cognition

inflammation & autoimmunity

PARP1

Fight Oxidative Stress, Inflammation, and Brain Fog (PARP1)

Written by Matt Carland, PhD on August 19th, 2019

Your brain is highly sensitive to the effects of oxidative stress and inflammation – two of the main factors that cause “brain fog” and other cognitive problems. The PARP1 gene is a key player when it comes to determining how sensitive you are to these factors, and understanding how it works can give you a major advantage when it comes to protecting your brain and optimizing your overall cognitive ability!

The PARP1 Gene: Balancing DNA Repair vs. Inflammation

The PARP1 enzyme is activated whenever your body detects DNA damage in its cells. This enzyme then binds to the damaged DNA to “mark” it so that other natural repair processes can come in and start fixing the damage [R, R, R].

Although being able to repair your DNA is obviously a good thing, there’s a catch: PARP1 activation also triggers your body’s inflammatory response [R, R, R].

This makes sense because inflammation is a natural side-effect of damage to any part of our body. It is actually caused by our repair mechanisms doing their job – so inflammation itself isn’t necessarily a bad thing on its own! It’s only when it becomes excessive or chronic that it should be considered a problem [R, R].

Nonetheless, the trade-off between DNA repair and increased inflammation means that your levels of the PARP1 enzyme have to be held in a delicate balance to ensure optimal health. Too little of it, and your body and brain will be more susceptible to common forms of cellular DNA damage, such as oxidative stress – but too much of it, and you will be more likely to experience chronic inflammation!

PARP1_figure

The PARP1 enzyme helps repair your DNA from damage – but in the process it also activates inflammatory responses. Therefore, your PARP1 levels need to be held in a delicate balance to ensure optimal health.

PARP1 and Cognitive Function

Oxidative stress and inflammation are obviously important for many aspects of your overall health. However, your brain is especially sensitive to the negative impact of these factors, which means that one of the earliest symptoms of oxidative stress or chronic inflammation is often impaired cognitive functioning, as well as other psychological symptoms, such as disrupted mood [R, R, R].

In fact, inflammation and oxidative stress are some of the main causes of common, hard-to-treat health conditions, such as “brain fog” [R, R].

The fact that your brain is particularly sensitive to the actions of PARP1 is probably why SNPs in this gene have been associated with diverse cognitive functions, such as cognitive flexibility (executive function), learning & memory, general intelligence (IQ), and even the size of certain key brain regions, such as the hippocampus [R, R, R].

Your brain is especially sensitive to the effects of PARP1 activity, which is why this gene can influence many aspects of your overall cognitive ability, and can even cause chronic “brain fog.”

How is Your PARP1 Genotype Affecting Your Brain?

Below you can see your genotype for the PARP1 SNP rs7515023, which plays a significant role in determining how vulnerable your brain is to oxidative stress and inflammation [R]:

SNP Table

variant	genotype	frequency	risk allele
rs7515023

The two possible alleles for this SNP are ‘C’ and ‘T’ – and when it comes to optimal cognitive function, it’s better to have the minor ‘T’ allele.

People who carry this allele tend to have PARP1 gene levels that are better regulated, which helps keeps them closer to the “sweet spot” between having too low or too high levels of the active PARP1 enzyme [R, R].

This, in turn, reduces their overall risk of experiencing the potential cognitive symptoms of oxidative stress and inflammation, such as brain fog. And because the beneficial effects of the ‘T’ allele are “additive”, two copies are even better than one [R]!

The more ‘T’ alleles you carry for rs7515023, the less vulnerable you are to oxidative stress and inflammation. This, in turn, reduces your relative risk of experiencing cognitive issues, such as “brain fog.”

Recommendations

What Can You Do About Your PARP1 Genotype?

Because PARP1 can have undesirable effects when it is too high or too low, we don’t recommend trying to affect your levels of the PARP1 gene directly.

However, you can steps to protect your brain – and therefore enhance your cognitive functioning – by addressing the root causes of these negative effects: oxidative stress and inflammation.

One great compound that fights against both of these factors at the same time is pyrroloquinoline quinone (PQQ).

For example, supplementing with PQQ dramatically decreases levels of inflammatory markers such as interleukin-6 (IL-6), nitric oxide (NOS), and C-reactive protein [R, R].

PQQ is also a remarkable antioxidant – for example, it is up to 100 times more effective at breaking down harmful free radicals compared to other common antioxidants, such as vitamin C [R, R, R].

PQQ also improves mitochondrial function. Abnormal mitochondrial activity is another one of the major factors that can worsen oxidative stress [R, R].

Supplementing with PQQ enhances cognitive function in rats – most likely because it is protecting their brains from the harmful effects of oxidative stress [R, R].

You can get PQQ from several common dietary sources, including green tea, leafy green vegetables like spinach, and soybeans or other soy-based products such as tofu and nattō. PQQ supplements are also available [R, R]!

Another great way to tackle oxidative stress and inflammation at their root is to use low-level laser therapy (LLLT).

LLLT involves shining a specially-designed set of lights (usually LEDs) on whatever part of the body you’re trying to treat – in this case, the head. Certain wavelengths of light then pass through your skin and bones to stimulate various biological processes that help reduce inflammation, increase blood flow, and many other major health benefits.

LLLT is especially effective at treating inflammation. For example, one of the ways that PARP1 causes inflammation is by activating nuclear factor kappa-beta (NF-kβ), a protein that stimulates the production of pro-inflammatory cytokines [R, R]. However, one of the main beneficial effects of LLLT is to inhibit NF-kβ, making it especially ideal when it comes to counteracting the potential negative effects of your PARP1 genotype [R, R, R, R]!

LLLT also decreases many other inflammatory markers, such as TNF-alpha, COX-2, nitric oxide synthase (NOS), and several types of interleukins (such as IL-1 and IL-6) [R, R, R].

LLLT also has other major health benefits that are especially critical for your brain, such as reducing oxidative stress [R, R] and increasing your production of BDNF and NGF [R, R].

Altogether, these many diverse benefits may explain why LLLT has also been associated with significant cognitive benefits, including improved attention, learning, and memory [R, R]. It also has other psychological benefits, such as boosting your mood [R, R]!

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.

More cognition blogs

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Content

The PARP1 Gene: Balancing DNA Repair vs. Inflammation PARP1 and Cognitive Function How is Your PARP1 Genotype Affecting Your Brain?

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