosyltransferase. This protein helps create glutathione, one of your body’s strongest natural antioxidant defenses against the harmful effects of oxidative stress [R, R, R].

Glutathione binds directly to reactive oxygen species and neutralizes them, thereby preventing them from causing damage to cells [R].

Although oxidative stress can affect many different aspects of your health, your brain is especially sensitive to the negative effects of oxidative stress. Therefore, the variants you carry in this gene can have significant effects on your overall cognitive functioning by determining how much glutathione you produce. The more glutathione you have, the more your brain is protected against inflammation and cellular DNA damage [R, R].

Maintaining proper glutathione levels in the brain can also help prevent cognitive decline due to normal aging and protect you against cognitive impairments from neurodegenerative diseases (such as Parkinson’s disease) [R, R].

UGT2A1 helps produce glutathione, one of your body’s strongest natural antioxidant defenses. The more glutathione you have, the better protected your brain is against many different factors that can potentially reduce your cognitive ability.

Your UGT2A1 Genotype

You can see your genotype for the UGT2A1 SNP rs10518065 in the table below:

SNP Table

variant	genotype	frequency	risk allele
rs10518065

The two possible alleles for this SNP are ‘A’ and ‘G’. When it comes to optimal cognitive function, it’s better to have two copies of the more common major ‘A’ allele (which about 70% of the general population carries).

For example, a large-scale study with over 3,000 participants found that this UGT2A1 SNP was significantly associated with overall intelligence levels, as measured by a large and diverse range of cognitive tests. People with the ‘A’ allele performed better across all of these tests, whereas people with the rarer ‘G’ allele tended to show relatively poorer cognitive performance [R].

Because increased oxidative stress has been associated with a wide variety of cognitive impairments in many different human populations, this strongly suggests that the negative effects of the ‘G’ allele are likely due to decreased production of glutathione [R, R].

In other words, people who carry the ‘A’ allele are better protected against oxidative stress, whereas people with the ‘G’ allele are more vulnerable.

Carriers of the ‘G’ allele for rs10518065 tend to have lower levels of general intelligence – most likely because they produce less glutathione, which makes their brain more vulnerable to the negative effects of oxidative stress.

Recommendations

What Can You Do About UGT2A1 Risk Factors?

If you carry the ‘G’ allele for this SNP, don’t worry! There are several steps you can take to counteract the negative effect that your genotype might be having on your overall cognitive ability.

Because this gene helps produce the antioxidant glutathione, there are two main approaches you can take to enhance your cognitive function: the first is to boost the activity of this gene directly, and the second is to increase your overall levels of glutathione in general.

Lifestyle

One potential way to directly increase this gene’s activity is to ensure that you get plenty of cognitive stimulation. For example, animal studies have found that the UGT2A1 gene is expressed more (“up-regulated”) when animals live in an enriched environment; that is, when they are constantly learning and experiencing new things [R]. This suggests that keeping your brain active – such as by learning new skills or using cognitive training programs – could be a great way to give your UGT2A1 gene a boost!

Supplements

As for increasing your overall glutathione levels, there are many different supplements that can potentially raise glutathione levels. However, many of these can have trouble getting to the brain before they are broken down by the liver, which can significantly reduce their overall effectiveness when it comes to boosting cognitive function [R, R, R, R, R]. Therefore, we recommend two specific glutathione-boosting supplements that don’t suffer from these limitations.

One of these is liposomal glutathione, a special formulation of glutathione that readily passes through the blood-brain barrier, allowing it to act on the brain directly [R, R].

This liposomal form effectively increases overall levels of glutathione in both the blood and the brain. It fights oxidative stress, stimulates the immune system, and even enhances the body’s ability to recover from physical exertion [R, R, R]. Therefore, liposomal glutathione would be a great supplement choice for carriers of the ‘G’ allele – especially for athletes and anyone else who exercises regularly!

Another effective form of glutathione supplement is N-acetylcysteine (NAC), a compound that is a key “ingredient” (metabolic precursor) of glutathione. NAC, therefore, boosts your levels of this critical antioxidant by supplying your body with the raw materials it needs to create glutathione naturally [R, R].

In fact, not only does NAC counteract oxidative stress, but it also fights inflammation, stimulates neurogenesis, and even enhances cognitive function directly [R, R] – once again making this a great supplement choice for anyone who carries risk alleles in their UGT2A1 gene!

The best ways to counteract potential UGT2A1 risk factors are with supplements that increase the levels of glutathione, as well as getting plenty of cognitive stimulation in your daily routine.

Matt Carland

PhD

Matt received his PhD at the Université de Montréal in Neuroscience.

Matt holds multiple degrees in psychology, cognitive science, and neuroscience. He has over a decade of experience in academic research and has published a number of articles in scholarly journals. He currently works as a neuropsychologist in Montreal, where he performs research on the links between personality traits and the development of clinical disorders such as addiction, compulsive gambling, and disordered eating.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

Content

What Is Oxidative Stress, And Why Is It Important? Your UGT2A1 Genotype

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